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Pathophysiology of cns 2017

The document discusses the nervous system and its role in disease pathogenesis. It notes that the nervous system participates in the pathology of diseases through both defensive responses as well as becoming damaged itself. When damaged, the nervous system can become a source of harmful reflexes and disturbances in nervous activity are always reflected in the function of internal organs. Later sections discuss specific neurological disorders like Parkinson's and Alzheimer's disease.

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Actuality of the lectureActuality of the lecture  The nervous system as a main regulatory system of an organism in this orThe nervous system as a main regulatory system of an organism in this or that measure participates in pathogenesis of each diseases. The earliest andthat measure participates in pathogenesis of each diseases. The earliest and obligatory form of participation of the nervous system in pathology isobligatory form of participation of the nervous system in pathology is defensive and adaptive the response. The protective reflexes (cough,defensive and adaptive the response. The protective reflexes (cough, vomiting), protective inhibition, response hypotalamo-hypophysial-adrenalvomiting), protective inhibition, response hypotalamo-hypophysial-adrenal system belong to such responses.system belong to such responses.  At the same time during development of diseases the nervous systemAt the same time during development of diseases the nervous system becomes the object of a defeat itself. It is defensive and adaptive thebecomes the object of a defeat itself. It is defensive and adaptive the response of the damaged nervous system are reduced, and it becomes aresponse of the damaged nervous system are reduced, and it becomes a source of pathological, harmful to an organism reflexes. Itself graving andsource of pathological, harmful to an organism reflexes. Itself graving and character of violations of nervous activity depend on localization ofcharacter of violations of nervous activity depend on localization of pathological process and appear as a complex of diverse symptoms.pathological process and appear as a complex of diverse symptoms. Frequently there is a pain, which on the essence is typical pathologicalFrequently there is a pain, which on the essence is typical pathological process, but at the same time has signal and adaptive significance. Theprocess, but at the same time has signal and adaptive significance. The disturbance of nervous activity is always reflected in the function of internaldisturbance of nervous activity is always reflected in the function of internal organs.organs.  Several neurologic disorders in which some of the molecular mechanisms ofSeveral neurologic disorders in which some of the molecular mechanisms of pathogenesis are known are discussed later in this chapter including motorpathogenesis are known are discussed later in this chapter including motor neuron disease, Parkinson's disease, myasthenia gravis, epilepsy, Alzheimer'sneuron disease, Parkinson's disease, myasthenia gravis, epilepsy, Alzheimer's disease, and stroke.disease, and stroke.  Exciting advances in our understanding and overlap of these diseases areExciting advances in our understanding and overlap of these diseases are leading to new therapeutic targets and the hope of better treating theseleading to new therapeutic targets and the hope of better treating these devastating diseases.devastating diseases.
CONTENTCONTENT • Nervous System: NeuronsNervous System: Neurons • Division of the Nervous SystemDivision of the Nervous System • Pain: features of pain as a kind of sensitivity. Etiology andPain: features of pain as a kind of sensitivity. Etiology and pathogenesis of pain. Antinociceptive systemspathogenesis of pain. Antinociceptive systems • Upper Motor NeuronsUpper Motor Neurons and Disordersand Disorders • Sensory LossSensory Loss • Spinal Cord InjuriesSpinal Cord Injuries • DysphasiaDysphasia • Diseases of the Basal GangliaDiseases of the Basal Ganglia • Disorders of integrative function of CNS.Disorders of integrative function of CNS. • Anxiety Disorders; Mood Disorders; SchizophreniaAnxiety Disorders; Mood Disorders; Schizophrenia • Acute and chronic disturbances of brain circulation. StrokeAcute and chronic disturbances of brain circulation. Stroke • Cerebral infarction and cerebral hemorrhage.Cerebral infarction and cerebral hemorrhage. • Seizure disorders. Epilepsy; Sleep Disorders; AphasiasSeizure disorders. Epilepsy; Sleep Disorders; Aphasias • Disorders of Memory. Alzheimer’s Disease. Creutzfeldt–Disorders of Memory. Alzheimer’s Disease. Creutzfeldt– Jakob diseaseJakob disease
FunctionFunction of neuronsof neurons  A). Sensory inputA). Sensory input  B). IntegrationB). Integration  C). ResponseC). Response
A). Non nervousA). Non nervous or glial cellsor glial cells.. 1). Astrocytes1). Astrocytes 2). Microglia2). Microglia 3). Ependymal3). Ependymal 4). Oliodendrocytes4). Oliodendrocytes 5). Satellite cells5). Satellite cells 6).6). Schwann cellsSchwann cells form myelin sheathsform myelin sheaths Types of cellsTypes of cells
Types ofTypes of cellscellsB). NeuronsB). Neurons 1). Structure1). Structure II).). cell bodycell body oror somasoma -- endoplasmicendoplasmic reticulum called thereticulum called the nissl bodynissl body.. IIII).). ProcessesProcesses oror tracts (nerves)tracts (nerves) a).a). Dendrites:Dendrites: input regioninput region b).b). Axon:Axon: Carries information awayCarries information away c).c). Synaptic knobsSynaptic knobs oror AxonalAxonal terminalsterminals.. ReleasesReleases neurotransmitters.neurotransmitters. 2).2). AxonsAxons a).a). myelin sheathmyelin sheath -- protects andprotects and electrically insulates fibers conductelectrically insulates fibers conduct nerve impulses faster thannerve impulses faster than nonmylenated fibers.nonmylenated fibers. b).b). nodes of Ranviernodes of Ranvier:: spaces between the sheathsspaces between the sheaths The action potential skips to the nodesThe action potential skips to the nodes
Nerve ImpulseNerve Impulse A). TermsA). Terms 1).1). Resting membrane PotentialResting membrane Potential::  PolarizedPolarized 2).2). DepolarizationDepolarization::  Change in ion concentrationChange in ion concentration 3).3). HyperpolarizationHyperpolarization  Change in ion concentration insideChange in ion concentration inside becomes more negativebecomes more negative 4).4). Graded PotentialGraded Potential  Localized change in ion; subthresholdLocalized change in ion; subthreshold 5).5). Action PotentialAction Potential  Change in ion concentration thatChange in ion concentration that does not decrease over distance.does not decrease over distance. B).B). Action PotentialAction Potential Stages of an Action PotentialStages of an Action Potential polarized resting potentialpolarized resting potential depolarizesdepolarizes repolarizesrepolarizes undershoot phaseundershoot phase UndershooUndershoott :: the K+ channels stay openthe K+ channels stay open once resting potential is reached;once resting potential is reached; hyperpolarizing the cell.hyperpolarizing the cell.
NerveNerve ImpulseImpulse C).C). PropagationPropagation  Cannot be depolarized again until the membrane hasCannot be depolarized again until the membrane has reached resting potential. The action potential moves at areached resting potential. The action potential moves at a constant velocityconstant velocity D).D). All or none phenomenonAll or none phenomenon  Not all depolarizations result in action potentialsNot all depolarizations result in action potentials.. TheThe depolarization must reach thedepolarization must reach the threshold pointthreshold point E).E). Refractory periodRefractory period  AAbsolute refractory periodbsolute refractory period cannot respond to anothercannot respond to another stimuli.stimuli.  RRelative refractory periodelative refractory period -- tthe threshold is higherhe threshold is higher F). Impulse VelocityF). Impulse Velocity  Strong stimuli result in more nerve impulses NotStrong stimuli result in more nerve impulses Not stronger impulses or fasterstronger impulses or faster
SynapseSynapse –– junction that carriesjunction that carries information between neuronsinformation between neurons  A). TypesA). Types 1). Electrical synapse: ions to cross junction1). Electrical synapse: ions to cross junction 2). Chemical synapse2). Chemical synapse  neurotransmittersneurotransmitters B). Termination of neurotransmitterB). Termination of neurotransmitter  1). Degradation enzymes1). Degradation enzymes  2). Neurotransmitter reabsorbed2). Neurotransmitter reabsorbed  3). Diffusion of the neurotransmitter3). Diffusion of the neurotransmitter ImpulseImpulse releasesreleases Ca++ (in neuron)Ca++ (in neuron) ± neurotransmitter released ± binds to receptors± neurotransmitter released ± binds to receptors ±± ion channels open on postsynaptic membraneion channels open on postsynaptic membrane
Neurotransmitters A). Acetylcholine (ACh) B). Biogenic Amines • 1). Dopamine • 2). Norepinephrine • 3). Epinephrine • 4). Serotonin C). Amino Acids D). Peptides • 1). endorphins E). Novel or Miscellaneous
Division of the Nervous System A). Central Nervous System: (CNS) • Brain and Spinal Cord only B). Peripheral Nervous System • Outside CNS 1). Sensory or afferent division: • Carries impulses to CNS 2). Motor or efferent division • Carries impulses from the CNS. I). Somatic Nervous System • voluntary II). Autonomic Nervous System • involuntary • a. Parasympathetic • b. Sympathetic
The SympatheticThe Sympathetic Nervous SystemNervous System  TheThe first fibersfirst fibers of the sympathetic nerves, called theof the sympathetic nerves, called the preganglionic fiberspreganglionic fibers, leave from the thoracic or lumbar, leave from the thoracic or lumbar regions of the spine.regions of the spine.  Soon afterSoon after leaving the spineleaving the spine, a preganglionic fiber, a preganglionic fiber joinsjoins other preganglionic fibersother preganglionic fibers to form anto form an autonomic ganglionautonomic ganglion..  At this point, theAt this point, the preganglionic fiber synapsespreganglionic fiber synapses on theon the second nerve fiber of the systemsecond nerve fiber of the system, the, the postganglionic fiberpostganglionic fiber,, andand releases acetylcholinereleases acetylcholine, which causes the, which causes the postganglionic fiber to fire anpostganglionic fiber to fire an action potentialaction potential..  From theFrom the autonomic gangliaautonomic ganglia, the postganglionic fiber travels, the postganglionic fiber travels to itsto its target organtarget organ, the muscle or gland., the muscle or gland.  TheThe sympathetic postganglionic fibersympathetic postganglionic fiber usually releases theusually releases the neurotransmitter norepinephrineneurotransmitter norepinephrine.. Target organ receptors forTarget organ receptors for norepinephrinenorepinephrine are calledare called adrenergic receptorsadrenergic receptors..
The Parasympathetic Nervous SystemThe Parasympathetic Nervous System  The fibers of the parasympathetic nervous systemThe fibers of the parasympathetic nervous system (PNS)(PNS) leave the brain in the cranial nervesleave the brain in the cranial nerves oror leave the spinal cordleave the spinal cord from the sacral areafrom the sacral area..  TheThe preganglionic fiberpreganglionic fiber of theof the PNSPNS is typically long and travelsis typically long and travels to an autonomic ganglionto an autonomic ganglion locatedlocated near the target organnear the target organ..  Preganglionic parasympathetic nervesPreganglionic parasympathetic nerves releaserelease acetylcholineacetylcholine thatthat then stimulates the postganglionic fiberthen stimulates the postganglionic fiber..  TheThe parasympathetic postganglionic fiberparasympathetic postganglionic fiber then travels a shortthen travels a short distancedistance to its target tissueto its target tissue, a, a muscle or a glandmuscle or a gland. This nerve. This nerve also releases acetylcholinealso releases acetylcholine..  Preganglionic acetylcholine receptorsPreganglionic acetylcholine receptors for sympathetic andfor sympathetic and parasympathetic fibersparasympathetic fibers are calledare called nicotinic receptorsnicotinic receptors ..  Postganglionic acetylcholine receptorsPostganglionic acetylcholine receptors are calledare called muscarinicmuscarinic receptorsreceptors. These names relate to the experimental. These names relate to the experimental stimulation of the receptors bystimulation of the receptors by nicotinenicotine andand muscarinemuscarine (a(a mushroom poison).mushroom poison).
The Autonomic Nervous System Structure Sympathetic Stimulation Parasympathetic Stimulation Iris (eye muscle) Pupil dilation Pupil constriction Salivary Glands Saliva production reduced Saliva production increased Oral/Nasal Mucosa Mucus production reduced Mucus production increased Heart Heart rate and force increased Heart rate and force decreased Lung Bronchial muscle relaxed Bronchial muscle contracted Stomach Peristalsis reduced Gastric juice secreted; motility increased Small Intestine Motility reduced Digestion increased Large Intestine Motility reduced Secretions and motility increased Liver Increased conversion of glycogen to glucose --- Kidney Decreased urine secretion Increased urine secretion Adrenal medulla Norepinephrine and epinephrine secreted --- Bladder Wall relaxed Sphincter closed Wall contracted Sphincter relaxed
THE SOMATOSENSORY SYSTEMTHE SOMATOSENSORY SYSTEM ■■ The somatosensory system relays information to theThe somatosensory system relays information to the CNS about four major body sensations:CNS about four major body sensations: touch,touch, temperature,temperature, pain,pain, body positionbody position.. Stimulation of receptorsStimulation of receptors on regions of the body wall ison regions of the body wall is required torequired to initiate the sensory response.initiate the sensory response. ■■ The system is organized intoThe system is organized into dermatomesdermatomes, with each, with each segment supplied by asegment supplied by a single dorsal root ganglionsingle dorsal root ganglion thatthat sequentially relays the sensory information tosequentially relays the sensory information to thethe spinal cord, the thalamus, and the sensoryspinal cord, the thalamus, and the sensory cortexcortex.. ■■ Two pathwaysTwo pathways carry sensory information throughcarry sensory information through thethe CNSCNS. The. The discriminative pathwaydiscriminative pathway crosses in thecrosses in the medulla and relaysmedulla and relays touchtouch andand body positionbody position. The. The anterolateral pathwayanterolateral pathway crosses in the spinal cordcrosses in the spinal cord andand relaysrelays temperaturetemperature andand pain sensationpain sensation fromfrom thethe opposite side of the body.opposite side of the body.
Kinds of SensitivityKinds of Sensitivity 1.1. PainfulPainful 2.2. TemperatureTemperature 3.3. TactileTactile 4.4. ProprioceptiveProprioceptive
DEFINITION OF PAINDEFINITION OF PAIN  PAINPAIN –– it is typical pathological processit is typical pathological process,, whichwhich was generated during evolutionwas generated during evolution andand which arise owing to action on an organismwhich arise owing to action on an organism painfulpainful ((nociceptivenociceptive)) irritantirritant oror weakeningweakening ofof antipainfulantipainful ((antinociceptiveantinociceptive)) systemsystem  PainPain is an “unpleasant sensory andis an “unpleasant sensory and emotional experience associatedemotional experience associated withwith potential tissue damage, or described inpotential tissue damage, or described in terms ofterms of such damage.”such damage.”
CLASSIFICATION OF PAIN • Physiological pain • Pathological pain • Acute pain • Chronical pain MEDIATORS OFMEDIATORS OF PAINPAIN• Substanse Р • Glutamic acid • Cholecystokinin • Neurotensin
TYPES OF PAINTYPES OF PAIN  Pain can be classified according to  location,  site of referral, and  duration.  Cutaneous pain is a sharp, burning pain that has its origin in the skin or subcutaneous tissues.  Deep pain is a more diffuse and throbbing pain that originates in structures such as the muscles, bones, and tendons and radiates to the surrounding tissues.  Visceral pain is a diffuse and poorly defined pain that results from stretching, distention, or ischemia of tissues in a body organ.  Referred pain is pain that originates at a visceral site but is perceived as originating in part of the body wall that is innervated by neurons entering the same segment of the nervous system.  Acute pain usually results from tissue damage and is characterized by autonomic nervous system responses.  Chronic pain is persistent pain that is accompanied by loss of appetite, sleep disturbances, depression,
PAIN SENSATION ■ Pain is both a protective and an unpleasant physical and emotionally disturbing sensation originating in pain receptors that respond to a number of stimuli that threaten tissue integrity. ■ There are two pathways for pain transmission: • The fast pathway for sharply discriminated pain that moves directly from the receptor to the spinal cord using myelinated Aδ fibers and from the spinal cord to the thalamus using the neospinothalamic tract • The slow pathway for continuously conducted pain that is transmitted to the spinal cord using unmyelinated C fibers and from the spinal cord to the thalamus using the more circuitous and slower-conducting paleospinothalamic tract. ■ The central processing of pain information includes transmission to the somatosensory cortex, where pain information is perceived and interpreted; the limbic system, where the emotional components of pain are experienced; and to brain stem centers, where autonomic nervous system responses are recruited. ■ Modulation of the pain experience occurs by way of the endogenous analgesic center in the midbrain, the pontine noradrenergic neurons, and the nucleus raphe magnus in the medulla, which sends inhibitory signals to dorsal horn neurons in the spinal cord.
Primary pain pathways NociceptiveNociceptive stimulistimuli Somesthetic association cortexSomesthetic association cortex (perception and meaning)(perception and meaning) Limbic cortexLimbic cortex (emotional experience)(emotional experience) PontinePontine noradrenergic neuronsnoradrenergic neurons Primary somesthetic cortexPrimary somesthetic cortex (discrimination: location and intensity)(discrimination: location and intensity) Medullary raphe nucleusMedullary raphe nucleus Thalamus (sensation)Thalamus (sensation) Somesthetic nucleiSomesthetic nuclei Spinal cord and dorsal hornSpinal cord and dorsal horn pain modulating circuitspain modulating circuits Periaqueductal gray (PAG)Periaqueductal gray (PAG) (endogenous analgesic center)(endogenous analgesic center) Medullary NRMMedullary NRM NeospinothalamictractNeospinothalamictract (sharp,brightpain)(sharp,brightpain) PaleospinothalamictractPaleospinothalamictract (dull,achingpain)(dull,achingpain) Primary touch fibers A-delta (fast) C-fiber (slow)
Characteristics ofCharacteristics of Acute and Chronic PainAcute and Chronic Pain Characteristic Acute Pain Chronic Pain Onset Recent Continuous or intermittent Duration Short duration (<6 months) 6 months or more Autonomic responses Consistent with sympathetic fight- or-flight response* Increased heart rate Increased stroke volume Increased blood pressure Increased pupillary dilation Increased muscle tension Decreased gut motility Decreased salivary flow (dry mouth) Absence of autonomic responses Psychological component Associated anxiety Increased irritability Associated depression Somatic preoccupation Withdrawal from outside interests Decreased strength of relationships Other types of response Decreased sleep Decreased libido Appetite changes
Pain Threshold and Tolerance Cando Baseline Dolorimeter  Pain threshold and tolerance affect an individual’s response to a painful stimulus. Although the terms often are used interchangeably, pain threshold and pain tolerance have distinct meanings. Pain threshold is closely associated with tissue damage and the point at which a stimulus is perceived as painful.  Pain tolerance relates more to the total pain experience; it is defined as the maximum intensity or duration of pain that a person is willing to endure before the person wants something done about the pain. Psychological, familial, cultural, and environmental factors significantly influence the amount of pain a person is willing to tolerate. The threshold to pain is fairly uniform from one person to another, whereas pain tolerance is extremely variable. Separation and identification of the role of each of these two aspects of pain continue to pose fundamental problems for the pain management team and for pain researchers.
Alterations in Pain Sensitivity  Hypersensitivity (i.e., hyperesthesia) or increased painfulness (i.e., hyperalgesia)  Primary hyperalgesia occurs at the site of injury.  Secondary hyperalgesia occurs in nearby uninjured tissue.  Hyperpathia is a syndrome in which the sensory threshold is raised, but when it is reached, continued stimulation, especially if repetitive, results in a prolonged and unpleasant experience. This pain can be explosive and radiates through a peripheral nerve distribution. It is associated with pathologic changes in peripheral nerves, such as localized ischemia.  Spontaneous, unpleasant sensations called paresthesias occur with more severe irritation (e.g., the pins-and-needles sensation that follows temporary compression of a peripheral nerve).  The general term dysesthesia is given to distortions (usually unpleasant) of somesthetic sensation that typically accompany partial loss of sensory innervation.
Alterations in Pain Sensitivity • Severe pathologic processes can result in reduced or lost tactile (e.g., hypoesthesia, anesthesia), temperature (e.g., hypothermia, athermia), and pain sensation (i.e., hypalgesia). • Analgesia is the absence of pain on noxious stimulation or the relief of pain without loss of consciousness. The inability to sense pain may result in trauma, infection, and even loss of a body part or parts. Inherited insensitivity to pain may take the form of congenital indifference or congenital insensitivity to pain. • Allodynia (Greek allo, “other,” and odynia, “painful”) is the term used for the puzzling phenomenon of pain that follows a non-noxious stimulus to apparently normal skin. This term is intended to refer to instances in which otherwise normal tissues may be abnormally innervated or may be referral sites for other loci that give rise to pain with non-noxious stimuli. • Trigger points are highly localized points on the skin or mucous membrane that can produce immediate intense pain at that site or elsewhere when stimulated by light tactile stimulation.
CHRONICAL PAINFUL SYNDROMES Phantom pain Causalgia Neuralgia Eccentric pain Projectional pain
NeuralgiaNeuralgia  NeuralgiaNeuralgia is characterized by severe, brief,is characterized by severe, brief, often repetitive attacksoften repetitive attacks of lightning-like orof lightning-like or throbbing pain. It occurs along the distributionthrobbing pain. It occurs along the distribution ofof a spinal or cranial nerve and usually isa spinal or cranial nerve and usually is precipitatedprecipitated by stimulation of the cutaneousby stimulation of the cutaneous region supplied by that nerve.region supplied by that nerve.  Trigeminal Neuralgia.Trigeminal Neuralgia. Trigeminal neuralgia, orTrigeminal neuralgia, or tictic douloureuxdouloureux,, is one of theis one of the most common and severemost common and severe neuralgias. It is manifestedneuralgias. It is manifested byby facial ticsfacial tics oror grimacesgrimaces and characterized byand characterized by stabbing,stabbing, paroxysmalparoxysmal attacks of pain that usuallyattacks of pain that usually are limited to the unilateralare limited to the unilateral sensory distribution of onesensory distribution of one or more branches of theor more branches of the trigeminal nerve, mosttrigeminal nerve, most often the maxillary oroften the maxillary or mandibular divisions.mandibular divisions.
Postherpetic Neuralgia.Postherpetic Neuralgia. Postherpetic pain is painPostherpetic pain is pain that persiststhat persists as aas a complication of herpescomplication of herpes zoster or shingles. Itzoster or shingles. It describes thedescribes the presence ofpresence of pain more than 1 monthpain more than 1 month after the onset of theafter the onset of the acuteacute attack.attack. Postherpetic neuralgiaPostherpetic neuralgia develops in from 10% todevelops in from 10% to 70% of70% of patients withpatients with shingles; the riskshingles; the risk increases with age.increases with age. The pain ofThe pain of postherpeticpostherpetic neuralgia occurs in theneuralgia occurs in the areas of innervation ofareas of innervation of thethe infected gangliainfected ganglia.. During the acute attack ofDuring the acute attack of herpes zosterherpes zoster, the, the reactivated virus travelsreactivated virus travels from the ganglia to thefrom the ganglia to the skin of the correspondingskin of the corresponding dermatomes, causingdermatomes, causing localized vesicularlocalized vesicular eruptioneruption and hyperpathiaand hyperpathia ((i.e.i.e., abnormally, abnormally exaggerated subjectiveexaggerated subjective responseresponse to pain).to pain).
Postherpetic Neuralgia
Phantom Limb Pain • Phantom limb pain, a type of neurologic pain, follows amputation of a limb or part of a limb. As many as 70% of those who under amputation experience phantom pain. • The pain often begins as sensations of tingling, heat and cold, or heaviness, followed by burning, cramping, or shooting pain. It may disappear spontaneously or persist for many years. One of the more troublesome aspects of phantom pain is that the person may experience painful sensations that were present before the amputation, such as that of a painful ulcer or bunion.
• Several theories have been proposed as to the causes of phantom pain. • One theory is that the end of a regenerating nerve becomes trapped in the scar tissue of the amputation site. It is known that when a peripheral nerve is cut, the scar tissue that forms becomes a barrier to regenerating outgrowth of the axon. The growing axon often becomes trapped in the scar tissue, forming a tangled growth (i.e., neuroma) of smalldiameter axons, including primary nociceptive afferents and sympathetic efferents. It has been proposed that these afferents show increased sensitivity to innocuous mechanical stimuli and to sympathetic activity and circulating catecholamines. • A related theory moves the source of phantom limb pain to the spinal cord, suggesting that the pain is caused by the spontaneous firing of spinal cord neurons that have lost their normal sensory input from the body. In this case, a closed self-exciting neuronal loop in the posterior horn of the spinal cord is postulated to send impulses to the brain, resulting in pain. Even the slightest irritation to the amputated limb area can initiate this cycle. • Other theories propose that the phantom limb pain may arise in the brain. In one hypothesis, the pain is caused by changes in the flow of signals through somatosensory areas of the brain. • Treatment of phantom limb pain has been accomplished by the use of sympathetic blocks, TENS of the large myelinated afferents innervating the area, hypnosis, and relaxation training.
Antinociceptive systemsAntinociceptive systems  NeuronalNeuronal opiate systemopiate system –– metmet-- and leuencephalinand leuencephalin  NeuronalNeuronal unopiate systemunopiate system –– noradrenalinnoradrenalin,, serotoninserotonin,, dopaminedopamine  HormonalHormonal opiate systemopiate system –– hormoneshormones ofof adenohypophysisadenohypophysis  HormonalHormonal unopiate systemunopiate system –– vasopressinvasopressin
Hormonal unopiate systemHormonal unopiate system  1.1. Adrenocorticotropic hormoneAdrenocorticotropic hormone  2.2. MelanostimulatingMelanostimulating hormoneshormones  3.3. ββ --LipotropicLipotropic hormonehormone  4.4. LargeLarge endorphinesendorphines:: kitorphinkitorphin ββ--kosomorphinkosomorphin dinorphindinorphin
1.1. Opening of abscessOpening of abscess 2.2. Reposition ofReposition of fragmentsfragments 3.3. Splintation of extremitySplintation of extremity 4.4. Section of scarsSection of scars 5.5. DesympathizationDesympathization 1.1. AcupunctureAcupuncture 2.2. ElectroacupunctureElectroacupuncture 3.3. LaseropunctureLaseropuncture 4.4. ElectrostimulationElectrostimulation 5.5. ElectrophoresisElectrophoresis 6.6. UltrasoundUltrasound 7.7. Magnetico-laserMagnetico-laser therapytherapy 8.8. MassageMassage 9.9. ManualManual therapytherapy METHODS OFMETHODS OF ANAESTIZATIONANAESTIZATION  PsycologicalPsycological  PhysicalPhysical  PharmacologicalPharmacological  SurgicalSurgical  NeurosurgicalNeurosurgical 1.1. ConversationConversation 2.2. RelaxationRelaxation 3.3. HypnosisHypnosis 4.4. AutotrainingAutotraining 5.5. CorrectCorrect stereotypestereotype of motionof motion 6.6. Self-removel of painSelf-removel of pain
Upper Motor NeuronsUpper Motor Neurons  Planned movements and those guided by sensory, visual, or auditory stimuli are preceded by discharges from prefrontal, somatosensory, visual, or auditory cortices, which are then followed by motor cortex pyramidal cell discharges that occur several milliseconds before the onset of movement  AnatomyAnatomy  TheThe motor cortexmotor cortex is theis the region from whichregion from which movements can be elicitedmovements can be elicited by electrical stimuli (Figure).by electrical stimuli (Figure).  This includes:  the primary motor area (Brodmann area 4),  premotor cortex (area 6),  supplementary motor cortex (medial portions of 6),  primary sensory cortex (areas 3, 1, and 2).  In the motor cortex, groups of neurons are organized in vertical columns, and discrete groups control contraction of individual muscles.
► Cortical motor neuronsCortical motor neurons contribute axons thatcontribute axons that converge in the corona radiata and descend in theconverge in the corona radiata and descend in the posterior limb of the internal capsule, cerebralposterior limb of the internal capsule, cerebral peduncles, ventral pons, and medullapeduncles, ventral pons, and medulla. These fibers. These fibers constitute theconstitute the corticospinalcorticospinal andand corticobulbarcorticobulbar tractstracts and together areand together are known asknown as upper motorupper motor neuron fibersneuron fibers. As they descend through the. As they descend through the diencephalon and brainstem, fibers separate todiencephalon and brainstem, fibers separate to innervate extrapyramidal and cranial nerve motorinnervate extrapyramidal and cranial nerve motor nuclei. The lower brainstem motor neurons receivenuclei. The lower brainstem motor neurons receive input from crossed and uncrossed corticobulbarinput from crossed and uncrossed corticobulbar fibers, although neurons that innervate lower facialfibers, although neurons that innervate lower facial muscles receive primarily crossed fibers.muscles receive primarily crossed fibers. ► In the ventral medullaIn the ventral medulla, the remaining corticospinal, the remaining corticospinal fibers course in a tract that is pyramidal in shape infibers course in a tract that is pyramidal in shape in cross section—thus, the namecross section—thus, the name pyramidal tractpyramidal tract.. AtAt thethe lower end of the medullalower end of the medulla, most fibers, most fibers decussate, although the proportion of crossed anddecussate, although the proportion of crossed and uncrossed fibers varies somewhat betweenuncrossed fibers varies somewhat between individuals. The bulk of these fibers descend as theindividuals. The bulk of these fibers descend as the lateral corticospinal tractlateral corticospinal tract of the spinal cord.of the spinal cord. ► Different groups ofDifferent groups of neurons in the cortex controlneurons in the cortex control muscle groupsmuscle groups of the contralateral face, arm, andof the contralateral face, arm, and legleg. Neurons near the ventral end of the central. Neurons near the ventral end of the central sulcus control muscles of the face, whereassulcus control muscles of the face, whereas neurons on the medial surface of the hemisphereneurons on the medial surface of the hemisphere control leg muscles. Because thecontrol leg muscles. Because the movements of themovements of the face, tongue, and hand are complex in humans, aface, tongue, and hand are complex in humans, a large share of the motor cortex is devoted to theirlarge share of the motor cortex is devoted to their controlcontrol. A. A somatotopic organizationsomatotopic organization is also apparentis also apparent in thein the lateral corticospinal tractlateral corticospinal tract of the cervicalof the cervical cord, where fibers to motor neurons that control legcord, where fibers to motor neurons that control leg muscles lie laterally and fibers to cervical motormuscles lie laterally and fibers to cervical motor neurons lie medially.neurons lie medially.
Upper and Lower motoneurons innervate the skeletal muscles and are essential for motor function. Amyotrophic lateral sclerosis (ALS), fatal combined degeneration of motoneurons and motor fiber tracts (i.e. combined gray and white matter disease). Motoneurons of entire neuraxis! ALS - most devastating neurodegenerative disease of aging CNS that so resembles Alzheimer and Parkinson diseases.
Upper and Lower motoneurons innervate the skeletal muscles and are essential for motor function. • Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease after the famous New York Yankees baseball player, is a devastating neurologic disorder that selectively affects motor function. ALS is primarily a disorder of middle to late adulthood, affecting persons between 55 and 60 years of age, with men developing the disease nearly twice as often as women. ETIOPATHOPHYSIOLOGY, PATHOLOGY • Neuron degeneration, atrophy, and loss → glial replacement. No inflammation! Degeneration of motoneurons: • 1. Motor cortex (pyramidal cells in precentral cortex) → loss of large myelinated fibers in anterior & lateral spinal columns (gliotic sclerosis of lateral columns = LATERAL SCLEROSIS) N.B. posterior columns are usually spared in SALS.N.B. posterior columns are usually spared in SALS. • 2. Brain stem - lower nuclei are more often / more extensively involved than upper nuclei (e.g. oculomotor nuclei loss is modest and rarely demonstrable clinically, whereas hypoglossal nuclei are prominently degenerated). • 3. Spinal anterior horns → loss of myelinated fibers in anterior root →muscle denervation atrophy (AMYOTROPHY); reinnervation is possible (but much less extensive as in poliomyelitis, peripheral neuropathy).
Stephen Hawking's EpidemiologyEpidemiology a. ALS is a degenerative disease involving loss of upper and lower motor neurons. b. Symptoms usually appear between 40 and 60 years of age. c. Most cases are sporadic (90%–95% of cases). PathogenesisPathogenesis • Possibly due to mutated superoxide dismutase (SOD) 1 (neuron destruction by superoxide free radicals) or misfolded SOD 1 leading to apoptosis of neurons (most likely mechanism) Clinical findingsClinical findings a. Upper motor neuron (UMN) signs  Spasticity, Babinski sign; b. Lower motor neuron (LMN) signs: 1) Muscle weakness  Begins with atrophy of intrinsic muscles of the hands; 2) Eventual paralysis of respiratory muscles. c. No sensory changes. d. Preservation of bowel and bladder function. DiagnosisDiagnosis  Electromyography and nerve conduction studies. TreatmentTreatment  Riluzole (glutamate antagonist). Average survivalAverage survival time is 3 to 5 years. Lower motor neuron disease that occurs in children.
DemyelinationDemyelination  InIn myelinated nervesmyelinated nerves, the axon between two nodes of Ranvier (internodal, the axon between two nodes of Ranvier (internodal segment) is surrounded by asegment) is surrounded by a myelin sheathmyelin sheath. This is a precondition for. This is a precondition for saltatory conduction of the action potentials, i.e., the “jumping” propagationsaltatory conduction of the action potentials, i.e., the “jumping” propagation of excitation from one nodal constriction (R1) to the next (R2). Theof excitation from one nodal constriction (R1) to the next (R2). The internodal segment itself cannot generate an action potential, i.e.,internodal segment itself cannot generate an action potential, i.e., depolarization of the second node (R2) is completely dependent on thedepolarization of the second node (R2) is completely dependent on the current from the first node (R1). However, the current is usually so strongcurrent from the first node (R1). However, the current is usually so strong that it can even jump across the nodes.that it can even jump across the nodes.  Nevertheless, on the way along the internodal segment the amplitude of theNevertheless, on the way along the internodal segment the amplitude of the current will diminish. First of all, the membrane in the internodal segmentcurrent will diminish. First of all, the membrane in the internodal segment must change its polarity, i.e., themust change its polarity, i.e., the membrane capacitancemembrane capacitance must bemust be discharged, for which a current is needed. Secondly, current can alsodischarged, for which a current is needed. Secondly, current can also escape through individualescape through individual ionic channelsionic channels in the axonal membrane (orangein the axonal membrane (orange arrow). However, myelination of the internodal segment causes thearrow). However, myelination of the internodal segment causes the membrane resistance (Rm) to be elevated and the capacity (Cm) of themembrane resistance (Rm) to be elevated and the capacity (Cm) of the membrane condensor to be reduced.membrane condensor to be reduced.  TheThe resistanceresistance of the axonal membrane of the internodal segment is veryof the axonal membrane of the internodal segment is very high because of the low density of ionic channels there. Furthermore, thehigh because of the low density of ionic channels there. Furthermore, the perimembranous space is insulated by a layer of fat from the freeperimembranous space is insulated by a layer of fat from the free extracellular space. The lowextracellular space. The low capacitancecapacitance of the condensor is due to theof the condensor is due to the large distance between the interior of the axon and the free extracellularlarge distance between the interior of the axon and the free extracellular space as well as the low polarity of the fatty material in the space betweenspace as well as the low polarity of the fatty material in the space between them.them.
DemyelinationDemyelination can becan be caused by degenerative,caused by degenerative, toxic, or inflammatorytoxic, or inflammatory damage to the nerves,damage to the nerves, or by a deficiency ofor by a deficiency of vitamins B6 or B12.vitamins B6 or B12. If this happens, Rm willIf this happens, Rm will be reduced and Cmbe reduced and Cm raised in the internodalraised in the internodal segment.segment. As a result, more currentAs a result, more current will be required towill be required to change the polarity ofchange the polarity of the internodal segmentthe internodal segment and, through opening upand, through opening up the ionic channels, largethe ionic channels, large losses of current maylosses of current may occur.occur.
Multiple SclerosisMultiple Sclerosis • Multiple sclerosis (MS), a demyelinating disease of the CNS, is a major cause of neurologic disability among young and middleaged adults. Approximately two thirds of persons with MS experience their first symptoms between 20 and 40 years of age. In approximately 80% of the cases, the disease is characterized by exacerbations and remissions over many years in several different sites in the CNS. • Initially, there is normal or nearnormal neurologic function between exacerbations. As the disease progresses, there is less improvement between exacerbations and increasing neurologic dysfunction.
Pathogenesis 1. Autoimmune disease initiated by: a) Genetic factors (e.g., HLA-DR2) b) Environmental factors • Microbial pathogens (e.g., Epstein-Barr virus, human herpesvirus 6, Chlamydophila pneumoniae), vitamin D, sun exposure. 2. CD4 TH1 cells and TH17 cells react against self myelin antigens (e.g., myelin basic protein [MBP] and other antigens; type IV hypersensitivity reaction). 3. CD4 TH1 cells secrete interferon γ (γ-IFN), which activates macrophages (produce tumor necrosis factor-α; TNF-α) and TH17 cells release cytokines that recruit neutrophils and monocytes. 4. Both leukocytes and TNF-α attack the myelin sheath and oligodendrocytes, causing demyelination. 5. Antibodies produced by autoreactive B cells are directed against the myelin sheath and oligodendrocytes as well (type II hypersensitivity reaction). Gross and microscopic findings 1. Demyelinating plaques occur in white matter of brain/spinal cord. • White matter looks like gray matter in areas of demyelination. 2. Inflammatory infiltrate in plaques is composed predominantly of CD4 T cells, monocytes, and microglial cells with phagocytosed lipid. MULTIPLE SCLEROSISMULTIPLE SCLEROSIS
Clinical findings 1) Episodic course punctuated by acute relapses and remissions (80%–90% of cases) 2) Sensory dysfunction: a) Paresthesias b) Loss of pain/temperature sensation c) Loss of vibratory sensation 3) Upper motor neuron (UMN) dysfunction a) Spasticity; b) Increased deep tendon reflexes (DTRs); c) Muscle spasms; d) Extensor plantar response (Babinski); e) Weakness  Shoulder abduction, finger extension, foot dorsiflexion, hip/knee flexion 4) Autonomic dysfunction: a)Urge incontinence  Hyperactive detrusor muscle; b)Sexual dysfunction; c) Bowel motility problems. 5) Optic neuritis a) Inflammation of the optic nerve  MS is the most common cause of optic neuritis. b) Blurry vision or sudden loss of vision 6) Cerebellar ataxia 7) Scanning speech (sound drunk) 8) Intention tremor, nystagmus 9) Bilateral internuclear ophthalmoplegia  Demyelination of medial longitudinal fasciculus (MLF) 10) Flexion of the neck produces an electrical sensation down the spine. MULTIPLE SCLEROSISMULTIPLE SCLEROSIS
Epidemiology Most common acute peripheral neuropathy Most common cause of acute flaccid paralysis Predominantly motor involvement Variants can be motor and sensory Autoimmune demyelination syndrome: a) Involves nerve roots and peripheral nerves; b) Common preceding infections  Mycoplasma pneumoniae pneumonia, Campylobacter jejuni enteritis, viral infection (HIV, EBV, cytomegalovirus, influenza) b. Rapidly progressive ascending motor weakness: Less commonly descending motor weakness. Usually starts in the proximal muscles and eventually includes the distal muscles. Danger of respiratory muscle paralysis and death. c. Depressed or absent deep tendon reflexes in the arms and legs d. Glove and stocking paresthesias/anesthesia Laboratory findings: 1) Increased CSF protein Oligoclonal bands present on high- resolution electrophoresis; 2) CSF glucose, cell count normal Diagnosis:Diagnosis: 1) Spinal tap with increased CSF protein; 2) Electromyography and nerve conduction studies. Treatment:Treatment: 1) Infusion IV immunoglobulin or plasma exchange; 2) Mechanical ventilation if required. Prognosis: 1) Mortality 5% to 10% of cases; 2) Full motor recovery 60% of cases; 3) Residual weakness 15% of cases
Huntington'sHuntington's diseasediseaseEpidemiologyEpidemiology a. Autosomal dominant diseasea. Autosomal dominant disease b. Trinucleotide repeat disorder (CAG) involvingb. Trinucleotide repeat disorder (CAG) involving chromosomechromosome c. Delayed appearance of symptoms until 30 toc. Delayed appearance of symptoms until 30 to 40 years of age40 years of age d. No gender dominanced. No gender dominance Atrophy/loss of striatal neuronsAtrophy/loss of striatal neurons  •• Caudate, putamen, globus pallidusCaudate, putamen, globus pallidus Clinical findings:Clinical findings: a.a. ChoreaChorea  1) Irregular, rapid, nonstereotyped1) Irregular, rapid, nonstereotyped involuntary movements; 2) Calledinvoluntary movements; 2) Called choreoathetosischoreoathetosis if it has a writhing quality.if it has a writhing quality. b. Oculomotor abnormalitiesb. Oculomotor abnormalities c. Parkinsonism in later stagesc. Parkinsonism in later stages d. Depressiond. Depression Diagnosis:Diagnosis: a. Genetic testing is availablea. Genetic testing is available b. Imaging studies (CT, MRI)b. Imaging studies (CT, MRI)  Atrophy ofAtrophy of caudate and putamencaudate and putamen Treatment is supportive.Treatment is supportive.
HUNTINGTON DISEASEHUNTINGTON DISEASE Classical familial,Classical familial, genetic diseasegenetic disease ProgressiveProgressive motor loss andmotor loss and dementiadementia ““chorea”, i.e.chorea”, i.e. “jerky”“jerky” movementsmovements Progressive, fatalProgressive, fatal Atrophy of basalAtrophy of basal ganglia, i.e.,ganglia, i.e., corpus striatumcorpus striatum Cortical (basal ganglia) atrophyCortical (basal ganglia) atrophy Ventricular enlargementVentricular enlargement
CNS DEGENERATIVE DISEASESCNS DEGENERATIVE DISEASES • SPINOCEREBELLARSPINOCEREBELLAR DEGENERATIONSDEGENERATIONS (ATAXIAS)(ATAXIAS) – Spinocerebellar ataxiasSpinocerebellar ataxias – Friedrich AtaxiaFriedrich Ataxia – Ataxia-TelangiectasiaAtaxia-Telangiectasia
EpidemiologyEpidemiology a. Autosomal recessive (AR) disease 1)Trinucleotide repeat disorder (GAA); 2)Frataxin deficiency: Deficiency leads to impaired mitochondrial iron homeostasis. Cells are more prone to apoptosis. b. Most common neurodegenerative hereditary ataxic disorder c. Sites of degeneration: 1) Dorsal root ganglia; 4) Lateral corticospinal tracts 2) Posterior columns 5) Large sensory peripheral neurons 3) Spinocerebellar tract d. Hypertrophic cardiomyopathy e. Type 1 diabetes mellitus (10% of cases) Clinical findingsClinical findings a. Progressive gait ataxia b. Loss of deep tendon reflexes  Initially at the ankles c. Loss of vibratory sensation and proprioception d. Muscle weakness in the legs DiagnosisDiagnosis a. Gene testing is available. b. Imaging (MRI) shows spinal cord atrophy. Treatment is supportive.Treatment is supportive.
ACQUIREDACQUIRED TOXIC/METABOLICTOXIC/METABOLIC CNS DISEASESCNS DISEASES VitaminVitamin B1B1 deficiency (Wernicke-Korsakoff)deficiency (Wernicke-Korsakoff)  VitaminVitamin B12B12 deficiency (vibratory sense)deficiency (vibratory sense)  DiabetesDiabetes Increased/Decreased GLUCOSEIncreased/Decreased GLUCOSE  Hepatic FailureHepatic Failure (NH4+)(NH4+)  COCO (Cortex, hippocampus, Purkinje cells)(Cortex, hippocampus, Purkinje cells)  CH3-OHCH3-OH, Methanol (Retinal ganglion cells), Methanol (Retinal ganglion cells)  CH3-CH2-OHCH3-CH2-OH (acute/chronic, direct/nutrit’l)(acute/chronic, direct/nutrit’l)  RadiationRadiation (Brain MOST resistant to Rad. Rx.)(Brain MOST resistant to Rad. Rx.)  ChemoChemo (Methotrexate + Radiation)(Methotrexate + Radiation)
Discriminative SensationDiscriminative Sensation  Primary sensory cortex providesPrimary sensory cortex provides awareness of somatosensory informationawareness of somatosensory information and the ability to make sensoryand the ability to make sensory discriminations.discriminations.  Touch, pain, temperature, and vibrationTouch, pain, temperature, and vibration sense are considered the primarysense are considered the primary modalities of sensation and are relativelymodalities of sensation and are relatively preserved in patients with damage topreserved in patients with damage to sensory cortex or its projections from thesensory cortex or its projections from the thalamus.thalamus.  In contrast, complex tasks that requireIn contrast, complex tasks that require integration of multiple somatosensoryintegration of multiple somatosensory stimuli and of somatosensory stimuli withstimuli and of somatosensory stimuli with auditory or visual information are impaired.auditory or visual information are impaired.  These include the ability to distinguishThese include the ability to distinguish twotwo pointspoints from one when touched on the skinfrom one when touched on the skin ((two-point discriminationtwo-point discrimination), localize tactile), localize tactile stimuli, perceive the position of body partsstimuli, perceive the position of body parts in space, recognize letters or numbersin space, recognize letters or numbers drawn on the skin (drawn on the skin (graphesthesiagraphesthesia), and), and identify objects by their shape, size, andidentify objects by their shape, size, and texture (texture (stereognosisstereognosis).).
Anatomy of Sensory LossAnatomy of Sensory Loss The patterns of sensory loss often indicate the level of nervous system involvement. Symmetric distal sensory loss in the limbs, affecting the legs more than the arms, usually signifies a generalized disorder of multiple peripheral nerves (polyneuropathy). Sensory symptoms and deficits may be restricted to the distribution of a single peripheral nerve (mononeuropathy) or two or more peripheral nerves (mononeuropathy multiplex). Symptoms limited to a dermatome indicate a spinal root lesion (radiculopathy).
Alterations in Motor Responses andAlterations in Motor Responses and MovementMovement  Abnormal motor responses include inappropriate or absentAbnormal motor responses include inappropriate or absent movements in response to painful stimuli. Brainstem reflexesmovements in response to painful stimuli. Brainstem reflexes such as sucking and grasping responses will occur if highersuch as sucking and grasping responses will occur if higher brain centers have been damaged.brain centers have been damaged.  Flexion and rigidity of limbs also are motor responses indicativeFlexion and rigidity of limbs also are motor responses indicative of brain damage.of brain damage.  Muscle conditionsMuscle conditions that indicate abnormal brain function includethat indicate abnormal brain function include hyperkinesiahyperkinesia ((excessive muscle movementsexcessive muscle movements),), hypokinesiahypokinesia ((decreased muscle movementsdecreased muscle movements),), paresisparesis ((muscle weaknessmuscle weakness),), andand paralysisparalysis ((loss of motor functionloss of motor function).).  Specific loss of cerebral cortex functioning, but no loss ofSpecific loss of cerebral cortex functioning, but no loss of brainstem function, results in a particular body posture calledbrainstem function, results in a particular body posture called flexor posturingflexor posturing..  Flexor posturingFlexor posturing is characterized by flexion of the upperis characterized by flexion of the upper extremities at the elbows and external rotation and extension ofextremities at the elbows and external rotation and extension of the lower extremities. This posturethe lower extremities. This posture may be unilateral ormay be unilateral or bilateralbilateral. Extensor posturing occurs with severe injury to higher. Extensor posturing occurs with severe injury to higher brain centers and the brainstem and is characterized bybrain centers and the brainstem and is characterized by rigidrigid extension of the limbs and neckextension of the limbs and neck..
Brown-Séquard syndrome In the spinal cord, segregation of fiber tracts and the somatotopic arrangement of fibers give rise to distinct patterns of sensory loss. Loss of pain and temperature sensation on one side of the body and of proprioception on the opposite side occurs with lesions that involve one half of the cord on the side of the proprioceptive deficit (Brown-Séquard syndrome). Compression of the upper spinal cord causes loss of pain, temperature, and touch sensation first in the legs, because the leg spinothalamic fibers are most superficial. More severe cord compression compromises fibers from the trunk. In patients with spinal cord compression, the lesion is often above the highest dermatome involved in the deficit. Thus, radiographic studies should be tailored to visualize the cord at and above the level of the sensory deficit detected on examination. Intrinsic cord lesions that involve the central portions of the cord often impair pain and temperature sensation at the level of the lesion because the fibers crossing the anterior commissure and entering the spinothalamic tracts are most centrally situated. Thus, enlargement of the central cervical canal in syringomyelia typically causes loss of pain and temperature sensation across the shoulders and upper arms.
SPINAL CORD INJURIES (SCI)SPINAL CORD INJURIES (SCI) CAUSES:CAUSES:  TRAUMATRAUMA  FALLSFALLS  GSWGSW  TUMORSTUMORS TYPES:TYPES:  CONCUSSIONCONCUSSION  COMPRESSIONCOMPRESSION  CONTUSION &CONTUSION & TRANSECTIONTRANSECTION  LACERATIONLACERATION  HEMORRHAGEHEMORRHAGE (HEMATOMYALIA)(HEMATOMYALIA)  COMPRESSION OFCOMPRESSION OF BLOOD SUPPLY TOBLOOD SUPPLY TO THE CORDTHE CORD
Injury Level Segmental Sensorimotor Function Dressing, Eating Elimination Mobility C1 Little or no sensation or control of head and neck; no diaphragm control; requires Continuous ventilation Dependent Dependent Limited. Voice or sip-n-puff controlled electric wheelchair C2 to C3 Head and neck sensation; some neck control. Independent of mechanical ventilation for short periods Dependent Dependent Same as for C1 C4 Good head and neck sensation and motor control; some shoulder elevation; diaphragm movement Dependent; may be able to eat with adaptive sling Dependent Limited to voice, mouth, head, chin, or shoulder-controlled electric wheelchair C5 Full head and neck control; shoulder strength; elbow flexion Independent with assistance Maximal assistance Electric or modified manual wheel chair, needs transfer assistance C6 Fully innervated shoulder; wrist extension or dorsiflexion Independent or with minimal assistance Independent or with minimal assistance Independent in transfers and wheelchair C7 to C8 Full elbow extension; wrist plantar flexion; some finger control Independent Independent Independent; manual wheelchair T1 to T5 Full hand and finger control; use of intercostal and thoracic muscles Independent Independent Independent; manual wheelchair T6 to T10 Abdominal muscle control, partial to good balance with trunk muscles Independent Independent Independent; manual wheelchair T11 to L5 Hip flexors, hip abductors (L1–3); knee extension (L2–4); knee flexion and ankle dorsiflexion (L4–5) Independent Independent Short distance to full ambulation with assistance S1 to S5 Full leg, foot, and ankle control; innervation of perineal muscles for bowel, bladder, and sexual function (S2–4) Independent Normal to impaired bowel and bladder function Ambulate independently with or without assistance Functional Abilities by Level of Cord InjuryFunctional Abilities by Level of Cord Injury
CLINICAL EFFECTS OF SCICLINICAL EFFECTS OF SCI • SPINAL SHOCK • REFLEX ACTIVITY • WHIPLASH INJURY • HERNIATED NUCLEUS PULPOSUS
• IMMEDIATE FLACCID PARALYSIS & SENSORY LOSS BELOW THE LEVEL OF LESION • PRIAPISM • BULBOCAVERNOUS REFLEX IS LOST BUT REUTRNS AFTER A FEW HRS • OTHER REFLEXES REMAIN ABSENT • 3-6 WKS UTONOMIC DISTURBANCES:UTONOMIC DISTURBANCES: WEATING IS ABOLISHED BELOW THE LEVEL OF INJURY RINE & FECES RETAINED ASTRIC ATONY RTHOSTATIC HYPOTENSION LOW, & STEADY PULSE
REFLEX ACTIVITY • REPLACE SPINAL SHOCK AFTER 2-3 WEEKS IF LUMBO-SACRAL SEGMENTS ARE UNDAMAGED • OCCURS IN ACUTE SPINAL INJURY, NOT IN PROGRESSIVE ONES • AUTOMATIC BLADDER; REFLEX SWEATING & DEFECATION • FIRST SIGN OF WEARING OFF: – CONTRACTION OF HAMSTRING – FLEXION/ EXTENSION OF TOES WITH PLANTAR STIMULATION
ParalysisParalysis  ParalysisParalysis is the loss of sensory and voluntary motoris the loss of sensory and voluntary motor function. With spinal cord transection, paralysis isfunction. With spinal cord transection, paralysis is permanent.permanent.  ParalysisParalysis of theof the upper and lower extremitiesupper and lower extremities occurs withoccurs with transection of the cord at level C6 or higher and is calledtransection of the cord at level C6 or higher and is called quadriplegiaquadriplegia..  ParalysisParalysis of the lower half of the body occurs withof the lower half of the body occurs with transection of the cord below C6 and is calledtransection of the cord below C6 and is called paraplegiaparaplegia..  If only one half of the cord is transectedIf only one half of the cord is transected,, hemiparalysishemiparalysis may occur.may occur.  Permanent paralysisPermanent paralysis may occur even when the cord ismay occur even when the cord is not transected, as a result of the destruction of thenot transected, as a result of the destruction of the nerves following cordnerves following cord hemorrhage and swellinghemorrhage and swelling..  In addition, demyelination of the axons in the cord canIn addition, demyelination of the axons in the cord can lead to clinically complete lesions, even though thelead to clinically complete lesions, even though the spinal cord may not be transected.spinal cord may not be transected.  DemyelinationDemyelination of the axons most likely occurs as part ofof the axons most likely occurs as part of the inflammatory response to cord injury.the inflammatory response to cord injury.
Clinical Manifestations of Paralysis • Loss of sensation, motor control, and reflexes below the level of injury, and up to two levels above, will occur. • Body temperature will reflect ambient temperature, and blood pressure will be reduced. • The pulse rate is often normal, with low blood pressure.
Complications • If damage and swelling around the cord is in the cervical spine (down to approximately C5), respirations may cease because of compression of the phrenic nerve, which exits between C3 and C5 and controls the movement of the diaphragm. • Autonomic hyper-reflexia is characterized by high blood pressure with bradycardia (low heart rate), and sweating and flushing of the skin on the face and upper torso. • In the past, individuals suffering from a C2 or higher transection invariably died as a result of respiratory arrest. Although this is still true for many, recent advances in treatment modalities and better emergency rescue service responses have resulted in the survival of many individuals with high cord transection. • A severe spinal cord injury affects virtually all systems of the body to some degree. Commonly, urinary tract and kidney infections, skin breakdown and the development of pressure ulcers, and muscle atrophy occur. Depression, marital and family stress, loss of income, and large medical expenses are some of the psychosocial complications.
DysphasiaDysphasia  Dysphasia is impairment of language comprehension or production.is impairment of language comprehension or production. AphasiaAphasia is total loss of language comprehension or production.is total loss of language comprehension or production. Dysphasia usually results from cerebral hypoxia, which is oftenDysphasia usually results from cerebral hypoxia, which is often associated with a stroke but can result from trauma or infection. Brainassociated with a stroke but can result from trauma or infection. Brain damage leading to dysphasia usually involves the left cerebraldamage leading to dysphasia usually involves the left cerebral hemisphere.hemisphere.  Broca's dysphasia results from damage to Broca's area inresults from damage to Broca's area in the frontalthe frontal lobelobe. Persons with. Persons with Broca's dysphasia will understand languageBroca's dysphasia will understand language, but, but their ability to meaningfullytheir ability to meaningfully express words in speech or writing will beexpress words in speech or writing will be impairedimpaired. This is called expressive dysphasia.. This is called expressive dysphasia.  Wernicke's dysphasia results from damage to Wernicke's area in theresults from damage to Wernicke's area in the leftleft temporal lobetemporal lobe. With Wernicke's dysphasia,. With Wernicke's dysphasia, verbal expression ofverbal expression of language is intactlanguage is intact, but meaningful, but meaningful understanding of spoken or writtenunderstanding of spoken or written words is impairedwords is impaired. This is called receptive dysphasia.. This is called receptive dysphasia.  Agnosia is the failure to recognize an object because of the inabilityis the failure to recognize an object because of the inability to make sense of incoming sensory stimuli.to make sense of incoming sensory stimuli. Agnosia may be visual,Agnosia may be visual, auditory, tactile, or related to taste or smellauditory, tactile, or related to taste or smell. Agnosia develops from. Agnosia develops from damage to a particular primary or associative sensory area in thedamage to a particular primary or associative sensory area in the cerebral cortex.cerebral cortex.
Alterations in Pupil Responses • The ability of our eyes to dilate or constrict, rapidly and equally, depends on an intact brainstem. • Cerebral hypoxia and many drugs change pupil size and reactivity. Therefore, pupil size and reactivity offer valuable information concerning brain integrity and function. • Important pupil changes seen with brain damage are pinpoint pupils seen with opiate (heroin) overdose and bilaterally fixed and dilated pupils usually seen with severe hypoxia. • Fixed pupils are typically seen with barbiturate overdose. • Brainstem injury presents with pupils fixed bilaterally in the midposition.
DISORDERS OFDISORDERS OF THE MIDDLE EARTHE MIDDLE EAR ■ The middle ear is a small air-filled compartment in the temporal bone. It is separated from the outer ear by the tympanic membrane, contains tiny bony ossicles that aid in the amplification and transmission of sound to the inner ear, and is ventilated by the eustachian tube, which is connected to the nasopharynx. ■■ The eustachian tube, which is lined with a mucousThe eustachian tube, which is lined with a mucous membrane that ismembrane that is continuous with the nasopharynx,continuous with the nasopharynx, provides a passageway forprovides a passageway for pathogens to enter thepathogens to enter the middle ear.middle ear. ■■ Otitis media (OM) refers to inflammation of the middleOtitis media (OM) refers to inflammation of the middle ear, usuallyear, usually associated with an acute infectionassociated with an acute infection (acute OM) or an accumulation of(acute OM) or an accumulation of fluid (OME). Itfluid (OME). It commonly is associated with disorders of eustachiancommonly is associated with disorders of eustachian tube function.tube function. ■■ Impaired conduction of sound waves and hearingImpaired conduction of sound waves and hearing loss occur when theloss occur when the tympanic membrane has beentympanic membrane has been perforated; air in the middle ear hasperforated; air in the middle ear has been replacedbeen replaced with fluid (OME); or the function of the bonywith fluid (OME); or the function of the bony ossicles hasossicles has been impaired (otosclerosis).been impaired (otosclerosis).
HEARING LOSS ■ Hearing loss represents impairment of the ability to detect and perceive sound. ■ Conductive hearing loss is caused by disorders in which auditory stimuli are not transmitted through the structures of the outer and middle ears to the sensory receptors in the inner ear. ■ Sensorineural hearing loss is caused by disorders that affect the inner ear, auditory nerve, or auditory pathways.
Diseases of the Basal GangliaDiseases of the Basal Ganglia  The basal ganglia areThe basal ganglia are made up of:made up of:  –– thethe corpus striatumcorpus striatum (consisting of the(consisting of the caudatecaudate nucleusnucleus and theand the putamenputamen););  –– the inner and outerthe inner and outer globus pallidusglobus pallidus (pallidum, consisting of an(pallidum, consisting of an internal and an externalinternal and an external part);part);  –– thethe subthalamicsubthalamic nucleusnucleus; and; and  –– thethe substantia nigrasubstantia nigra (pars reticulata [p. r.] and(pars reticulata [p. r.] and pars compacta [p. c.]).pars compacta [p. c.]).  TheirTheir functionfunction is mainlyis mainly to control movement into control movement in conjunction with theconjunction with the cerebellum,motor cortex,cerebellum,motor cortex, corticospinal tracts, andcorticospinal tracts, and motor nuclei in the brainmotor nuclei in the brain stem.stem.
Parkinson’s Disease Parkinson’s diseaseParkinson’s disease is a diseaseis a disease of theof the substantia nigrasubstantia nigra (p. c.)(p. c.) which via dopaminergic tractswhich via dopaminergic tracts influences GABAergic cells in theinfluences GABAergic cells in the corpus striatumcorpus striatum. The. The causecause isis frequently afrequently a hereditary dispositionhereditary disposition that in middle to old age leads tothat in middle to old age leads to degeneration of dopaminergicdegeneration of dopaminergic neurons in the substantianeurons in the substantia nigranigra. Further causes are. Further causes are traumatrauma (e.g., in boxers),(e.g., in boxers), inflammationinflammation (encephalitis),(encephalitis), impaired circulationimpaired circulation (atherosclerosis),(atherosclerosis), tumorstumors andand poisoningpoisoning (especially by CO,(especially by CO, manganese, and 1-methyl-4-manganese, and 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridinephenyl-1,2,3,6-tetrahydropyridine [MPTP], which was once used as[MPTP], which was once used as a substitute for heroin). The cella substitute for heroin). The cell destruction probably occurs partlydestruction probably occurs partly by apoptosis; superoxides areby apoptosis; superoxides are thought to play a causal role.thought to play a causal role.  For symptoms to occur, over 70%For symptoms to occur, over 70% of neurons in the substantia nigraof neurons in the substantia nigra (p. c.) must have been destroyed.(p. c.) must have been destroyed.  The loss of cells in the substantiaThe loss of cells in the substantia nigra (p. c.) decreases thenigra (p. c.) decreases the correspondingcorresponding dopaminergicdopaminergic innervationinnervation of the striatum.of the striatum.
Brain centres and theirBrain centres and their disorderdisorder  The brain is conventionally considered in sixThe brain is conventionally considered in six main anatomicalmain anatomical and functional areas:and functional areas: 1. Cerebrum1. Cerebrum – two hemispheres of cerebral– two hemispheres of cerebral cortex, containingcortex, containing the limbic system andthe limbic system and basal ganglia.basal ganglia. 2. Diencephalon2. Diencephalon, containing the hypothalamus, containing the hypothalamus and thalamus.and thalamus. 3. Midbrain.3. Midbrain. 4. Pons.4. Pons. 5. Medulla oblongata.5. Medulla oblongata. 6. Cerebellum.6. Cerebellum.  Alternatively, the brain may be subdividedAlternatively, the brain may be subdivided into distinct regions:into distinct regions: •• TheThe forebrainforebrain, which includes areas 1 and 2., which includes areas 1 and 2. •• TheThe hindbrainhindbrain, which includes areas 4, 5, which includes areas 4, 5 and 6.and 6. •• TheThe brainstembrainstem, which includes the midbrain,, which includes the midbrain, medulla andmedulla and pons.pons.  Interconnections between these areas areInterconnections between these areas are manifold andmanifold and complex, accounting for the richnesscomplex, accounting for the richness and diversity of humanand diversity of human activity, experienceactivity, experience and achievement.and achievement.
Principal anatomical centresPrincipal anatomical centres of brain functionof brain function FunctionFunction CentreCentre InputInput PerceptionPerception Sensory cortex, thalamus,Sensory cortex, thalamus, reticular formationreticular formation ProcessingProcessing Cognitive (intellectual)Cognitive (intellectual) EmotionalEmotional Cerebral cortexCerebral cortex Limbic systemLimbic system OutputOutput MotorMotor HomeostasisHomeostasis Motor cortex, cerebellum,Motor cortex, cerebellum, basal gangliabasal ganglia Medulla, hypothalamus,Medulla, hypothalamus, pituitarypituitary
Cerebral cortexCerebral cortex  The cerebral cortex is, in evolutionary terms, the youngest centre. It is the principal distinguishing feature of higher mammals. Notably developed in man, where it contains 90% of the total brain neurones,  the cerebral cortex is the location of:  It functions like afunctions like a computercomputer, providing an objective, logical assessment of the environment as perceived via the senses,  and then producing a plan for action depending on past experience and biological goals.  Specific areas of the cortex are dedicated to subsidiary functions, such as the speech centre and the visual, auditory and motor cortexes.  Anatomically, the cerebral cortex is subdivided into various lobes, i.e. abstract thought judgement reasoning memory interpretation of sensory inputcreativity frontal temporal parietal occipital
Cortical disordersCortical disorders  Cortical disorders usually have a profoundCortical disorders usually have a profound effect oneffect on all CNS function. They are commonlyall CNS function. They are commonly manifested asmanifested as disorders ofdisorders of intellectintellect, e.g., e.g.  MentalMental handicaphandicap,, dementiadementia oror Alzheimer’sAlzheimer’s disease,disease, or ofor of movementmovement, e.g., e.g. epilepsyepilepsy..  StrokesStrokes are caused byare caused by obstruction of blood flowobstruction of blood flow usually to discreteusually to discrete cortical areas.cortical areas.  TheThe thought disorderthought disorder characteristiccharacteristic ofof schizophreniaschizophrenia is partly cortical, but disorderedis partly cortical, but disordered limbic or thalamiclimbic or thalamic influences on theinfluences on the ortex are probably more important.ortex are probably more important.  Most proven and putative neurotransmittersMost proven and putative neurotransmitters areare found in the cortex. Many of the morefound in the cortex. Many of the more recentlyrecently discovered mediators, such as thediscovered mediators, such as the endorphinsendorphins andand peptidespeptides, have yet to be definitely, have yet to be definitely linked withlinked with specific CNS functions, disorders orspecific CNS functions, disorders or drug actions.drug actions. They may modulate the action ofThey may modulate the action of the traditionalthe traditional transmitters.transmitters.
Limbic systemLimbic system  This interesting evolutionaryThis interesting evolutionary development ofdevelopment of the higher mammalsthe higher mammals providesprovides mental activitymental activity with anwith an emotional dimensionemotional dimension ..  TheThe limbiclimbic systemsystem is responsibleis responsible forfor feelingsfeelings rather thanrather than objectiveobjective reasoningreasoning and is perceivedand is perceived consciouslyconsciously as anas an emotionalemotional overlayoverlay, i.e. the, i.e. the affect or moodaffect or mood,, which can modify the decisionswhich can modify the decisions taken by thetaken by the cortex.cortex.  The system mayThe system may mediate rage,mediate rage, fear, pleasurefear, pleasure and loveand love and, byand, by its influence on corticalits influence on cortical function, isfunction, is responsible for beliefs as opposedresponsible for beliefs as opposed toto rational thoughtrational thought ..  A materialistic interpretationA materialistic interpretation of oneof one of the objectives of some Easternof the objectives of some Eastern philosophies,philosophies, especiallyespecially meditationmeditation, would be that it, would be that it attempts to achieve control or evenattempts to achieve control or even eliminationelimination of limbic influencesof limbic influences (‘the(‘the self’, ‘desire’)self’, ‘desire’) on theon the cortex.cortex.
Limbic systemLimbic system  The contrast betweenThe contrast between limbiclimbic andand cortical functionscortical functions is illustrated by ouris illustrated by our response to beingresponse to being caught for a motoring offence.caught for a motoring offence.  One part of usOne part of us –– ourour limbic system – is angrylimbic system – is angry,, fearfulfearful oror ashamedashamed (depending on our personality):(depending on our personality): at the sameat the same time, our cortextime, our cortex is calculatingis calculating the effect on ourthe effect on our insurance premium,insurance premium, the most effective way tothe most effective way to appeaseappease the policeman, or perhaps even how tothe policeman, or perhaps even how to manage without a drivingmanage without a driving licencelicence..  TheThe limbic systemlimbic system has evolved from a structurehas evolved from a structure in lower mammalsin lower mammals concerned withconcerned with olfactionolfaction (sense of smell),(sense of smell), and indeed it retains thisand indeed it retains this functionfunction in humans.in humans. Possibly this accounts for thePossibly this accounts for the emotional power thatemotional power that smells have on humans.smells have on humans.  TheThe limbic systemlimbic system is also involved inis also involved in memorymemory,, and we are all familiar withand we are all familiar with how strongly smellshow strongly smells can evoke evencan evoke even distant memoriesdistant memories..  The system isThe system is structurally complex with many componentstructurally complex with many component nuclei andnuclei and important connections with theimportant connections with the frontalfrontal andand temporal lobes of the cortextemporal lobes of the cortex,, withwith thethe reticular systemreticular system and with theand with the hypothalamushypothalamus (all of which are(all of which are sometimes considered assometimes considered as partially within the limbic system).partially within the limbic system). DopamineDopamine isis an important transmitter, as arean important transmitter, as are noradrenalinenoradrenaline (NA, norepinephrine) and(NA, norepinephrine) and 5-hydroxytryptamine5-hydroxytryptamine (5-HT, serotonin).(5-HT, serotonin). Gamma-aminobutyric acidGamma-aminobutyric acid ((GABA) is an inhibitory transmitter here.GABA) is an inhibitory transmitter here.
Disorders of theDisorders of the LLimbicimbic SSystemystem  Disorders of the limbic systemDisorders of the limbic system are likely toare likely to cause inappropriate emotions, such ascause inappropriate emotions, such as::  depression,depression,  mania ormania or  excessive anxiety.excessive anxiety.  DelusionsDelusions ((inappropriate beliefs) may arise ininappropriate beliefs) may arise in the limbicthe limbic system. The now discreditedsystem. The now discredited prefrontalprefrontal lobotomy (leucotomy), an operationlobotomy (leucotomy), an operation to sever theto sever the links between the limbic systemlinks between the limbic system and the cortexand the cortex in severe psychiatric disorders,in severe psychiatric disorders, resulted in theresulted in the patient becoming emotionallypatient becoming emotionally flat.flat.  A similarA similar phenomenon is sometimes seen inphenomenon is sometimes seen in patients onpatients on long-term antipsychoticslong-term antipsychotics..
Psychological DisordersPsychological Disorders  Its mental processes and/or behavior patterns that causeIts mental processes and/or behavior patterns that cause emotional distress and/or substantial impairment in functioningemotional distress and/or substantial impairment in functioning  The presence of a constellation of symptoms that createThe presence of a constellation of symptoms that create significant distress; impair work, school, family, relationships,significant distress; impair work, school, family, relationships, or daily living; or lead to significant risk or harmor daily living; or lead to significant risk or harm  SymptomsSymptoms  CognitiveCognitive  EmotionalEmotional  BehavioralBehavioral  What criteria can be used to determine whether behavior isWhat criteria can be used to determine whether behavior is abnormal?abnormal?  Behavior may be considered abnormal ifBehavior may be considered abnormal if  It is considered strange within a person’s own cultureIt is considered strange within a person’s own culture  It causes personal distressIt causes personal distress  It is maladaptiveIt is maladaptive  It is a danger to the self or othersIt is a danger to the self or others  A person is not legally responsible for his or her actsA person is not legally responsible for his or her acts
Types/CategoriesTypes/Categories  Organic Brain Syndromes (Caused by Damage)Organic Brain Syndromes (Caused by Damage)  Developmental Disorders (autism, retardation)Developmental Disorders (autism, retardation)  ““Psychoses” – Schizophrenia, Mood Disorders (Bipolar)Psychoses” – Schizophrenia, Mood Disorders (Bipolar)  ““Neuroses” – Anxiety Disorders (Phobias, OCD, PTSD)Neuroses” – Anxiety Disorders (Phobias, OCD, PTSD)  Somatoform Disorders (Ulcers)Somatoform Disorders (Ulcers)  Dissociative Disorders – D.I.D.Dissociative Disorders – D.I.D.  Personality Disorders – Antisocial Personality Disorder,Personality Disorders – Antisocial Personality Disorder, Substances Abuse (problems with relationships)Substances Abuse (problems with relationships)  Behavioral Disorders – Sleep Disorders, TurretsBehavioral Disorders – Sleep Disorders, Turrets  General ProblemsGeneral Problems  Seek Counseling (relationships)Seek Counseling (relationships)
General Adaptation Syndrome Three stages: 1. Alarm stage - Emergency reaction (fight-or-flight) 1. Resistance stage - Coping and adaptation 1. Exhaustion stage - Termination of stress response and onset of stress pathology  StressStress refers to a number of biological changes that can be triggered by any disturbance to our normal physiology.  Stress is neutral –Stress is neutral – the body responds the same to positive or negative stressors.
Anxiety DisordersAnxiety Disorders  Components of Anxiety ResponsesComponents of Anxiety Responses
Phobic DisordersPhobic Disorders  PhobiaPhobia – an intense– an intense and irrational fear ofand irrational fear of particular object orparticular object or situationsituation Psychological DisorderPsychological Disorder  InsanityInsanity is a legal term. Insanity is beingis a legal term. Insanity is being unableunable to appreciate theto appreciate the nature and quality of the wrongfulness of his or her acts, because ofnature and quality of the wrongfulness of his or her acts, because of mental disease or defect.mental disease or defect.  AbnormalityAbnormality is a condition or behavior that deviates from the usualis a condition or behavior that deviates from the usual physical or psychological state. Culture and context are important inphysical or psychological state. Culture and context are important in defining abnormality. Talking to the dead is normal in some cultures.defining abnormality. Talking to the dead is normal in some cultures.
Anxiety DisordersAnxiety Disorders  PhobiasPhobias - strong and irrational fears of- strong and irrational fears of certain objects or situationscertain objects or situations  AgoraphobiaAgoraphobia: fear of open and public: fear of open and public spaces from which escape would bespaces from which escape would be difficultdifficult  Social phobiasSocial phobias: fear of situations in: fear of situations in which evaluation might occurwhich evaluation might occur  Lifetime prevalence 13%Lifetime prevalence 13%  Specific phobiasSpecific phobias: fear of specific: fear of specific objects such as animals or situationsobjects such as animals or situations  Animal fearsAnimal fears  Blood-injection-injury fearsBlood-injection-injury fears  Natural environment fearsNatural environment fears  Situation fearsSituation fears  Miscellaneous fearsMiscellaneous fears  Lifetime prevalence 10%Lifetime prevalence 10%
Anxiety DisordersAnxiety Disorders  Panic DisorderPanic Disorder an extreme anxiety that manifestsan extreme anxiety that manifests itself in the form of panic attacksitself in the form of panic attacks  Panic occurs suddenly and unpredictablyPanic occurs suddenly and unpredictably  Much more intense than typical anxietyMuch more intense than typical anxiety  Panic attackPanic attack  An episode of overwhelming anxiety, fear, or terrorAn episode of overwhelming anxiety, fear, or terror  The brains of panic-attack sufferers respond to normal changes in the body as if they were lifeThe brains of panic-attack sufferers respond to normal changes in the body as if they were life threateningthreatening
Anxiety DisordersAnxiety Disorders  Obsessive-Compulsive DisorderObsessive-Compulsive Disorder  ObsessionsObsessions  Repetitive and unwelcome thoughts, images, or impulsesRepetitive and unwelcome thoughts, images, or impulses  CompulsionsCompulsions  Repetitive behavioral responsesRepetitive behavioral responses  CheckingChecking  WashingWashing  OrderingOrdering  Lifetime prevalence 2-3%Lifetime prevalence 2-3%  Caudate nucleusCaudate nucleus  Obsession –Obsession – Constantly on your mindConstantly on your mind  Compulsions –Compulsions – Keep repeating behaviorKeep repeating behavior
Posttraumatic Stress DisorderPosttraumatic Stress Disorder • Severe anxiety disorderSevere anxiety disorder – Can occur in people exposed to extreme traumaCan occur in people exposed to extreme trauma • PTSD – disorder in which victims of traumatic eventsPTSD – disorder in which victims of traumatic events experience the original event in the form of dreams orexperience the original event in the form of dreams or flashbacksflashbacks – SymptomsSymptoms • Re-experience eventRe-experience event • Avoidance and emotionalAvoidance and emotional numbingnumbing • Heightened arousalHeightened arousal – Lifetime prevalence 8% (among Americans)Lifetime prevalence 8% (among Americans) – Genetic predispositionGenetic predisposition
Somatoform DisordersSomatoform Disorders  Used to be called “Used to be called “hysteriahysteria” by Freud” by Freud  ““Physical symptoms for which there is noPhysical symptoms for which there is no apparent physical causeapparent physical cause  Two general typesTwo general types 1.1. Conversion DisordersConversion Disorders 2.2. HypochondriasisHypochondriasis
Conversion DisordersConversion Disorders  Changing emotional difficulties into a lossChanging emotional difficulties into a loss of specific voluntary body functionof specific voluntary body function  Subconsciously doneSubconsciously done  Reinforced by increased attentionReinforced by increased attention  Motor Deficits or Sensory DeficitsMotor Deficits or Sensory Deficits  RareRare
HypochondriasisHypochondriasis  Good health but intense worry about smallGood health but intense worry about small problems being really bigproblems being really big  Extensive doctor visits, second opinions,Extensive doctor visits, second opinions, self diagnosisself diagnosis  From repressed emotions?From repressed emotions?  Get more reinforcement (positiveGet more reinforcement (positive attention)attention)
Mood DisordersMood Disorders
Mood DisordersMood Disorders  Long-lasting, severeLong-lasting, severe  not just really sadnot just really sad  BereavementBereavement  not necessarily depressionnot necessarily depression Types:Types:  Major Depressive DisorderMajor Depressive Disorder  Bipolar DisorderBipolar Disorder  Season Affective DisorderSeason Affective Disorder  DysthymiaDysthymia  Lifetime prevalence 6%Lifetime prevalence 6%  SuicideSuicide  Attempted by 30% of depressed peopleAttempted by 30% of depressed people
Major Depressive DisorderMajor Depressive Disorder  Severe form of lowered mood, feelings ofSevere form of lowered mood, feelings of worthlessness, apathy, disinterested inworthlessness, apathy, disinterested in pleasurable activities, intense sadness,pleasurable activities, intense sadness, hopelessnesshopelessness  2+ weeks, can’t be due to bereavement2+ weeks, can’t be due to bereavement (grieving)(grieving)  Need 4 of following symptoms (consistently andNeed 4 of following symptoms (consistently and higher in intensity) – problems eating, sleeping,higher in intensity) – problems eating, sleeping, thinking, focusing, making decisions, low energy,thinking, focusing, making decisions, low energy, suicidal thoughts, feel worthless/guilty, lack ofsuicidal thoughts, feel worthless/guilty, lack of interest in enjoyable activitiesinterest in enjoyable activities
Bipolar Disorder (Manic Depression)Bipolar Disorder (Manic Depression) Individual alternates between feelings of maniaIndividual alternates between feelings of mania and depressionand depression ManiaMania – little sleep, elation, confusion, delusions,– little sleep, elation, confusion, delusions, distractibility, racing thoughts, overly optimisticdistractibility, racing thoughts, overly optimistic DepressiveDepressive – feel worthless, sinful, despair, failure,– feel worthless, sinful, despair, failure, lethargy, unresponsivenesslethargy, unresponsiveness
Seasonal Affective Disorder • Depression during certain seasons, • increase sleep, eating Causes • Melatonin? • Vitamin D? • Conditioning? • Social Learning?
What is SchizophreniaWhat is Schizophrenia  Includes positive and negative symptomsIncludes positive and negative symptoms  Positive – add – Negative – take awayPositive – add – Negative – take away  Type IType I  mostly positive symptomsmostly positive symptoms -delusions, hallucinations, disorders of thoughts and behavior-delusions, hallucinations, disorders of thoughts and behavior  Type IIType II  mostly negative symptomsmostly negative symptoms -flat affect (emotions), avolition (motivation), alogia (speech)-flat affect (emotions), avolition (motivation), alogia (speech) • Disorders characterized by confused andDisorders characterized by confused and disconnected thoughts, emotions,disconnected thoughts, emotions, perceptionsperceptions • Considered by many to be most severeConsidered by many to be most severe disorderdisorder • Often a variety of symptoms presentOften a variety of symptoms present
Types of SchizophreniaTypes of Schizophrenia  CatatonicCatatonic – motor disturbances– motor disturbances  ParanoidParanoid – preoccupied with– preoccupied with delusions, people out to get themdelusions, people out to get them  DisorganizedDisorganized – incoherent language,– incoherent language, inappropriate emotion, delusions,inappropriate emotion, delusions, hallucinationshallucinations  UndifferentiatedUndifferentiated – many symptoms– many symptoms  RemissionRemission – no current symptoms– no current symptoms EtiologyEtiology Biological Influences – 1% in population, 10% in familiesBiological Influences – 1% in population, 10% in families Biochemistry – imbalance in neurotransmitters (dopamine/serotonin)Biochemistry – imbalance in neurotransmitters (dopamine/serotonin) Family/interactionsFamily/interactions ““Diathesis-stress model” – biological, needs stress triggersDiathesis-stress model” – biological, needs stress triggers
StrokeStroke  StrokeStroke is a clinical syndrome characterizedis a clinical syndrome characterized by theby the suddensudden onset of a focal neurologiconset of a focal neurologic deficit that persists fordeficit that persists for at least 24 hoursat least 24 hours andand is due to anis due to an abnormality of the cerebralabnormality of the cerebral circulationcirculation..  TheThe incidence ofincidence of strokestroke increasesincreases and isand is higherhigher  Significant risk factors includeSignificant risk factors include:: hypercholesterolemiahypercholesterolemia diabetesdiabetes oral contraceptiveoral contraceptive useuse heavy alcoholheavy alcohol consumptionconsumption hypertensionhypertension in men than in womenin men than in women with age smokingsmoking
PathophysiologyPathophysiology The focal symptoms and signs that resultThe focal symptoms and signs that result from stroke correlate with the area of brainfrom stroke correlate with the area of brain supplied by the affected blood vessel.supplied by the affected blood vessel. Strokes may be classified into two majorStrokes may be classified into two major categories based on pathogenesis:categories based on pathogenesis: hemorrhagehemorrhageischemicischemic In ischemic stroke, vascular occlusion interrupts blood flow to a specific brain region, producing a fairly characteristic pattern of neurologic deficits resulting from loss of functions controlled by that region. The pattern of deficits resulting from hemorrhage is less predictable because it depends on the location of the bleed and also on factors that affect the function of brain regions distant from the hemorrhage (eg, increased intracranial pressure, brain edema, compression of neighboring brain tissue, and rupture of blood into ventricles or subarachnoid space).
Classification of StrokeClassification of Stroke Ischemic stroke Large vessels (major cerebral arteries) Small vessels (lacunar stroke) Venous occlusion Cardioembolic Artery to artery Thrombotic occlusion Embolic Hemorrhage Epidural hemorrhage Hemorrhagic ischemic infarction Subdural hemorrhage Subarachnoid hemorrhage Intraparenchymal hemorrhage
Common Stroke SymptomsCommon Stroke Symptoms  Weakness or paralysisWeakness or paralysis  Numbness, tingling, decreasedNumbness, tingling, decreased sensationsensation  Vision changesVision changes  Speech problemsSpeech problems  Swallowing difficulties orSwallowing difficulties or droolingdrooling  Loss of memoryLoss of memory  Vertigo (spinning sensation)Vertigo (spinning sensation)  Loss of balance andLoss of balance and coordinationcoordination  Personality changesPersonality changes  Mood changes (depression,Mood changes (depression, apathy)apathy)  Drowsiness, lethargy, or loss ofDrowsiness, lethargy, or loss of consciousnessconsciousness  Uncontrollable eye movementsUncontrollable eye movements or eyelid droopingor eyelid drooping
 Hemiplegia - most common result of CVA Paralysis of one side of the body May affect other functions, such as hearing, general sensation and circulation The degree of impairment depends on the part of the brain affected Stages: Flaccid – numbness and weakness of affected side Spastic – muscles contracted and tense, movement hard Recovery – therapy and rehab methods successful
Ischemic StrokeIschemic Stroke  Ischemic strokes result from thrombotic or embolic occlusion of cerebral vessels.  Neurologic deficits caused by occlusion of large arteries result from focal ischemia to the area of brain supplied by the affected vessel and produce recognizable clinical syndromes (next slide).  Not all signs are present in every patient, because the extent of the deficit depends on the presence of collateral blood flow, individual variations in vascular anatomy, blood pressure, and exact location of the occlusion.  Thrombosis usually involves the internal carotid, middle cerebral, or basilar arteries.  Symptoms typically evolve over several minutes and may be preceded by brief episodes of reversible focal deficits known as transient ischemic attacks.  Emboli from the heart, aortic arch, or carotid arteries usually occlude the middle cerebral artery, because it carries more than 80% of blood flow to the cerebral hemisphere.  Emboli that travel in the vertebral and basilar arteries commonly lodge at the apex of the basilar artery or in one or both posterior cerebral arteries.
Vascular Territories and Clinical Features in Ischemic StrokeVascular Territories and Clinical Features in Ischemic Stroke Artery Territory Symptoms and Signs Anterior cerebral Medial frontal and parietal cortex, anterior corpus callosum Paresis and sensory loss of contralateral leg and foot Middle cerebral Lateral frontal, parietal, occipital, and temporal cortex and adjacent white matter, caudate, putamen, internal capsule Aphasia (dominant hemisphere), neglect (nondominant hemisphere), contralateral hemisensory loss, homonymous hemianopia, hemiparesis Vertebral (posterior inferior cerebellar) Medulla, lower cerebellum Ipsilateral cerebellar ataxia, Horner's syndrome, crossed sensory loss, nystagmus, vertigo, hiccup, dysarthria, dysphagia Basilar (including anterior inferior cerebellar, superior cerebellar) Lower midbrain, pons, upper and mid cerebellum Nystagmus, vertigo, diplopia, skew deviation, gaze palsies, hemi- or crossed sensory loss, dysarthria, hemi- or quadriparesis, ipsilateral cerebellar ataxia, Horner's syndrome, coma Posterior cerebral Distal territory: medial occipital and temporal cortex and underlying white matter, posterior corpus callosum Contralateral homonymous hemianopia, dyslexia without agraphia, visual hallucinations and distortions, memory defect, cortical blindness (bilateral occlusion) Proximal territory: upper midbrain, thalamus Sensory loss, ataxia, third nerve palsy, contralateral hemiparesis, vertical gaze palsy, skew deviation, hemiballismus, choreoathetosis, impaired consciousness
Clinical features of a stroke involving the middle cerebral artery. (From Weyhenmeyer, J, Gallman, E: Neuroscience, Rapid Review Series, 1st edition, 2007, Philadelphia, Mosby, p 28, Table 3-1.)
Clinical features of a stroke involving the middle cerebral artery. (From Weyhenmeyer, J, Gallman, E: Neuroscience, Rapid Review Series, 1st edition, 2007, Philadelphia, Mosby, p 28, Table 3-1.)
Clinical features of a stroke involving the anterior cerebral artery.Clinical features of a stroke involving the anterior cerebral artery. (From Weyhenmeyer J, Gallman E: Neuroscience, Rapid Review Series, 1st ed, 2007, Philadelphia, Mosby, p 30, Table 3-2.)
Conditions Associated with Focal Cerebral Ischemia. Vascular disorders Fibromuscular dysplasia Vasculitis Atherosclerosis Systemic (polyarteritis nodosa, lupus, giant cell, Wegner's, Takayasu's) Primary CNS Meningitis (syphilis, tuberculosis, fungal, bacterial, herpes zoster) Drug induced (cocaine, amphetamines) Carotid or vertebral artery dissection Lacunar infarction Migraine Multiple progressive intracranial occlusions (moyamoya syndrome) Venous or sinus thrombosis Cardiac disorders Hematologic disorders Rheumatic heart disease Mural thrombus Arrhythmias Endocarditis Mitral valve prolapse Paradoxic embolus Atrial myxoma Prosthetic heart valves Thrombocytosis Polycythemia Sickle cell disease Leukocytosis Hypercoagulable states (homocysteinemia, protein S deficiency, antiphospholipid syndrome, sickle cell disease)
∗ Subarachnoid hemorrhage may occur - from head trauma, - extension of blood from another compartment into the subarachnoid space, - or rupture of an arterial aneurysm. ∗ Cerebral dysfunction occurs because of increased intracranial pressure and from poorly understood toxic effects of subarachnoid blood on brain tissue and cerebral vessels. Hemorrhage Stroke • The most common cause of spontaneous (nontraumatic) subarachnoid hemorrhage is rupture of a berry aneurysm, which is thought to arise from a congenital weakness in the walls of large vessels at the base of the brain. • The aneurysms become symptomatic in adulthood, usually after the third decade. Rupture suddenly elevates intracranial pressure, which can interrupt cerebral blood flow and cause a generalized concussive injury. This results in loss of consciousness in about half of patients. • With very large hemorrhages, global cerebral ischemia can cause severe brain damage and prolonged coma. • Focal ischemia may later result from vasospasm of arteries at or near the site of rupture. Recurrence of hemorrhage within the first few days is a common and often fatal complication.
HemorrhageHemorrhage StrokeStroke  Intraparenchymal hemorrhageIntraparenchymal hemorrhage may result from acute elevations inmay result from acute elevations in blood pressure or from a variety of disorders that weaken vessels. Theblood pressure or from a variety of disorders that weaken vessels. The resultant hematomaresultant hematoma causes acauses a focal neurologic deficit by compressingfocal neurologic deficit by compressing adjacent structuresadjacent structures. In addition, metabolic effects of extravasated blood. In addition, metabolic effects of extravasated blood disturb the function of surrounding brain tissuedisturb the function of surrounding brain tissue, and, and nearby vessels arenearby vessels are compressedcompressed, causing, causing local ischemialocal ischemia..  Chronic hypertensionChronic hypertension is theis the most common predisposingmost common predisposing factor. In hypertensivefactor. In hypertensive patients, smallpatients, small Charcot-Charcot- Bouchard aneurysmsBouchard aneurysms appear in the walls of smallappear in the walls of small penetrating arteries and arepenetrating arteries and are thought to be the major sitesthought to be the major sites of rupture. Most vulnerable areof rupture. Most vulnerable are the small vessels that are alsothe small vessels that are also involved in lacunar infarction.involved in lacunar infarction. Hypertensive hemorrhagesHypertensive hemorrhages occur mainly in the basaloccur mainly in the basal ganglia, thalamus, pons, andganglia, thalamus, pons, and cerebellum and lesscerebellum and less commonly in subcortical whitecommonly in subcortical white matter.matter.
Intraparenchymal hemorrhageIntraparenchymal hemorrhage  Other causes of intraparenchymal hemorrhage includeOther causes of intraparenchymal hemorrhage include vascular malformations,vascular malformations, which contain abnormally fragile vessels susceptible to rupture at normal arterialwhich contain abnormally fragile vessels susceptible to rupture at normal arterial pressures, and certainpressures, and certain brain tumors,brain tumors, such as glioblastoma multiforme, whichsuch as glioblastoma multiforme, which induce proliferation of fragile vessels within the tumor.induce proliferation of fragile vessels within the tumor.  CertainCertain plateletplatelet andand coagulation disorderscoagulation disorders may predispose to intracerebralmay predispose to intracerebral hemorrhage by inhibiting coagulation.hemorrhage by inhibiting coagulation. CocaineCocaine andand amphetaminesamphetamines causecause rapid elevation of blood pressurerapid elevation of blood pressure andand are common causes ofare common causes of intraparenchymal hemorrhageintraparenchymal hemorrhage in youngin young adults.adults. HemorrhageHemorrhage may be related tomay be related to spontaneous bleeding from the acutespontaneous bleeding from the acute elevation in blood pressure, rupture ofelevation in blood pressure, rupture of an occult vascular abnormality, or drug-an occult vascular abnormality, or drug- induced vasculitis.induced vasculitis. Cerebral amyloid angiopathyCerebral amyloid angiopathy is ais a disorder that occurs mainly in thedisorder that occurs mainly in the elderly and may be associated withelderly and may be associated with Alzheimer's diseaseAlzheimer's disease. Deposition of. Deposition of amyloid weakens the walls of smallamyloid weakens the walls of small cortical vessels and causes lobarcortical vessels and causes lobar hemorrhage, often at several sites.hemorrhage, often at several sites.
Seizure disordersSeizure disorders ►Seizure is and abnormal discharge of electrical activity within the brain. It is a rapidly evolving disturbance of brain function that may produce impaired consciousness, abnormalities of sensation or mental function or convulsive movements. ►Convulsions are episodes of widespread and intense motor activity
EpilepsyEpilepsy  AnAn epileptic seizureepileptic seizure (epileptic attack, epileptic(epileptic attack, epileptic fit) is triggered by afit) is triggered by a spontaneous,spontaneous, synchronized, massivesynchronized, massive excitation of a largeexcitation of a large number of neuronsnumber of neurons,, resulting in localized orresulting in localized or generalizedgeneralized activation ofactivation of motormotor (fits or seizures),(fits or seizures), sensorysensory (sensory(sensory impressions),impressions), autonomicautonomic (e.g., salivation), or(e.g., salivation), or complexcomplex (cognitive,(cognitive, emotional) functions.emotional) functions.
Epilepsy Signs and symptoms vary:Signs and symptoms vary: petit mal – almost imperceptible alterations in– almost imperceptible alterations in consciousnessconsciousness grand mal – generalized– generalized tonic-clonic seizurestonic-clonic seizures –– dramatic loss of consciousness, falling, generalizeddramatic loss of consciousness, falling, generalized tonic-clonic convulsionstonic-clonic convulsions of all extremities,of all extremities, incontinence, and amnesia for the event.incontinence, and amnesia for the event.  Some attacks are proceeded by aSome attacks are proceeded by a prodrome – a set– a set of symptoms that warn of a seizureof symptoms that warn of a seizure  As the seizure begins, the patient may experienceAs the seizure begins, the patient may experience anan aura –– mental, sensory or motor phenomenamental, sensory or motor phenomena  Others have no warningOthers have no warning
Phases of a grand mal seizurePhases of a grand mal seizure 1.1. Tonic phaseTonic phase (10-20 seconds) – muscle(10-20 seconds) – muscle contractioncontraction Epileptic cryEpileptic cry – respiration stops– respiration stops 1.1. Clonic phaseClonic phase – (1/2 -2 minutes) muscle– (1/2 -2 minutes) muscle spasms; respiration is ineffective;spasms; respiration is ineffective; autonomic nervous system activeautonomic nervous system active 2.2. Terminal phaseTerminal phase (about 5 minutes) –(about 5 minutes) – limp and quiet, EEG flat lineslimp and quiet, EEG flat lines
Sleep Disorders • Disorders of the regulation of breathing during sleep have been held responsible for the sudden infant death syndrome (SIDS) and sleep apnea in adults. • Metabolic alkalosis is thought to favor sleep apnea. In addition, decreased muscle tone during sleep promotes the collapse of the airways, apnea, and hypoxia. • Normally one passes through several phases of varying depth during sleep. • During one night there are typically about 5 phases of rapid eye movement (REM) sleep, during which bursts of excitation from the brain stem produce twitches in the otherwise hypotonic musculature. • Several phases of non-REM (NREM) sleep must be passed through before REM sleep is reached, whereby increasing depth of sleep correlates with decreasing frequency of the EEG waves. • Chronic use of sleeping pills leads to lighter NREM sleep and only occasional REM phases.
ConsciousnessConsciousness  We become conscious of only a fractionWe become conscious of only a fraction of the information reaching our brain.of the information reaching our brain. The conscious contents are stored inThe conscious contents are stored in associative cortical areas that specializeassociative cortical areas that specialize in this task.in this task.  Conscious awareness requires not onlyConscious awareness requires not only that the specific afferents have beenthat the specific afferents have been transmitted to the cerebral cortex, buttransmitted to the cerebral cortex, but also nonspecific activation by thealso nonspecific activation by the ascending reticular activating systemascending reticular activating system (ARAS)(ARAS) through which neurons from thethrough which neurons from the reticular formation activate wide areas ofreticular formation activate wide areas of the cerebral cortex via intralaminarthe cerebral cortex via intralaminar neurons of the thalamus.neurons of the thalamus.
Loss of ConsciousnessLoss of Consciousness • Damage toDamage to large areas of the cortexlarge areas of the cortex and/or breakdown of theand/or breakdown of the ascendingascending reticular activating system (ARAS)reticular activating system (ARAS) brings aboutbrings about loss of consciousnessloss of consciousness.. • In addition, there may be primary causes influencing neuronal excitability inIn addition, there may be primary causes influencing neuronal excitability in the above-mentioned neuronal structures.the above-mentioned neuronal structures. • IschemiaIschemia (e.g., atherosclerotic vascular occlusion) or(e.g., atherosclerotic vascular occlusion) or hypoxiahypoxia (e.g.,(e.g., suffocation) impair excitability directly or bysuffocation) impair excitability directly or by cell swellingcell swelling.. • Swelling of glial cellsSwelling of glial cells impairs, among other functions, their capacity toimpairs, among other functions, their capacity to taketake up K+up K+ and thus to keep down the concentration of extracellular K+. This hasand thus to keep down the concentration of extracellular K+. This has an indirect effect onan indirect effect on neuronal excitabilityneuronal excitability.. • Part of the effect of tumors, abscesses, or bleeding is also exerted viaPart of the effect of tumors, abscesses, or bleeding is also exerted via ischemia or hypoxia in that they raise the cerebral pressure and thus impairischemia or hypoxia in that they raise the cerebral pressure and thus impair cerebral perfusion by narrowing the blood vessels.cerebral perfusion by narrowing the blood vessels. • HypoglycemiaHypoglycemia also modifies excitability, partly via cellular swelling.also modifies excitability, partly via cellular swelling. • HyponatremiaHyponatremia andand ammoniaammonia (NH4+) also act via this mechanism. The(NH4+) also act via this mechanism. The riserise in NH4in NH4+ in+ in hepatic encephalopathyhepatic encephalopathy causes the formation of glutamine fromcauses the formation of glutamine from αα-ketoglutarate and-ketoglutarate and glutamate in glial cellsglutamate in glial cells; the accumulation of glutamine; the accumulation of glutamine causes them to swell.causes them to swell. • AtAt firstfirst this swelling is counteracted by thethis swelling is counteracted by the removal of osmolytesremoval of osmolytes, seen in, seen in magnetic resonance imaging as a decrease in the cerebral concentration ofmagnetic resonance imaging as a decrease in the cerebral concentration of inositol. When this compensatory mechanism is exhausted,inositol. When this compensatory mechanism is exhausted, consciousnessconsciousness is lostis lost..
Disorders of MemoryDisorders of Memory • It is needed, for example, in order to be able to recognize certain things (apples, animals, faces). Procedural, implicit memory does not require conscious activation for storage and recall. It is required, e.g. for learning to play the piano.  Two forms of memory are distinguished:Two forms of memory are distinguished: Declarative, explicitDeclarative, explicit memorymemory (semantic or episodic(semantic or episodic) stores memory that can only be) stores memory that can only be recalled consciously.recalled consciously.
Disorders ofDisorders of MemoryMemory ► To formTo form declarative memorydeclarative memory the informationthe information first of all reaches the corresponding associationfirst of all reaches the corresponding association cortex (e.g., the secondary visual cortex) via thecortex (e.g., the secondary visual cortex) via the particular primary sensory cortical area (e.g., theparticular primary sensory cortical area (e.g., the primary visual cortex). From here, via theprimary visual cortex). From here, via the entorhinal cortex (area 28), the informationentorhinal cortex (area 28), the information reaches the hippocampus, which is essential forreaches the hippocampus, which is essential for long-term storage of declarative memory.long-term storage of declarative memory. ► With mediation from structures in theWith mediation from structures in the diencephalon, basal forebrain, and prefrontaldiencephalon, basal forebrain, and prefrontal cortex the item is again stored in the asssociationcortex the item is again stored in the asssociation cortex. In this way the information is first takencortex. In this way the information is first taken up, via the sensory memory, by theup, via the sensory memory, by the short-termshort-term memorymemory, which can hold on to the content for, which can hold on to the content for only a few seconds to minutes.only a few seconds to minutes. ► The information can be transferred to theThe information can be transferred to the long-long- term memoryterm memory , for example, through being, for example, through being rehearsed. Such rehearsal is not an essentialrehearsed. Such rehearsal is not an essential precondition for the formation of long-termprecondition for the formation of long-term memory, however.`memory, however.`
Amnesia  Lesions in the hippocampus or its connections result in anterograde amnesia. The affected patients will from that moment on no longer be able to form any new declarative memory. They will remember events prior to the lesion but none subsequent to it.  Retrograde amnesia, i.e., the loss of already stored information, occurs in disorders in the relevant associative cortical fields. Depending on the extent and localization of the disorder, the loss can be reversible or irreversible. In the former case the patient will lose items of memory, but they can be retrieved. In irreversible loss the particular items are permanently lost.  Transitory bilateral functional disturbance of the hippocampus can cause anterograde and retrograde (days to years) amnesia (transient global amnesia). In Korsakoff’s syndrome (frequent in chronic alcoholics) both anterograde and retrograde amnesia can occur. Patients thus affected often try to cover up gaps in memory by means of confabulations.
Disorders of Memory The procedural (implicit) memory is not impaired in lesions of the hippocampus. It allows imprinting, learning of skills, sensitization, habituation, and conditioning. Depending on the task, cerebellum, basal ganglia, amygdala and cortical areas are involved. Both the cerebellum and basal ganglia play an important role when learning skills. Relevant afferent impulses reach the cerebellum via olivary and pontine nuclei. The storage capacity of the cerebellum can be lost by, for example, toxic damage, degenerative diseases, and trauma. Dopaminergic projections of the substantia nigra also play a part in the formation of procedural memory.
The amygdala is important in conditioning anxiety reactions. It receives its information from the cortex and thalamus and influences motor and autonomic functions (e.g., muscle tone, palpitations [awareness of tachycardias], goose- pimples) via the reticular formation and hypothalamus. Removal of the amygdala (e.g., by trauma or opiates) cancels conditioned anxiety reactions. Bilateral removal of the amygdala with portions of the hippocampus and temporal lobe results in amnesia and disinhibited behavior (Klüver–Bucy syndrome).
a. Most often due to thiamine deficiency b. Gross and microscopic findings: 1) Hemorrhages of small vessels with hemosiderin deposits  Mammillary bodies, wall of the third and fourth ventricles; 2) Neuronal loss, gliosis, vessel hemorrhage; c. Wernicke encephalopathy; reversible findings: • Confusion, ataxia, nystagmus, ophthalmoplegia (eye muscle weakness) d. Korsakoff psychosis 1) Advanced irreversible stage of Wernicke encephalopathy  Targets the limbic system; 2) Anterograde amnesia (inability to form new memories); 3) Retrograde amnesia (inability to recall old memories); 4) Confabulation, hallucinations 4. Treatment  Thiamine
Clinical Features of DementiaClinical Features of Dementia  DementiaDementia is anis an acquiredacquired decline in intellectual functiondecline in intellectual function resulting inresulting in lossloss of social independenceof social independence..  There isThere is impairment of memoryimpairment of memory and at least one other area ofand at least one other area of corticalcortical functionfunction, such as, such as language, calculation, spatial orientation,language, calculation, spatial orientation, decision making, judgment, and abstract reasoningdecision making, judgment, and abstract reasoning..  InIn contrast to patients withcontrast to patients with confusional statesconfusional states,, symptoms progress oversymptoms progress over months to yearsmonths to years, and alertness is preserved until the, and alertness is preserved until the very late stages ofvery late stages of diseasedisease..  DementiaDementia affects 5–20% of persons over age 65affects 5–20% of persons over age 65, and, although not, and, although not part of normal aging, its incidence increases with age.part of normal aging, its incidence increases with age.  The most common causes, which are listed inThe most common causes, which are listed in ttableable on the next slideon the next slide,, account for almostaccount for almost 90% of cases90% of cases..  Treatable causesTreatable causes are important to recognize and includeare important to recognize and include hypothyroidism, vitamin B12 deficiency, neurosyphilis, brain tumor,hypothyroidism, vitamin B12 deficiency, neurosyphilis, brain tumor, normal pressure (communicating) hydrocephalus, and chronic subduralnormal pressure (communicating) hydrocephalus, and chronic subdural hematomahematoma..  In addition,In addition, although not curable, dementiaalthough not curable, dementia associated withassociated with HIVHIV infection may be slowed byinfection may be slowed by antiretroviral treatmentantiretroviral treatment..  AboutAbout 10–15%10–15% of patients referred for evaluation of dementia sufferof patients referred for evaluation of dementia suffer from depression (from depression ("pseudodementia""pseudodementia"), which may also respond to), which may also respond to treatment.treatment.
Dementia with Lewy bodies Multiple cerebral infarcts Alzheimer's disease (> 50% of cases) Deficiency of vitamins B12, B6, B1, or niacin HIV infection Huntington'sHuntington's diseasedisease Pick's disease Prion diseases (eg, Creutzfeldt-Jakob disease) Parkinson'sParkinson's diseasedisease Subdural hematoma Frontotemporal dementia Alcoholism Normal pressure hydrocephalus Primary or metastatic CNS neoplasms Neurosyphilis Chronic meningitis Hypothyroidism Major Causes of Dementia
Alzheimer’s DiseaseAlzheimer’s Disease  The defective gene on chromosome 19,The defective gene on chromosome 19, for example, codes for apolipoprotein Efor example, codes for apolipoprotein E (ApoE 4), the relevant gene on(ApoE 4), the relevant gene on chromosome 21 for a protein (βchromosome 21 for a protein (β-- amyloid precursoramyloid precursor) that can be broken) that can be broken down to small amyloid peptides. Thesedown to small amyloid peptides. These can on their own bunch themselvescan on their own bunch themselves together into protein fibrils 7–10nm long.together into protein fibrils 7–10nm long. These amyloid fibrils can then formThese amyloid fibrils can then form aggregates, 10 μm to several hundredaggregates, 10 μm to several hundred μm in diameter (μm in diameter (senile plaquessenile plaques), that), that are frequently found in the brain ofare frequently found in the brain of patients with Alzheimer’s disease. Inpatients with Alzheimer’s disease. In addition to extracellular amyloid, theseaddition to extracellular amyloid, these plaques contain distorted dendrites andplaques contain distorted dendrites and axons with abnormal intracellularaxons with abnormal intracellular neurofibrils. The formation of theseneurofibrils. The formation of these atypical elements of the cytoskeletonatypical elements of the cytoskeleton apparently precedes the death of theapparently precedes the death of the neurons.neurons. • The occurrence of Alzheimer’s disease, the most common cause of (senile) dementia (about 70%), is favored by a genetic disposition. • However, the disease is not genetically uniform. An especially severe form of the disease has an autosomal dominant inheritance. • Defects on chromosomes 1, 12, 14, 19, or 21 were found in families with Alzheimer’s disease.
 Creutzfeldt–JakobCreutzfeldt–Jakob diseasedisease, possibly, possibly caused by prionscaused by prions (proteinaceous(proteinaceous infectious particles), isinfectious particles), is a neurodegenerativea neurodegenerative disease that, indisease that, in addition to motor (e.g.,addition to motor (e.g., ataxia) andataxia) and psychogenicpsychogenic disorders, also leadsdisorders, also leads to dementia.to dementia. Creutzfeldt–Jakob diseaseCreutzfeldt–Jakob disease
Literature:Literature: 1.1. General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia:General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia: Nova Knuha Publishers – 2011. – P.Nova Knuha Publishers – 2011. – P.627627––663838.. 2.2. Russell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinicalRussell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinical pharmacy practice / Russell J. Greene, Norman D. Harris // Published by thepharmacy practice / Russell J. Greene, Norman D. Harris // Published by the Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, LondonPharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rdSE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rd edition, USA. – 2008. – Chapter 7. – P. 455–512.edition, USA. – 2008. – Chapter 7. – P. 455–512. 3.3. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams &Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams & Wilkins), Trade paperback (2003)Wilkins), Trade paperback (2003) // Carol Mattson Porth, Kathryn J. Gaspard. –ChaptersCarol Mattson Porth, Kathryn J. Gaspard. –Chapters 36, 38-40. – P. 637–363, 456–777.36, 38-40. – P. 637–363, 456–777. 4.4. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing.Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing. – 2010. – P. 512–531.– 2010. – P. 512–531. 5.5. Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova //Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova // Study guide for medical students and practitioners.Study guide for medical students and practitioners. Edited by prof. Zaporozan, OSMU. –Edited by prof. Zaporozan, OSMU. – Odessa. – 2005. – P. 2Odessa. – 2005. – P. 29292––307307.. 6.6. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme.Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme. Stuttgart. New York. – 2000. – P. 298–331.Stuttgart. New York. – 2000. – P. 298–331. 7.7. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition. Copyright ВCopyright В.. – Lippincott Williams & Wilkins – 2008. –– Lippincott Williams & Wilkins – 2008. – Chapter 8. – P. 185–202, 208–Chapter 8. – P. 185–202, 208– 209, 220–224.209, 220–224. 8.8. Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. –Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. – 2007. – Chapter2007. – Chapter 2323. – P.. – P. 881–902881–902.. 9.9. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasik // Elsevier Inc, 4th edition. – 2010. – P. 998–1034, 1086–1123.Banasik // Elsevier Inc, 4th edition. – 2010. – P. 998–1034, 1086–1123. 10.10. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, GlennPathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin.Matfin. –– New York, Milwaukee.New York, Milwaukee. –– 2009.2009. –– P.P. 1181–12991181–1299..
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Pathophysiology of cns 2017

  • 2.
    Actuality of thelectureActuality of the lecture  The nervous system as a main regulatory system of an organism in this orThe nervous system as a main regulatory system of an organism in this or that measure participates in pathogenesis of each diseases. The earliest andthat measure participates in pathogenesis of each diseases. The earliest and obligatory form of participation of the nervous system in pathology isobligatory form of participation of the nervous system in pathology is defensive and adaptive the response. The protective reflexes (cough,defensive and adaptive the response. The protective reflexes (cough, vomiting), protective inhibition, response hypotalamo-hypophysial-adrenalvomiting), protective inhibition, response hypotalamo-hypophysial-adrenal system belong to such responses.system belong to such responses.  At the same time during development of diseases the nervous systemAt the same time during development of diseases the nervous system becomes the object of a defeat itself. It is defensive and adaptive thebecomes the object of a defeat itself. It is defensive and adaptive the response of the damaged nervous system are reduced, and it becomes aresponse of the damaged nervous system are reduced, and it becomes a source of pathological, harmful to an organism reflexes. Itself graving andsource of pathological, harmful to an organism reflexes. Itself graving and character of violations of nervous activity depend on localization ofcharacter of violations of nervous activity depend on localization of pathological process and appear as a complex of diverse symptoms.pathological process and appear as a complex of diverse symptoms. Frequently there is a pain, which on the essence is typical pathologicalFrequently there is a pain, which on the essence is typical pathological process, but at the same time has signal and adaptive significance. Theprocess, but at the same time has signal and adaptive significance. The disturbance of nervous activity is always reflected in the function of internaldisturbance of nervous activity is always reflected in the function of internal organs.organs.  Several neurologic disorders in which some of the molecular mechanisms ofSeveral neurologic disorders in which some of the molecular mechanisms of pathogenesis are known are discussed later in this chapter including motorpathogenesis are known are discussed later in this chapter including motor neuron disease, Parkinson's disease, myasthenia gravis, epilepsy, Alzheimer'sneuron disease, Parkinson's disease, myasthenia gravis, epilepsy, Alzheimer's disease, and stroke.disease, and stroke.  Exciting advances in our understanding and overlap of these diseases areExciting advances in our understanding and overlap of these diseases are leading to new therapeutic targets and the hope of better treating theseleading to new therapeutic targets and the hope of better treating these devastating diseases.devastating diseases.
  • 3.
    CONTENTCONTENT • Nervous System:NeuronsNervous System: Neurons • Division of the Nervous SystemDivision of the Nervous System • Pain: features of pain as a kind of sensitivity. Etiology andPain: features of pain as a kind of sensitivity. Etiology and pathogenesis of pain. Antinociceptive systemspathogenesis of pain. Antinociceptive systems • Upper Motor NeuronsUpper Motor Neurons and Disordersand Disorders • Sensory LossSensory Loss • Spinal Cord InjuriesSpinal Cord Injuries • DysphasiaDysphasia • Diseases of the Basal GangliaDiseases of the Basal Ganglia • Disorders of integrative function of CNS.Disorders of integrative function of CNS. • Anxiety Disorders; Mood Disorders; SchizophreniaAnxiety Disorders; Mood Disorders; Schizophrenia • Acute and chronic disturbances of brain circulation. StrokeAcute and chronic disturbances of brain circulation. Stroke • Cerebral infarction and cerebral hemorrhage.Cerebral infarction and cerebral hemorrhage. • Seizure disorders. Epilepsy; Sleep Disorders; AphasiasSeizure disorders. Epilepsy; Sleep Disorders; Aphasias • Disorders of Memory. Alzheimer’s Disease. Creutzfeldt–Disorders of Memory. Alzheimer’s Disease. Creutzfeldt– Jakob diseaseJakob disease
  • 4.
    FunctionFunction of neuronsofneurons  A). Sensory inputA). Sensory input  B). IntegrationB). Integration  C). ResponseC). Response
  • 5.
    A). Non nervousA).Non nervous or glial cellsor glial cells.. 1). Astrocytes1). Astrocytes 2). Microglia2). Microglia 3). Ependymal3). Ependymal 4). Oliodendrocytes4). Oliodendrocytes 5). Satellite cells5). Satellite cells 6).6). Schwann cellsSchwann cells form myelin sheathsform myelin sheaths Types of cellsTypes of cells
  • 6.
    Types ofTypes of cellscellsB).NeuronsB). Neurons 1). Structure1). Structure II).). cell bodycell body oror somasoma -- endoplasmicendoplasmic reticulum called thereticulum called the nissl bodynissl body.. IIII).). ProcessesProcesses oror tracts (nerves)tracts (nerves) a).a). Dendrites:Dendrites: input regioninput region b).b). Axon:Axon: Carries information awayCarries information away c).c). Synaptic knobsSynaptic knobs oror AxonalAxonal terminalsterminals.. ReleasesReleases neurotransmitters.neurotransmitters. 2).2). AxonsAxons a).a). myelin sheathmyelin sheath -- protects andprotects and electrically insulates fibers conductelectrically insulates fibers conduct nerve impulses faster thannerve impulses faster than nonmylenated fibers.nonmylenated fibers. b).b). nodes of Ranviernodes of Ranvier:: spaces between the sheathsspaces between the sheaths The action potential skips to the nodesThe action potential skips to the nodes
  • 7.
    Nerve ImpulseNerve Impulse A).TermsA). Terms 1).1). Resting membrane PotentialResting membrane Potential::  PolarizedPolarized 2).2). DepolarizationDepolarization::  Change in ion concentrationChange in ion concentration 3).3). HyperpolarizationHyperpolarization  Change in ion concentration insideChange in ion concentration inside becomes more negativebecomes more negative 4).4). Graded PotentialGraded Potential  Localized change in ion; subthresholdLocalized change in ion; subthreshold 5).5). Action PotentialAction Potential  Change in ion concentration thatChange in ion concentration that does not decrease over distance.does not decrease over distance. B).B). Action PotentialAction Potential Stages of an Action PotentialStages of an Action Potential polarized resting potentialpolarized resting potential depolarizesdepolarizes repolarizesrepolarizes undershoot phaseundershoot phase UndershooUndershoott :: the K+ channels stay openthe K+ channels stay open once resting potential is reached;once resting potential is reached; hyperpolarizing the cell.hyperpolarizing the cell.
  • 8.
    NerveNerve ImpulseImpulse C).C). PropagationPropagation Cannot be depolarized again until the membrane hasCannot be depolarized again until the membrane has reached resting potential. The action potential moves at areached resting potential. The action potential moves at a constant velocityconstant velocity D).D). All or none phenomenonAll or none phenomenon  Not all depolarizations result in action potentialsNot all depolarizations result in action potentials.. TheThe depolarization must reach thedepolarization must reach the threshold pointthreshold point E).E). Refractory periodRefractory period  AAbsolute refractory periodbsolute refractory period cannot respond to anothercannot respond to another stimuli.stimuli.  RRelative refractory periodelative refractory period -- tthe threshold is higherhe threshold is higher F). Impulse VelocityF). Impulse Velocity  Strong stimuli result in more nerve impulses NotStrong stimuli result in more nerve impulses Not stronger impulses or fasterstronger impulses or faster
  • 9.
    SynapseSynapse –– junctionthat carriesjunction that carries information between neuronsinformation between neurons  A). TypesA). Types 1). Electrical synapse: ions to cross junction1). Electrical synapse: ions to cross junction 2). Chemical synapse2). Chemical synapse  neurotransmittersneurotransmitters B). Termination of neurotransmitterB). Termination of neurotransmitter  1). Degradation enzymes1). Degradation enzymes  2). Neurotransmitter reabsorbed2). Neurotransmitter reabsorbed  3). Diffusion of the neurotransmitter3). Diffusion of the neurotransmitter ImpulseImpulse releasesreleases Ca++ (in neuron)Ca++ (in neuron) ± neurotransmitter released ± binds to receptors± neurotransmitter released ± binds to receptors ±± ion channels open on postsynaptic membraneion channels open on postsynaptic membrane
  • 10.
    Neurotransmitters A). Acetylcholine (ACh) B).Biogenic Amines • 1). Dopamine • 2). Norepinephrine • 3). Epinephrine • 4). Serotonin C). Amino Acids D). Peptides • 1). endorphins E). Novel or Miscellaneous
  • 11.
    Division of theNervous System A). Central Nervous System: (CNS) • Brain and Spinal Cord only B). Peripheral Nervous System • Outside CNS 1). Sensory or afferent division: • Carries impulses to CNS 2). Motor or efferent division • Carries impulses from the CNS. I). Somatic Nervous System • voluntary II). Autonomic Nervous System • involuntary • a. Parasympathetic • b. Sympathetic
  • 12.
    The SympatheticThe Sympathetic NervousSystemNervous System  TheThe first fibersfirst fibers of the sympathetic nerves, called theof the sympathetic nerves, called the preganglionic fiberspreganglionic fibers, leave from the thoracic or lumbar, leave from the thoracic or lumbar regions of the spine.regions of the spine.  Soon afterSoon after leaving the spineleaving the spine, a preganglionic fiber, a preganglionic fiber joinsjoins other preganglionic fibersother preganglionic fibers to form anto form an autonomic ganglionautonomic ganglion..  At this point, theAt this point, the preganglionic fiber synapsespreganglionic fiber synapses on theon the second nerve fiber of the systemsecond nerve fiber of the system, the, the postganglionic fiberpostganglionic fiber,, andand releases acetylcholinereleases acetylcholine, which causes the, which causes the postganglionic fiber to fire anpostganglionic fiber to fire an action potentialaction potential..  From theFrom the autonomic gangliaautonomic ganglia, the postganglionic fiber travels, the postganglionic fiber travels to itsto its target organtarget organ, the muscle or gland., the muscle or gland.  TheThe sympathetic postganglionic fibersympathetic postganglionic fiber usually releases theusually releases the neurotransmitter norepinephrineneurotransmitter norepinephrine.. Target organ receptors forTarget organ receptors for norepinephrinenorepinephrine are calledare called adrenergic receptorsadrenergic receptors..
  • 13.
    The Parasympathetic NervousSystemThe Parasympathetic Nervous System  The fibers of the parasympathetic nervous systemThe fibers of the parasympathetic nervous system (PNS)(PNS) leave the brain in the cranial nervesleave the brain in the cranial nerves oror leave the spinal cordleave the spinal cord from the sacral areafrom the sacral area..  TheThe preganglionic fiberpreganglionic fiber of theof the PNSPNS is typically long and travelsis typically long and travels to an autonomic ganglionto an autonomic ganglion locatedlocated near the target organnear the target organ..  Preganglionic parasympathetic nervesPreganglionic parasympathetic nerves releaserelease acetylcholineacetylcholine thatthat then stimulates the postganglionic fiberthen stimulates the postganglionic fiber..  TheThe parasympathetic postganglionic fiberparasympathetic postganglionic fiber then travels a shortthen travels a short distancedistance to its target tissueto its target tissue, a, a muscle or a glandmuscle or a gland. This nerve. This nerve also releases acetylcholinealso releases acetylcholine..  Preganglionic acetylcholine receptorsPreganglionic acetylcholine receptors for sympathetic andfor sympathetic and parasympathetic fibersparasympathetic fibers are calledare called nicotinic receptorsnicotinic receptors ..  Postganglionic acetylcholine receptorsPostganglionic acetylcholine receptors are calledare called muscarinicmuscarinic receptorsreceptors. These names relate to the experimental. These names relate to the experimental stimulation of the receptors bystimulation of the receptors by nicotinenicotine andand muscarinemuscarine (a(a mushroom poison).mushroom poison).
  • 14.
    The Autonomic NervousSystem Structure Sympathetic Stimulation Parasympathetic Stimulation Iris (eye muscle) Pupil dilation Pupil constriction Salivary Glands Saliva production reduced Saliva production increased Oral/Nasal Mucosa Mucus production reduced Mucus production increased Heart Heart rate and force increased Heart rate and force decreased Lung Bronchial muscle relaxed Bronchial muscle contracted Stomach Peristalsis reduced Gastric juice secreted; motility increased Small Intestine Motility reduced Digestion increased Large Intestine Motility reduced Secretions and motility increased Liver Increased conversion of glycogen to glucose --- Kidney Decreased urine secretion Increased urine secretion Adrenal medulla Norepinephrine and epinephrine secreted --- Bladder Wall relaxed Sphincter closed Wall contracted Sphincter relaxed
  • 15.
    THE SOMATOSENSORY SYSTEMTHESOMATOSENSORY SYSTEM ■■ The somatosensory system relays information to theThe somatosensory system relays information to the CNS about four major body sensations:CNS about four major body sensations: touch,touch, temperature,temperature, pain,pain, body positionbody position.. Stimulation of receptorsStimulation of receptors on regions of the body wall ison regions of the body wall is required torequired to initiate the sensory response.initiate the sensory response. ■■ The system is organized intoThe system is organized into dermatomesdermatomes, with each, with each segment supplied by asegment supplied by a single dorsal root ganglionsingle dorsal root ganglion thatthat sequentially relays the sensory information tosequentially relays the sensory information to thethe spinal cord, the thalamus, and the sensoryspinal cord, the thalamus, and the sensory cortexcortex.. ■■ Two pathwaysTwo pathways carry sensory information throughcarry sensory information through thethe CNSCNS. The. The discriminative pathwaydiscriminative pathway crosses in thecrosses in the medulla and relaysmedulla and relays touchtouch andand body positionbody position. The. The anterolateral pathwayanterolateral pathway crosses in the spinal cordcrosses in the spinal cord andand relaysrelays temperaturetemperature andand pain sensationpain sensation fromfrom thethe opposite side of the body.opposite side of the body.
  • 16.
    Kinds of SensitivityKindsof Sensitivity 1.1. PainfulPainful 2.2. TemperatureTemperature 3.3. TactileTactile 4.4. ProprioceptiveProprioceptive
  • 17.
    DEFINITION OF PAINDEFINITIONOF PAIN  PAINPAIN –– it is typical pathological processit is typical pathological process,, whichwhich was generated during evolutionwas generated during evolution andand which arise owing to action on an organismwhich arise owing to action on an organism painfulpainful ((nociceptivenociceptive)) irritantirritant oror weakeningweakening ofof antipainfulantipainful ((antinociceptiveantinociceptive)) systemsystem  PainPain is an “unpleasant sensory andis an “unpleasant sensory and emotional experience associatedemotional experience associated withwith potential tissue damage, or described inpotential tissue damage, or described in terms ofterms of such damage.”such damage.”
  • 18.
    CLASSIFICATION OF PAIN • Physiologicalpain • Pathological pain • Acute pain • Chronical pain MEDIATORS OFMEDIATORS OF PAINPAIN• Substanse Р • Glutamic acid • Cholecystokinin • Neurotensin
  • 19.
    TYPES OF PAINTYPESOF PAIN  Pain can be classified according to  location,  site of referral, and  duration.  Cutaneous pain is a sharp, burning pain that has its origin in the skin or subcutaneous tissues.  Deep pain is a more diffuse and throbbing pain that originates in structures such as the muscles, bones, and tendons and radiates to the surrounding tissues.  Visceral pain is a diffuse and poorly defined pain that results from stretching, distention, or ischemia of tissues in a body organ.  Referred pain is pain that originates at a visceral site but is perceived as originating in part of the body wall that is innervated by neurons entering the same segment of the nervous system.  Acute pain usually results from tissue damage and is characterized by autonomic nervous system responses.  Chronic pain is persistent pain that is accompanied by loss of appetite, sleep disturbances, depression,
  • 20.
    PAIN SENSATION ■ Painis both a protective and an unpleasant physical and emotionally disturbing sensation originating in pain receptors that respond to a number of stimuli that threaten tissue integrity. ■ There are two pathways for pain transmission: • The fast pathway for sharply discriminated pain that moves directly from the receptor to the spinal cord using myelinated Aδ fibers and from the spinal cord to the thalamus using the neospinothalamic tract • The slow pathway for continuously conducted pain that is transmitted to the spinal cord using unmyelinated C fibers and from the spinal cord to the thalamus using the more circuitous and slower-conducting paleospinothalamic tract. ■ The central processing of pain information includes transmission to the somatosensory cortex, where pain information is perceived and interpreted; the limbic system, where the emotional components of pain are experienced; and to brain stem centers, where autonomic nervous system responses are recruited. ■ Modulation of the pain experience occurs by way of the endogenous analgesic center in the midbrain, the pontine noradrenergic neurons, and the nucleus raphe magnus in the medulla, which sends inhibitory signals to dorsal horn neurons in the spinal cord.
  • 21.
    Primary pain pathways NociceptiveNociceptive stimulistimuli Somestheticassociation cortexSomesthetic association cortex (perception and meaning)(perception and meaning) Limbic cortexLimbic cortex (emotional experience)(emotional experience) PontinePontine noradrenergic neuronsnoradrenergic neurons Primary somesthetic cortexPrimary somesthetic cortex (discrimination: location and intensity)(discrimination: location and intensity) Medullary raphe nucleusMedullary raphe nucleus Thalamus (sensation)Thalamus (sensation) Somesthetic nucleiSomesthetic nuclei Spinal cord and dorsal hornSpinal cord and dorsal horn pain modulating circuitspain modulating circuits Periaqueductal gray (PAG)Periaqueductal gray (PAG) (endogenous analgesic center)(endogenous analgesic center) Medullary NRMMedullary NRM NeospinothalamictractNeospinothalamictract (sharp,brightpain)(sharp,brightpain) PaleospinothalamictractPaleospinothalamictract (dull,achingpain)(dull,achingpain) Primary touch fibers A-delta (fast) C-fiber (slow)
  • 22.
    Characteristics ofCharacteristics of Acuteand Chronic PainAcute and Chronic Pain Characteristic Acute Pain Chronic Pain Onset Recent Continuous or intermittent Duration Short duration (<6 months) 6 months or more Autonomic responses Consistent with sympathetic fight- or-flight response* Increased heart rate Increased stroke volume Increased blood pressure Increased pupillary dilation Increased muscle tension Decreased gut motility Decreased salivary flow (dry mouth) Absence of autonomic responses Psychological component Associated anxiety Increased irritability Associated depression Somatic preoccupation Withdrawal from outside interests Decreased strength of relationships Other types of response Decreased sleep Decreased libido Appetite changes
  • 23.
    Pain Threshold andTolerance Cando Baseline Dolorimeter  Pain threshold and tolerance affect an individual’s response to a painful stimulus. Although the terms often are used interchangeably, pain threshold and pain tolerance have distinct meanings. Pain threshold is closely associated with tissue damage and the point at which a stimulus is perceived as painful.  Pain tolerance relates more to the total pain experience; it is defined as the maximum intensity or duration of pain that a person is willing to endure before the person wants something done about the pain. Psychological, familial, cultural, and environmental factors significantly influence the amount of pain a person is willing to tolerate. The threshold to pain is fairly uniform from one person to another, whereas pain tolerance is extremely variable. Separation and identification of the role of each of these two aspects of pain continue to pose fundamental problems for the pain management team and for pain researchers.
  • 24.
    Alterations in PainSensitivity  Hypersensitivity (i.e., hyperesthesia) or increased painfulness (i.e., hyperalgesia)  Primary hyperalgesia occurs at the site of injury.  Secondary hyperalgesia occurs in nearby uninjured tissue.  Hyperpathia is a syndrome in which the sensory threshold is raised, but when it is reached, continued stimulation, especially if repetitive, results in a prolonged and unpleasant experience. This pain can be explosive and radiates through a peripheral nerve distribution. It is associated with pathologic changes in peripheral nerves, such as localized ischemia.  Spontaneous, unpleasant sensations called paresthesias occur with more severe irritation (e.g., the pins-and-needles sensation that follows temporary compression of a peripheral nerve).  The general term dysesthesia is given to distortions (usually unpleasant) of somesthetic sensation that typically accompany partial loss of sensory innervation.
  • 25.
    Alterations in PainSensitivity • Severe pathologic processes can result in reduced or lost tactile (e.g., hypoesthesia, anesthesia), temperature (e.g., hypothermia, athermia), and pain sensation (i.e., hypalgesia). • Analgesia is the absence of pain on noxious stimulation or the relief of pain without loss of consciousness. The inability to sense pain may result in trauma, infection, and even loss of a body part or parts. Inherited insensitivity to pain may take the form of congenital indifference or congenital insensitivity to pain. • Allodynia (Greek allo, “other,” and odynia, “painful”) is the term used for the puzzling phenomenon of pain that follows a non-noxious stimulus to apparently normal skin. This term is intended to refer to instances in which otherwise normal tissues may be abnormally innervated or may be referral sites for other loci that give rise to pain with non-noxious stimuli. • Trigger points are highly localized points on the skin or mucous membrane that can produce immediate intense pain at that site or elsewhere when stimulated by light tactile stimulation.
  • 26.
  • 28.
    NeuralgiaNeuralgia  NeuralgiaNeuralgia ischaracterized by severe, brief,is characterized by severe, brief, often repetitive attacksoften repetitive attacks of lightning-like orof lightning-like or throbbing pain. It occurs along the distributionthrobbing pain. It occurs along the distribution ofof a spinal or cranial nerve and usually isa spinal or cranial nerve and usually is precipitatedprecipitated by stimulation of the cutaneousby stimulation of the cutaneous region supplied by that nerve.region supplied by that nerve.  Trigeminal Neuralgia.Trigeminal Neuralgia. Trigeminal neuralgia, orTrigeminal neuralgia, or tictic douloureuxdouloureux,, is one of theis one of the most common and severemost common and severe neuralgias. It is manifestedneuralgias. It is manifested byby facial ticsfacial tics oror grimacesgrimaces and characterized byand characterized by stabbing,stabbing, paroxysmalparoxysmal attacks of pain that usuallyattacks of pain that usually are limited to the unilateralare limited to the unilateral sensory distribution of onesensory distribution of one or more branches of theor more branches of the trigeminal nerve, mosttrigeminal nerve, most often the maxillary oroften the maxillary or mandibular divisions.mandibular divisions.
  • 29.
    Postherpetic Neuralgia.Postherpetic Neuralgia. Postherpeticpain is painPostherpetic pain is pain that persiststhat persists as aas a complication of herpescomplication of herpes zoster or shingles. Itzoster or shingles. It describes thedescribes the presence ofpresence of pain more than 1 monthpain more than 1 month after the onset of theafter the onset of the acuteacute attack.attack. Postherpetic neuralgiaPostherpetic neuralgia develops in from 10% todevelops in from 10% to 70% of70% of patients withpatients with shingles; the riskshingles; the risk increases with age.increases with age. The pain ofThe pain of postherpeticpostherpetic neuralgia occurs in theneuralgia occurs in the areas of innervation ofareas of innervation of thethe infected gangliainfected ganglia.. During the acute attack ofDuring the acute attack of herpes zosterherpes zoster, the, the reactivated virus travelsreactivated virus travels from the ganglia to thefrom the ganglia to the skin of the correspondingskin of the corresponding dermatomes, causingdermatomes, causing localized vesicularlocalized vesicular eruptioneruption and hyperpathiaand hyperpathia ((i.e.i.e., abnormally, abnormally exaggerated subjectiveexaggerated subjective responseresponse to pain).to pain).
  • 30.
  • 31.
    Phantom Limb Pain •Phantom limb pain, a type of neurologic pain, follows amputation of a limb or part of a limb. As many as 70% of those who under amputation experience phantom pain. • The pain often begins as sensations of tingling, heat and cold, or heaviness, followed by burning, cramping, or shooting pain. It may disappear spontaneously or persist for many years. One of the more troublesome aspects of phantom pain is that the person may experience painful sensations that were present before the amputation, such as that of a painful ulcer or bunion.
  • 32.
    • Several theorieshave been proposed as to the causes of phantom pain. • One theory is that the end of a regenerating nerve becomes trapped in the scar tissue of the amputation site. It is known that when a peripheral nerve is cut, the scar tissue that forms becomes a barrier to regenerating outgrowth of the axon. The growing axon often becomes trapped in the scar tissue, forming a tangled growth (i.e., neuroma) of smalldiameter axons, including primary nociceptive afferents and sympathetic efferents. It has been proposed that these afferents show increased sensitivity to innocuous mechanical stimuli and to sympathetic activity and circulating catecholamines. • A related theory moves the source of phantom limb pain to the spinal cord, suggesting that the pain is caused by the spontaneous firing of spinal cord neurons that have lost their normal sensory input from the body. In this case, a closed self-exciting neuronal loop in the posterior horn of the spinal cord is postulated to send impulses to the brain, resulting in pain. Even the slightest irritation to the amputated limb area can initiate this cycle. • Other theories propose that the phantom limb pain may arise in the brain. In one hypothesis, the pain is caused by changes in the flow of signals through somatosensory areas of the brain. • Treatment of phantom limb pain has been accomplished by the use of sympathetic blocks, TENS of the large myelinated afferents innervating the area, hypnosis, and relaxation training.
  • 33.
    Antinociceptive systemsAntinociceptive systems NeuronalNeuronal opiate systemopiate system –– metmet-- and leuencephalinand leuencephalin  NeuronalNeuronal unopiate systemunopiate system –– noradrenalinnoradrenalin,, serotoninserotonin,, dopaminedopamine  HormonalHormonal opiate systemopiate system –– hormoneshormones ofof adenohypophysisadenohypophysis  HormonalHormonal unopiate systemunopiate system –– vasopressinvasopressin
  • 34.
    Hormonal unopiate systemHormonalunopiate system  1.1. Adrenocorticotropic hormoneAdrenocorticotropic hormone  2.2. MelanostimulatingMelanostimulating hormoneshormones  3.3. ββ --LipotropicLipotropic hormonehormone  4.4. LargeLarge endorphinesendorphines:: kitorphinkitorphin ββ--kosomorphinkosomorphin dinorphindinorphin
  • 35.
    1.1. Opening ofabscessOpening of abscess 2.2. Reposition ofReposition of fragmentsfragments 3.3. Splintation of extremitySplintation of extremity 4.4. Section of scarsSection of scars 5.5. DesympathizationDesympathization 1.1. AcupunctureAcupuncture 2.2. ElectroacupunctureElectroacupuncture 3.3. LaseropunctureLaseropuncture 4.4. ElectrostimulationElectrostimulation 5.5. ElectrophoresisElectrophoresis 6.6. UltrasoundUltrasound 7.7. Magnetico-laserMagnetico-laser therapytherapy 8.8. MassageMassage 9.9. ManualManual therapytherapy METHODS OFMETHODS OF ANAESTIZATIONANAESTIZATION  PsycologicalPsycological  PhysicalPhysical  PharmacologicalPharmacological  SurgicalSurgical  NeurosurgicalNeurosurgical 1.1. ConversationConversation 2.2. RelaxationRelaxation 3.3. HypnosisHypnosis 4.4. AutotrainingAutotraining 5.5. CorrectCorrect stereotypestereotype of motionof motion 6.6. Self-removel of painSelf-removel of pain
  • 36.
    Upper Motor NeuronsUpperMotor Neurons  Planned movements and those guided by sensory, visual, or auditory stimuli are preceded by discharges from prefrontal, somatosensory, visual, or auditory cortices, which are then followed by motor cortex pyramidal cell discharges that occur several milliseconds before the onset of movement  AnatomyAnatomy  TheThe motor cortexmotor cortex is theis the region from whichregion from which movements can be elicitedmovements can be elicited by electrical stimuli (Figure).by electrical stimuli (Figure).  This includes:  the primary motor area (Brodmann area 4),  premotor cortex (area 6),  supplementary motor cortex (medial portions of 6),  primary sensory cortex (areas 3, 1, and 2).  In the motor cortex, groups of neurons are organized in vertical columns, and discrete groups control contraction of individual muscles.
  • 37.
    ► Cortical motorneuronsCortical motor neurons contribute axons thatcontribute axons that converge in the corona radiata and descend in theconverge in the corona radiata and descend in the posterior limb of the internal capsule, cerebralposterior limb of the internal capsule, cerebral peduncles, ventral pons, and medullapeduncles, ventral pons, and medulla. These fibers. These fibers constitute theconstitute the corticospinalcorticospinal andand corticobulbarcorticobulbar tractstracts and together areand together are known asknown as upper motorupper motor neuron fibersneuron fibers. As they descend through the. As they descend through the diencephalon and brainstem, fibers separate todiencephalon and brainstem, fibers separate to innervate extrapyramidal and cranial nerve motorinnervate extrapyramidal and cranial nerve motor nuclei. The lower brainstem motor neurons receivenuclei. The lower brainstem motor neurons receive input from crossed and uncrossed corticobulbarinput from crossed and uncrossed corticobulbar fibers, although neurons that innervate lower facialfibers, although neurons that innervate lower facial muscles receive primarily crossed fibers.muscles receive primarily crossed fibers. ► In the ventral medullaIn the ventral medulla, the remaining corticospinal, the remaining corticospinal fibers course in a tract that is pyramidal in shape infibers course in a tract that is pyramidal in shape in cross section—thus, the namecross section—thus, the name pyramidal tractpyramidal tract.. AtAt thethe lower end of the medullalower end of the medulla, most fibers, most fibers decussate, although the proportion of crossed anddecussate, although the proportion of crossed and uncrossed fibers varies somewhat betweenuncrossed fibers varies somewhat between individuals. The bulk of these fibers descend as theindividuals. The bulk of these fibers descend as the lateral corticospinal tractlateral corticospinal tract of the spinal cord.of the spinal cord. ► Different groups ofDifferent groups of neurons in the cortex controlneurons in the cortex control muscle groupsmuscle groups of the contralateral face, arm, andof the contralateral face, arm, and legleg. Neurons near the ventral end of the central. Neurons near the ventral end of the central sulcus control muscles of the face, whereassulcus control muscles of the face, whereas neurons on the medial surface of the hemisphereneurons on the medial surface of the hemisphere control leg muscles. Because thecontrol leg muscles. Because the movements of themovements of the face, tongue, and hand are complex in humans, aface, tongue, and hand are complex in humans, a large share of the motor cortex is devoted to theirlarge share of the motor cortex is devoted to their controlcontrol. A. A somatotopic organizationsomatotopic organization is also apparentis also apparent in thein the lateral corticospinal tractlateral corticospinal tract of the cervicalof the cervical cord, where fibers to motor neurons that control legcord, where fibers to motor neurons that control leg muscles lie laterally and fibers to cervical motormuscles lie laterally and fibers to cervical motor neurons lie medially.neurons lie medially.
  • 38.
    Upper and Lowermotoneurons innervate the skeletal muscles and are essential for motor function. Amyotrophic lateral sclerosis (ALS), fatal combined degeneration of motoneurons and motor fiber tracts (i.e. combined gray and white matter disease). Motoneurons of entire neuraxis! ALS - most devastating neurodegenerative disease of aging CNS that so resembles Alzheimer and Parkinson diseases.
  • 39.
    Upper and Lowermotoneurons innervate the skeletal muscles and are essential for motor function. • Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease after the famous New York Yankees baseball player, is a devastating neurologic disorder that selectively affects motor function. ALS is primarily a disorder of middle to late adulthood, affecting persons between 55 and 60 years of age, with men developing the disease nearly twice as often as women. ETIOPATHOPHYSIOLOGY, PATHOLOGY • Neuron degeneration, atrophy, and loss → glial replacement. No inflammation! Degeneration of motoneurons: • 1. Motor cortex (pyramidal cells in precentral cortex) → loss of large myelinated fibers in anterior & lateral spinal columns (gliotic sclerosis of lateral columns = LATERAL SCLEROSIS) N.B. posterior columns are usually spared in SALS.N.B. posterior columns are usually spared in SALS. • 2. Brain stem - lower nuclei are more often / more extensively involved than upper nuclei (e.g. oculomotor nuclei loss is modest and rarely demonstrable clinically, whereas hypoglossal nuclei are prominently degenerated). • 3. Spinal anterior horns → loss of myelinated fibers in anterior root →muscle denervation atrophy (AMYOTROPHY); reinnervation is possible (but much less extensive as in poliomyelitis, peripheral neuropathy).
  • 40.
    Stephen Hawking's EpidemiologyEpidemiology a. ALSis a degenerative disease involving loss of upper and lower motor neurons. b. Symptoms usually appear between 40 and 60 years of age. c. Most cases are sporadic (90%–95% of cases). PathogenesisPathogenesis • Possibly due to mutated superoxide dismutase (SOD) 1 (neuron destruction by superoxide free radicals) or misfolded SOD 1 leading to apoptosis of neurons (most likely mechanism) Clinical findingsClinical findings a. Upper motor neuron (UMN) signs  Spasticity, Babinski sign; b. Lower motor neuron (LMN) signs: 1) Muscle weakness  Begins with atrophy of intrinsic muscles of the hands; 2) Eventual paralysis of respiratory muscles. c. No sensory changes. d. Preservation of bowel and bladder function. DiagnosisDiagnosis  Electromyography and nerve conduction studies. TreatmentTreatment  Riluzole (glutamate antagonist). Average survivalAverage survival time is 3 to 5 years. Lower motor neuron disease that occurs in children.
  • 41.
    DemyelinationDemyelination  InIn myelinatednervesmyelinated nerves, the axon between two nodes of Ranvier (internodal, the axon between two nodes of Ranvier (internodal segment) is surrounded by asegment) is surrounded by a myelin sheathmyelin sheath. This is a precondition for. This is a precondition for saltatory conduction of the action potentials, i.e., the “jumping” propagationsaltatory conduction of the action potentials, i.e., the “jumping” propagation of excitation from one nodal constriction (R1) to the next (R2). Theof excitation from one nodal constriction (R1) to the next (R2). The internodal segment itself cannot generate an action potential, i.e.,internodal segment itself cannot generate an action potential, i.e., depolarization of the second node (R2) is completely dependent on thedepolarization of the second node (R2) is completely dependent on the current from the first node (R1). However, the current is usually so strongcurrent from the first node (R1). However, the current is usually so strong that it can even jump across the nodes.that it can even jump across the nodes.  Nevertheless, on the way along the internodal segment the amplitude of theNevertheless, on the way along the internodal segment the amplitude of the current will diminish. First of all, the membrane in the internodal segmentcurrent will diminish. First of all, the membrane in the internodal segment must change its polarity, i.e., themust change its polarity, i.e., the membrane capacitancemembrane capacitance must bemust be discharged, for which a current is needed. Secondly, current can alsodischarged, for which a current is needed. Secondly, current can also escape through individualescape through individual ionic channelsionic channels in the axonal membrane (orangein the axonal membrane (orange arrow). However, myelination of the internodal segment causes thearrow). However, myelination of the internodal segment causes the membrane resistance (Rm) to be elevated and the capacity (Cm) of themembrane resistance (Rm) to be elevated and the capacity (Cm) of the membrane condensor to be reduced.membrane condensor to be reduced.  TheThe resistanceresistance of the axonal membrane of the internodal segment is veryof the axonal membrane of the internodal segment is very high because of the low density of ionic channels there. Furthermore, thehigh because of the low density of ionic channels there. Furthermore, the perimembranous space is insulated by a layer of fat from the freeperimembranous space is insulated by a layer of fat from the free extracellular space. The lowextracellular space. The low capacitancecapacitance of the condensor is due to theof the condensor is due to the large distance between the interior of the axon and the free extracellularlarge distance between the interior of the axon and the free extracellular space as well as the low polarity of the fatty material in the space betweenspace as well as the low polarity of the fatty material in the space between them.them.
  • 42.
    DemyelinationDemyelination can becanbe caused by degenerative,caused by degenerative, toxic, or inflammatorytoxic, or inflammatory damage to the nerves,damage to the nerves, or by a deficiency ofor by a deficiency of vitamins B6 or B12.vitamins B6 or B12. If this happens, Rm willIf this happens, Rm will be reduced and Cmbe reduced and Cm raised in the internodalraised in the internodal segment.segment. As a result, more currentAs a result, more current will be required towill be required to change the polarity ofchange the polarity of the internodal segmentthe internodal segment and, through opening upand, through opening up the ionic channels, largethe ionic channels, large losses of current maylosses of current may occur.occur.
  • 43.
    Multiple SclerosisMultiple Sclerosis •Multiple sclerosis (MS), a demyelinating disease of the CNS, is a major cause of neurologic disability among young and middleaged adults. Approximately two thirds of persons with MS experience their first symptoms between 20 and 40 years of age. In approximately 80% of the cases, the disease is characterized by exacerbations and remissions over many years in several different sites in the CNS. • Initially, there is normal or nearnormal neurologic function between exacerbations. As the disease progresses, there is less improvement between exacerbations and increasing neurologic dysfunction.
  • 44.
    Pathogenesis 1. Autoimmune diseaseinitiated by: a) Genetic factors (e.g., HLA-DR2) b) Environmental factors • Microbial pathogens (e.g., Epstein-Barr virus, human herpesvirus 6, Chlamydophila pneumoniae), vitamin D, sun exposure. 2. CD4 TH1 cells and TH17 cells react against self myelin antigens (e.g., myelin basic protein [MBP] and other antigens; type IV hypersensitivity reaction). 3. CD4 TH1 cells secrete interferon γ (γ-IFN), which activates macrophages (produce tumor necrosis factor-α; TNF-α) and TH17 cells release cytokines that recruit neutrophils and monocytes. 4. Both leukocytes and TNF-α attack the myelin sheath and oligodendrocytes, causing demyelination. 5. Antibodies produced by autoreactive B cells are directed against the myelin sheath and oligodendrocytes as well (type II hypersensitivity reaction). Gross and microscopic findings 1. Demyelinating plaques occur in white matter of brain/spinal cord. • White matter looks like gray matter in areas of demyelination. 2. Inflammatory infiltrate in plaques is composed predominantly of CD4 T cells, monocytes, and microglial cells with phagocytosed lipid. MULTIPLE SCLEROSISMULTIPLE SCLEROSIS
  • 45.
    Clinical findings 1) Episodiccourse punctuated by acute relapses and remissions (80%–90% of cases) 2) Sensory dysfunction: a) Paresthesias b) Loss of pain/temperature sensation c) Loss of vibratory sensation 3) Upper motor neuron (UMN) dysfunction a) Spasticity; b) Increased deep tendon reflexes (DTRs); c) Muscle spasms; d) Extensor plantar response (Babinski); e) Weakness  Shoulder abduction, finger extension, foot dorsiflexion, hip/knee flexion 4) Autonomic dysfunction: a)Urge incontinence  Hyperactive detrusor muscle; b)Sexual dysfunction; c) Bowel motility problems. 5) Optic neuritis a) Inflammation of the optic nerve  MS is the most common cause of optic neuritis. b) Blurry vision or sudden loss of vision 6) Cerebellar ataxia 7) Scanning speech (sound drunk) 8) Intention tremor, nystagmus 9) Bilateral internuclear ophthalmoplegia  Demyelination of medial longitudinal fasciculus (MLF) 10) Flexion of the neck produces an electrical sensation down the spine. MULTIPLE SCLEROSISMULTIPLE SCLEROSIS
  • 46.
    Epidemiology Most common acuteperipheral neuropathy Most common cause of acute flaccid paralysis Predominantly motor involvement Variants can be motor and sensory Autoimmune demyelination syndrome: a) Involves nerve roots and peripheral nerves; b) Common preceding infections  Mycoplasma pneumoniae pneumonia, Campylobacter jejuni enteritis, viral infection (HIV, EBV, cytomegalovirus, influenza) b. Rapidly progressive ascending motor weakness: Less commonly descending motor weakness. Usually starts in the proximal muscles and eventually includes the distal muscles. Danger of respiratory muscle paralysis and death. c. Depressed or absent deep tendon reflexes in the arms and legs d. Glove and stocking paresthesias/anesthesia Laboratory findings: 1) Increased CSF protein Oligoclonal bands present on high- resolution electrophoresis; 2) CSF glucose, cell count normal Diagnosis:Diagnosis: 1) Spinal tap with increased CSF protein; 2) Electromyography and nerve conduction studies. Treatment:Treatment: 1) Infusion IV immunoglobulin or plasma exchange; 2) Mechanical ventilation if required. Prognosis: 1) Mortality 5% to 10% of cases; 2) Full motor recovery 60% of cases; 3) Residual weakness 15% of cases
  • 47.
    Huntington'sHuntington's diseasediseaseEpidemiologyEpidemiology a. Autosomaldominant diseasea. Autosomal dominant disease b. Trinucleotide repeat disorder (CAG) involvingb. Trinucleotide repeat disorder (CAG) involving chromosomechromosome c. Delayed appearance of symptoms until 30 toc. Delayed appearance of symptoms until 30 to 40 years of age40 years of age d. No gender dominanced. No gender dominance Atrophy/loss of striatal neuronsAtrophy/loss of striatal neurons  •• Caudate, putamen, globus pallidusCaudate, putamen, globus pallidus Clinical findings:Clinical findings: a.a. ChoreaChorea  1) Irregular, rapid, nonstereotyped1) Irregular, rapid, nonstereotyped involuntary movements; 2) Calledinvoluntary movements; 2) Called choreoathetosischoreoathetosis if it has a writhing quality.if it has a writhing quality. b. Oculomotor abnormalitiesb. Oculomotor abnormalities c. Parkinsonism in later stagesc. Parkinsonism in later stages d. Depressiond. Depression Diagnosis:Diagnosis: a. Genetic testing is availablea. Genetic testing is available b. Imaging studies (CT, MRI)b. Imaging studies (CT, MRI)  Atrophy ofAtrophy of caudate and putamencaudate and putamen Treatment is supportive.Treatment is supportive.
  • 48.
    HUNTINGTON DISEASEHUNTINGTON DISEASE Classicalfamilial,Classical familial, genetic diseasegenetic disease ProgressiveProgressive motor loss andmotor loss and dementiadementia ““chorea”, i.e.chorea”, i.e. “jerky”“jerky” movementsmovements Progressive, fatalProgressive, fatal Atrophy of basalAtrophy of basal ganglia, i.e.,ganglia, i.e., corpus striatumcorpus striatum Cortical (basal ganglia) atrophyCortical (basal ganglia) atrophy Ventricular enlargementVentricular enlargement
  • 49.
    CNS DEGENERATIVE DISEASESCNSDEGENERATIVE DISEASES • SPINOCEREBELLARSPINOCEREBELLAR DEGENERATIONSDEGENERATIONS (ATAXIAS)(ATAXIAS) – Spinocerebellar ataxiasSpinocerebellar ataxias – Friedrich AtaxiaFriedrich Ataxia – Ataxia-TelangiectasiaAtaxia-Telangiectasia
  • 50.
    EpidemiologyEpidemiology a. Autosomal recessive(AR) disease 1)Trinucleotide repeat disorder (GAA); 2)Frataxin deficiency: Deficiency leads to impaired mitochondrial iron homeostasis. Cells are more prone to apoptosis. b. Most common neurodegenerative hereditary ataxic disorder c. Sites of degeneration: 1) Dorsal root ganglia; 4) Lateral corticospinal tracts 2) Posterior columns 5) Large sensory peripheral neurons 3) Spinocerebellar tract d. Hypertrophic cardiomyopathy e. Type 1 diabetes mellitus (10% of cases) Clinical findingsClinical findings a. Progressive gait ataxia b. Loss of deep tendon reflexes  Initially at the ankles c. Loss of vibratory sensation and proprioception d. Muscle weakness in the legs DiagnosisDiagnosis a. Gene testing is available. b. Imaging (MRI) shows spinal cord atrophy. Treatment is supportive.Treatment is supportive.
  • 51.
    ACQUIREDACQUIRED TOXIC/METABOLICTOXIC/METABOLIC CNS DISEASESCNS DISEASESVitaminVitamin B1B1 deficiency (Wernicke-Korsakoff)deficiency (Wernicke-Korsakoff)  VitaminVitamin B12B12 deficiency (vibratory sense)deficiency (vibratory sense)  DiabetesDiabetes Increased/Decreased GLUCOSEIncreased/Decreased GLUCOSE  Hepatic FailureHepatic Failure (NH4+)(NH4+)  COCO (Cortex, hippocampus, Purkinje cells)(Cortex, hippocampus, Purkinje cells)  CH3-OHCH3-OH, Methanol (Retinal ganglion cells), Methanol (Retinal ganglion cells)  CH3-CH2-OHCH3-CH2-OH (acute/chronic, direct/nutrit’l)(acute/chronic, direct/nutrit’l)  RadiationRadiation (Brain MOST resistant to Rad. Rx.)(Brain MOST resistant to Rad. Rx.)  ChemoChemo (Methotrexate + Radiation)(Methotrexate + Radiation)
  • 52.
    Discriminative SensationDiscriminative Sensation Primary sensory cortex providesPrimary sensory cortex provides awareness of somatosensory informationawareness of somatosensory information and the ability to make sensoryand the ability to make sensory discriminations.discriminations.  Touch, pain, temperature, and vibrationTouch, pain, temperature, and vibration sense are considered the primarysense are considered the primary modalities of sensation and are relativelymodalities of sensation and are relatively preserved in patients with damage topreserved in patients with damage to sensory cortex or its projections from thesensory cortex or its projections from the thalamus.thalamus.  In contrast, complex tasks that requireIn contrast, complex tasks that require integration of multiple somatosensoryintegration of multiple somatosensory stimuli and of somatosensory stimuli withstimuli and of somatosensory stimuli with auditory or visual information are impaired.auditory or visual information are impaired.  These include the ability to distinguishThese include the ability to distinguish twotwo pointspoints from one when touched on the skinfrom one when touched on the skin ((two-point discriminationtwo-point discrimination), localize tactile), localize tactile stimuli, perceive the position of body partsstimuli, perceive the position of body parts in space, recognize letters or numbersin space, recognize letters or numbers drawn on the skin (drawn on the skin (graphesthesiagraphesthesia), and), and identify objects by their shape, size, andidentify objects by their shape, size, and texture (texture (stereognosisstereognosis).).
  • 53.
    Anatomy of SensoryLossAnatomy of Sensory Loss The patterns of sensory loss often indicate the level of nervous system involvement. Symmetric distal sensory loss in the limbs, affecting the legs more than the arms, usually signifies a generalized disorder of multiple peripheral nerves (polyneuropathy). Sensory symptoms and deficits may be restricted to the distribution of a single peripheral nerve (mononeuropathy) or two or more peripheral nerves (mononeuropathy multiplex). Symptoms limited to a dermatome indicate a spinal root lesion (radiculopathy).
  • 54.
    Alterations in MotorResponses andAlterations in Motor Responses and MovementMovement  Abnormal motor responses include inappropriate or absentAbnormal motor responses include inappropriate or absent movements in response to painful stimuli. Brainstem reflexesmovements in response to painful stimuli. Brainstem reflexes such as sucking and grasping responses will occur if highersuch as sucking and grasping responses will occur if higher brain centers have been damaged.brain centers have been damaged.  Flexion and rigidity of limbs also are motor responses indicativeFlexion and rigidity of limbs also are motor responses indicative of brain damage.of brain damage.  Muscle conditionsMuscle conditions that indicate abnormal brain function includethat indicate abnormal brain function include hyperkinesiahyperkinesia ((excessive muscle movementsexcessive muscle movements),), hypokinesiahypokinesia ((decreased muscle movementsdecreased muscle movements),), paresisparesis ((muscle weaknessmuscle weakness),), andand paralysisparalysis ((loss of motor functionloss of motor function).).  Specific loss of cerebral cortex functioning, but no loss ofSpecific loss of cerebral cortex functioning, but no loss of brainstem function, results in a particular body posture calledbrainstem function, results in a particular body posture called flexor posturingflexor posturing..  Flexor posturingFlexor posturing is characterized by flexion of the upperis characterized by flexion of the upper extremities at the elbows and external rotation and extension ofextremities at the elbows and external rotation and extension of the lower extremities. This posturethe lower extremities. This posture may be unilateral ormay be unilateral or bilateralbilateral. Extensor posturing occurs with severe injury to higher. Extensor posturing occurs with severe injury to higher brain centers and the brainstem and is characterized bybrain centers and the brainstem and is characterized by rigidrigid extension of the limbs and neckextension of the limbs and neck..
  • 55.
    Brown-Séquard syndrome In thespinal cord, segregation of fiber tracts and the somatotopic arrangement of fibers give rise to distinct patterns of sensory loss. Loss of pain and temperature sensation on one side of the body and of proprioception on the opposite side occurs with lesions that involve one half of the cord on the side of the proprioceptive deficit (Brown-Séquard syndrome). Compression of the upper spinal cord causes loss of pain, temperature, and touch sensation first in the legs, because the leg spinothalamic fibers are most superficial. More severe cord compression compromises fibers from the trunk. In patients with spinal cord compression, the lesion is often above the highest dermatome involved in the deficit. Thus, radiographic studies should be tailored to visualize the cord at and above the level of the sensory deficit detected on examination. Intrinsic cord lesions that involve the central portions of the cord often impair pain and temperature sensation at the level of the lesion because the fibers crossing the anterior commissure and entering the spinothalamic tracts are most centrally situated. Thus, enlargement of the central cervical canal in syringomyelia typically causes loss of pain and temperature sensation across the shoulders and upper arms.
  • 56.
    SPINAL CORD INJURIES(SCI)SPINAL CORD INJURIES (SCI) CAUSES:CAUSES:  TRAUMATRAUMA  FALLSFALLS  GSWGSW  TUMORSTUMORS TYPES:TYPES:  CONCUSSIONCONCUSSION  COMPRESSIONCOMPRESSION  CONTUSION &CONTUSION & TRANSECTIONTRANSECTION  LACERATIONLACERATION  HEMORRHAGEHEMORRHAGE (HEMATOMYALIA)(HEMATOMYALIA)  COMPRESSION OFCOMPRESSION OF BLOOD SUPPLY TOBLOOD SUPPLY TO THE CORDTHE CORD
  • 57.
    Injury Level Segmental Sensorimotor FunctionDressing, Eating Elimination Mobility C1 Little or no sensation or control of head and neck; no diaphragm control; requires Continuous ventilation Dependent Dependent Limited. Voice or sip-n-puff controlled electric wheelchair C2 to C3 Head and neck sensation; some neck control. Independent of mechanical ventilation for short periods Dependent Dependent Same as for C1 C4 Good head and neck sensation and motor control; some shoulder elevation; diaphragm movement Dependent; may be able to eat with adaptive sling Dependent Limited to voice, mouth, head, chin, or shoulder-controlled electric wheelchair C5 Full head and neck control; shoulder strength; elbow flexion Independent with assistance Maximal assistance Electric or modified manual wheel chair, needs transfer assistance C6 Fully innervated shoulder; wrist extension or dorsiflexion Independent or with minimal assistance Independent or with minimal assistance Independent in transfers and wheelchair C7 to C8 Full elbow extension; wrist plantar flexion; some finger control Independent Independent Independent; manual wheelchair T1 to T5 Full hand and finger control; use of intercostal and thoracic muscles Independent Independent Independent; manual wheelchair T6 to T10 Abdominal muscle control, partial to good balance with trunk muscles Independent Independent Independent; manual wheelchair T11 to L5 Hip flexors, hip abductors (L1–3); knee extension (L2–4); knee flexion and ankle dorsiflexion (L4–5) Independent Independent Short distance to full ambulation with assistance S1 to S5 Full leg, foot, and ankle control; innervation of perineal muscles for bowel, bladder, and sexual function (S2–4) Independent Normal to impaired bowel and bladder function Ambulate independently with or without assistance Functional Abilities by Level of Cord InjuryFunctional Abilities by Level of Cord Injury
  • 58.
    CLINICAL EFFECTS OFSCICLINICAL EFFECTS OF SCI • SPINAL SHOCK • REFLEX ACTIVITY • WHIPLASH INJURY • HERNIATED NUCLEUS PULPOSUS
  • 60.
    • IMMEDIATE FLACCIDPARALYSIS & SENSORY LOSS BELOW THE LEVEL OF LESION • PRIAPISM • BULBOCAVERNOUS REFLEX IS LOST BUT REUTRNS AFTER A FEW HRS • OTHER REFLEXES REMAIN ABSENT • 3-6 WKS UTONOMIC DISTURBANCES:UTONOMIC DISTURBANCES: WEATING IS ABOLISHED BELOW THE LEVEL OF INJURY RINE & FECES RETAINED ASTRIC ATONY RTHOSTATIC HYPOTENSION LOW, & STEADY PULSE
  • 61.
    REFLEX ACTIVITY • REPLACESPINAL SHOCK AFTER 2-3 WEEKS IF LUMBO-SACRAL SEGMENTS ARE UNDAMAGED • OCCURS IN ACUTE SPINAL INJURY, NOT IN PROGRESSIVE ONES • AUTOMATIC BLADDER; REFLEX SWEATING & DEFECATION • FIRST SIGN OF WEARING OFF: – CONTRACTION OF HAMSTRING – FLEXION/ EXTENSION OF TOES WITH PLANTAR STIMULATION
  • 62.
    ParalysisParalysis  ParalysisParalysis isthe loss of sensory and voluntary motoris the loss of sensory and voluntary motor function. With spinal cord transection, paralysis isfunction. With spinal cord transection, paralysis is permanent.permanent.  ParalysisParalysis of theof the upper and lower extremitiesupper and lower extremities occurs withoccurs with transection of the cord at level C6 or higher and is calledtransection of the cord at level C6 or higher and is called quadriplegiaquadriplegia..  ParalysisParalysis of the lower half of the body occurs withof the lower half of the body occurs with transection of the cord below C6 and is calledtransection of the cord below C6 and is called paraplegiaparaplegia..  If only one half of the cord is transectedIf only one half of the cord is transected,, hemiparalysishemiparalysis may occur.may occur.  Permanent paralysisPermanent paralysis may occur even when the cord ismay occur even when the cord is not transected, as a result of the destruction of thenot transected, as a result of the destruction of the nerves following cordnerves following cord hemorrhage and swellinghemorrhage and swelling..  In addition, demyelination of the axons in the cord canIn addition, demyelination of the axons in the cord can lead to clinically complete lesions, even though thelead to clinically complete lesions, even though the spinal cord may not be transected.spinal cord may not be transected.  DemyelinationDemyelination of the axons most likely occurs as part ofof the axons most likely occurs as part of the inflammatory response to cord injury.the inflammatory response to cord injury.
  • 63.
    Clinical Manifestations of Paralysis • Lossof sensation, motor control, and reflexes below the level of injury, and up to two levels above, will occur. • Body temperature will reflect ambient temperature, and blood pressure will be reduced. • The pulse rate is often normal, with low blood pressure.
  • 64.
    Complications • If damageand swelling around the cord is in the cervical spine (down to approximately C5), respirations may cease because of compression of the phrenic nerve, which exits between C3 and C5 and controls the movement of the diaphragm. • Autonomic hyper-reflexia is characterized by high blood pressure with bradycardia (low heart rate), and sweating and flushing of the skin on the face and upper torso. • In the past, individuals suffering from a C2 or higher transection invariably died as a result of respiratory arrest. Although this is still true for many, recent advances in treatment modalities and better emergency rescue service responses have resulted in the survival of many individuals with high cord transection. • A severe spinal cord injury affects virtually all systems of the body to some degree. Commonly, urinary tract and kidney infections, skin breakdown and the development of pressure ulcers, and muscle atrophy occur. Depression, marital and family stress, loss of income, and large medical expenses are some of the psychosocial complications.
  • 65.
    DysphasiaDysphasia  Dysphasia isimpairment of language comprehension or production.is impairment of language comprehension or production. AphasiaAphasia is total loss of language comprehension or production.is total loss of language comprehension or production. Dysphasia usually results from cerebral hypoxia, which is oftenDysphasia usually results from cerebral hypoxia, which is often associated with a stroke but can result from trauma or infection. Brainassociated with a stroke but can result from trauma or infection. Brain damage leading to dysphasia usually involves the left cerebraldamage leading to dysphasia usually involves the left cerebral hemisphere.hemisphere.  Broca's dysphasia results from damage to Broca's area inresults from damage to Broca's area in the frontalthe frontal lobelobe. Persons with. Persons with Broca's dysphasia will understand languageBroca's dysphasia will understand language, but, but their ability to meaningfullytheir ability to meaningfully express words in speech or writing will beexpress words in speech or writing will be impairedimpaired. This is called expressive dysphasia.. This is called expressive dysphasia.  Wernicke's dysphasia results from damage to Wernicke's area in theresults from damage to Wernicke's area in the leftleft temporal lobetemporal lobe. With Wernicke's dysphasia,. With Wernicke's dysphasia, verbal expression ofverbal expression of language is intactlanguage is intact, but meaningful, but meaningful understanding of spoken or writtenunderstanding of spoken or written words is impairedwords is impaired. This is called receptive dysphasia.. This is called receptive dysphasia.  Agnosia is the failure to recognize an object because of the inabilityis the failure to recognize an object because of the inability to make sense of incoming sensory stimuli.to make sense of incoming sensory stimuli. Agnosia may be visual,Agnosia may be visual, auditory, tactile, or related to taste or smellauditory, tactile, or related to taste or smell. Agnosia develops from. Agnosia develops from damage to a particular primary or associative sensory area in thedamage to a particular primary or associative sensory area in the cerebral cortex.cerebral cortex.
  • 67.
    Alterations in PupilResponses • The ability of our eyes to dilate or constrict, rapidly and equally, depends on an intact brainstem. • Cerebral hypoxia and many drugs change pupil size and reactivity. Therefore, pupil size and reactivity offer valuable information concerning brain integrity and function. • Important pupil changes seen with brain damage are pinpoint pupils seen with opiate (heroin) overdose and bilaterally fixed and dilated pupils usually seen with severe hypoxia. • Fixed pupils are typically seen with barbiturate overdose. • Brainstem injury presents with pupils fixed bilaterally in the midposition.
  • 68.
    DISORDERS OFDISORDERS OF THEMIDDLE EARTHE MIDDLE EAR ■ The middle ear is a small air-filled compartment in the temporal bone. It is separated from the outer ear by the tympanic membrane, contains tiny bony ossicles that aid in the amplification and transmission of sound to the inner ear, and is ventilated by the eustachian tube, which is connected to the nasopharynx. ■■ The eustachian tube, which is lined with a mucousThe eustachian tube, which is lined with a mucous membrane that ismembrane that is continuous with the nasopharynx,continuous with the nasopharynx, provides a passageway forprovides a passageway for pathogens to enter thepathogens to enter the middle ear.middle ear. ■■ Otitis media (OM) refers to inflammation of the middleOtitis media (OM) refers to inflammation of the middle ear, usuallyear, usually associated with an acute infectionassociated with an acute infection (acute OM) or an accumulation of(acute OM) or an accumulation of fluid (OME). Itfluid (OME). It commonly is associated with disorders of eustachiancommonly is associated with disorders of eustachian tube function.tube function. ■■ Impaired conduction of sound waves and hearingImpaired conduction of sound waves and hearing loss occur when theloss occur when the tympanic membrane has beentympanic membrane has been perforated; air in the middle ear hasperforated; air in the middle ear has been replacedbeen replaced with fluid (OME); or the function of the bonywith fluid (OME); or the function of the bony ossicles hasossicles has been impaired (otosclerosis).been impaired (otosclerosis).
  • 69.
    HEARING LOSS ■ Hearingloss represents impairment of the ability to detect and perceive sound. ■ Conductive hearing loss is caused by disorders in which auditory stimuli are not transmitted through the structures of the outer and middle ears to the sensory receptors in the inner ear. ■ Sensorineural hearing loss is caused by disorders that affect the inner ear, auditory nerve, or auditory pathways.
  • 70.
    Diseases of theBasal GangliaDiseases of the Basal Ganglia  The basal ganglia areThe basal ganglia are made up of:made up of:  –– thethe corpus striatumcorpus striatum (consisting of the(consisting of the caudatecaudate nucleusnucleus and theand the putamenputamen););  –– the inner and outerthe inner and outer globus pallidusglobus pallidus (pallidum, consisting of an(pallidum, consisting of an internal and an externalinternal and an external part);part);  –– thethe subthalamicsubthalamic nucleusnucleus; and; and  –– thethe substantia nigrasubstantia nigra (pars reticulata [p. r.] and(pars reticulata [p. r.] and pars compacta [p. c.]).pars compacta [p. c.]).  TheirTheir functionfunction is mainlyis mainly to control movement into control movement in conjunction with theconjunction with the cerebellum,motor cortex,cerebellum,motor cortex, corticospinal tracts, andcorticospinal tracts, and motor nuclei in the brainmotor nuclei in the brain stem.stem.
  • 71.
    Parkinson’s Disease Parkinson’sdiseaseParkinson’s disease is a diseaseis a disease of theof the substantia nigrasubstantia nigra (p. c.)(p. c.) which via dopaminergic tractswhich via dopaminergic tracts influences GABAergic cells in theinfluences GABAergic cells in the corpus striatumcorpus striatum. The. The causecause isis frequently afrequently a hereditary dispositionhereditary disposition that in middle to old age leads tothat in middle to old age leads to degeneration of dopaminergicdegeneration of dopaminergic neurons in the substantianeurons in the substantia nigranigra. Further causes are. Further causes are traumatrauma (e.g., in boxers),(e.g., in boxers), inflammationinflammation (encephalitis),(encephalitis), impaired circulationimpaired circulation (atherosclerosis),(atherosclerosis), tumorstumors andand poisoningpoisoning (especially by CO,(especially by CO, manganese, and 1-methyl-4-manganese, and 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridinephenyl-1,2,3,6-tetrahydropyridine [MPTP], which was once used as[MPTP], which was once used as a substitute for heroin). The cella substitute for heroin). The cell destruction probably occurs partlydestruction probably occurs partly by apoptosis; superoxides areby apoptosis; superoxides are thought to play a causal role.thought to play a causal role.  For symptoms to occur, over 70%For symptoms to occur, over 70% of neurons in the substantia nigraof neurons in the substantia nigra (p. c.) must have been destroyed.(p. c.) must have been destroyed.  The loss of cells in the substantiaThe loss of cells in the substantia nigra (p. c.) decreases thenigra (p. c.) decreases the correspondingcorresponding dopaminergicdopaminergic innervationinnervation of the striatum.of the striatum.
  • 72.
    Brain centres andtheirBrain centres and their disorderdisorder  The brain is conventionally considered in sixThe brain is conventionally considered in six main anatomicalmain anatomical and functional areas:and functional areas: 1. Cerebrum1. Cerebrum – two hemispheres of cerebral– two hemispheres of cerebral cortex, containingcortex, containing the limbic system andthe limbic system and basal ganglia.basal ganglia. 2. Diencephalon2. Diencephalon, containing the hypothalamus, containing the hypothalamus and thalamus.and thalamus. 3. Midbrain.3. Midbrain. 4. Pons.4. Pons. 5. Medulla oblongata.5. Medulla oblongata. 6. Cerebellum.6. Cerebellum.  Alternatively, the brain may be subdividedAlternatively, the brain may be subdivided into distinct regions:into distinct regions: •• TheThe forebrainforebrain, which includes areas 1 and 2., which includes areas 1 and 2. •• TheThe hindbrainhindbrain, which includes areas 4, 5, which includes areas 4, 5 and 6.and 6. •• TheThe brainstembrainstem, which includes the midbrain,, which includes the midbrain, medulla andmedulla and pons.pons.  Interconnections between these areas areInterconnections between these areas are manifold andmanifold and complex, accounting for the richnesscomplex, accounting for the richness and diversity of humanand diversity of human activity, experienceactivity, experience and achievement.and achievement.
  • 74.
    Principal anatomical centresPrincipalanatomical centres of brain functionof brain function FunctionFunction CentreCentre InputInput PerceptionPerception Sensory cortex, thalamus,Sensory cortex, thalamus, reticular formationreticular formation ProcessingProcessing Cognitive (intellectual)Cognitive (intellectual) EmotionalEmotional Cerebral cortexCerebral cortex Limbic systemLimbic system OutputOutput MotorMotor HomeostasisHomeostasis Motor cortex, cerebellum,Motor cortex, cerebellum, basal gangliabasal ganglia Medulla, hypothalamus,Medulla, hypothalamus, pituitarypituitary
  • 75.
    Cerebral cortexCerebral cortex The cerebral cortex is, in evolutionary terms, the youngest centre. It is the principal distinguishing feature of higher mammals. Notably developed in man, where it contains 90% of the total brain neurones,  the cerebral cortex is the location of:  It functions like afunctions like a computercomputer, providing an objective, logical assessment of the environment as perceived via the senses,  and then producing a plan for action depending on past experience and biological goals.  Specific areas of the cortex are dedicated to subsidiary functions, such as the speech centre and the visual, auditory and motor cortexes.  Anatomically, the cerebral cortex is subdivided into various lobes, i.e. abstract thought judgement reasoning memory interpretation of sensory inputcreativity frontal temporal parietal occipital
  • 76.
    Cortical disordersCortical disorders Cortical disorders usually have a profoundCortical disorders usually have a profound effect oneffect on all CNS function. They are commonlyall CNS function. They are commonly manifested asmanifested as disorders ofdisorders of intellectintellect, e.g., e.g.  MentalMental handicaphandicap,, dementiadementia oror Alzheimer’sAlzheimer’s disease,disease, or ofor of movementmovement, e.g., e.g. epilepsyepilepsy..  StrokesStrokes are caused byare caused by obstruction of blood flowobstruction of blood flow usually to discreteusually to discrete cortical areas.cortical areas.  TheThe thought disorderthought disorder characteristiccharacteristic ofof schizophreniaschizophrenia is partly cortical, but disorderedis partly cortical, but disordered limbic or thalamiclimbic or thalamic influences on theinfluences on the ortex are probably more important.ortex are probably more important.  Most proven and putative neurotransmittersMost proven and putative neurotransmitters areare found in the cortex. Many of the morefound in the cortex. Many of the more recentlyrecently discovered mediators, such as thediscovered mediators, such as the endorphinsendorphins andand peptidespeptides, have yet to be definitely, have yet to be definitely linked withlinked with specific CNS functions, disorders orspecific CNS functions, disorders or drug actions.drug actions. They may modulate the action ofThey may modulate the action of the traditionalthe traditional transmitters.transmitters.
  • 77.
    Limbic systemLimbic system This interesting evolutionaryThis interesting evolutionary development ofdevelopment of the higher mammalsthe higher mammals providesprovides mental activitymental activity with anwith an emotional dimensionemotional dimension ..  TheThe limbiclimbic systemsystem is responsibleis responsible forfor feelingsfeelings rather thanrather than objectiveobjective reasoningreasoning and is perceivedand is perceived consciouslyconsciously as anas an emotionalemotional overlayoverlay, i.e. the, i.e. the affect or moodaffect or mood,, which can modify the decisionswhich can modify the decisions taken by thetaken by the cortex.cortex.  The system mayThe system may mediate rage,mediate rage, fear, pleasurefear, pleasure and loveand love and, byand, by its influence on corticalits influence on cortical function, isfunction, is responsible for beliefs as opposedresponsible for beliefs as opposed toto rational thoughtrational thought ..  A materialistic interpretationA materialistic interpretation of oneof one of the objectives of some Easternof the objectives of some Eastern philosophies,philosophies, especiallyespecially meditationmeditation, would be that it, would be that it attempts to achieve control or evenattempts to achieve control or even eliminationelimination of limbic influencesof limbic influences (‘the(‘the self’, ‘desire’)self’, ‘desire’) on theon the cortex.cortex.
  • 78.
    Limbic systemLimbic system The contrast betweenThe contrast between limbiclimbic andand cortical functionscortical functions is illustrated by ouris illustrated by our response to beingresponse to being caught for a motoring offence.caught for a motoring offence.  One part of usOne part of us –– ourour limbic system – is angrylimbic system – is angry,, fearfulfearful oror ashamedashamed (depending on our personality):(depending on our personality): at the sameat the same time, our cortextime, our cortex is calculatingis calculating the effect on ourthe effect on our insurance premium,insurance premium, the most effective way tothe most effective way to appeaseappease the policeman, or perhaps even how tothe policeman, or perhaps even how to manage without a drivingmanage without a driving licencelicence..  TheThe limbic systemlimbic system has evolved from a structurehas evolved from a structure in lower mammalsin lower mammals concerned withconcerned with olfactionolfaction (sense of smell),(sense of smell), and indeed it retains thisand indeed it retains this functionfunction in humans.in humans. Possibly this accounts for thePossibly this accounts for the emotional power thatemotional power that smells have on humans.smells have on humans.  TheThe limbic systemlimbic system is also involved inis also involved in memorymemory,, and we are all familiar withand we are all familiar with how strongly smellshow strongly smells can evoke evencan evoke even distant memoriesdistant memories..  The system isThe system is structurally complex with many componentstructurally complex with many component nuclei andnuclei and important connections with theimportant connections with the frontalfrontal andand temporal lobes of the cortextemporal lobes of the cortex,, withwith thethe reticular systemreticular system and with theand with the hypothalamushypothalamus (all of which are(all of which are sometimes considered assometimes considered as partially within the limbic system).partially within the limbic system). DopamineDopamine isis an important transmitter, as arean important transmitter, as are noradrenalinenoradrenaline (NA, norepinephrine) and(NA, norepinephrine) and 5-hydroxytryptamine5-hydroxytryptamine (5-HT, serotonin).(5-HT, serotonin). Gamma-aminobutyric acidGamma-aminobutyric acid ((GABA) is an inhibitory transmitter here.GABA) is an inhibitory transmitter here.
  • 79.
    Disorders of theDisordersof the LLimbicimbic SSystemystem  Disorders of the limbic systemDisorders of the limbic system are likely toare likely to cause inappropriate emotions, such ascause inappropriate emotions, such as::  depression,depression,  mania ormania or  excessive anxiety.excessive anxiety.  DelusionsDelusions ((inappropriate beliefs) may arise ininappropriate beliefs) may arise in the limbicthe limbic system. The now discreditedsystem. The now discredited prefrontalprefrontal lobotomy (leucotomy), an operationlobotomy (leucotomy), an operation to sever theto sever the links between the limbic systemlinks between the limbic system and the cortexand the cortex in severe psychiatric disorders,in severe psychiatric disorders, resulted in theresulted in the patient becoming emotionallypatient becoming emotionally flat.flat.  A similarA similar phenomenon is sometimes seen inphenomenon is sometimes seen in patients onpatients on long-term antipsychoticslong-term antipsychotics..
  • 80.
    Psychological DisordersPsychological Disorders Its mental processes and/or behavior patterns that causeIts mental processes and/or behavior patterns that cause emotional distress and/or substantial impairment in functioningemotional distress and/or substantial impairment in functioning  The presence of a constellation of symptoms that createThe presence of a constellation of symptoms that create significant distress; impair work, school, family, relationships,significant distress; impair work, school, family, relationships, or daily living; or lead to significant risk or harmor daily living; or lead to significant risk or harm  SymptomsSymptoms  CognitiveCognitive  EmotionalEmotional  BehavioralBehavioral  What criteria can be used to determine whether behavior isWhat criteria can be used to determine whether behavior is abnormal?abnormal?  Behavior may be considered abnormal ifBehavior may be considered abnormal if  It is considered strange within a person’s own cultureIt is considered strange within a person’s own culture  It causes personal distressIt causes personal distress  It is maladaptiveIt is maladaptive  It is a danger to the self or othersIt is a danger to the self or others  A person is not legally responsible for his or her actsA person is not legally responsible for his or her acts
  • 81.
    Types/CategoriesTypes/Categories  Organic BrainSyndromes (Caused by Damage)Organic Brain Syndromes (Caused by Damage)  Developmental Disorders (autism, retardation)Developmental Disorders (autism, retardation)  ““Psychoses” – Schizophrenia, Mood Disorders (Bipolar)Psychoses” – Schizophrenia, Mood Disorders (Bipolar)  ““Neuroses” – Anxiety Disorders (Phobias, OCD, PTSD)Neuroses” – Anxiety Disorders (Phobias, OCD, PTSD)  Somatoform Disorders (Ulcers)Somatoform Disorders (Ulcers)  Dissociative Disorders – D.I.D.Dissociative Disorders – D.I.D.  Personality Disorders – Antisocial Personality Disorder,Personality Disorders – Antisocial Personality Disorder, Substances Abuse (problems with relationships)Substances Abuse (problems with relationships)  Behavioral Disorders – Sleep Disorders, TurretsBehavioral Disorders – Sleep Disorders, Turrets  General ProblemsGeneral Problems  Seek Counseling (relationships)Seek Counseling (relationships)
  • 83.
    General Adaptation Syndrome Threestages: 1. Alarm stage - Emergency reaction (fight-or-flight) 1. Resistance stage - Coping and adaptation 1. Exhaustion stage - Termination of stress response and onset of stress pathology  StressStress refers to a number of biological changes that can be triggered by any disturbance to our normal physiology.  Stress is neutral –Stress is neutral – the body responds the same to positive or negative stressors.
  • 84.
    Anxiety DisordersAnxiety Disorders Components of Anxiety ResponsesComponents of Anxiety Responses
  • 85.
    Phobic DisordersPhobic Disorders PhobiaPhobia – an intense– an intense and irrational fear ofand irrational fear of particular object orparticular object or situationsituation Psychological DisorderPsychological Disorder  InsanityInsanity is a legal term. Insanity is beingis a legal term. Insanity is being unableunable to appreciate theto appreciate the nature and quality of the wrongfulness of his or her acts, because ofnature and quality of the wrongfulness of his or her acts, because of mental disease or defect.mental disease or defect.  AbnormalityAbnormality is a condition or behavior that deviates from the usualis a condition or behavior that deviates from the usual physical or psychological state. Culture and context are important inphysical or psychological state. Culture and context are important in defining abnormality. Talking to the dead is normal in some cultures.defining abnormality. Talking to the dead is normal in some cultures.
  • 86.
    Anxiety DisordersAnxiety Disorders PhobiasPhobias - strong and irrational fears of- strong and irrational fears of certain objects or situationscertain objects or situations  AgoraphobiaAgoraphobia: fear of open and public: fear of open and public spaces from which escape would bespaces from which escape would be difficultdifficult  Social phobiasSocial phobias: fear of situations in: fear of situations in which evaluation might occurwhich evaluation might occur  Lifetime prevalence 13%Lifetime prevalence 13%  Specific phobiasSpecific phobias: fear of specific: fear of specific objects such as animals or situationsobjects such as animals or situations  Animal fearsAnimal fears  Blood-injection-injury fearsBlood-injection-injury fears  Natural environment fearsNatural environment fears  Situation fearsSituation fears  Miscellaneous fearsMiscellaneous fears  Lifetime prevalence 10%Lifetime prevalence 10%
  • 87.
    Anxiety DisordersAnxiety Disorders Panic DisorderPanic Disorder an extreme anxiety that manifestsan extreme anxiety that manifests itself in the form of panic attacksitself in the form of panic attacks  Panic occurs suddenly and unpredictablyPanic occurs suddenly and unpredictably  Much more intense than typical anxietyMuch more intense than typical anxiety  Panic attackPanic attack  An episode of overwhelming anxiety, fear, or terrorAn episode of overwhelming anxiety, fear, or terror  The brains of panic-attack sufferers respond to normal changes in the body as if they were lifeThe brains of panic-attack sufferers respond to normal changes in the body as if they were life threateningthreatening
  • 88.
    Anxiety DisordersAnxiety Disorders Obsessive-Compulsive DisorderObsessive-Compulsive Disorder  ObsessionsObsessions  Repetitive and unwelcome thoughts, images, or impulsesRepetitive and unwelcome thoughts, images, or impulses  CompulsionsCompulsions  Repetitive behavioral responsesRepetitive behavioral responses  CheckingChecking  WashingWashing  OrderingOrdering  Lifetime prevalence 2-3%Lifetime prevalence 2-3%  Caudate nucleusCaudate nucleus  Obsession –Obsession – Constantly on your mindConstantly on your mind  Compulsions –Compulsions – Keep repeating behaviorKeep repeating behavior
  • 89.
    Posttraumatic Stress DisorderPosttraumaticStress Disorder • Severe anxiety disorderSevere anxiety disorder – Can occur in people exposed to extreme traumaCan occur in people exposed to extreme trauma • PTSD – disorder in which victims of traumatic eventsPTSD – disorder in which victims of traumatic events experience the original event in the form of dreams orexperience the original event in the form of dreams or flashbacksflashbacks – SymptomsSymptoms • Re-experience eventRe-experience event • Avoidance and emotionalAvoidance and emotional numbingnumbing • Heightened arousalHeightened arousal – Lifetime prevalence 8% (among Americans)Lifetime prevalence 8% (among Americans) – Genetic predispositionGenetic predisposition
  • 90.
    Somatoform DisordersSomatoform Disorders Used to be called “Used to be called “hysteriahysteria” by Freud” by Freud  ““Physical symptoms for which there is noPhysical symptoms for which there is no apparent physical causeapparent physical cause  Two general typesTwo general types 1.1. Conversion DisordersConversion Disorders 2.2. HypochondriasisHypochondriasis
  • 91.
    Conversion DisordersConversion Disorders Changing emotional difficulties into a lossChanging emotional difficulties into a loss of specific voluntary body functionof specific voluntary body function  Subconsciously doneSubconsciously done  Reinforced by increased attentionReinforced by increased attention  Motor Deficits or Sensory DeficitsMotor Deficits or Sensory Deficits  RareRare
  • 92.
    HypochondriasisHypochondriasis  Good healthbut intense worry about smallGood health but intense worry about small problems being really bigproblems being really big  Extensive doctor visits, second opinions,Extensive doctor visits, second opinions, self diagnosisself diagnosis  From repressed emotions?From repressed emotions?  Get more reinforcement (positiveGet more reinforcement (positive attention)attention)
  • 93.
  • 94.
    Mood DisordersMood Disorders Long-lasting, severeLong-lasting, severe  not just really sadnot just really sad  BereavementBereavement  not necessarily depressionnot necessarily depression Types:Types:  Major Depressive DisorderMajor Depressive Disorder  Bipolar DisorderBipolar Disorder  Season Affective DisorderSeason Affective Disorder  DysthymiaDysthymia  Lifetime prevalence 6%Lifetime prevalence 6%  SuicideSuicide  Attempted by 30% of depressed peopleAttempted by 30% of depressed people
  • 95.
    Major Depressive DisorderMajorDepressive Disorder  Severe form of lowered mood, feelings ofSevere form of lowered mood, feelings of worthlessness, apathy, disinterested inworthlessness, apathy, disinterested in pleasurable activities, intense sadness,pleasurable activities, intense sadness, hopelessnesshopelessness  2+ weeks, can’t be due to bereavement2+ weeks, can’t be due to bereavement (grieving)(grieving)  Need 4 of following symptoms (consistently andNeed 4 of following symptoms (consistently and higher in intensity) – problems eating, sleeping,higher in intensity) – problems eating, sleeping, thinking, focusing, making decisions, low energy,thinking, focusing, making decisions, low energy, suicidal thoughts, feel worthless/guilty, lack ofsuicidal thoughts, feel worthless/guilty, lack of interest in enjoyable activitiesinterest in enjoyable activities
  • 96.
    Bipolar Disorder (ManicDepression)Bipolar Disorder (Manic Depression) Individual alternates between feelings of maniaIndividual alternates between feelings of mania and depressionand depression ManiaMania – little sleep, elation, confusion, delusions,– little sleep, elation, confusion, delusions, distractibility, racing thoughts, overly optimisticdistractibility, racing thoughts, overly optimistic DepressiveDepressive – feel worthless, sinful, despair, failure,– feel worthless, sinful, despair, failure, lethargy, unresponsivenesslethargy, unresponsiveness
  • 97.
    Seasonal Affective Disorder • Depressionduring certain seasons, • increase sleep, eating Causes • Melatonin? • Vitamin D? • Conditioning? • Social Learning?
  • 98.
    What is SchizophreniaWhatis Schizophrenia  Includes positive and negative symptomsIncludes positive and negative symptoms  Positive – add – Negative – take awayPositive – add – Negative – take away  Type IType I  mostly positive symptomsmostly positive symptoms -delusions, hallucinations, disorders of thoughts and behavior-delusions, hallucinations, disorders of thoughts and behavior  Type IIType II  mostly negative symptomsmostly negative symptoms -flat affect (emotions), avolition (motivation), alogia (speech)-flat affect (emotions), avolition (motivation), alogia (speech) • Disorders characterized by confused andDisorders characterized by confused and disconnected thoughts, emotions,disconnected thoughts, emotions, perceptionsperceptions • Considered by many to be most severeConsidered by many to be most severe disorderdisorder • Often a variety of symptoms presentOften a variety of symptoms present
  • 99.
    Types of SchizophreniaTypesof Schizophrenia  CatatonicCatatonic – motor disturbances– motor disturbances  ParanoidParanoid – preoccupied with– preoccupied with delusions, people out to get themdelusions, people out to get them  DisorganizedDisorganized – incoherent language,– incoherent language, inappropriate emotion, delusions,inappropriate emotion, delusions, hallucinationshallucinations  UndifferentiatedUndifferentiated – many symptoms– many symptoms  RemissionRemission – no current symptoms– no current symptoms EtiologyEtiology Biological Influences – 1% in population, 10% in familiesBiological Influences – 1% in population, 10% in families Biochemistry – imbalance in neurotransmitters (dopamine/serotonin)Biochemistry – imbalance in neurotransmitters (dopamine/serotonin) Family/interactionsFamily/interactions ““Diathesis-stress model” – biological, needs stress triggersDiathesis-stress model” – biological, needs stress triggers
  • 101.
    StrokeStroke  StrokeStroke isa clinical syndrome characterizedis a clinical syndrome characterized by theby the suddensudden onset of a focal neurologiconset of a focal neurologic deficit that persists fordeficit that persists for at least 24 hoursat least 24 hours andand is due to anis due to an abnormality of the cerebralabnormality of the cerebral circulationcirculation..  TheThe incidence ofincidence of strokestroke increasesincreases and isand is higherhigher  Significant risk factors includeSignificant risk factors include:: hypercholesterolemiahypercholesterolemia diabetesdiabetes oral contraceptiveoral contraceptive useuse heavy alcoholheavy alcohol consumptionconsumption hypertensionhypertension in men than in womenin men than in women with age smokingsmoking
  • 102.
    PathophysiologyPathophysiology The focal symptomsand signs that resultThe focal symptoms and signs that result from stroke correlate with the area of brainfrom stroke correlate with the area of brain supplied by the affected blood vessel.supplied by the affected blood vessel. Strokes may be classified into two majorStrokes may be classified into two major categories based on pathogenesis:categories based on pathogenesis: hemorrhagehemorrhageischemicischemic In ischemic stroke, vascular occlusion interrupts blood flow to a specific brain region, producing a fairly characteristic pattern of neurologic deficits resulting from loss of functions controlled by that region. The pattern of deficits resulting from hemorrhage is less predictable because it depends on the location of the bleed and also on factors that affect the function of brain regions distant from the hemorrhage (eg, increased intracranial pressure, brain edema, compression of neighboring brain tissue, and rupture of blood into ventricles or subarachnoid space).
  • 103.
    Classification of StrokeClassificationof Stroke Ischemic stroke Large vessels (major cerebral arteries) Small vessels (lacunar stroke) Venous occlusion Cardioembolic Artery to artery Thrombotic occlusion Embolic Hemorrhage Epidural hemorrhage Hemorrhagic ischemic infarction Subdural hemorrhage Subarachnoid hemorrhage Intraparenchymal hemorrhage
  • 104.
    Common Stroke SymptomsCommonStroke Symptoms  Weakness or paralysisWeakness or paralysis  Numbness, tingling, decreasedNumbness, tingling, decreased sensationsensation  Vision changesVision changes  Speech problemsSpeech problems  Swallowing difficulties orSwallowing difficulties or droolingdrooling  Loss of memoryLoss of memory  Vertigo (spinning sensation)Vertigo (spinning sensation)  Loss of balance andLoss of balance and coordinationcoordination  Personality changesPersonality changes  Mood changes (depression,Mood changes (depression, apathy)apathy)  Drowsiness, lethargy, or loss ofDrowsiness, lethargy, or loss of consciousnessconsciousness  Uncontrollable eye movementsUncontrollable eye movements or eyelid droopingor eyelid drooping
  • 105.
     Hemiplegia -most common result of CVA Paralysis of one side of the body May affect other functions, such as hearing, general sensation and circulation The degree of impairment depends on the part of the brain affected Stages: Flaccid – numbness and weakness of affected side Spastic – muscles contracted and tense, movement hard Recovery – therapy and rehab methods successful
  • 106.
    Ischemic StrokeIschemic Stroke Ischemic strokes result from thrombotic or embolic occlusion of cerebral vessels.  Neurologic deficits caused by occlusion of large arteries result from focal ischemia to the area of brain supplied by the affected vessel and produce recognizable clinical syndromes (next slide).  Not all signs are present in every patient, because the extent of the deficit depends on the presence of collateral blood flow, individual variations in vascular anatomy, blood pressure, and exact location of the occlusion.  Thrombosis usually involves the internal carotid, middle cerebral, or basilar arteries.  Symptoms typically evolve over several minutes and may be preceded by brief episodes of reversible focal deficits known as transient ischemic attacks.  Emboli from the heart, aortic arch, or carotid arteries usually occlude the middle cerebral artery, because it carries more than 80% of blood flow to the cerebral hemisphere.  Emboli that travel in the vertebral and basilar arteries commonly lodge at the apex of the basilar artery or in one or both posterior cerebral arteries.
  • 107.
    Vascular Territories andClinical Features in Ischemic StrokeVascular Territories and Clinical Features in Ischemic Stroke Artery Territory Symptoms and Signs Anterior cerebral Medial frontal and parietal cortex, anterior corpus callosum Paresis and sensory loss of contralateral leg and foot Middle cerebral Lateral frontal, parietal, occipital, and temporal cortex and adjacent white matter, caudate, putamen, internal capsule Aphasia (dominant hemisphere), neglect (nondominant hemisphere), contralateral hemisensory loss, homonymous hemianopia, hemiparesis Vertebral (posterior inferior cerebellar) Medulla, lower cerebellum Ipsilateral cerebellar ataxia, Horner's syndrome, crossed sensory loss, nystagmus, vertigo, hiccup, dysarthria, dysphagia Basilar (including anterior inferior cerebellar, superior cerebellar) Lower midbrain, pons, upper and mid cerebellum Nystagmus, vertigo, diplopia, skew deviation, gaze palsies, hemi- or crossed sensory loss, dysarthria, hemi- or quadriparesis, ipsilateral cerebellar ataxia, Horner's syndrome, coma Posterior cerebral Distal territory: medial occipital and temporal cortex and underlying white matter, posterior corpus callosum Contralateral homonymous hemianopia, dyslexia without agraphia, visual hallucinations and distortions, memory defect, cortical blindness (bilateral occlusion) Proximal territory: upper midbrain, thalamus Sensory loss, ataxia, third nerve palsy, contralateral hemiparesis, vertical gaze palsy, skew deviation, hemiballismus, choreoathetosis, impaired consciousness
  • 108.
    Clinical features ofa stroke involving the middle cerebral artery. (From Weyhenmeyer, J, Gallman, E: Neuroscience, Rapid Review Series, 1st edition, 2007, Philadelphia, Mosby, p 28, Table 3-1.)
  • 109.
    Clinical features ofa stroke involving the middle cerebral artery. (From Weyhenmeyer, J, Gallman, E: Neuroscience, Rapid Review Series, 1st edition, 2007, Philadelphia, Mosby, p 28, Table 3-1.)
  • 110.
    Clinical features ofa stroke involving the anterior cerebral artery.Clinical features of a stroke involving the anterior cerebral artery. (From Weyhenmeyer J, Gallman E: Neuroscience, Rapid Review Series, 1st ed, 2007, Philadelphia, Mosby, p 30, Table 3-2.)
  • 111.
    Conditions Associated withFocal Cerebral Ischemia. Vascular disorders Fibromuscular dysplasia Vasculitis Atherosclerosis Systemic (polyarteritis nodosa, lupus, giant cell, Wegner's, Takayasu's) Primary CNS Meningitis (syphilis, tuberculosis, fungal, bacterial, herpes zoster) Drug induced (cocaine, amphetamines) Carotid or vertebral artery dissection Lacunar infarction Migraine Multiple progressive intracranial occlusions (moyamoya syndrome) Venous or sinus thrombosis Cardiac disorders Hematologic disorders Rheumatic heart disease Mural thrombus Arrhythmias Endocarditis Mitral valve prolapse Paradoxic embolus Atrial myxoma Prosthetic heart valves Thrombocytosis Polycythemia Sickle cell disease Leukocytosis Hypercoagulable states (homocysteinemia, protein S deficiency, antiphospholipid syndrome, sickle cell disease)
  • 113.
    ∗ Subarachnoid hemorrhagemay occur - from head trauma, - extension of blood from another compartment into the subarachnoid space, - or rupture of an arterial aneurysm. ∗ Cerebral dysfunction occurs because of increased intracranial pressure and from poorly understood toxic effects of subarachnoid blood on brain tissue and cerebral vessels. Hemorrhage Stroke • The most common cause of spontaneous (nontraumatic) subarachnoid hemorrhage is rupture of a berry aneurysm, which is thought to arise from a congenital weakness in the walls of large vessels at the base of the brain. • The aneurysms become symptomatic in adulthood, usually after the third decade. Rupture suddenly elevates intracranial pressure, which can interrupt cerebral blood flow and cause a generalized concussive injury. This results in loss of consciousness in about half of patients. • With very large hemorrhages, global cerebral ischemia can cause severe brain damage and prolonged coma. • Focal ischemia may later result from vasospasm of arteries at or near the site of rupture. Recurrence of hemorrhage within the first few days is a common and often fatal complication.
  • 114.
    HemorrhageHemorrhage StrokeStroke  IntraparenchymalhemorrhageIntraparenchymal hemorrhage may result from acute elevations inmay result from acute elevations in blood pressure or from a variety of disorders that weaken vessels. Theblood pressure or from a variety of disorders that weaken vessels. The resultant hematomaresultant hematoma causes acauses a focal neurologic deficit by compressingfocal neurologic deficit by compressing adjacent structuresadjacent structures. In addition, metabolic effects of extravasated blood. In addition, metabolic effects of extravasated blood disturb the function of surrounding brain tissuedisturb the function of surrounding brain tissue, and, and nearby vessels arenearby vessels are compressedcompressed, causing, causing local ischemialocal ischemia..  Chronic hypertensionChronic hypertension is theis the most common predisposingmost common predisposing factor. In hypertensivefactor. In hypertensive patients, smallpatients, small Charcot-Charcot- Bouchard aneurysmsBouchard aneurysms appear in the walls of smallappear in the walls of small penetrating arteries and arepenetrating arteries and are thought to be the major sitesthought to be the major sites of rupture. Most vulnerable areof rupture. Most vulnerable are the small vessels that are alsothe small vessels that are also involved in lacunar infarction.involved in lacunar infarction. Hypertensive hemorrhagesHypertensive hemorrhages occur mainly in the basaloccur mainly in the basal ganglia, thalamus, pons, andganglia, thalamus, pons, and cerebellum and lesscerebellum and less commonly in subcortical whitecommonly in subcortical white matter.matter.
  • 115.
    Intraparenchymal hemorrhageIntraparenchymal hemorrhage Other causes of intraparenchymal hemorrhage includeOther causes of intraparenchymal hemorrhage include vascular malformations,vascular malformations, which contain abnormally fragile vessels susceptible to rupture at normal arterialwhich contain abnormally fragile vessels susceptible to rupture at normal arterial pressures, and certainpressures, and certain brain tumors,brain tumors, such as glioblastoma multiforme, whichsuch as glioblastoma multiforme, which induce proliferation of fragile vessels within the tumor.induce proliferation of fragile vessels within the tumor.  CertainCertain plateletplatelet andand coagulation disorderscoagulation disorders may predispose to intracerebralmay predispose to intracerebral hemorrhage by inhibiting coagulation.hemorrhage by inhibiting coagulation. CocaineCocaine andand amphetaminesamphetamines causecause rapid elevation of blood pressurerapid elevation of blood pressure andand are common causes ofare common causes of intraparenchymal hemorrhageintraparenchymal hemorrhage in youngin young adults.adults. HemorrhageHemorrhage may be related tomay be related to spontaneous bleeding from the acutespontaneous bleeding from the acute elevation in blood pressure, rupture ofelevation in blood pressure, rupture of an occult vascular abnormality, or drug-an occult vascular abnormality, or drug- induced vasculitis.induced vasculitis. Cerebral amyloid angiopathyCerebral amyloid angiopathy is ais a disorder that occurs mainly in thedisorder that occurs mainly in the elderly and may be associated withelderly and may be associated with Alzheimer's diseaseAlzheimer's disease. Deposition of. Deposition of amyloid weakens the walls of smallamyloid weakens the walls of small cortical vessels and causes lobarcortical vessels and causes lobar hemorrhage, often at several sites.hemorrhage, often at several sites.
  • 116.
    Seizure disordersSeizure disorders ►Seizureis and abnormal discharge of electrical activity within the brain. It is a rapidly evolving disturbance of brain function that may produce impaired consciousness, abnormalities of sensation or mental function or convulsive movements. ►Convulsions are episodes of widespread and intense motor activity
  • 117.
    EpilepsyEpilepsy  AnAn epilepticseizureepileptic seizure (epileptic attack, epileptic(epileptic attack, epileptic fit) is triggered by afit) is triggered by a spontaneous,spontaneous, synchronized, massivesynchronized, massive excitation of a largeexcitation of a large number of neuronsnumber of neurons,, resulting in localized orresulting in localized or generalizedgeneralized activation ofactivation of motormotor (fits or seizures),(fits or seizures), sensorysensory (sensory(sensory impressions),impressions), autonomicautonomic (e.g., salivation), or(e.g., salivation), or complexcomplex (cognitive,(cognitive, emotional) functions.emotional) functions.
  • 118.
    Epilepsy Signs and symptomsvary:Signs and symptoms vary: petit mal – almost imperceptible alterations in– almost imperceptible alterations in consciousnessconsciousness grand mal – generalized– generalized tonic-clonic seizurestonic-clonic seizures –– dramatic loss of consciousness, falling, generalizeddramatic loss of consciousness, falling, generalized tonic-clonic convulsionstonic-clonic convulsions of all extremities,of all extremities, incontinence, and amnesia for the event.incontinence, and amnesia for the event.  Some attacks are proceeded by aSome attacks are proceeded by a prodrome – a set– a set of symptoms that warn of a seizureof symptoms that warn of a seizure  As the seizure begins, the patient may experienceAs the seizure begins, the patient may experience anan aura –– mental, sensory or motor phenomenamental, sensory or motor phenomena  Others have no warningOthers have no warning
  • 119.
    Phases of agrand mal seizurePhases of a grand mal seizure 1.1. Tonic phaseTonic phase (10-20 seconds) – muscle(10-20 seconds) – muscle contractioncontraction Epileptic cryEpileptic cry – respiration stops– respiration stops 1.1. Clonic phaseClonic phase – (1/2 -2 minutes) muscle– (1/2 -2 minutes) muscle spasms; respiration is ineffective;spasms; respiration is ineffective; autonomic nervous system activeautonomic nervous system active 2.2. Terminal phaseTerminal phase (about 5 minutes) –(about 5 minutes) – limp and quiet, EEG flat lineslimp and quiet, EEG flat lines
  • 120.
    Sleep Disorders • Disordersof the regulation of breathing during sleep have been held responsible for the sudden infant death syndrome (SIDS) and sleep apnea in adults. • Metabolic alkalosis is thought to favor sleep apnea. In addition, decreased muscle tone during sleep promotes the collapse of the airways, apnea, and hypoxia. • Normally one passes through several phases of varying depth during sleep. • During one night there are typically about 5 phases of rapid eye movement (REM) sleep, during which bursts of excitation from the brain stem produce twitches in the otherwise hypotonic musculature. • Several phases of non-REM (NREM) sleep must be passed through before REM sleep is reached, whereby increasing depth of sleep correlates with decreasing frequency of the EEG waves. • Chronic use of sleeping pills leads to lighter NREM sleep and only occasional REM phases.
  • 121.
    ConsciousnessConsciousness  We becomeconscious of only a fractionWe become conscious of only a fraction of the information reaching our brain.of the information reaching our brain. The conscious contents are stored inThe conscious contents are stored in associative cortical areas that specializeassociative cortical areas that specialize in this task.in this task.  Conscious awareness requires not onlyConscious awareness requires not only that the specific afferents have beenthat the specific afferents have been transmitted to the cerebral cortex, buttransmitted to the cerebral cortex, but also nonspecific activation by thealso nonspecific activation by the ascending reticular activating systemascending reticular activating system (ARAS)(ARAS) through which neurons from thethrough which neurons from the reticular formation activate wide areas ofreticular formation activate wide areas of the cerebral cortex via intralaminarthe cerebral cortex via intralaminar neurons of the thalamus.neurons of the thalamus.
  • 122.
    Loss of ConsciousnessLossof Consciousness • Damage toDamage to large areas of the cortexlarge areas of the cortex and/or breakdown of theand/or breakdown of the ascendingascending reticular activating system (ARAS)reticular activating system (ARAS) brings aboutbrings about loss of consciousnessloss of consciousness.. • In addition, there may be primary causes influencing neuronal excitability inIn addition, there may be primary causes influencing neuronal excitability in the above-mentioned neuronal structures.the above-mentioned neuronal structures. • IschemiaIschemia (e.g., atherosclerotic vascular occlusion) or(e.g., atherosclerotic vascular occlusion) or hypoxiahypoxia (e.g.,(e.g., suffocation) impair excitability directly or bysuffocation) impair excitability directly or by cell swellingcell swelling.. • Swelling of glial cellsSwelling of glial cells impairs, among other functions, their capacity toimpairs, among other functions, their capacity to taketake up K+up K+ and thus to keep down the concentration of extracellular K+. This hasand thus to keep down the concentration of extracellular K+. This has an indirect effect onan indirect effect on neuronal excitabilityneuronal excitability.. • Part of the effect of tumors, abscesses, or bleeding is also exerted viaPart of the effect of tumors, abscesses, or bleeding is also exerted via ischemia or hypoxia in that they raise the cerebral pressure and thus impairischemia or hypoxia in that they raise the cerebral pressure and thus impair cerebral perfusion by narrowing the blood vessels.cerebral perfusion by narrowing the blood vessels. • HypoglycemiaHypoglycemia also modifies excitability, partly via cellular swelling.also modifies excitability, partly via cellular swelling. • HyponatremiaHyponatremia andand ammoniaammonia (NH4+) also act via this mechanism. The(NH4+) also act via this mechanism. The riserise in NH4in NH4+ in+ in hepatic encephalopathyhepatic encephalopathy causes the formation of glutamine fromcauses the formation of glutamine from αα-ketoglutarate and-ketoglutarate and glutamate in glial cellsglutamate in glial cells; the accumulation of glutamine; the accumulation of glutamine causes them to swell.causes them to swell. • AtAt firstfirst this swelling is counteracted by thethis swelling is counteracted by the removal of osmolytesremoval of osmolytes, seen in, seen in magnetic resonance imaging as a decrease in the cerebral concentration ofmagnetic resonance imaging as a decrease in the cerebral concentration of inositol. When this compensatory mechanism is exhausted,inositol. When this compensatory mechanism is exhausted, consciousnessconsciousness is lostis lost..
  • 123.
    Disorders of MemoryDisordersof Memory • It is needed, for example, in order to be able to recognize certain things (apples, animals, faces). Procedural, implicit memory does not require conscious activation for storage and recall. It is required, e.g. for learning to play the piano.  Two forms of memory are distinguished:Two forms of memory are distinguished: Declarative, explicitDeclarative, explicit memorymemory (semantic or episodic(semantic or episodic) stores memory that can only be) stores memory that can only be recalled consciously.recalled consciously.
  • 124.
    Disorders ofDisorders of MemoryMemory ►To formTo form declarative memorydeclarative memory the informationthe information first of all reaches the corresponding associationfirst of all reaches the corresponding association cortex (e.g., the secondary visual cortex) via thecortex (e.g., the secondary visual cortex) via the particular primary sensory cortical area (e.g., theparticular primary sensory cortical area (e.g., the primary visual cortex). From here, via theprimary visual cortex). From here, via the entorhinal cortex (area 28), the informationentorhinal cortex (area 28), the information reaches the hippocampus, which is essential forreaches the hippocampus, which is essential for long-term storage of declarative memory.long-term storage of declarative memory. ► With mediation from structures in theWith mediation from structures in the diencephalon, basal forebrain, and prefrontaldiencephalon, basal forebrain, and prefrontal cortex the item is again stored in the asssociationcortex the item is again stored in the asssociation cortex. In this way the information is first takencortex. In this way the information is first taken up, via the sensory memory, by theup, via the sensory memory, by the short-termshort-term memorymemory, which can hold on to the content for, which can hold on to the content for only a few seconds to minutes.only a few seconds to minutes. ► The information can be transferred to theThe information can be transferred to the long-long- term memoryterm memory , for example, through being, for example, through being rehearsed. Such rehearsal is not an essentialrehearsed. Such rehearsal is not an essential precondition for the formation of long-termprecondition for the formation of long-term memory, however.`memory, however.`
  • 125.
    Amnesia  Lesions inthe hippocampus or its connections result in anterograde amnesia. The affected patients will from that moment on no longer be able to form any new declarative memory. They will remember events prior to the lesion but none subsequent to it.  Retrograde amnesia, i.e., the loss of already stored information, occurs in disorders in the relevant associative cortical fields. Depending on the extent and localization of the disorder, the loss can be reversible or irreversible. In the former case the patient will lose items of memory, but they can be retrieved. In irreversible loss the particular items are permanently lost.  Transitory bilateral functional disturbance of the hippocampus can cause anterograde and retrograde (days to years) amnesia (transient global amnesia). In Korsakoff’s syndrome (frequent in chronic alcoholics) both anterograde and retrograde amnesia can occur. Patients thus affected often try to cover up gaps in memory by means of confabulations.
  • 126.
    Disorders of Memory Theprocedural (implicit) memory is not impaired in lesions of the hippocampus. It allows imprinting, learning of skills, sensitization, habituation, and conditioning. Depending on the task, cerebellum, basal ganglia, amygdala and cortical areas are involved. Both the cerebellum and basal ganglia play an important role when learning skills. Relevant afferent impulses reach the cerebellum via olivary and pontine nuclei. The storage capacity of the cerebellum can be lost by, for example, toxic damage, degenerative diseases, and trauma. Dopaminergic projections of the substantia nigra also play a part in the formation of procedural memory.
  • 127.
    The amygdala isimportant in conditioning anxiety reactions. It receives its information from the cortex and thalamus and influences motor and autonomic functions (e.g., muscle tone, palpitations [awareness of tachycardias], goose- pimples) via the reticular formation and hypothalamus. Removal of the amygdala (e.g., by trauma or opiates) cancels conditioned anxiety reactions. Bilateral removal of the amygdala with portions of the hippocampus and temporal lobe results in amnesia and disinhibited behavior (Klüver–Bucy syndrome).
  • 128.
    a. Most oftendue to thiamine deficiency b. Gross and microscopic findings: 1) Hemorrhages of small vessels with hemosiderin deposits  Mammillary bodies, wall of the third and fourth ventricles; 2) Neuronal loss, gliosis, vessel hemorrhage; c. Wernicke encephalopathy; reversible findings: • Confusion, ataxia, nystagmus, ophthalmoplegia (eye muscle weakness) d. Korsakoff psychosis 1) Advanced irreversible stage of Wernicke encephalopathy  Targets the limbic system; 2) Anterograde amnesia (inability to form new memories); 3) Retrograde amnesia (inability to recall old memories); 4) Confabulation, hallucinations 4. Treatment  Thiamine
  • 130.
    Clinical Features ofDementiaClinical Features of Dementia  DementiaDementia is anis an acquiredacquired decline in intellectual functiondecline in intellectual function resulting inresulting in lossloss of social independenceof social independence..  There isThere is impairment of memoryimpairment of memory and at least one other area ofand at least one other area of corticalcortical functionfunction, such as, such as language, calculation, spatial orientation,language, calculation, spatial orientation, decision making, judgment, and abstract reasoningdecision making, judgment, and abstract reasoning..  InIn contrast to patients withcontrast to patients with confusional statesconfusional states,, symptoms progress oversymptoms progress over months to yearsmonths to years, and alertness is preserved until the, and alertness is preserved until the very late stages ofvery late stages of diseasedisease..  DementiaDementia affects 5–20% of persons over age 65affects 5–20% of persons over age 65, and, although not, and, although not part of normal aging, its incidence increases with age.part of normal aging, its incidence increases with age.  The most common causes, which are listed inThe most common causes, which are listed in ttableable on the next slideon the next slide,, account for almostaccount for almost 90% of cases90% of cases..  Treatable causesTreatable causes are important to recognize and includeare important to recognize and include hypothyroidism, vitamin B12 deficiency, neurosyphilis, brain tumor,hypothyroidism, vitamin B12 deficiency, neurosyphilis, brain tumor, normal pressure (communicating) hydrocephalus, and chronic subduralnormal pressure (communicating) hydrocephalus, and chronic subdural hematomahematoma..  In addition,In addition, although not curable, dementiaalthough not curable, dementia associated withassociated with HIVHIV infection may be slowed byinfection may be slowed by antiretroviral treatmentantiretroviral treatment..  AboutAbout 10–15%10–15% of patients referred for evaluation of dementia sufferof patients referred for evaluation of dementia suffer from depression (from depression ("pseudodementia""pseudodementia"), which may also respond to), which may also respond to treatment.treatment.
  • 131.
    Dementia with Lewy bodies Multiplecerebral infarcts Alzheimer's disease (> 50% of cases) Deficiency of vitamins B12, B6, B1, or niacin HIV infection Huntington'sHuntington's diseasedisease Pick's disease Prion diseases (eg, Creutzfeldt-Jakob disease) Parkinson'sParkinson's diseasedisease Subdural hematoma Frontotemporal dementia Alcoholism Normal pressure hydrocephalus Primary or metastatic CNS neoplasms Neurosyphilis Chronic meningitis Hypothyroidism Major Causes of Dementia
  • 132.
    Alzheimer’s DiseaseAlzheimer’s Disease The defective gene on chromosome 19,The defective gene on chromosome 19, for example, codes for apolipoprotein Efor example, codes for apolipoprotein E (ApoE 4), the relevant gene on(ApoE 4), the relevant gene on chromosome 21 for a protein (βchromosome 21 for a protein (β-- amyloid precursoramyloid precursor) that can be broken) that can be broken down to small amyloid peptides. Thesedown to small amyloid peptides. These can on their own bunch themselvescan on their own bunch themselves together into protein fibrils 7–10nm long.together into protein fibrils 7–10nm long. These amyloid fibrils can then formThese amyloid fibrils can then form aggregates, 10 μm to several hundredaggregates, 10 μm to several hundred μm in diameter (μm in diameter (senile plaquessenile plaques), that), that are frequently found in the brain ofare frequently found in the brain of patients with Alzheimer’s disease. Inpatients with Alzheimer’s disease. In addition to extracellular amyloid, theseaddition to extracellular amyloid, these plaques contain distorted dendrites andplaques contain distorted dendrites and axons with abnormal intracellularaxons with abnormal intracellular neurofibrils. The formation of theseneurofibrils. The formation of these atypical elements of the cytoskeletonatypical elements of the cytoskeleton apparently precedes the death of theapparently precedes the death of the neurons.neurons. • The occurrence of Alzheimer’s disease, the most common cause of (senile) dementia (about 70%), is favored by a genetic disposition. • However, the disease is not genetically uniform. An especially severe form of the disease has an autosomal dominant inheritance. • Defects on chromosomes 1, 12, 14, 19, or 21 were found in families with Alzheimer’s disease.
  • 135.
     Creutzfeldt–JakobCreutzfeldt–Jakob diseasedisease, possibly,possibly caused by prionscaused by prions (proteinaceous(proteinaceous infectious particles), isinfectious particles), is a neurodegenerativea neurodegenerative disease that, indisease that, in addition to motor (e.g.,addition to motor (e.g., ataxia) andataxia) and psychogenicpsychogenic disorders, also leadsdisorders, also leads to dementia.to dementia. Creutzfeldt–Jakob diseaseCreutzfeldt–Jakob disease
  • 138.
    Literature:Literature: 1.1. General andclinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia:General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia: Nova Knuha Publishers – 2011. – P.Nova Knuha Publishers – 2011. – P.627627––663838.. 2.2. Russell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinicalRussell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinical pharmacy practice / Russell J. Greene, Norman D. Harris // Published by thepharmacy practice / Russell J. Greene, Norman D. Harris // Published by the Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, LondonPharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rdSE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rd edition, USA. – 2008. – Chapter 7. – P. 455–512.edition, USA. – 2008. – Chapter 7. – P. 455–512. 3.3. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams &Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams & Wilkins), Trade paperback (2003)Wilkins), Trade paperback (2003) // Carol Mattson Porth, Kathryn J. Gaspard. –ChaptersCarol Mattson Porth, Kathryn J. Gaspard. –Chapters 36, 38-40. – P. 637–363, 456–777.36, 38-40. – P. 637–363, 456–777. 4.4. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing.Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing. – 2010. – P. 512–531.– 2010. – P. 512–531. 5.5. Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova //Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova // Study guide for medical students and practitioners.Study guide for medical students and practitioners. Edited by prof. Zaporozan, OSMU. –Edited by prof. Zaporozan, OSMU. – Odessa. – 2005. – P. 2Odessa. – 2005. – P. 29292––307307.. 6.6. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme.Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme. Stuttgart. New York. – 2000. – P. 298–331.Stuttgart. New York. – 2000. – P. 298–331. 7.7. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition. Copyright ВCopyright В.. – Lippincott Williams & Wilkins – 2008. –– Lippincott Williams & Wilkins – 2008. – Chapter 8. – P. 185–202, 208–Chapter 8. – P. 185–202, 208– 209, 220–224.209, 220–224. 8.8. Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. –Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. – 2007. – Chapter2007. – Chapter 2323. – P.. – P. 881–902881–902.. 9.9. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasik // Elsevier Inc, 4th edition. – 2010. – P. 998–1034, 1086–1123.Banasik // Elsevier Inc, 4th edition. – 2010. – P. 998–1034, 1086–1123. 10.10. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, GlennPathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin.Matfin. –– New York, Milwaukee.New York, Milwaukee. –– 2009.2009. –– P.P. 1181–12991181–1299..

Editor's Notes

  • #5 http://legacy.owensboro.kctcs.edu/gcaplan/anat/notes/api%20notes%20k%20%20neurons.htm
  • #8 Depolarization Steps: 1) Negative charge inside of membrane (due to K ions) positive charge on outside (Na), more negative than positive. 2) Action potential causes the sodium channels to open and Na ions flow into inner membrane; K+ ions flow out. 3) Sodium-potassium pump depolarize cell during refractory period; 2:3 Na:K pumped into cell Actions potential do not vary but the rate/ number of neuron stimulated will result in high-intensity stimulation Axons covered by myelin sheath= insulation/ protective Nodes of Ranvier: section of axon where myelin sheath are not present or absent. Impulses hope along these nodes to get better conductivity and speed. Synapse: connection between neurons (axons and dendrites) Neurotransmission occurs between axon and dendrites in synaptic cleft 5 steps Synthesis- chemicals have made within the neuron Storage- these chemicals are stored within the synaptic vesicles Release- chemicals move across the synaptic cleft from presynaptic neuron (axon) to post synaptic neuron (dendrites) Binding: the vesicle bind to the receptor sites on the neurons. These chemicals will (a) depolarize the neuron by exciting it or (b) hyperpolarize the neuron and inhibit it. Deactivation: shuts off, is depolarized
  • #11 Somatic Nervous system: voluntary movements (muscles, senses) Autonomic Nervous system: controls glands, heart, etc. Fight-or-Flight: Sympathetic: arousal to stress Parasympathetic: recovery from stress [HOMOEOSTATIS]
  • #12 http://legacy.owensboro.kctcs.edu/gcaplan/anat/notes/api%20notes%20k%20%20neurons.htm
  • #22 Primary pain pathways. The transmission of incoming nociceptive impulses is modulated by dorsal horn circuitry that receives input from peripheral touch receptors and from descending pathways that involve the limbic cortical systems (orbital frontal cortex, amygdala, and hypothalamus), periaqueductal endogenous analgesic center in the midbrain, pontine noradrenergic neurons, and the nucleus raphe magnus (NRM) in the medulla. Dashed lines indicate inhibition or modulation.
  • #24 Evaluates pain threshold. Standardized (1.52cm2) flat circular probe is pushed against subject’s skin until pain threshold is reached. (lbs. and kgs).
  • #26 Analgesia is the absence of pain on noxious stimulation or the relief of pain without loss of consciousness. The inability to sense pain may result in trauma, infection, and even loss of a body part or parts. Inherited insensitivity to pain may take the form of congenital indifference or congenital insensitivity to pain. In the former, transmission of nerve impulses appears normal, but the appreciation of painful stimuli at higher levels appears to be absent. In the latter, a peripheral nerve defect apparently exists such that transmission of painful nerve impulses does not result in perception of pain. Whatever the cause, persons who lack the ability to perceive pain are at constant risk of tissue damage because pain is not serving its protective function. Myofascial trigger points are foci of exquisite tenderness found in many muscles and can be responsible for pain projected to sites remote from the points of tenderness. Trigger points are widely distributed in the back of the head and neck and in the lumbar and thoracic regions. These trigger points cause reproducible myofascial pain syndromes in specific muscles. These pain syndromes are the major source of pain in clients at chronic pain treatment centers.
  • #30 In the acute infection, proportionately more of the large nerve fibers are destroyed. Regenerated fibers appear to have smaller diameters. Because there is a relative loss of large fibers with age, elderly persons are particularly prone to suffering because of the shift in the proportion of large- to small-diameter nerve fibers. Older patients have pain, dysesthesia, and hyperesthesia after the acute phase; these are increased by minor stimuli. Early treatment of shingles with high doses of systemic corticosteroids and an oral antiviral drug such as acyclovir or valacyclovir, a medication that inhibits herpesvirus DNA replication, may reduce the incidence of postherpetic neuralgia. Initially, postherpetic neuralgia can be treated with a topical anesthetic agent. A tricyclic antidepressant medication may be used for pain relief. Regional nerve blockade (i.e., stellate ganglion, epidural, local infiltration, or peripheral nerve block) has been used with limited success.
  • #39 http://www.neurologyresident.net/Spin.%20Spinal%20Disorders/Spin21.%20UMN%20and%20LMN%20disease%20%28ALS%29.pdf
  • #40 The disease typically follows a progressive course, with a mean survival period of 2 to 5 years from the onset of symptoms. ALS affects motoneurons in three locations: the anterior horn cells of the spinal cord; the motor nuclei of the brain stem, particularly the hypoglossal nuclei; and the UMNs of the cerebral cortex. The fact that the disease is more extensive in the distal, rather than the proximal, parts of the affected tracts in the lower spinal cord suggests that affected neurons first undergo degeneration at their distal terminals and that the diseasem proceeds in a centripetal direction until ultimately the parent nerve cell dies. A remarkable feature of the disease is that the entire sensory system, the regulatory mechanisms of control and coordination of movement, and the intellect remain intact. The neurons for eye movement and the parasympathetic neurons in the sacral spinal cord also are spared. Degeneration and loss of neurons in the primary motor cortex leads to loss of fibers within the corticospinal tract and lateral and anterior columns of the spinal cord.6 It is this fiber atrophy, called amyotrophy, that appears in the name of the disease. The loss of nerve fibers in lateral columns of the white matter of the spinal cord along with fibrillary gliosis imparts a firmness or sclerosis to this CNS tissue; the term lateral sclerosis designates these changes. The cause of LMN and UMN destruction in ALS is uncertain. Five percent to 10% of cases are familial; the others are believed to be sporadic, with no family history of the disease. Recently, mutations to a gene encoding superoxide dismutase 1 (SOD1) was mapped to chromosome. This enzyme functions in the prevention of free radical formation. The mutation accounts for 20% of familial ALS, with the remaining 80% being caused by mutations in other genes. Five percent of persons with sporadic ALS also have SOD1 mutations. Possible targets of SOD1-induced toxicity include the neurofilament proteins, which function in the axonal transport of molecules necessary for the maintenance of axons. Another suggested mechanism of pathogenesis in ALS is exotoxic injury through activation of glutamate-gated ion channels, which are distinguished by their sensitivity to N-methyl-D-aspartic acid. The possibility of glutamate excitotoxicity in the pathogenesis of ALS was suggested by the finding of increased glutamine levels in the cerebrospinal fluid of patients with sporadic ALS. Although autoimmunity has been suggested as a cause of ALS, the disease does not respond to the immunosuppressant agents that normally are used in treatment of autoimmune disorders.
  • #41 http://www.neurologyresident.net/Spin.%20Spinal%20Disorders/Spin21.%20UMN%20and%20LMN%20disease%20%28ALS%29.pdf
  • #44 The prevalence of MS varies considerably around the world. The disease is more prevalent in the colder northern latitudes; it is more common in the northern Atlantic states, the Great Lakes region, and the Pacific Northwest than in the southern parts of the United States. Other high-incidence areas include northern Europe, Great Britain, southern Australia, and New Zealand. The incidence among women is almost double that of men. Although MS is not directly inherited, there is a familial predisposition in some cases, suggesting a genetic influence on susceptibility. For example, there is evidence of a genetic linkage of MS susceptibility to the inherited major histocompatibility complex DR2 haplotype. The pathophysiology of MS involves the demyelination of nerve fibers in the white matter of the brain, spinal cord, and optic nerve. In the CNS, myelin is formed by the oligodendrocytes, chiefly those lying among the nerve fibers in the white matter. The properties of the myelin sheath—high electrical resistance and low capacitance—permit it to function as an electrical insulator. Demyelinated nerve fibers display a variety of conduction abnormalities, ranging from decreased conduction velocity to conduction blocks. The lesions of MS consist of hard, sharp-edged demyelinated or sclerotic patches that are macroscopically visible throughout the white matter of the CNS. These lesions, which represent the end result of acute myelin breakdown, are called plaques. The lesions have a predilection for the optic nerves, periventricular white matter, brain stem, cerebellum, and spinal cord white matter. In an active plaque, there is evidence of ongoing myelin breakdown. The sequence of myelin breakdown is not well understood, although it is known that the lesions contain small amounts of myelin basic proteins and increased amounts of proteolytic enzymes, macrophages, lymphocytes, and plasma cells. Oligodendrocytes are decreased in number and may be absent, especially in older lesions. Acute, subacute, and chronic lesions often are seen at multiple sites throughout the CNS. The lesions of MS are generally thought to result from an immune-mediated inflammatory response that occurs in genetically susceptible individuals. The demyelination process in MS is marked by prominent lymphocytic invasion in the lesion. The infiltrate in plaques contains both CD8+ and CD4+ T cells as well as macrophages. Both macrophages and cytotoxic CD8+ T cells are thought to induce oligodendrocyte injury. There also is evidence of antibody-mediated damage involving myelin oligodendroglial protein. Magnetic resonance imaging has shown that the lesions of MS may occur in two stages: a first stage that involves the sequential development of small inflammatory lesions, and a second stage during which the lesions extend and consolidate and when demyelination and gliosis (scar formation) occur. It is not known whether the inflammatory process, present during the first stage, is directed against the myelin or against the oligodendrocytes that produce myelin. There is evidence that remyelination can occur in the CNS if the process that initiated the demyelination is halted before the oligodendrocyte dies
  • #49 Huntington&amp;apos;s disease is inherited as an autosomal dominant disorder. When disease onset occurs later in life, patients develop involuntary, rapid, jerky movements (chorea) and slow writhing movements of the proximal limbs and trunk (athetosis). When disease onset occurs earlier in life, patients develop signs of parkinsonism with tremor (cogwheeling) and stiffness. The spiny GABAergic neurons of the striatum preferentially degenerate, resulting in a net decrease in GABAergic output from the striatum. This contributes to the development of chorea and athetosis. Dopamine antagonists, which block inhibition of remaining striatal neurons by dopaminergic striatal fibers, reduce the involuntary movements. Neurons in deep layers of the cerebral cortex also degenerate early in the disease, and later this extends to other brain regions, including the hippocampus and hypothalamus. Thus, the disease is characterized by cognitive defects and psychiatric disturbances in addition to the movement disorder. The gene for the disease is located on chromosome 4p and encodes for a 3144-amino acid protein, huntingtin, which is widely expressed and interacts with several proteins involved in intracellular trafficking and endocytosis, gene transcription, and intracellular signaling. The protein contains a trinucleotide (CAG) repeat of 11–34 copies that encodes a polyglutamine domain and is expanded in patients with the disease. Deletion of the gene in mice causes embryonic death, whereas heterozygous animals are healthy. Transgenic mice with an expanded repeat develop a neurodegenerative disorder, suggesting that the disease results from the toxic effect of a gain of function mutation. The mechanisms by which mutant huntingtin causes disease are not certain. The mutant protein is degraded, and the resulting fragments that contain the glutamine repeats form aggregates, which are deposited in nuclear and cytoplasmic inclusions. These fragments may bind abnormally to other proteins and interfere with normal protein processing or disrupt mitochondrial function. Nuclear fragments may interfere with nuclear functions such as gene expression. For example, in the cerebral cortex, mutant huntingtin reduces the production of brain-derived neurotrophic factor by suppressing its transcription. In addition, normal huntingtin is protective for cortical and striatal neurons and blocks the processing of procaspase 9, thereby reducing apoptosis (programmed cell death). Therefore, both loss of neurotrophic support and enhanced caspase activity could promote striatal cell loss in Huntington&amp;apos;s disease.
  • #68 Alterations in Eye Movements In a fully conscious person, the steady gaze of the eyes at rest results from an intact cerebral cortex exerting control over the brainstem. With brain injury that involves loss of cortical function, the eyes typically rove and move together toward or away from the side of the brain injured, depending on the type of injury. Loss of higher brain centers results in reflexive eye movements, called doll&amp;apos;s head movements. A doll&amp;apos;s head movement is that which occurs when the eyes stare forward, always following the position of the head. Normally, when an individual&amp;apos;s head is passively turned to one side, the eyes move to face the previous, forward direction. With injury to the brainstem, loss of ocular movement occurs, and the eyes become fixed in a direct forward position. A skewed deviation, with one eye looking up and one down, suggests a compressive injury to the brainstem. Normal involuntary cyclic movements of the eyeball (nystagmus responses) in response to ice water delivered into the ear are lost with cortical and brainstem dysfunction.
  • #81 Copyright © 2008 Allyn &amp; Bacon
  • #102 It is the third leading cause of death in the United States.
  • #107 Ischemic strokes involving occlusion of small arteries occur at select locations, where perfusion depends on small vessels that are end arteries. Most result from a degenerative change in the vessel, described pathologically as lipohyalinosis, that is caused by chronic hypertension and predisposes to occlusion. The most common vessels involved are the lenticulostriate arteries, which arise from the proximal middle cerebral artery and perfuse the basal ganglia and internal capsule. Also commonly affected are small branches of the basilar and posterior cerebral arteries that penetrate the brainstem and thalamus. Occlusion of these vessels causes small areas of tissue damage known as lacunar infarctions. These typically occur in the putamen, caudate, thalamus, pons, and internal capsule and less commonly in subcortical white matter and cerebellum. Lacunar infarctions produce several fairly stereotyped clinical syndromes. The two most common are pure motor stroke and pure sensory stroke. In pure motor stroke, the infarction is usually within the internal capsule or pons contralateral to the weak side. In pure sensory stroke, the infarction is usually in the contralateral thalamus. Several vascular, cardiac, and hematologic disorders can cause focal cerebral ischemia. The most common is atherosclerosis of the large arteries of the neck and base of the brain. Atherosclerosis is thought to arise from injury to vascular endothelial cells by mechanical, biochemical, or inflammatory insults. Endothelial injury stimulates attachment of circulating monocytes and lymphocytes that migrate into the vessel wall and stimulate proliferation of smooth muscle cells and fibroblasts. This leads to the formation of a fibrous plaque. Damaged endothelial cells also provide a nidus for aggregation and activation of platelets. Activated platelets secrete growth factors that encourage further proliferation of smooth muscle and fibroblasts. The plaque may eventually enlarge to occlude the vessel or may rupture, releasing emboli.
  • #118 The epileptic seizures can occur locally, for example, in the left precentral gyrus in the area of those neurons that control the right foot (partial seizure). They can spread from there to the entire precentral gyrus (Jacksonian epilepsy). Clonic cramps may spread, as in this example, from the right foot to the entire right half of the body (“Jacksonian motor march”), the patient not necessarily losing consciousness. However, should the seizures spread to the other side of the body, the patient will lose consciousness (partial seizure with secondary generalization). Primary generalized seizures are always associated with loss of consciousness. Certain seizures (“absences”) can also lead to isolated loss of consciousness. The triggering phenomenon is paroxysmal depolarization of individual neurons (paroxysmal depolarization shift [PDS]). This is caused by activation of Ca2+ channels (4-1). The entering Ca2+ first of all opens nonspecific cation channels and thus causes massive depolarization, which is terminated by opening of the Ca2+-activated K+ and Cl– channels. An epileptic seizure occurs when a sufficient number of neurons has been excited. Causes or factors which favor epilepsy are, for example, genetic defects (of K+ channels and others), malformation of the brain, trauma to the brain (glial scars), tumor, bleeding, or abscesses. Seizures may also be provoked or promoted by poisoning (e.g., alcohol), inflammation, fever, cell swelling or (less likely) shrinkage, hypoglycemia, hypomagnesemia, hypocalcemia, lack of sleep, ischemia or hypoxia, and repetitive stimuli (e.g., a flickering light). Hyperventilation can lead to cerebral hypoxia, via hypocapnia and cerebral vasoconstriction, and may thus promote the onset of a seizure. Epileptic seizures have a higher incidence among pregnant women. Neuronal excitation or the spread of excitation to neighboring neurons is promoted by a number of cellular mechanisms: The dendrites of the pyramidal cells contain voltage-gated Ca2+ channels that open on depolarization and thus increase depolarization. In lesions of neurons more of these Ca2+ channels are expressed. They are inhibited by Mg2+, while hypomagnesemia promotes the activity of these channels (4-2). An increased extracellular concentration of K+ reduces K+ efflux through the K+ channels, i.e., it has a depolarizing effect and thus at the same time promotes the activation of Ca2+ channels. The dendrites of pyramidal cells are also depolarized by glutamate from excitatory synapses (4-3). Glutamate acts on a cation channel that is impermeable to Ca2+ (AMPA channel) and one that is permeable to Ca2+ (NMDA channel). The NMDA channel is normally blocked by Mg2+. However, the depolarization that is triggered by activation of the AMPA channel abolishes the Mg2+ block (co-operation of the two channels). Mg2+ deficiency and depolarization thus favor activation of the NMDA channel. The membrane potential of the neurons is normally maintained by the K+ channels. A precondition for this is an adequate K+ gradient across the cell membrane. This gradient is created by Na+/K+-ATPase (!A4). A lack of available energy (e.g., due to O2 deficiency or hypoglycemia) impairs Na+/K+-ATPase and thus promotes depolarization of the cell. Normally depolarizations are reduced by inhibitory neurons that activate K+ and/or Cl– channels via GABA, among others (4-5). GABA is formed by glutamate decarboxylase (GD), an enzyme that needs pyridoxine (vitamin B6) as co-factor. Vitamin B6 deficiency or a reduced affinity of the enzyme for vitamin B6 (genetic defect) favors the occurrence of epilepsy. Hyperpolarization of thalamic neurons can increase the readiness of T-type Ca2+ channels to be activated, thereby promoting the onset of absences.
  • #119 Pathogenesis Normal neuronal activity occurs in a nonsynchronized manner, with groups of neurons inhibited and excited sequentially during the transfer of information between different brain areas. Seizures occur when neurons are activated synchronously. The kind of seizure depends on the location of the abnormal activity and the pattern of spread to different parts of the brain. Interictal spike discharges are often observed on EEG recordings from epileptic patients. These are due to synchronous depolarization of a group of neurons in an abnormally excitable area of brain. Experimentally, this is known as the paroxysmal depolarizing shift and is followed by a hyperpolarizing afterpotential that is the cellular correlate of the slow wave that follows spike discharges on the EEG. The shift is produced by depolarizing currents generated at excitatory synapses and by subsequent influx of sodium or calcium through voltage-gated channels. Normally, discharging excitatory neurons activate nearby inhibitory interneurons that suppress the activity of the discharging cell and its neighbors. Most inhibitory synapses utilize the neurotransmitter GABA. Voltage-gated and calcium-dependent potassium currents are also activated in the discharging neuron to suppress excitability. In addition, adenosine generated from adenosine triphosphate (ATP) released during excitation further suppresses neuronal excitation by binding to adenosine receptors present on nearby neurons. Disruption of these inhibitory mechanisms by alterations in ion channels, or by injury to inhibitory neurons and synapses, may allow for the development of a seizure focus. In addition, groups of neurons may become synchronized if local excitatory circuits are enhanced by reorganization of neural networks after brain injury. Spread of a local discharge occurs by a combination of mechanisms. During the paroxysmal depolarizing shift, extracellular potassium accumulates, depolarizing nearby neurons. Increased frequency of discharges enhances calcium influx into nerve terminals, increasing neurotransmitter release at excitatory synapses by a process known as posttetanic potentiation. This involves increased calcium influx through voltage-gated channels and through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor-gated ion channels. NMDA receptor-gated channels preferentially pass calcium ions but are relatively quiescent during normal synaptic transmission because they are blocked by magnesium ions. Magnesium block is relieved by depolarization. In contrast, the effect of inhibitory synaptic neurotransmission appears to decrease with high-frequency stimulation. This may be partly due to rapid desensitization of GABA receptors at high concentrations of released GABA. The net effect of these changes is to recruit neighboring neurons into a synchronous discharge and cause a seizure. In secondary epilepsy, loss of inhibitory circuits and sprouting of fibers from excitatory neurons appear to be important for the generation of a seizure focus. In several of the idiopathic epilepsies, genetic studies have identified mutations in ion channels. For example, benign familial neonatalconvulsions have been linked to mutations in two homologous voltage-gated K+ channels: KCNQ2 encoded by a gene on chromosome 20q13.3 and KCNQ3 encoded by a gene on chromosome 8q24. Two forms of generalized epilepsy associated with febrile seizures have been linked to mutations in voltage-gated Na+ channel subunits. Another rare condition, autosomal dominant nocturnal frontal lobe epilepsy, is associated with mutations on chromosome 20q13.2 in the gene for the 4 subunit of neuronal nicotinic cholinergic receptors. Animal models have provided clues to the pathogenesis of absence seizures. Absence seizures arise from synchronous thalamic discharges that are mediated by activation of low-threshold calcium currents (T or &amp;quot;transient&amp;quot; currents) in thalamic neurons. The anticonvulsant ethosuximide blocks T channels and suppresses absence seizures in humans. T channels are more likely to be activated after hyperpolarization of the cell membrane. Activation of GABAB receptors hyperpolarizes thalamic neurons and facilitates T-channel activation. Lethargic (lh/lh) mice demonstrate frequent absence spells accompanied by 5- to 6-Hz spike-wave discharges on the EEG and respond to drugs used in human absence epilepsy. A single mutation in a gene on chromosome 2 results in this autosomal recessive disorder. There is an increase in the number of GABAB receptors in the cerebral cortex in these mice, and the GABAB agonist baclofen worsens the seizures, whereas antagonists alleviate them. This suggests that abnormal regulation of GABAB receptor function or expression may be important in the pathogenesis of absence seizures. This is supported by the finding that -hydroxybutyrate, which causes behavioral and electroencephalographic alterations similar to those seen during absence attacks, activates GABAB receptors and that GABAB agonists increase and GABAB antagonists reduce spike-wave discharges in rats genetically susceptible to absence seizures (GAERS rats). The main targets for currently available anticonvulsants are (1) voltage-gated ion channels that are involved in the generation of action potentials and in neurotransmitter release and (2) ligand-gated channels that modulate synaptic excitation and inhibition.
  • #120 5-8 % are at risk of status epilepticus – a series of GTCS without regaining consciousness – medical emergency Seizure activity lasts more than 30 minutes Acidosis Elevated pCO2 Hypoglycemia Fall in blood pressure Can lead to severe brain damage or death
  • #121 During the awake phases endogenous sleep factors accumulate, such as the sleep-inducing peptides that are broken down again during sleep. It is possible that serotonin stimulates the formation of sleep factors, because inhibiting serotonin formation, release or action (e.g., by the antihypertensive drug reserpine) causes insomnia. The sleep-inducing peptides cause “sleep pressure” (NREM sleep pressure or slow wave sleep [SWS]). The net sleep pressure is the difference between sleep pressure (violet) and the reciprocal of the REM sleep pressure (green) that follows a circadian rhythm essentially in parallel to body temperature and similar bodily parameters, such as “readiness for activity and effort”. The ability to fall asleep is a function of this net sleep pressure. When experiencing a change of time zone (jet lag) or when doing shift work, the circadian rhythm at first continues to oscillate in the original phase. When the day is shortened, it is impossible to go to sleep at the local time because of the low net sleep pressure. When the day gets longer, the sleep pressure is increased by the longer waking period and falling asleep at the local time is no problem. The subsequent circadian rhythm, however, causes early awakening. Falling asleep is also disturbed by delayed sleep phase insomnia, caused by an inflexible circadian rhythm that cannot be shortened. When going to sleep too early the net sleep pressure is too low. During chronotherapy a lengthened daily rhythm (27 hours) is forced upon the patient until the desired circadian periodicity has been obtained.
  • #123 The excitability of neurons is also affected by epilepsy, hyperosmolarity (hypernatremia, hyperglycemia) as well as by disorders of electrolyte (Ca2+,Mg2+, HPO42–) and acid-base metabolism. Uremia (in renal failure) and diabetes mellitus act partly via changes in extracellular osmolarity and electrolyte composition. Numerous substances can impair the excitability of the ARAS, such as NMDA receptor antagonists, alcohol, narcotics, hypnotics, psychoactive drugs, anticonvulsives, Na+/K+-ATPase inhibitors (cardiac glycosides), heavy metals. Extreme excess or lack of hormones (e.g T3, T4, parathyroid hormone, adrenocorticoid hormones, pheochromocytoma) as well as massive neuronal excitation, for example, caused by pain or psychogenic disease (schizophrenia), can lead to loss of consciousness. Lastly, neuronal excitability can also be so severely impaired by hyperthyroidism, hypothermia, inflammatory (e.g., meningitis) or mechanical damage, and neurodegenerative disease that it could lead to loss of consciousness. Loss of consciousness can be divided into several stages: in a state of drowsiness the patient can still be roused and will respond; in a stupor (profound sleep) patients can be awakened by vigorous stimuli; when in a coma this is no longer possible. In socalled “coma dépassé” vital functions will also have ceased (e.g., respiratory arrest). The split brain represents a special abnormality of consciousness. Uniform consciousness presupposes communication between the two cerebral hemispheres. This takes place along large commissural fiber bundles through the corpus callosum and the anterior commissure. In treating uncontrollable epilepsy the commissural fibers have been transected in some patients, stopping this communication between the two hemispheres. The two hemispheres now produce two distinct kinds of consciousness: if an object (e.g., a saucepan) is placed into the right hand or placed in the right visual field, the patient can correctly name the object. But if the object is placed into the left hand or projected into the left visual field, the patient is able to recognize the object and, for example, find the appropriate saucepan cover with the left hand, but will not be able to name it.
  • #125 It is particularly the transfer into long-term memory that is impaired in lesions of the above-named structures in neurodegenerative diseases (e.g., Alzheimer’s disease), trauma, ischemia, alcohol, carbon monoxide, and inflammation. In addition, memory formation can be temporarily stopped by electric shock. The most important transmitter in the hippocampus is glutamate (NMDA receptors). Memory formation is promoted by norepinephrine and acetylcholine (nicotinergic receptors).
  • #133 Certain mutations of the ß-amyloid precursor gene promote the formation of senile plaques. Amyloid deposits can also occur under the influence of other genetic or external factors. It is thought, for example, that toxins can penetrate the brain via the olfactory nerves and cause the disease. Amyloid deposits also occur in trisomy 21 (Down’s syndrome) that also leads to dementia. ß-amyloid fibrils can react with receptors at the cell surface, such as the receptor for advanced glycation end products (RAGE), and a scavenger receptor (RA). Oxygen radicals formed as a result may increase the neuronal intracellular concentration of Ca2+ (9-1), possibly via depolarization of the cell membrane and activation of NMDA receptors. The O2 radicals and Ca2+ promote cell death. In microglial cells (9-1) the activation of RAGE and RA stimulates the formation or release, respectively, of NO, prostaglandins, excitotoxins, cytokines, tumor necrosis factor (TNF-α), tumor growth factor (TGF-ß1), and fibroblast growth factor (b-FGF). This results in inflammation that also impairs neurons. Increased concentration of the osmolyte inositol points to a disorder of cell volume regulation. The death of neurons is accelerated by a lack of NGF or of NGF receptors and can be delayed by NGF. Cholinergic neurons in the basal nucleus of Meynert, in the hippocampus (especially CA1, the subiculum) and in the entorhinal cortex (9-2) are particularly affected by cell death, but neurons also die in other cerebral areas, such as the frontal lobes, anterior temporal lobes, parietal lobes, olfactory cortex, hypothalamus, locus ceruleus, and raphe nuclei. Neuronal death is accompanied by decreased formation and concentration of neurotransmitters in the brain. Acetylcholine is markedly affected: in the cerebral cortex and the hippocampus there is an up to 90% decrease in the concentration of choline-acetyl transferase, the enzyme that is necessary for the formation of acetylcholine. The concentration of other neurotransmitters is also reduced, for example, norepinephrine, serotonin, somatotropin, neuropeptide Y, substance P, and corticotropin-releasing hormone ([CRH] corticoliberin).