prepared by MD, PhD Marta R. Gerasymchuk Ivano-Frankivsk National Medical University, pathophysiology department

2. Actuality
The major functions of the nervous system are to detect,
analyze, and transmit information. Information is gathered
by sensory systems, integrated by the brain, and used to
generate signals to motor and autonomic pathways for
control of movement and of visceral and endocrine
functions.
Understanding the causes of neurologic diseases requires
knowledge of molecular and biochemical mechanisms.
Discoveries in the fields of molecular biology and genetics
have made available important information about the
mechanisms of several disease states.
Several neurologic disorders in which some of the
molecular mechanisms of pathogenesis are known are
discussed later in this chapter including motor neuron
disease, Parkinson's disease, myasthenia gravis, epilepsy,
Alzheimer's disease, and stroke.
Exciting advances in our understanding and overlap of
these diseases are leading to new therapeutic targets and
the hope of better treating these devastating diseases.

3. ContentContent
 Disorders of integrative function of CNS.Disorders of integrative function of CNS.
 Brain centres and their disorderBrain centres and their disorder..
 Anxiety DisordersAnxiety Disorders
 Mood DisordersMood Disorders
 SchizophreniaSchizophrenia
 Acute and chronic disturbances of brainAcute and chronic disturbances of brain
circulation. Strokecirculation. Stroke
 Cerebral infarction and cerebral hemorrhage.Cerebral infarction and cerebral hemorrhage.
 Seizure disorders.EpilepsySeizure disorders.Epilepsy
 Sleep DisordersSleep Disorders
 AphasiasAphasias
 Disorders of Memory. Alzheimer’s Disease.Disorders of Memory. Alzheimer’s Disease.
Creutzfeldt–Jakob diseaseCreutzfeldt–Jakob disease

4. 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 and pons.medulla and 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.

6. Principal anatomical centres ofPrincipal anatomical centres of
brain functionbrain 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

7. 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 tempora
l
parietal
occipital

8. Cortical disordersCortical disorders
• Cortical disorders usually have a profoundCortical disorders usually have a profound effect on alleffect on all
CNS function. They are commonlyCNS function. They are commonly manifested asmanifested as
disorders ofdisorders of intellectintellect, e.g., e.g.
• MentalMental handicaphandicap,, dementiadementia oror Alzheimer’sAlzheimer’s disease, ordisease, or
ofof 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 are foundare found
in the cortex. Many of the morein the cortex. Many of the more recently discoveredrecently discovered
mediators, such as themediators, such as the endorphinsendorphins and peptidesand peptides, have, have
yet to be definitelyyet to be definitely linked with specific CNS functions,linked with specific CNS functions,
disorders ordisorders or drug actions. They may modulate thedrug actions. They may modulate the
action ofaction of the traditional transmitters.the traditional transmitters.

9. 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.

10. Limbic systemLimbic system
 The contrast betweenThe contrast between limbiclimbic andand cortical functionscortical functions isis
illustrated by our response to beingillustrated by our response to being caught for a motoringcaught for a motoring
offence.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, ourtime, our
cortexcortex is calculating the effect on ouris calculating the effect on our insurance premium,insurance premium, thethe
most effective way tomost effective way to appease the policeman, or perhapsappease the policeman, or perhaps
even how toeven how to manage without a driving licencemanage without a driving licence..
 TheThe limbic systemlimbic system has evolved from a structurehas evolved from a structure in lowerin lower
mammals concerned withmammals concerned with olfactionolfaction (sense of smell),(sense of smell), andand
indeed it retains this functionindeed it retains this function in humans.in humans. Possibly this accountsPossibly this accounts
for thefor the emotional power that smells have on humans.emotional power that smells have on humans.
 TheThe limbic systemlimbic system is also involved inis also involved in memorymemory,, and we are alland we are all
familiar with how strongly smellsfamiliar with how strongly smells can evoke evencan evoke even distantdistant
memoriesmemories..
 The system isThe system is structurally complex with many componentstructurally complex with many component nucleinuclei
and important connections with theand important connections with the frontalfrontal andand temporal lobestemporal lobes
of the cortexof the cortex, with, with thethe reticular systemreticular system and with theand with the
hypothalamushypothalamus (all of which are sometimes considered as(all of which are sometimes considered as
partially within the limbic system).partially within the limbic system). DopamineDopamine isis an importantan important
transmitter, as aretransmitter, as are noradrenalinenoradrenaline (NA, norepinephrine) and(NA, norepinephrine) and 5-5-
hydroxytryptaminehydroxytryptamine (5-HT, serotonin).(5-HT, serotonin). Gamma-aminobutyricGamma-aminobutyric
acidacid ((GABA) is an inhibitory transmitter here.GABA) is an inhibitory transmitter here.

11. 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 operation tolobotomy (leucotomy), an operation to
sever thesever the links between the limbic system andlinks between the limbic system and
the cortexthe cortex in severe psychiatric disorders,in severe psychiatric disorders,
resulted in theresulted in the patient becoming emotionally flat.patient becoming emotionally flat.
 A similarA similar phenomenon is sometimes seen inphenomenon is sometimes seen in
patients onpatients on long-term antipsychoticslong-term antipsychotics..

12. Psychological DisordersPsychological Disorders
 Its mental processes and/or behavior patterns that cause emotionalIts mental processes and/or behavior patterns that cause emotional
distress and/or substantial impairment in functioningdistress and/or substantial impairment in functioning
 The presence of a constellation of symptoms that create significantThe presence of a constellation of symptoms that create significant
distress; impair work, school, family, relationships, or daily living; ordistress; impair work, school, family, relationships, or daily living; or
lead to significant risk or harmlead 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

13. 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)

15. General Adaptation Syndrome
Three stages:
1. Alarm stage
- Emergency reaction (fight-or-flight)
2. Resistance stage
- Coping and adaptation
3. 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.

16. Anxiety Disorders
• Components of Anxiety Responses

17. 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.

18. Anxiety DisordersAnxiety Disorders
 PhobiasPhobias - strong and irrational fears- strong and irrational fears
of certain objects or situationsof certain objects or situations
 AgoraphobiaAgoraphobia: fear of open and: fear of open and
public spaces from which escapepublic spaces from which escape
would be difficultwould be difficult
 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 orobjects such as animals or
situationssituations
 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%

19. 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

20. 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

21. Posttraumatic StressPosttraumatic Stress
DisorderDisorder 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 traumaticPTSD – disorder in which victims of traumatic
events experience the original event in the formevents experience the original event in the form
of dreams or flashbacksof dreams or flashbacks
 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

22. Somatoform DisordersSomatoform Disorders
 Used to be called “hysteria” by FreudUsed to be called “hysteria” 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

23. 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

24. 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, selfExtensive doctor visits, second opinions, self
diagnosisdiagnosis
 From repressed emotions?From repressed emotions?
 Get more reinforcement (positive attention)Get more reinforcement (positive attention)

25. Mood Disorders

26. 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

27. 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

28. Bipolar Disorder (Manic Depression)Bipolar Disorder (Manic Depression)
• Individual alternates between feelings of mania andIndividual alternates between feelings of mania and
depressiondepression
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

29. Seasonal Affective DisorderSeasonal Affective Disorder
 Depression during certain seasons,Depression during certain seasons,
 increase sleep, eatingincrease sleep, eating
CausesCauses
 Melatonin?Melatonin?
 Vitamin D?Vitamin D?
 Conditioning?Conditioning?
 Social Learning?Social Learning?

30. What is SchizophreniaWhat is Schizophrenia
• 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
• 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)

31. Types of SchizophreniaTypes of Schizophrenia
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
Catatonic – motor disturbancesCatatonic – motor disturbances
Paranoid – preoccupied withParanoid – preoccupied with
delusions, people out to get themdelusions, people out to get them
Disorganized – incoherentDisorganized – incoherent
language, inappropriate emotion,language, inappropriate emotion,
delusions, hallucinationsdelusions, hallucinations
Undifferentiated – manyUndifferentiated – many
symptomssymptoms
Remission – no current symptomsRemission – no current symptoms

33. StrokeStroke
 StrokeStroke is a clinical syndromeis a clinical syndrome
characterized by thecharacterized by the suddensudden onset of aonset of a
focal neurologic deficit that persists forfocal neurologic deficit that persists for
at least 24 hoursat least 24 hours and is due to anand is due to an
abnormality of the cerebral circulationabnormality of the cerebral circulation..
 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

34. 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).

35. 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

36. Common Stroke SymptomsCommon Stroke Symptoms
 Weakness or paralysisWeakness or paralysis
 Numbness, tingling,Numbness, tingling,
decreased sensationdecreased sensation
 Vision changesVision changes
 Speech problemsSpeech problems
 Swallowing difficulties orSwallowing difficulties or
droolingdrooling
 Loss of memoryLoss of memory
 Vertigo (spinningVertigo (spinning
sensation)sensation)
 Loss of balance andLoss of balance and
coordinationcoordination
 Personality changesPersonality changes
 Mood changesMood changes
(depression, apathy)(depression, apathy)
 Drowsiness, lethargy, orDrowsiness, lethargy, or
loss of consciousnessloss of consciousness
 Uncontrollable eyeUncontrollable eye
movements or eyelidmovements or eyelid
droopingdrooping

37. Major Effects of Stroke
• 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

38. • Aphasia and Dysphasia
• Brain Damage – extent of brain damage
determines chances of recovery
• Hemianopsia – blindness in half of the
visual field of one or both eyes
• Pain – usually very little; injection of local
anesthetic provides temporary relief
• Autonomic Disturbances
– Such as perspiration or “goose flesh” above the
level of paralysis
– May have dilated pupils, high or low BP or
headache
– Treated with atropine-like drugs
• Personality Changes – either functional or
organic

39. Ischemic 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.

40. 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

41. 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)

42. HemorrhageHemorrhage StrokeStroke EpiduralEpidural andand subdural hematomassubdural hematomas
typically occur as sequelae of head injury.typically occur as sequelae of head injury.
 Epidural hematomasEpidural hematomas arise from damagearise from damage
to an artery, typically the middleto an artery, typically the middle
meningeal artery, which can be rupturedmeningeal artery, which can be ruptured
by a blow to the temporal bone. Bloodby a blow to the temporal bone. Blood
dissects the dura from the skull anddissects the dura from the skull and
compresses the hemisphere lying below.compresses the hemisphere lying below.
Initial loss of consciousness from theInitial loss of consciousness from the
injury is due to concussion and may beinjury is due to concussion and may be
transient.transient.
 Neurologic symptomsNeurologic symptoms then return a fewthen return a few
hours later as the hematoma exerts ahours later as the hematoma exerts a
mass effect that may be severe enough tomass effect that may be severe enough to
cause brain herniation.cause brain herniation.
 Subdural hematomasSubdural hematomas usually arise fromusually arise from
venous blood that leaks from torn corticalvenous blood that leaks from torn cortical
veins bridging the subdural space. Theseveins bridging the subdural space. These
may be ruptured by relatively minormay be ruptured by relatively minor
trauma, particularly in the elderly. Thetrauma, particularly in the elderly. The
blood is under low pressure, andblood is under low pressure, and
symptoms resulting from mass effect maysymptoms resulting from mass effect may
not appear for several days.not appear for several days.

44. 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.
• 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.

45. 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 hypertensive patients,factor. In hypertensive patients,
smallsmall Charcot-BouchardCharcot-Bouchard
aneurysmsaneurysms appear in theappear in the
walls of small penetratingwalls of small penetrating
arteries and are thought to bearteries and are thought to be
the major sites of rupture. Mostthe major sites of rupture. Most
vulnerable are the smallvulnerable are the small
vessels that are also involvedvessels that are also involved
in lacunar infarction.in lacunar infarction.
Hypertensive hemorrhagesHypertensive hemorrhages
occur mainly in the basaloccur mainly in the basal
ganglia, thalamus, pons, andganglia, thalamus, pons, and
cerebellum and less commonlycerebellum and less commonly
in subcortical white matter.in subcortical white matter.

46. Intraparenchymal hemorrhageIntraparenchymal hemorrhage
Other causes of intraparenchymal hemorrhage includeOther causes of intraparenchymal hemorrhage include vascularvascular
malformations,malformations, which contain abnormally fragile vesselswhich contain abnormally fragile vessels
susceptible to rupture at normal arterial pressures, and certainsusceptible to rupture at normal arterial pressures, and certain
brain tumors,brain tumors, such as glioblastoma multiforme, which inducesuch as glioblastoma multiforme, which induce
proliferation of fragile vessels within the tumor.proliferation of fragile vessels within the tumor.
CertainCertain plateletplatelet andand coagulation disorderscoagulation disorders may predispose tomay predispose to
intracerebral hemorrhage by inhibiting coagulation.intracerebral hemorrhage by inhibiting coagulation.
CocaineCocaine andand amphetaminesamphetamines causecause rapidrapid
elevation of blood pressureelevation of blood pressure and are commonand are common
causes ofcauses of intraparenchymal hemorrhageintraparenchymal hemorrhage inin
young adults.young adults. HemorrhageHemorrhage may be relatedmay be related
to spontaneous bleeding from the acuteto spontaneous bleeding from the acute
elevation in blood pressure, rupture of anelevation in blood pressure, rupture of an
occult vascular abnormality, or drug-inducedoccult vascular abnormality, or drug-induced
vasculitis.vasculitis.
Cerebral amyloid angiopathyCerebral amyloid angiopathy is a disorderis a disorder
that occurs mainly in the elderly and may bethat occurs mainly in the elderly and may be
associated withassociated with Alzheimer's diseaseAlzheimer's disease..
Deposition of amyloid weakens the walls ofDeposition of amyloid weakens the walls of
small cortical vessels and causes lobarsmall cortical vessels and causes lobar
hemorrhage, often at several sites.hemorrhage, often at several sites.

47. Seizure disordersSeizure disorders
►SeizureSeizure is and abnormal discharge ofis and abnormal discharge of
electrical activity within the brain. It is aelectrical activity within the brain. It is a
rapidly evolving disturbance of brainrapidly evolving disturbance of brain
function that may produce impairedfunction that may produce impaired
consciousness, abnormalities of sensationconsciousness, abnormalities of sensation
or mental function or convulsiveor mental function or convulsive
movements.movements.
►ConvulsionsConvulsions are episodes of widespreadare episodes of widespread
and intense motor activityand intense motor activity

48. Epilepsy
• An epileptic seizure
(epileptic attack, epileptic
fit) is triggered by a
spontaneous,
synchronized, massive
excitation of a large
number of neurons,
resulting in localized or
generalized activation of
motor (fits or seizures),
sensory (sensory
impressions), autonomic
(e.g., salivation), or
complex (cognitive,
emotional) functions.

49. 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

50. 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
2.2. 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
3.3. Terminal phaseTerminal phase (about 5 minutes) –(about 5 minutes) –
limp and quiet, EEG flat lineslimp and quiet, EEG flat lines

51. Sleep Disorders
• Normal sleep requires the
interplay of several cerebral
structures, among them the loci
ceruleus and subceruleus
(norepinephrine being the
transmitter), the raphe nucleus
(serotonin as transmitter), tractus
solitarius nucleus, and neurons in
the hypothalamus.
• A lesion in the subceruleus nucleus results in rapid eye movement
(REM) insomnia (see below); lesions in the raphe nuclei or the anterior
hypothalamus lead to (transient) insomnia; lesions in the posterior
hypothalamus cause narcolepsy. Excitation of the tractus solitarius
nucleus (e.g., by gastric distension) causes fatigue. Sleep is also very
dependent on the circadian rhythm, in that destruction of the central
rhythm generator, the suprachiasmatic nucleus (SCN) leads to irregular
periods of falling asleep and of difficulty in awakening. The latter is
mediated by the ascending reticular activating system (ARAS), a
connection between the reticular formation via intralaminar nuclei of the
thalamus to large areas of the brain. Destruction of the intralaminar
thalamic nuclei (e.g., by ischemia) leads to somnolence.
Desynchronization between subcortical activity and cortical sleep may be
the cause of sleepwalking (somnambulism).

52. 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

53. 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.

54. 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 in theIn addition, there may be primary causes influencing neuronal excitability in the
above-mentioned neuronal structures.above-mentioned neuronal structures.
• IschemiaIschemia (e.g., atherosclerotic vascular occlusion) or(e.g., atherosclerotic vascular occlusion) or hypoxiahypoxia (e.g., suffocation)(e.g., suffocation)
impair excitability directly or byimpair 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 take up K+take up K+
and thus to keep down the concentration of extracellular K+. This has an indirectand thus to keep down the concentration of extracellular K+. This has an indirect
effect oneffect on neuronal excitabilityneuronal excitability..
• Part of the effect of tumors, abscesses, or bleeding is also exerted via ischemia orPart of the effect of tumors, abscesses, or bleeding is also exerted via ischemia or
hypoxia in that they raise the cerebral pressure and thus impair cerebral perfusionhypoxia in that they raise the cerebral pressure and thus impair cerebral perfusion
by narrowing the blood vessels.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 rise inrise in
NH4NH4+ in+ in hepatic encephalopathyhepatic encephalopathy causes the formation of glutamine fromcauses the formation of glutamine from αα--
ketoglutarate andketoglutarate and glutamate in glial cellsglutamate in glial cells; the accumulation of glutamine causes; the accumulation of glutamine causes
them to swell.them to swell.
• AtAt firstfirst this swelling is counteracted by thethis swelling is counteracted by the removal of osmolytesremoval of osmolytes, seen in magnetic, seen in magnetic
resonance imaging as a decrease in the cerebral concentration of inositol. Whenresonance imaging as a decrease in the cerebral concentration of inositol. When
this compensatory mechanism is exhausted,this compensatory mechanism is exhausted, consciousness is lostconsciousness is lost..

55. Aphasias
• Speech and language comprehension are
tasks that engage a large part of the
cerebral cortex. For this reason, lesions in
various parts of the cortex may lead to an
impairment of speech and of language
comprehension.
• Simply put, spoken language is first
perceived in the primary auditory cortex (7)
and then in the sensory speech center
(Wernicke’s area, marked in light blue).
Written words are transmitted via the
primary (gray-blue) and secondary (dark
blue) visual cortex to area 39, where
acoustic, optical, and sensory perceptions
are integrated. When writing, the premotor
cortex is activated via the arcuate
fasciculus of the premotor cortex that, in
turn, activates the motor cortex via the
basal ganglia and the thalamus. In right-
handed people the structures involved are
predominantly localized in the left
hemisphere, and speech disorders
(aphasia) are almost always the result of
lesions in the left hemisphere.
• Each of the above-mentioned structures
can cease functioning, for example, due to
traumatic or ischemic damage. Depending
on which cerebral area is affected,
abnormalities characteristic for each will
develop.

56. Broca’s aphasiaBroca’s aphasia
• Broca’s aphasia is caused by a lesion of the
motor speech center in area 44 and the
neighboring areas 9, 46, and 47.
• Spontaneous speech (verbal output) is
grammatically incorrect and the patient typically
communicates by using single words and is
incapable of repeating someone else’s words
(impaired repitition ability).
• Language comphrehension is not, or less
markedly, impaired. As a rule patients cannot
write normally. However, if the lesion is limited to
area 44, the ability to write is preserved (a rare
disorder, called aphemia).

57. Wernicke’s aphasiaWernicke’s aphasia
 Wernicke’s aphasiaWernicke’s aphasia results from a lesion in theresults from a lesion in the sensorysensory
speech regionspeech region, i.e., in the, i.e., in the posterior portion of the temporalposterior portion of the temporal
gyrusgyrus of theof the auditory association cortexauditory association cortex (area 22) and/or the(area 22) and/or the
supramarginal gyrussupramarginal gyrus (area 40).(area 40).
 Language comprehensionLanguage comprehension isis
impaired in these patients.impaired in these patients.
At the same time they alsoAt the same time they also
lose the ability to repeatlose the ability to repeat
words spoken by somebodywords spoken by somebody
else.else.
 Spontaneous speechSpontaneous speech isis
fluent; sometimes patientsfluent; sometimes patients
speak all the timespeak all the time
((logorrhealogorrhea). However, in). However, in
doing so they may makedoing so they may make
occasional phonetic (“spill”occasional phonetic (“spill”
instead of “spin”) orinstead of “spin”) or
semantic errors (“mother”semantic errors (“mother”
instead of “woman”instead of “woman”
[[paraphasiaparaphasia]) or create new]) or create new
words (words (neologismsneologisms).).

58. Aphasia
• In conductive aphasia the connection between sensory and
motor speech center (arcuate fasciculus) is interrupted.
Speech is fluent (although sometimes paraphasic) and
comprehension is good. However, their repetition ability is
greatly impaired. They are also unable to read aloud, even
though they understand the text they read.
• In global aphasia (damage to both the sensory and the motor
centers, e.g., by occlusion of the medial cerebral artery) both
spontaneous speech and comprehension are impaired.
• Anomic aphasia is the result of a lesion in the temporal lobe
in the region of the medial and inferior gyrus. Patients’
speech is largely normal but it is difficult for them to find the
right word for certain objects.
• In achromatic aphasia (lesion at the left inferior temporal
lobe close to temporal-occipital border) the person cannot
name a color (even though it is correctly recognized and
objects can normally be sorted by color).

59. Aphasia
• Transcortical motor aphasia is caused by a lesion in the
anterior inferior frontal lobe near the Broca speech center.
Spontaneous speech is markedly impaired, while repetition
and comprehension are normal.
• Transcortical sensory aphasia occurs after a lesion in the
parietal–temporal association cortex near the Wernicke
speech center or area 39. The patient can speak fluently
and repetition is normal. However, there is a problem
understanding words and finding the right word; reading and
writing are impossible.
• Subcortical aphasia is due to lesions in the region of the
basal ganglia (especially the caudate nucleus) and the
thalamus. There are transient disorders of comprehension
and finding of words.

60. Disorders 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: Declarative, explicit
memory (semantic or episodic) stores memory that can only be
recalled consciously.

61. Disorders of Memory
• To form declarative memory the information first
of all reaches the corresponding association
cortex (e.g., the secondary visual cortex) via the
particular primary sensory cortical area (e.g., the
primary visual cortex). From here, via the
entorhinal cortex (area 28), the information
reaches the hippocampus, which is essential for
long-term storage of declarative memory.
• With mediation from structures in the
diencephalon, basal forebrain, and prefrontal
cortex the item is again stored in the asssociation
cortex. In this way the information is first taken
up, via the sensory memory, by the short-term
memory, which can hold on to the content for
only a few seconds to minutes.
• The information can be transferred to the long-
term memory, for example, through being
rehearsed. Such rehearsal is not an essential
precondition for the formation of long-term
memory, however.`

63. AmnesiaAmnesia
• 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.

64. 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.

65. Disorders of MemoryDisorders of Memory
TheThe amygdalaamygdala is important inis important in
conditioningconditioning anxiety reactionsanxiety reactions. It. It
receives its information from thereceives its information from the
cortexcortex andand thalamusthalamus andand influencesinfluences
motor and autonomic functionsmotor and autonomic functions
(e.g., muscle tone, palpitations(e.g., muscle tone, palpitations
[awareness of tachycardias], goose-[awareness of tachycardias], goose-
pimples)pimples) via the reticular formationvia the reticular formation
and hypothalamusand hypothalamus..
Removal of the amygdalaRemoval of the amygdala (e.g.,(e.g.,
by trauma or opiates)by trauma or opiates) cancelscancels
conditioned anxiety reactionsconditioned anxiety reactions..
Bilateral removal of the amygdalaBilateral removal of the amygdala
with portions of the hippocampuswith portions of the hippocampus
and temporal lobe results inand temporal lobe results in
amnesia and disinhibited behavioramnesia and disinhibited behavior
((Klüver–Bucy syndromeKlüver–Bucy syndrome).).

67. Clinical Features of DementiaClinical Features of Dementia
 DementiaDementia is anis an acquiredacquired decline in intellectual functiondecline in intellectual function resulting inresulting in
loss of social independenceloss of 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.

68. 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

69. Alzheimer’s Disease
• The defective gene on chromosome 19,
for example, codes for apolipoprotein E
(ApoE 4), the relevant gene on
chromosome 21 for a protein (β-
amyloid precursor) that can be broken
down to small amyloid peptides. These
can on their own bunch themselves
together into protein fibrils 7–10nm long.
These amyloid fibrils can then form
aggregates, 10 μm to several hundred
μm in diameter (senile plaques), that
are frequently found in the brain of
patients with Alzheimer’s disease. In
addition to extracellular amyloid, these
plaques contain distorted dendrites and
axons with abnormal intracellular
neurofibrils. The formation of these
atypical elements of the cytoskeleton
apparently precedes the death of the
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.

70. • A consequence of the degenerative
changes is an increased loss of
cerebral functions.
• The disease typically begins
insidiously with subtle deficits of
memory, neglect of appearance
and body hygiene, phases of
confusion, and taking wrong
decisions.
• As the disease progresses,
anterograde amnesia will be
followed by impairment of past
memories as well as procedural
memory.
• Lesions in the limbic system
express themselves alternately
through restlessness and lethargy.
• Motor deficits (speech disorders,
abnormal muscle tone, ataxia,
hyperkinesia, myoclonus) occur
relatively late.
Alzheimer’s Disease

74. • Creutzfeldt–Jakob
disease, possibly
caused by prions
(proteinaceous
infectious particles), is
a neurodegenerative
disease that, in
addition to motor (e.g.,
ataxia) and
psychogenic
disorders, also leads
to dementia.
Creutzfeldt–Jakob disease

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