2. Seizures
• Definition
– Disorderly excessive discharge of electrical
energy within the neurons of the CNS
• Transient alteration in brain function
– Etiology
• Metabolic disorders: hypoglycemia, hyponatremia
• Hypoxia
• Degenerative disorders
• Infections
• Genetic
• Brain Mass
• Trauma
• Idiopathic
3. Seizures
• Pathophysiology
– Loss of directionality of impulse
– Primary abnormality may be membrane defect
leading to the instability in resting potential,
abnormalities of calcium or potassium, defects
in GABA inhibitory system
– Neurons under electron microscope look bare
with abnormal dendritic processes
4. Seizures
• Seizure initiation
– Firing of abnormal group of neurons will gradually increase in
intensity; threshold reached the discharge can spread through
the cortex, thalamus, and brain stem = TONIC phase
• Muscle contraction with increased tone
• LOC and possible ANS manifestations: brief apnea
– CLONIC phase begins as inhibitory neurons in the cortex,
thalamus, and basal ganglia begin to interrupt the cortical
stimulation
• Alternating contraction and relaxation of muscles
– Increased oxygen and ATP use
• 250% increase in ATP; cerebral oxygen consumption up 60%
• If severe = secondary hypoxia, acidosis (lactic acid)
– Progressive brain injury and destruction
5. Seizures
• Classifications
– Generalized seizures
• Tonic-Clonic (Grand mal)
– Often preceded by an aura
– Abrupt loss of consciousness is followed by tonic
contractions that occur for several seconds
– Alternating contraction/relaxation = tonic-clonic phase
– Neuronal exhaustion with termination of seizure
» Low energy stores
– Stupor or coma for about 5-15 minutes
» Postictal state
– Gradual re-awakening with amnesia of the event
6. Seizures
• Generalized
– Absence (petit mal – old term)
• Occurs in childhood usually after age 4
• Characterized by a brief alternation in
consciousness that can last 5-10 seconds
– Eyes become vacant
– Lips may droop or twitch
• Child immediately resumes activities after seizure
– No postictal state
7. Seizures
• Generalized
– Myoclonic or infantile spasms
• Usually affects children 3 months to 2 years old
– Characterized by flexor spasms of the
extremities and head
• Injury from falling can occur
– Lasts for seconds and can present in clusters
– Usually associated with metabolic,
degenerative, or structural disorders
8. Seizures
• Generalized
– Atonic
• Sudden loss of consciousness
– Individual falls to ground due to loss of postural control
• Partial
– Simple
• Focal motor
– Jacksonian: seizure spreads to adjacent areas after the initial
clonic movement increases
» May begin at finger and move up arm
– Occasionally can have focal motor without Jacksonian march
(progression)
• Focal sensory
– Lesion in the sensory cortex with expression of sensory
changes in the area that is stimulated
» Numbness & tingling of lips, finger, or toes
» Smells or sounds
9. Seizures
• Partial
– Complex
• Temporal lobe
– Impaired consciousness
• Bizarre behavior and exaggerated emotions and
inappropriate verbal responses
– Illusions, hallucinations
• Can interact with environment but may have
inappropriate movements
– May continue to drive or other complex activity
10. Alterations in Cognition
• Data processing defects
– Agnosia
• Failure to recognize form and nature of objects
– Can be tactile, visual, or auditory
• Dysfunction in the primary sensory or interpretive areas of
the cerebral cortex
– Dysphasia
• Impairment in the comprehension or production of language
– Expressive – can’t express thought verbally
– Receptive – can’t understand speech
• Usually due to CVA
– Middle cerebral artery and its branches
11. Alterations in Cognition
• Acute confusional states
– Etiology: associated with delirium and can be caused
by
• Nervous tissue injury
• Toxins exposure
• Drug intoxication
• Metabolic disorders
– Clinical manifestations
• Decreased attention
• Inability to concentrate
• Restlessness
• Poor appetite
• Misperception
• Hallucinations
12. Alterations in Cognition
• Dementia
– Progressive failure of multiple cerebral
functions
– Reduction in intellectual function, decreased
orientation, recent memory loss, decreased
language function, change in behavior
– Etiology: trauma, vascular disorders,
infections, and Alzheimer’s Dz
• Vascular – Lewy Bodies, Lacunar infarcts
13. Alterations in Cognition
• Dementia
– Pathophysiology
• Multiple infarcts with actual destruction of cortical
tissue
• Decrease in NT Acetylcholine with abnormalities in
amyloid production and deposition
• See table 16-18 on page 553
14. Alzheimer’s Disease
• Severe cognitive dysfunction
– Etiology:
• Loss of neurotransmitter stimulation by choline
acetyltransferase
• Mutation of encoding amyloid precursor protein
• Abnormalities in apolipoprotein E (apoE4) which
binds amyloid-beta
• Excessive influx of calcium due to abnormal
activation of N-methyl – D – aspartate receptors
• Other chromosomal abnormalities linked to early
and late onset FAD
15. Alzheimer’s Disease -
pathogenesis
• Each of the etiologies are
linked to the aggregation and
precipitation of insoluble
amyloid in the form of plaques
in brain tissue and blood
vessels
• There may be a lysosomal
breakdown of amyloid where
beta amyloid, a neurotoxin, is
the end product
• It is thought once amyloid
plaques form, complement
proteins attach and attract
microglia
– Release toxins to try to
destroy the plaque
• Tau proteins detach from
microtubules and form
neurofibrillary tangles
16. Alzheimer’s Disease
• Clinical manifestations
– Forgetfulness
– Loss of recent memory
– Loss of attention
– Decreased abstract
thinking
– Decreased cognitive and
intellectual function
– Irritability, confusion,
disorientation
– Mood swings
17. Cerebral Hemodynamics
• Definitions
– Cerebral blood volume (CBV): amount of
blood in cranial vault. 10%
– Cerebral blood flow (CBF): controlled by
localized metabolic needs associated with
changes in O2 and CO2
• 15-20% of cardiac output
– Cerebral perfusion pressure (CPP): pressure
required to perfuse cerebral cortical cells
• CPP = MAP - ICP
18. Cerebral Hemodynamics
• Intracranial pressure (ICP)
– Normal value 5-15 mm Hg
– Increasing ICP etiology:
• Increased content (brain mass)
• Increased interstitial fluid (cerebral edema)
• hemorrhage
• Increased CSF
– Pathophysiology
• When there is a change in one of the above there will be an
increase in ICP
• Adaptation:
– Initially the body will decrease the CSF in order to keep ICP in
normal range
19. Cerebral Hemodynamics
• Increasing ICP
– Adaptive responses
• If decreasing the CSF is not effective
– Vasoconstriction of the vasculature and external
compression of the venous system to decrease in ICP
– Increased vasoconstriction will cause stage 1 intracranial
HTN but there will not be an increase in ICP if the
adaptation is effective
– As ICP reaches MAP there will be a marked reduction in
cerebral blood flow and increased hypoxia
– Systemic HTN will occur in order to continue to perfuse
the brain during high ICP
20. Cerebral Hemodynamics
• Increasing ICP continues
– When compensatory mechanisms of reabsorbed CSF,
vasoconstriction of cerebral arteries, venous
compression, and increased SBP fails:
• ICP: dramatic rise in short time period; ICP > MAP
– Marked hypoxia will increase inflammation = increased cerebral
edema = marked deterioration in the patient’s condition
– Brain tissue will shift and herniate under or through bony
structures within the skull:
» Falx cerebri, tentorium, tentorial notch, foramen magnum
– Coma and death
21. Cerebral Hemodynamics
• Cerebral edema
– Definition: increased fluid content in the brain
– Types
• Vasogenic – increased permeability of the capillary
endothelium after injury to the vascular structure
with disruption of the blood brain barrier
– Leakage of plasma proteins into interstitial tissue
» Increased water content in the parenchyma = edema
– Increased edema = increased hypoxia = increased
edema cycle (white matter)
22. Cerebral Hemodynamics
• Cerebral edema
– Types (cont.)
• Cytotoxic (metabolic) – toxic factors directed affect
cellular elements of neuronal, glial, or endothelial
cells with failure of active transport systems,
– Blood brain barrier is intact
– Failure of the Na-K ATPase pump
» Cells will lose K and gain a lot of Na
» Water follows by osmosis
» Cells swell (primarily gray matter)
– May increase vasogenic edema
23. Cerebral Hemodynamics
• Cerebral edema
– Types (cont.)
– Ischemic – cerebral infarction
• Release of lysosomal enzymes with destruction of cells
– Initiates both vasogenic and cytotoxic mechanisms
» Increased membrane permeability and active transport
failure
– Interstitial – associated with hydrocephalus
• Increased amount of CSF
– Ependymal cells moves CSF from ventricles to extracellular
spaces of the brain tissue
» Hydrostatic pressure in white matter around the ventricles
increase
25. Traumatic Brain Injury
• Types of TBI:
– Blunt (closed) trauma: head striking hard
surface or rapidly moving object
• Dura mater remains intact
– Open (penetrating) trauma: mechanism of
injury may be the same but there is a break in
the dura mater
• Brain tissue exposed to environment
26. Traumatic Brain Injury
• Definitions:
– Coup injury: injury directly below the area of trauma
– Contrecoup: occurs on the opposite side of the injury
– Focal brain injury: specific grossly observable brain
lesion with:
• Cortical contusions
• Epidural hemorrhage
• Subdural hematoma
• Intracerebral hematoma
– Diffuse axonal injury (DAI): diffuse injury due to
acceleration/deceleration
• Brain experiences shearing, tearing, or stretching of nerve
fibers
28. Traumatic Brain Injury
• Focal brain injury
– Pathophysiology: force of impact produces
contusions due to the compression of the skull
at the point of impact and a rebound effect
– Contusion is associated with hemorrhage,
infarction, cerebral edema, and increasing
ICP
29. Traumatic Brain Injury
• Focal brain injury
– Associated bleeding can cause:
• Epidural hematomas – arterial bleeding between the dura
mater and skull
– Most common arterial tear is in the middle meningeal artery
» Lateral shift and uncal herniation
• Subdural hematoma – venous bleeding into the subdural
space; acute or chronic presentations
– Increase ICP
• Intracerebral hematoma – injury to smaller vessel within the
brain
– Hematoma acts like expanding mass with increasing ICP
30. Traumatic Brain Injury
• Focal brain injury
– Clinical manifestations
• Immediate loss of consciousness
– No longer than 5 minutes
• Brief period of bradycardia, decreased BP
• Epidural hematoma Hx: period of LOC followed by
period of lucidity and potential for rapid
deterioration depending on level of this arterial
bleeding
• Subdural hematoma Hx: HA, drowsiness,
restlessness, agitation, slowed cognition, and
confusion which can progress to herniation
32. Traumatic Brain Injury
• Diffuse brain injury
– Etiology
• Usually results for shaking, rotational effect, high levels of
acceleration and deceleration
– Causes shearing, tearing, stretching of axons
» Most common in the frontal and temporal axonal tracts
• Diffuse brain injury
– Types
• Mild concussion: temporary interruption in axonal function
resulting in memory loss and confusion
• Classic cerebral contusion: diffuse cerebral disconnections
that result from neurological dysfunction without anatomical
disruption.
– LOC up to 6 hours
33. Traumatic Brain Injury
• Diffuse brain injury
– Types (cont.)
• Mild DAI: posttraumatic coma lasting 6-24 hours
with resultant cognitive, psychological, and
sensorimotor deficits
• Moderate DAI: widespread disruption with actual
tearing of some axons. Prolonged coma > 24
hours with incomplete recovery
• Severe DAI: major brain stem and axonal damage
associated with prolonged coma if patient survives
36. Cerebrovascular
Disorders
• Types of strokes
– Thrombotic Stroke:
• Arterial occlusion caused by thrombi formed in
the vessels supplying the brain or in the
intracranial vessels
• Etiology
– Atherosclerosis
– Inflammation as in arteritis
– Increased coagulation
– Decreased cerebral blood flow
37. Cerebrovascular
Disorders
• Thrombotic Strokes
– TIA: transient ischemic attacks caused by an
intermittent blockage of vessel or spasm
causing clinical manifestations that clear
within 24 hours
– Stroke in evolution: intermittent progression
of clinical manifestations over hours or days
– Completed stroke: Stroke has reached
maximum destructiveness
38. Cerebrovascular
Disorders
• Embolic Stroke
– Fragments that break from a thrombus
formed outside of the brain (examples heart,
aorta, common carotid)
– Risk factors
• Atrial fibrillation
• Endocarditis
• Valve prosthesis
• Fat emboli secondary to long bone fractures
39. Cerebrovascular
Disorders
• Hemorrhagic Stroke
– Risk factors
• Hypertension
• Malformations of cerebral vasculature
• Bleeding into a tumor
• Anti-coagulation
• Lacunar Stroke
– Micro-infarcts that involve the small
perforating arteries that are associated with
hypertension and diabetes
40. Cerebrovascular
Disorders
• Cerebral Infarction
– Pathophysiology
• Infarction is associated with hypoxia of tissues
and the following cellular events:
– Altered cell membranes with influx of calcium, failure
of the mitochondria, alterations in the sodium and
potassium pump function, cerebral edema, with fall in
pH
– Cerebral edema reaches it maximum at 72 hours
– Clinical manifestations are dependent upon the
localization of the stroke
– See Table 17-6 page 604-605
41. Cerebrovascular
Disorders
• Intra-cranial Aneurysms
– Definition: weakness in the vessel wall
• Etiology
– Congenital malformation
– Arteriosclerosis
– TraumaInfection
– Cocaine use
• Types:
– Saccular: gradual growth over time of sac in the vessel
walls
– Fusiform: greater than 25 mm and result from diffuse
arteriosclerosis. Commonly found in the basilar arteries or
terminal internal carotids
42. Aneurysm
• Intracranial Aneurysms
No Clinical manifestations
– until they rupture or
increase in size and put
pressure on surrounding
brain structures
43. Cerebrovascular
Disorders
• Subarachnoid.Hemorrhage
– Definition: bleeding into the subarachnoid space
– Risk factors
• Hypertension
• AV Malformations
• Trauma
– Pathophysiology
• Blood enters the subarachnoid space, increases inflammation,
impairs cerebral spinal fluid reabsorption, increases intracranial
pressure with a decrease in cerebral perfusion pressure
– Clinical manifestations:
• Ruptured vessel with severe, throbbing explosive headache, n/v,
motor deficits, and loss of consciousness
• Increased ICP, meningeal irritation
45. Cerebrovascular
Disorders
• Vascular Malformations
– Types:
• Arteriovenous malformations: arteries feed
directly into veins through a tangle of malformed
vessels. Increased incidence of bleeding
• Cavernous Angiomas: sinusoidal collections of
blood vessels without brain tissue interspersed.
Rarely bleed
• Capillary telangiectasis: dilated capillaries
with interspersed normal brain tissue. Bleed
only rarely and are associated with Rendu-
Oster-Weber disease
46. • Put picture of AV malformation here – try
to find all three types
48. Headache
• Migraine
– Pathophysiology
• Theories
– Vascular theory: abnormalities in cerebral blood flow with
vasoconstriction during the during the aura phase and
vasodilatation during the headache phase. Blood flow is
impaired but research does not support a reduction that
could be responsible for the development of the common
clinical manifestations
– Cortical spreading depression: reduction in brain and
electrical activity with depressed blood flow, release of
potassium and hydrogen ions with stimulation of sensory
neurons
49. Migraine Headache
• Pathophysiology
– Theories
• Serotonergic and neurotransmitter alteration
– Increased release of serotonin, norepi, subst P that activates
neurotransmissions to the cerebral arteries
» Altering blood flow
» Increased inflammation
– Phases
• Trigger phase
• Aura with inhibition of cortical activity and reduction in blood
flow
• Release of vasoactive neuropeptides, ionic alterations,
platelet release of serotonin, and degranulation of mast cells
• Activation of the locus ceruleus and excitation of the
trigeminal nuclei resulting in dilation of dural arteries
50. Headache
• Cluster Headaches
– Etiology/Pathophysiology
• Unknown
– Clinical Manifestations
• Lacrimation
• Reddening of the eye
• Nasal stuffiness
• Eyelid ptosis
• Nausea and vomiting
• Pain referred to midface and teeth
51. Headache
• Tension
– Pathophysiology
• Central mechanism: involves hypersensitivity of
the pain fibers from the trigeminal nerve with
increased pain
• Peripheral mechanism: related to contraction of
the jaw and neck muscles
• Likely occurs on a continuum with migraine
headaches and most people will have both at
one time or another
52. CNS Infections
• Meningitis
– Definition: infection of the meninges that can
be caused by bacteria, fungi, viruses, or
parasites
– Bacterial:
• Most common causes:
– Pneumococcus (Strep pneumoniae)
– Meningococcus (Neisseria meningitdis)
• Most common spread is by blood stream from
the extracranial site of infection
53. CNS Infections
• Meningitis
– Viral
• Infection that is most likely limited to the meninges
• Can be caused by all of the common upper respiratory
viruses
– Fungal
• More insidious in its onset and occurs most often in
individuals who are immunocompromised
• Infection with coccidiomycosis, histoplasmosis,
cryptococcosis are the most common
• Tuberculosis
– Increased in immunocompromised individuals
54. CNS Infections
• Pathophysiology
– Entry of the bacteria through the choroid plexus
– Toxins stimulate inflammatory response
– Increased permeability of the meningeal vessels with
movement of white blood cells into the subarachnoid
space
– Exudate production with potential for obstruction of
arachnoid villi and the production of hydrocephalus
– Edema of tissue with increased intracranial pressure
– Fungi can also cause the formation of granulomas,
arteritis, thrombosis, and hydrocephalus
57. Degenerative
Neurological Diseases
• Parkinson‘s
– Degenerative disease of the basal ganglia involving
the dopaminergic neurons (substantia nigra and
others)
– Types
• Primary: idiopathic
• Secondary: impact of toxins, drugs, infection
– Pathophysiology
• Cerebral atrophy and neuronal loss
• Degeneration of the dopaminergic neurons of the
nigrostriatal pathway
• Lewy bodies and intracytoplasmic eosinophila inclusion
bodies are found in the neurons that have not been
destroyed
58. Degenerative
Neurological Diseases
• Parkinson‘s Disease
– Pathophysiology
• Depletion of dopamine which is a inhibitory
neurotransmitter is responsible for the
development of the typical clinical
manifestations
• Imbalance of dopaminergic (inhibitory) and
cholinergic (excitatory) activity which is
responsible for the hypertonia and akinesia
59. Degenerative
Neurological Diseases
• Parkinson's Disease
– Clinical Manifestations
• Resting tremor
• Rigidity
• Akinesia
• Bradykinesia
• Postural Abnormalities:
– Involuntary flexion of the head and neck
– Shuffling gait secondary to disorders in equilibrium
– Difficulty in maintaining balance or righting when balance is
lost
• Depression
• Dementia
• Bradyphrenia
60. Degenerative
Neurological Diseases
• Multiple Sclerosis
– Progressive demyelinating disease of the central
nervous
system
• Etiology: viral insult in a genetically susceptible
individual causes an increased immune response with an
immunogenic destruction of the myelin
– Pathophysiology
• Immune system response to environmental challenge
• Immune cells arriving at the myelin sheath excrete glutamate
which is then ingested by oligodendrocytes
• Plaques and diffuse CNS lesions produce slowing of
conduction initially with a progressive conduction block
• Glial scarring with degenerations of axons
61. Degenerative
Neurological Diseases
• Multiple Sclerosis
– Types by classifications:
• Relapsing Remitting: characterized by distinct periods of
Improvement and acute attacks
• Primary Progressive: steady worsening of symptoms
from the beginning
• Secondary Progressive: begins with periods of
remission and relapses but becomes steadily more
progressive
• Progressive Relapsing: steadily progressive but has
periods of acute attacks as well
62. Degenerative
Neurological Diseases
• Multiple Sclerosis
– Clinical Manifestations (Syndromes)
• Spinal type: spastic ataxia, deep sensory changes
in the extremities, and bowel and bladder
symptoms, weakness and numbness
• Cerebellar: motor ataxia, hypotonia, asthenia,
nystagmus
• Mixed: optic neuritis, diplopia, vertigo, cerebellar
signs, visual field defects,
64. Degenerative
Neurological Diseases
• Amyotrophic Lateral Sclerosis
– Involves upper and lower motor neuron degeneration
– Predominant lower motor neuron dysfunction in the
early stages
– Usually begins in one muscle group
– Lower motor neuron symptoms
• Flaccid paralysis
• Hypoactive reflexes
• Atrophy
• Fasciculations
65. Degenerative Neurological Diseases
• Amyotrophic Lateral Sclerosis
– Upper motor neuron syndromes
– Spastic paresis
– Atrophy
– Hyperactive deep tendon reflexes
– Clonus
– Clinical manifestations
• Progressive muscle weakness
– Paresis begins in one muscle group
– Muscle groups – asymmetrically affects
– Gradually affects all striated muscles
» Exceptions: extraocular and heart
– Spastic paresis may be masked by flaccid paresis
66. CNS Tumors
• Primary
– Astrocytomas
• most common tumor that grows by expansion and
infiltration, located within the cerebellum
– Most common lobes: frontal, temporal, and parietal
– Gradual growth and increase in ICP
– Often found initially with the onset of a new seizure
– Oligodendrogliomas
• less common tumor that is slow growing and found
in the frontal lobe
– Ependymomas
• arise from the fourth ventricle
Increased incidence in children
68. Diseases of the Neuromuscular
Junction
• Myasthenia Gravis
– Etiology: autoimmune disease mediated by the anti-
acetylcholine receptor antibodies that act at the
neuromuscular junction
– Pathophysiology
• Defect in nerve impulse transmission at the neuromuscular
junction
• Post synaptic receptors on the muscle cell membrane are
selectively destroyed by the immune system production of
receptor antibodies
• Decreased receptor sites, decreases the effectiveness
of ACH at the neuromuscular junction, with slowing of
transmission
69. Diseases of the Neuromuscular
Junction
• Myasthenia Gravis
– Clinical Manifestations
• Insidious onset
• Fatigue and weakness with increased symptoms
after exercise
• Diplopia, ptosis, ocular palsies
• facial droop, difficulty swallowing, weight loss
• Respiratory depression, increasing weakness of
the legs and arm muscles (proximal)
