Neurological Neurological PathophysiologyPathophysiology

11

Edema in the CNSEdema in the CNS Increase in tissue mass that results from Increase in tissue mass that results from

the excess movement of body fluid from the excess movement of body fluid from the vascular compartment or its abnormal the vascular compartment or its abnormal retention in the tissue.retention in the tissue.

Why is this a special problem in the brain Why is this a special problem in the brain and spinal cord?and spinal cord?

Enclosed spaceEnclosed space Lack of lymphaticsLack of lymphatics Lack of anastomoses in venous drainageLack of anastomoses in venous drainage

22

Vasogenic edemaVasogenic edema Occurs when the blood-brain barrier is Occurs when the blood-brain barrier is

upsetupset– Inflammation due to infectionInflammation due to infection– Toxic agents that damage capillary Toxic agents that damage capillary

endotheliumendothelium– Abnormal capillaries associated with Abnormal capillaries associated with

malignant neoplasmmalignant neoplasm Leakage of proteins Leakage of proteins fluid into interstitium fluid into interstitium

→→ swelling swelling Plasma filtrate accumulation alters ionic Plasma filtrate accumulation alters ionic

balance and impairs functionbalance and impairs function33

Cytotoxic edemaCytotoxic edema Intracellular phenomenonIntracellular phenomenon HypoxiaHypoxia

– Cardiac arrestCardiac arrest– Near drowningNear drowning– StrangulationStrangulation– Focal edema due to blockage of an end Focal edema due to blockage of an end

arteryartery Toxic substances that:Toxic substances that:

– Impair sodium/potassium pumpImpair sodium/potassium pump– Impair production of ATPImpair production of ATP

44

In practice, swelling often caused by In practice, swelling often caused by bothboth

Treatment is differentTreatment is different If swelling is due to cytotoxicity, can If swelling is due to cytotoxicity, can

give I.V. bolus of a hypertonic solution give I.V. bolus of a hypertonic solution such as mannitol to draw water into such as mannitol to draw water into the vasculature and out of the brainthe vasculature and out of the brain

If the cause is vasogenic would this If the cause is vasogenic would this help?help?

No! would draw fluid into interstitial No! would draw fluid into interstitial space and increase swelling!!space and increase swelling!!

55

Increased intracranial pressure Increased intracranial pressure (IICP)(IICP)

Normal intracranial pressure is 5-15 mm Normal intracranial pressure is 5-15 mm HgHg

May be due to:May be due to:– Tumor growthTumor growth– EdemaEdema– Excess cerebrospinal fluidExcess cerebrospinal fluid– HemorrhageHemorrhage

66

Contents of craniumContents of cranium Tissue of the Central Nervous System Tissue of the Central Nervous System Cerebrospinal Fluid (CSF)Cerebrospinal Fluid (CSF) BloodBlood An increase in any one of these increases An increase in any one of these increases

intracranial pressure.intracranial pressure. Clinical hallmarks of IICP:Clinical hallmarks of IICP:

– HeadacheHeadache– VomitingVomiting– Papilledema – swelling of the optic discsPapilledema – swelling of the optic discs

77

88

Since the brain is encased in the cranium, the only way pressure can be relieved is by decreasing cranial contents.

• Most readily displaced is CSF

• If ICP still high, cerebral blood volume is altered:

•Stage 1 – vasoconstriction and external compression of the venous system

•Compensating, so few symptoms

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If ICP continues to increase, may exceed brain’s ability to adjust.

• Stage 2:

•IICP (gradually rising) causes a decrease of oxygenation of neural tissue

•Systemic vasoconstriction occurs to increase blood pressure to get blood to brain

•Clinical manifestations transient: episodes of confusion, restlessness, drowsiness, and slight pupillary and breathing changes

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When ICP begins to = arterial pressure, there is a lack of compensation- beginning decompensation

Stage 3

•Hypoxia and hypercapnia → cytotoxic edema

•Decreasing levels of arousal

•Widened pulse pressure

•May begin Cheynes-Stokes respirations

•Bradycardia – due to increased pressure in carotid arteries

•Pupils small and sluggish

•Surgical or medical intervention needed

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When all compensatory mechanisms have been exhausted:•Stage 4:

•Dramatic rise in ICP in a short time

•Autoregulation is lost, and get vasodilation, further increasing intracranial volume

•↓ cerebral perfusion = severe hypoxia and acidosis

•Brain contents shift (herniate) from area of high pressure to areas of lower pressure ↓ blood flow

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•Small hemorrhages develop

•Ipsilateral pupil dilation and fixation, progressing to bilateral fixed and dilated pupils

•When mean systolic arterial pressure equal ICP, cerebral blood flow ceases

TreatmentTreatment Remove the cause of the IICPRemove the cause of the IICP Mechanical hyperventilation to medicated Mechanical hyperventilation to medicated

and comatose patientand comatose patient Reduce blood pressure through diuretics, Reduce blood pressure through diuretics,

which slows production of CSF and which slows production of CSF and decreases blood-brain volumedecreases blood-brain volume

Drugs, us. Barbiturates to slow brain Drugs, us. Barbiturates to slow brain metabolism and metabolism and ↓↓ effects of hypoxia effects of hypoxia

Emergency craniotomy to relieve pressureEmergency craniotomy to relieve pressure

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1414

Brain TraumaBrain Trauma

Highest risk:Highest risk:– 15 to 30 years of age15 to 30 years of age– Infants 6 mo. to two yearsInfants 6 mo. to two years– Young school age childrenYoung school age children– Elderly personsElderly persons

Male: female = 3:1Male: female = 3:1

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1616

Most likely causes of head injury:

• Transportation accidents

• Falls

• Sports related events

• Violence

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Two major categories of head trauma:

closed (blunt) trauma

open (penetrating) trauma

Open (penetrating) traumaOpen (penetrating) trauma

1818

Break in dura results in exposure of brain tissues to environment.

Results in focal (localized) injury

May be due to skull fracture or wound – intracerebral hematoma

Traumatic pneumocephalus - injury to a nasal sinus that allows air into brain or ventricles - cerebrospinal rhinorrhea

1919

Blunt Head TraumaBlunt Head Trauma

2020

More common than open trauma.

Involves head hitting hard surface or rapidly moving object strikes head

Dura is intact – no brain tissue exposed

May cause focal or diffuse axonal injury (DAI)

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Serious injury decrease due to :Seat belt useImproved management

Mild cerebral Mild cerebral concussionconcussion 75- 90 % of all head injuries75- 90 % of all head injuries

Not severeNot severe Diffuse axonal injury – no visible signs Diffuse axonal injury – no visible signs

on brainon brain May see transient dizziness, paralysis, May see transient dizziness, paralysis,

unconsciousness, unequal pupils and unconsciousness, unequal pupils and shock.shock.

Reactive period: vomiting, Temp 99 -Reactive period: vomiting, Temp 99 -100100oo, rapid pulse, headache, and , rapid pulse, headache, and cerebral irritation lasting 12 -24 hours.cerebral irritation lasting 12 -24 hours.

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Contusions (bruise) : impacts which lead to hemorrhage and possibly hematoma

Coup (strike) – head strikes against object

shearing forces cause small tears in blood vessels (subdural vessels)

edema

severity = force

smaller area = greater force

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Contrecoup (rebound) – brain hits opposite side of skull

shearing forces

and damage opposite to site of impact

2525

Extradural (Epidural) Extradural (Epidural) HematomasHematomas

1-2% of major head injuries1-2% of major head injuries Most common in 20-40 year oldsMost common in 20-40 year olds Often caused by temporal skull Often caused by temporal skull

fracture or injuryfracture or injury Artery is often the source of bleeding Artery is often the source of bleeding Get herniation (shift) of temporal Get herniation (shift) of temporal

lobe of brain through tentorial notchlobe of brain through tentorial notch

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Subdural hematomasSubdural hematomas

10 - 20 % of persons with 10 - 20 % of persons with traumatic brain injurytraumatic brain injury

Develop rapidly (within hours)Develop rapidly (within hours) Typically on top of skullTypically on top of skull Often due to tearing of veins or Often due to tearing of veins or

dural sinusesdural sinuses Acts as an expanding mass Acts as an expanding mass → →

IICPIICP→ → herniation of brainherniation of brain2828

Intracerebral Intracerebral hematomashematomas 2-3% of head injuries2-3% of head injuries

Single or multipleSingle or multiple Usually frontal and temporal lobesUsually frontal and temporal lobes May occur in deep white matterMay occur in deep white matter Small blood vessels injured by Small blood vessels injured by

shearing forcesshearing forces Acts as expanding mass, compresses Acts as expanding mass, compresses

tissue, and causes edematissue, and causes edema May appear 3- 10 days after head May appear 3- 10 days after head

injuryinjury 2929

Clinical manifestations of Clinical manifestations of contusionscontusions

Loss of consciousness, loss of Loss of consciousness, loss of reflexesreflexes

Transient cessation of breathingTransient cessation of breathing Brief bradycardiaBrief bradycardia Decreased blood pressureDecreased blood pressure As hematoma enlarges:As hematoma enlarges: headache, vomiting, drowsiness, headache, vomiting, drowsiness,

confusion, seizure, hemiparesisconfusion, seizure, hemiparesis3030

TreatmentTreatment

Contusions:Contusions:– Control intracranial pressureControl intracranial pressure

Drugs can relieve fluid pressures; Drugs can relieve fluid pressures; may alter Na+ conc. in brain may alter Na+ conc. in brain fluidsfluids

– Manage symptomsManage symptoms hematomas:hematomas:

– Surgical ligationSurgical ligation

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Cerebrovascular Cerebrovascular DiseaseDisease Most frequent of all neurological Most frequent of all neurological

problemsproblems Due to blood vessel pathology:Due to blood vessel pathology:

– Lesions on walls of vessels leading to Lesions on walls of vessels leading to brainbrain

– Occlusions of vessel lumen by thrombus Occlusions of vessel lumen by thrombus or embolusor embolus

– Vessel ruptureVessel rupture– Alterations of blood qualityAlterations of blood quality

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CV disease leads to two types of brain abnormalities :

Ischemia (with or without infarct)

Hemorrhage

Cerebrovascular AccidentCerebrovascular Accident(Stroke)(Stroke)

Clinical expression of Clinical expression of cerebrovascular disease: a cerebrovascular disease: a sudden, nonconvulsive focal sudden, nonconvulsive focal neurological deficitneurological deficit

Incidence: third leading cause of Incidence: third leading cause of death in U.S. – half a million death in U.S. – half a million people a year – one third will die people a year – one third will die from itfrom it

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IncidenceIncidence

Highest risk > 65 years of ageHighest risk > 65 years of age But about 1/3 (28%) are < 65 But about 1/3 (28%) are < 65

years oldyears old Tends to run in familiesTends to run in families More often seen in femalesMore often seen in females More often seen in Blacks, perhaps More often seen in Blacks, perhaps

due to increased incidence of due to increased incidence of hypertensionhypertension

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Three types :Three types :

Global hypoperfusion – shockGlobal hypoperfusion – shock Ischemia – thrombotic and Ischemia – thrombotic and

embolicembolic HemorrhagicHemorrhagic

3636

Risk FactorsRisk Factors Arterial hypertensionArterial hypertension Heart diseaseHeart disease

– Myocardial infarction or endocarditisMyocardial infarction or endocarditis– Atrial fibrillationAtrial fibrillation

Elevated plasma cholesterolElevated plasma cholesterol Diabetes mellitusDiabetes mellitus Oral contraceptivesOral contraceptives SmokingSmoking Polycythemia and thrombocythemiaPolycythemia and thrombocythemia

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Occlusive strokesOcclusive strokes Occurs with blockage of blood vessel Occurs with blockage of blood vessel

by a thrombus or embolusby a thrombus or embolus May be temporary or permanentMay be temporary or permanent Thrombotic stroke:Thrombotic stroke:

– 3 clinical types:3 clinical types: TIAsTIAs Stroke-in-evolutionStroke-in-evolution Completed strokeCompleted stroke

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Transient Ischemic Transient Ischemic AttacksAttacks Last for only a few minutes, Last for only a few minutes,

always less than 24 hoursalways less than 24 hours All neurological deficits resolveAll neurological deficits resolve Symptom of developing Symptom of developing

thrombosisthrombosis

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Causes:Causes: Thrombus formationThrombus formation

– AtherosclerosisAtherosclerosis– ArteritisArteritis– HypertensionHypertension

VasospasmVasospasm Other:Other:

– HypotensionHypotension– AnemiaAnemia– PolycythemiaPolycythemia

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Symptoms depend on Symptoms depend on locationlocation Ophthalmic branch of internal carotid Ophthalmic branch of internal carotid

artery – amaurosis fugax – fleeting artery – amaurosis fugax – fleeting blindnessblindness

Anterior or middle cerebral arteries – Anterior or middle cerebral arteries – contralateral monoparesis, contralateral monoparesis, hemiparesis, localized, tingling hemiparesis, localized, tingling numbness in one arm, loss of right or numbness in one arm, loss of right or left visual field or aphasialeft visual field or aphasia

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TreatmentTreatment Without Tx 80% have a recurrence in Without Tx 80% have a recurrence in

symptoms, and 1/3 go on to have a symptoms, and 1/3 go on to have a full stroke within 5 yearsfull stroke within 5 years

Give anticoagulants prophylactically , Give anticoagulants prophylactically , usually ½ to 1 aspirin / dayusually ½ to 1 aspirin / day

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Stroke-in-evolutionStroke-in-evolution Can have abrupt onset, but develop Can have abrupt onset, but develop

in a step-by-step fashion over in a step-by-step fashion over minutes to hours, occasionally, from minutes to hours, occasionally, from days to weeksdays to weeks

Characteristic of thrombotic stroke or Characteristic of thrombotic stroke or slow hemorrhageslow hemorrhage

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Thrombotic CVAThrombotic CVA Involves permanent damage to brain Involves permanent damage to brain

due to ischemia, hypoxia and due to ischemia, hypoxia and necrosis of neuronsnecrosis of neurons

Most common form of CVAMost common form of CVA Causes: Causes:

– Atherosclerosis assoc. with hypertensionAtherosclerosis assoc. with hypertension– Diabetes mellitus, and vascular diseaseDiabetes mellitus, and vascular disease– TraumaTrauma

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May take years to develop, often May take years to develop, often asymptomatic until major narrowing asymptomatic until major narrowing of arterial lumenof arterial lumen

Anything that lowers systemic B.P. Anything that lowers systemic B.P. will exacerbate symptoms (60 % will exacerbate symptoms (60 % during sleep)during sleep)

Area affected depends on artery and Area affected depends on artery and presence of anastomosespresence of anastomoses

Area affected initially is greater than Area affected initially is greater than damage due to edemadamage due to edema

Infarcted tissue undergoes Infarcted tissue undergoes liquifaction necrosisliquifaction necrosis

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Embolic strokeEmbolic stroke Second most common CVASecond most common CVA Fragments that break from a Fragments that break from a

thrombus outside the brain, or thrombus outside the brain, or occasionally air, fat, clumps of occasionally air, fat, clumps of bacteria, or tumorsbacteria, or tumors

4646

Common causesCommon causes Atrial fibrillationAtrial fibrillation Myocardial infarctionMyocardial infarction EndocarditisEndocarditis Rheumatic heart disease and other Rheumatic heart disease and other

defectsdefects

4747

Impact is the same for thrombotic Impact is the same for thrombotic strokestroke

Rapid onset of symptomsRapid onset of symptoms Often have a second strokeOften have a second stroke

4848

Hemorrhagic StrokeHemorrhagic Stroke Third most common, but most lethalThird most common, but most lethal Bleeding into cerebrum or Bleeding into cerebrum or

subarachnoid spacesubarachnoid space

4949

Causes:Causes: Ruptured aneurysmsRuptured aneurysms Vascular malformationsVascular malformations HypertensionHypertension Bleeding into tumorsBleeding into tumors Bleeding disordersBleeding disorders Head traumaHead trauma

5050

Often a history of physical or Often a history of physical or emotional exertion immediately prior emotional exertion immediately prior to eventto event

Causes infarction by interrupting Causes infarction by interrupting blood flow to region downstream blood flow to region downstream from hemorrhagefrom hemorrhage

Further damage by hematoma or IICPFurther damage by hematoma or IICP Onset less rapid than embolic CVA, Onset less rapid than embolic CVA,

evolving over an hour or twoevolving over an hour or two

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Usually chronic hypertension, and Usually chronic hypertension, and B.P. may continue to riseB.P. may continue to rise

About half report severe headacheAbout half report severe headache In about 70 % hematoma expands, In about 70 % hematoma expands,

destroying vital brain centers, shifts destroying vital brain centers, shifts of brain tissue, and deathof brain tissue, and death

5252

Degenerative DisordersDegenerative Disorders

Progressive neurodisordersProgressive neurodisorders Long-lastingLong-lasting Permanent effectsPermanent effects Many present as syndromesMany present as syndromes No cure, but much researchNo cure, but much research

5353

Alzheimer Disease Alzheimer Disease (Dementia of Alzheimer (Dementia of Alzheimer Type)Type)

5454

Dementia is a loss of Dementia is a loss of ordered neural functionordered neural function Discrimination and attending to stimuliDiscrimination and attending to stimuli Storing new memories and retrieving Storing new memories and retrieving

oldold Planning and delay of gratificationPlanning and delay of gratification Abstraction and problem solvingAbstraction and problem solving Judgement and reasoningJudgement and reasoning Orientation in time and spaceOrientation in time and space Language processingLanguage processing Appropriate use of objectsAppropriate use of objects Planning and execution of voluntary Planning and execution of voluntary

movementsmovements 5555

Course : slow Course : slow progression (5years or progression (5years or more)more) At first affects only short term memory, At first affects only short term memory,

but gradually extends to long termbut gradually extends to long term Many experience restlessnessMany experience restlessness Many patients retain insight, which Many patients retain insight, which

leads to anxiety and depressionleads to anxiety and depression Personality may be lostPersonality may be lost Ultimately, mute and paralyzedUltimately, mute and paralyzed Death comes from infectionDeath comes from infection

5656

Onset may be as young as 50, and Onset may be as young as 50, and incidence increases with age:incidence increases with age:– 6 % of people over 65 years have AD6 % of people over 65 years have AD– Almost half over 85 have ADAlmost half over 85 have AD

Diagnosis is by ruling out all other Diagnosis is by ruling out all other causes –specific diagnosis only by causes –specific diagnosis only by biopsy or autopsybiopsy or autopsy

5757

Pathology restricted to cerebral Pathology restricted to cerebral cortex, hippocampus, amygdala, cortex, hippocampus, amygdala, and another basal nucleus called and another basal nucleus called nucleus of Meynertnucleus of Meynert

Nucleus of Meynert produces Nucleus of Meynert produces Acetylcholine – loss results in Acetylcholine – loss results in impaired neural functionimpaired neural function

5858

PathologyPathology

Pyramidal cells die; loss of white Pyramidal cells die; loss of white mattermatter

Gyri shrink and and ventricles and sulci Gyri shrink and and ventricles and sulci expand – walnut like appearanceexpand – walnut like appearance

Neurofibrillary tanglesNeurofibrillary tangles Neuritic (senile) plaques : filaments, Neuritic (senile) plaques : filaments,

microglia, astrocytes around core of microglia, astrocytes around core of amyloidamyloid

Amyloid angiopathyAmyloid angiopathy5959

6060http://www.ahaf.org/alzdis/about/plaques_tanglesBorder.jpg

6161

www.infoaging.org/ d-alz-8-r-tangles.html

6262http://homepage.psy.utexas.edu/homepage/class/Psy332/Salinas/Disorders%20/Disorders.html

About 10 % of cases are familial, About 10 % of cases are familial, usually early onsetusually early onset

Gene on chromosome 21 – carries Gene on chromosome 21 – carries gene for amyloid proteingene for amyloid protein

Almost all people with Down Almost all people with Down syndrome who live beyond 45 years syndrome who live beyond 45 years develop ADdevelop AD

Also linked to mutations on Also linked to mutations on chromosomes 14 and 19chromosomes 14 and 19

Prions have been isolatedPrions have been isolated

6363

TreatmentTreatment So far resistantSo far resistant May revolve around amyloid proteinMay revolve around amyloid protein See high levels of aluminum – chelating See high levels of aluminum – chelating

agents temporarily arrest or reverse some agents temporarily arrest or reverse some symptomssymptoms

THA(tetrahydroaminoacridine) used THA(tetrahydroaminoacridine) used experimentally – liver toxicityexperimentally – liver toxicity

Arthritics have lower incidence of ADArthritics have lower incidence of AD Therapy centers on problems of failing Therapy centers on problems of failing

cognitive skillscognitive skills6464

Parkinson Disease – Parkinson Disease – movement disordermovement disorder

Described over 180 years ago by Described over 180 years ago by James ParkinsonJames Parkinson

Combination of slowed, reduced Combination of slowed, reduced movements and restless tremoringmovements and restless tremoring

Paralysis agitansParalysis agitans Slowly degenerative CNS disorder Slowly degenerative CNS disorder

affecting 80,000 adults in North affecting 80,000 adults in North AmericaAmerica

6565

Parkinson DiseaseParkinson Disease

Degenerative disease of the basal Degenerative disease of the basal ganglia involving the failure of ganglia involving the failure of dopamine-secreting neurons dopamine-secreting neurons (substantia nigra)(substantia nigra)

Can be primary or secondaryCan be primary or secondary Secondary caused by trauma, Secondary caused by trauma,

infection, neoplasm, atherosclerosis, infection, neoplasm, atherosclerosis, toxins and drug intoxicationtoxins and drug intoxication

6666

6767

Primary Parkinson Primary Parkinson DiseaseDisease

Begins after the age of 40, with peak Begins after the age of 40, with peak age of onset between 58 – 62age of onset between 58 – 62

Course of 10- 20 years – slowly Course of 10- 20 years – slowly progressiveprogressive

More prevalent in males (slightly to More prevalent in males (slightly to 2X)2X)

6868

Substantia nigra – two nuclei in Substantia nigra – two nuclei in midbrainmidbrain

Outflow pathway from basal nuclei to Outflow pathway from basal nuclei to cortex via thalamuscortex via thalamus

Damage impairs flow of motor Damage impairs flow of motor programsprograms

Expressed as difficulty initiating Expressed as difficulty initiating movements, general lack and movements, general lack and slowing of movement (bradykinesia)slowing of movement (bradykinesia)

6969

Loss of feedback loop impairs flow of Loss of feedback loop impairs flow of programs and expresses as resting programs and expresses as resting tremortremor

Most disabling symptoms are muscle Most disabling symptoms are muscle rigidity and bradykinesiarigidity and bradykinesia

Muscle strength is more or less normalMuscle strength is more or less normal Poor balance Poor balance Face becomes immobile and inexpressiveFace becomes immobile and inexpressive Autonomic function is decreased:Autonomic function is decreased:

– orthostatic hypotension, excess sweating, orthostatic hypotension, excess sweating, constipation, etc.constipation, etc.

7070

Some patients suffer dementia Some patients suffer dementia similar to Alzheimer Diseasesimilar to Alzheimer Disease

Not fatal, but shortens life Not fatal, but shortens life expectancyexpectancy

7171

TreatmentTreatment

Active exercise and good nutritionActive exercise and good nutrition Strategies to overcome bradykinesiaStrategies to overcome bradykinesia Only when symptoms are severeOnly when symptoms are severe

are drugs given – levodopaare drugs given – levodopa Side effects: cardiac arrhythmias, Side effects: cardiac arrhythmias,

gastrointestinal hemorrhage, gastrointestinal hemorrhage, psychiatric problems, unpredictable psychiatric problems, unpredictable involuntary movement disordersinvoluntary movement disorders

7272

Possible therapiesPossible therapies

Foreign or autograft of tissue still Foreign or autograft of tissue still experimentalexperimental

Lesions in the subthalamic Lesions in the subthalamic nucleus, thalamus or internal nucleus, thalamus or internal segment of globus pallidus segment of globus pallidus promisingpromising

Stem cell research?Stem cell research?

7373

Multiple SclerosisMultiple Sclerosis

Focal, chronic, progressive, usually Focal, chronic, progressive, usually exacerbating and remitting exacerbating and remitting demyelination of CNS tracts.demyelination of CNS tracts.

Lesions can occur in a wide variety of Lesions can occur in a wide variety of locations and give rise to complex locations and give rise to complex symptomssymptoms

Areas of demyelination are called Areas of demyelination are called plaques, and can occur anywhere plaques, and can occur anywhere oligodendrocytes provide myelin oligodendrocytes provide myelin sheathsheath

7474

OnsetOnset

Onset is between Onset is between 20 and 40 years, 20 and 40 years, rarely before 15 or rarely before 15 or after 50after 50

Females: Males Females: Males 2:12:1

7575

Clinical presentation depends on site Clinical presentation depends on site of lesionof lesion

Involvement of optic nerve produces Involvement of optic nerve produces monocular visual disturbances – first monocular visual disturbances – first symptom in ¼ of patientssymptom in ¼ of patients

Half of people with optic neuritis are Half of people with optic neuritis are diagnosed with MSdiagnosed with MS

7676

Common symptoms:Common symptoms:

Double visionDouble vision Tingling in the back and anterior Tingling in the back and anterior

thigh upon neck flexion – thigh upon neck flexion – Lhermitte’s signLhermitte’s sign

Symptoms worsen when patient Symptoms worsen when patient becomes heated – Uhthoff’s signbecomes heated – Uhthoff’s sign

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DiagnosisDiagnosis

CSF obtained by lumbar puncture CSF obtained by lumbar puncture shows slight increase in protein; on shows slight increase in protein; on electrophoresis shows specific electrophoresis shows specific banding pattern – antibodies within banding pattern – antibodies within CSF suggest immune reactionCSF suggest immune reaction

Changes in velocities of visual and Changes in velocities of visual and auditory pathwaysauditory pathways

Plaques visible on MRIPlaques visible on MRI7878

CauseCause

Myelin undergoes breakdown and Myelin undergoes breakdown and phagocytic destruction – antibodies phagocytic destruction – antibodies may play a rolemay play a role

Decreased signal conduction due to Decreased signal conduction due to edema and demyelination that edema and demyelination that exposes potassium channels that exposes potassium channels that short-circuit signal (edema resolves short-circuit signal (edema resolves and have partial remyelination)and have partial remyelination)

7979

Epidemiology hints at interaction Epidemiology hints at interaction between a viral illness in the teen between a viral illness in the teen years and a genetic predispositionyears and a genetic predisposition

Growing up in northern temperate Growing up in northern temperate climates increases riseclimates increases rise

Non Asian heritage increases riskNon Asian heritage increases risk

8080

CourseCourse Pattern of exacerbation and Pattern of exacerbation and

remissionremission Stresses can trigger exacerbation: Stresses can trigger exacerbation:

infection, medication, stress, fatigueinfection, medication, stress, fatigue Course is unstable and unpredictableCourse is unstable and unpredictable 10 % undergo severe, rapid 10 % undergo severe, rapid

progressive deteriorationprogressive deterioration Some have died with 7 months of Some have died with 7 months of

first symptom due to acute brain first symptom due to acute brain inflammation and infectioninflammation and infection 8181

A significant number never severely A significant number never severely incapacitatedincapacitated

Some experience only a single Some experience only a single episodeepisode

Death is usually attributable to Death is usually attributable to complications of MS (infections due complications of MS (infections due to decreased function)to decreased function)

8282

SymptomsSymptoms

Increased urinary frequencyIncreased urinary frequency Lesions in frontal or temporal lobes can Lesions in frontal or temporal lobes can

cause emotional outburstscause emotional outbursts Depression and euphoria can be Depression and euphoria can be

problemsproblems Unpredictable progression taxes ability Unpredictable progression taxes ability

to copeto cope Occasionally, plaques can cause Occasionally, plaques can cause

paraplegia or quadriplegiaparaplegia or quadriplegia8383

TherapiesTherapies

Only corticosteroids and ACTH Only corticosteroids and ACTH appear to have effects – reduce appear to have effects – reduce the duration of exacrerbation, but the duration of exacrerbation, but have no impact on long term have no impact on long term outcomeoutcome

Interferon Interferon ββ Maintaining a healthy lifestyle Maintaining a healthy lifestyle

and outlookand outlook8484

Acute Acute encephalopathies:encephalopathies: Reye’s SyndromeReye’s Syndrome First recognized in 1963First recognized in 1963 Characterized by encephalopathy and Characterized by encephalopathy and

fatty changes in several organs, esp. fatty changes in several organs, esp. liverliver

Incidence has declined in past 20 Incidence has declined in past 20 years due to awareness of ingestion of years due to awareness of ingestion of aspirin during illness and development aspirin during illness and development of Reye’s syndrome.of Reye’s syndrome.

8585

Reye’s syndromeReye’s syndrome Typically develops in a healthy child of 6 Typically develops in a healthy child of 6

mo. to 15 years recovering from mo. to 15 years recovering from varicella, influenza B, upper respiratory varicella, influenza B, upper respiratory tract infection, or gastroenteritis.tract infection, or gastroenteritis.

Stage I: vomiting, lethargy, drowsinessStage I: vomiting, lethargy, drowsiness Stage II: disorientation, delirium, Stage II: disorientation, delirium,

aggressiveness and combativeness, aggressiveness and combativeness, central neurological hyperventilation, central neurological hyperventilation, shallow breathing, hyperactive reflexes, shallow breathing, hyperactive reflexes, stuporstupor

8686

Reye’s syndromeReye’s syndrome Stage III: Insensitivity to pain, coma, Stage III: Insensitivity to pain, coma,

hyperventilation, rigidityhyperventilation, rigidity Stage IV: deepening coma, loss of Stage IV: deepening coma, loss of

ocular reflexes; large, fixed pupils; ocular reflexes; large, fixed pupils; divergent eye movementsdivergent eye movements

Stage V: seizures, loss of deep tendon Stage V: seizures, loss of deep tendon reflex, flaccidity, respiratory arrestreflex, flaccidity, respiratory arrest

Mortality is 10 or moreMortality is 10 or more Formerly 40 to as high as 80%Formerly 40 to as high as 80% In a few cases death is due to liver In a few cases death is due to liver

failurefailure8787

Reye’s syndromeReye’s syndrome Cause:Cause:

– May have a genetic predispositionMay have a genetic predisposition– May be due in part to exhaustion of May be due in part to exhaustion of

glycogen stores and use of fatty acids -glycogen stores and use of fatty acids -Mitochondrial injuryMitochondrial injury

Treatment: Treatment: – Aggressive intensive careAggressive intensive care– Treatment for brain edema and IICPTreatment for brain edema and IICP– Fluids I.V. and control of blood Fluids I.V. and control of blood

electrolyteselectrolytes– Prevent hyperthermiaPrevent hyperthermia 8888

Seizure disordersSeizure disorders

SeizureSeizure is and abnormal discharge is and abnormal discharge of electrical activity within the brain. of electrical activity within the brain. It is a rapidly evolving disturbance of It is a rapidly evolving disturbance of brain function that may produce brain function that may produce impaired consciousness, impaired consciousness, abnormalities of sensation or mental abnormalities of sensation or mental function or convulsive movements.function or convulsive movements.

ConvulsionsConvulsions are episodes of are episodes of widespread and intense motor widespread and intense motor activityactivity

8989

EpilepsyEpilepsy A recurrent disorder of cerebral A recurrent disorder of cerebral

function marked by sudden, brief function marked by sudden, brief attacks of altered consciousness, attacks of altered consciousness, motor activity or sensory motor activity or sensory phenomenon.phenomenon.

Convulsive seizures are the most Convulsive seizures are the most common formcommon form

Some, but not all, recurrent seizures Some, but not all, recurrent seizures are due to epilepsyare due to epilepsy

9090

EpilepsyEpilepsy

Second most common neurological Second most common neurological disorderdisorder

Incidence increases with age, with Incidence increases with age, with 30% initially occurring before 4 30% initially occurring before 4 years and 75 -80 % before 20 years.years and 75 -80 % before 20 years.

Causes: brain tumor, scar tissue, Causes: brain tumor, scar tissue, neurological disease, great majority neurological disease, great majority of cases are idiopathic.of cases are idiopathic.

9191

Signs and symptoms vary:Signs and symptoms vary:

petit malpetit mal – almost imperceptible – almost imperceptible alterations in consciousnessalterations in consciousness

grand malgrand mal – generalized tonic-clonic – generalized tonic-clonic seizures – dramatic loss of seizures – dramatic loss of consciousness, falling, generalized consciousness, falling, generalized tonic-clonic convulsions of all tonic-clonic convulsions of all extremities, incontinence, and extremities, incontinence, and amnesia for the event.amnesia for the event.

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Some attacks are proceeded by a Some attacks are proceeded by a prodromeprodrome – a set of symptoms that – a set of symptoms that warn of a seizurewarn of a seizure

As the seizure begins, the patient As the seizure begins, the patient may experience an may experience an aura –aura – mental, mental, sensory or motor phenomenasensory or motor phenomena

Others have no warningOthers have no warning

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Phases of a grand mal Phases of a grand mal seizureseizure

1.1. Tonic phaseTonic phase ( 10 -20 seconds) – ( 10 -20 seconds) – muscle contractionmuscle contraction

Epileptic cryEpileptic cry – respiration stops – respiration stops

2.2. Clonic phaseClonic phase – (1/2 -2 minutes) – (1/2 -2 minutes) muscle spasms; respiration is muscle spasms; respiration is ineffective; autonomic nervous ineffective; autonomic nervous system activesystem active

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

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5-8 % are at risk of 5-8 % are at risk of status status epilepticusepilepticus – a series of GTCS without – a series of GTCS without regaining consciousness – medical regaining consciousness – medical emergencyemergency

Seizure activity lasts more than 30 Seizure activity lasts more than 30 minutesminutes– AcidosisAcidosis

– Elevated pCOElevated pCO22

– HypoglycemiaHypoglycemia– Fall in blood pressureFall in blood pressure

Can lead to severe brain damage or Can lead to severe brain damage or deathdeath

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Epileptogenic focusEpileptogenic focus

Group of brain neurons susceptible to Group of brain neurons susceptible to activationactivation

Plasma membranes may be more Plasma membranes may be more permeable to ion movementpermeable to ion movement

Firing of these neurons may be Firing of these neurons may be greater in frequency and amplitudegreater in frequency and amplitude

Electrical activity can spread to other Electrical activity can spread to other hemisphere and then to the spinal hemisphere and then to the spinal cordcord

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TreatmentTreatment Treat any underlying metabolic Treat any underlying metabolic

disorders, or tumors disorders, or tumors Most cases can be controlled through Most cases can be controlled through

routine use of antiepileptic medications routine use of antiepileptic medications – usually only one drug to minimize side – usually only one drug to minimize side effectseffects

Surgical intervention if drugs ineffectiveSurgical intervention if drugs ineffective Supportive therapy – patients learn to Supportive therapy – patients learn to

cope effectively with stress, eat well, cope effectively with stress, eat well, and get sufficient rest and avoid and get sufficient rest and avoid triggers.triggers.

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Eliciting stimuli:Eliciting stimuli: HypoglycemiaHypoglycemia FatigueFatigue Emotional or physical stressEmotional or physical stress FeverFever HyperventilationHyperventilation Environmental stimuliEnvironmental stimuli

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Patients are normal between attacksPatients are normal between attacks Can participate in sports, drive a car Can participate in sports, drive a car

(if no seizures for 6 mo – 1 year) (if no seizures for 6 mo – 1 year) Should not drink alcoholShould not drink alcohol

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