Parkinsons Disease

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Nervous System Pathology
Lecture 3 Cerebrovascular Disease and Seizure
Disorders
Alvin V. Terry, Jr., Ph.D. Associate Professor
UGA College of Pharmacy and MCG Alzheimers
Research Center
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Cerebrovascular Disease

• Most Frequently Occurring Neurologic Disorder
• Stroke (CVA) is the 3rd leading cause of death in
  US.

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Stroke (CVA)

• Tends to run in families
• More common in women
• Greater incidence in Blacks
• Major classifications
• Ischemic
• Hemorrhagic

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Major Risk Factors

• Hypertension
• Hyperlipidemia
• Smoking
• Diabetes Mellitus
• Heart Disease

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General Symptoms

• Motor
• weakness
• hemiparesis
• Sensory
• numbness

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General Symptoms(Cont)

• Speech
• dysarthria
• aphasia
• Visual
• hemianopsia
• diplopia

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General Symptoms(hemorrhagic stroke)

• Headache
• Ataxia
• Impaired conciousness

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Transient Ischemic Attach

• Defined as an ischemia-related, focal neurologic
  deficit lasting less than 24 hours.

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Ischemic Strokes

• Thrombotic
• Embolic
• Lacunar

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Thrombosis

• Definition-blood clot in a cerebral vessel
• Caused by atherosclerotic plaque accumulation
• Plaque causes endothelial damage

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Thrombosis (cont)

• Vessel wall degeneration occurs.
• Damage attracts platelets and fibrin.
• Thrombus grows leading to vessel occlusion .

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Thrombosis (cont)

• 60 develop during sleep.
• 20 develop step wise over several hours to a few
  days.
• Stroke in Evolution

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Embolism

• Definition-foreign substance which occludes a
  blood vessel
• Vessel occlusion occurs down stream from source
  of embolis
• Symptoms develop rapidly.

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Embolism (Cont)

• Normally do not progress
• Usually occurs during activity.
• Consciousness usually preserved
• Source is almost always the left side of the
  heart.

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Common Sources of Emboli

• Atrial fibrillation
• Myocardial infarction
• Defective heart valve
• Artificial heart valve

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Source Mosby Clinical Neurology CD Atlas
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Source Mosby Clinical Neurology CD Atlas
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Anatomical Variation
Source Mosby Clinical Neurology CD Atlas
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Source Mosby Clinical Neurology CD Atlas
20
Source Mosby Clinical Neurology CD Atlas
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Sclerotic Basilar Artery
Source Web Path The Internet Pathology
Laboratory for Medical Education
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Internal Carotid Increasing Stenosis
Source Web Path The Internet Pathology
Laboratory for Medical Education
23
Carotids-Atherosclerotic
Source Web Path The Internet Pathology
Laboratory for Medical Education
24
SPECT
CT
Grossly Diminished Perfusion
Early Stroke
Normal Perfusion
Source Mosby Clinical Neurology CD Atlas
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CT
Pre-Contrast
Post-Contrast
Cerebellar Infarct
Source Mosby Clinical Neurology CD Atlas
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Carotid Angiogram
MCA Occlusion
Source Mosby Clinical Neurology CD Atlas
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MCA - Remote Infarct (subacute)
Source Web Path The Internet Pathology
Laboratory for Medical Education
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Lacunar Stroke

• Microinfarcts smaller than 1 cm in diameter
• Involve small perforating arteries
• Affect basal ganglia, internal capsule and pons
  (most commonly)
• Pure motor or sensory deficits

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Pons-Lacunar Infarct
Source Web Path The Internet Pathology
Laboratory for Medical Education
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Hemorrhagic Stroke

• Intracranial Hemorrhage
• Sudden onset of symptoms
• Frequently associated with severe headache
• Loss of consciousness common (stupor, coma).

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Hemorrhagic Stroke

• Causes
• Hypertension
• Ruptured aneurysms
• Arteriovenous malformations
• Tumors
• Bleeding Disorders
• Drugs (e.g., cocaine)

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Circle of Willis (Berry Aneurysm)
Source Web Path The Internet Pathology
Laboratory for Medical Education
33
Vascular Malformation (parietal lobe)
Source Web Path The Internet Pathology
Laboratory for Medical Education
34
Subarachnoid Hemorrhage
Source Web Path The Internet Pathology
Laboratory for Medical Education
35
Cerebral Hemorrhage-Cocaine
Source Web Path The Internet Pathology
Laboratory for Medical Education
36
CT
Hemorrhagic Infarct
High Density
Low Density
Source Mosby Clinical Neurology CD Atlas
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Stroke-Therapy

• Thrombolytics
• Platelet inhibitors
• Warfarin
• Heparin
• Low molecular weight heparinoids

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Seizure Definition/Characteristics

• Involuntary, abnormal and excessive neuronal
  discharge in the CNS.
• Characterized by spontaneous, recurrent and
  paroxysmal episodes.
• May involve convulsions.

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Definition andCharacteristics (Cont)

• Usually are brief lasting a few seconds to 3
  minutes.
• Seizure and convulsion are not synonymous

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EpilepsyDefinition/Characteristics

• Epilepsy A syndrome of recurrent seizures.
• Epileptic Focus Location of sudden electrical
  activity.
• spontaneous depolarization

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SeizureCharacteristics (Cont)

• Usually originates in cerebral cortex.
• medial temporal lobe most common site

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Background (Epidemiology)

• 8-10 of the population will experience a single
  seizure during life.
• 1-2 of population will go on to have recurrent
  seizures (epilepsy)
• 2-4 million in US

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Background (Cont)

• Occurs in all races with equal distribution in
  males and females.
• 30 of Idiopathic type have genetic history

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Epilepsy Diagnosis

• H and P
• Neurologic Exam
• Blood Tests
• Electrolytes
• BUN
• Creatinine
• Drugs and Alcohol

• Procedures
• EEG
• CT
• MRI
• PET
• SPECT

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Seizure Classification

• Generalized Seizures
• Generalized Tonic-Clonic (GTCS)
• Absence
• Myoclonic
• Atonic

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Seizure Classification

• Partial Seizures
• Simple Partial
• Complex Partial
• Complex Partial with Secondary Generalization

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Generalized Tonic-Clonic (GTCS)

• Most Severe Form
• Prodrome
• Ictus
• Tonic Phase
• Clonic Phase

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Normal Tracing
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Generalized Tonic Clonic Seizure
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GTCS (Cont)

• Post-Ictal Period
• First Line Drugs
• phenytoin (Dilantin)
• carbamazepine (Tegretol)
• sodium valproate (Depakote)

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Absence Seizures

• Exclusively found in children
• Duration 5-30 seconds
• No prodrome

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Absence Seizure
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Absence Seizures(Cont)

• Characterized by a lapse in mental function
• First Line Drugs
• sodium valproate (Depakote)
• ethosuximde (Zarontin)

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Myoclonic

• Brief, non repetitive shock like contractions
• First Line Drug
• sodium valproate

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Atonic

• Sudden Loss of Muscle tone
• May be generalized or confined to the neck
• First Line Drug
• clonazepam (Klonopin)

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Partial Seizures

• Simple Partial
• Involves Single Hemisphere
• Locus is often close to a structural abnormality
• Patient Remains Conscious

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Partial Seizure
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Simple Partial (Cont)

• Duration several seconds to several minutes
• Often involves a single limb or other part of body

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Complex Partial

• Psychomotor or Temporal Lobe Epilepsy
• Complex characteristics and behavior
• Lip Smacking, Fumbling with Objects
• Fits of Emotion

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Complex Partial (Cont)

• Impaired Consciousness followed by disorientation
  and confusion
• Complex Partial with 20 Generalization

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Partial Seizures

• First Line Drugs
• carbamazepine, phenytoin, combinations
• Adjunctive Agents
• gabapentin, topiramate, lamotrigine, tiagabine,
  levetiracetam, others.

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Status Epilepticus

• Defined as a single seizure lasting more than 30
  minutes or intermittent seizures lasting for more
  than 30 minutes in which the patient does not
  regain consciousness

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Status Epilepticus

• Is a life threatening Situation
• Causes
• anticonvulsant withdrawal
• alcohol withdrawal
• cerebrovascular disease

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Status Epilepticus (Therapy)

• Restrain Patient
• Support Respiration
• IV diazepam or lorazepam
• Follow with phenytoin or phenobarbital
• May require general anesthesia in some cases

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Alcohol Withdrawal Seizures

• Up to 15 of Alcoholics will experience at least
  one seizure
• Usually is a GTCS type occurring 7-48 hours after
  alcohol cessation.

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Alcohol WD Seizures (Cont)

• Generally is a single seizure but may involve 2-6
  seizures in a 6 hour period.
• First Line therapy- IV diazepam
• Thiamine
• Nutritional Support

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Febrile Seizures

• Affects children between ages of 6 months to 5
  years.
• Usually occur with temperatures gt 390C (1020F)

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Febrile Seizures (cont)

• Therapy
• Primary- Treat Underlying cause if Known (e.g.,
  antibiotics)
• Fever reduction- acetaminophen
• Rectal diazepam to control seizure