Cerebrovascular Disorders and Stroke

Cerebrovascular Disorders

• Cerebrovascular disorders include cerebrovascular accident (stroke) and aneurysms.

Cerebrovascular Accident (CVA, Stroke)

• Stroke is the third leading cause of death in Canada
• Stroke is a leading cause of adult disability.
• Strokes are classified by pathophysiology: thrombotic, embolic, or hemorrhagic
• Ischemic strokes include thrombotic and embolic types, accounting for 80%+ of cases and are labeled as white strokes.
• Hemorrhagic strokes are termed red strokes.

Transient Ischemic Attack (TIA)

• TIA involves a reversible neurologic deficit caused by temporary ischemia.
• Speech, vision, and motor function are typically affected by TIA.
• TIAs are often caused by platelet clumps.
• TIA attacks last for a few seconds to minutes, completely clearing within 24 hours, and leave no residual dysfunction.
• There is a high recurrence if TIA is not treated.

Thrombotic CVA (Cerebral Thrombosis)

• Thrombotic CVA is the most common type of stroke.
• Thrombotic CVA is caused by arterial occlusions by thrombi formed in cerebral arteries.
• Atherosclerosis and inflammatory disease processes that damage arterial walls are frequently attributed to Thrombotic CVA.
• Thrombotic CVA results in cerebral infarction after ischemia.
• Clots form and enlarge at branches and curves in cerebral vessels.

Embolic CVA

• Embolic CVA is due to fragments that break from thrombi formed outside the brain.
• There is a high recurrence rate if an embolic CVA is not treated.
• Emboli usually originate from the left side of the heart.
• Emboli obstruct small brain vessels at points of bifurcation or narrowing.

Cerebrovascular Accident Manifestations

• Manifestations may vary depending on the artery involved.
• There may be sudden transient weakness, numbness, or tingling in the face, arm, or leg, typically on one side of the body (hemiparesis).
• One can experience temporary loss of speech, failure to comprehend, or confusion.
• Sudden loss of vision, severe headache, or unusual dizziness/unsteadiness may occur.

Cerebrovascular Accident Treatment

• Treatment for ischemic strokes involves Angiogram and brain imaging (CT/MRI).
• Reperfusion techniques must be administered before ischemic cells die, usually within hours of the stroke.
• Fibrinolytic drugs may be administered.
• Later treatment involves anti-platelet therapy or warfarin (anticoagulant).

Hemorrhagic CVA

• Hemorrhagic CVA results from the rupture of a blood vessel, leading to a mass of blood that compresses local brain tissue.
• Causes include hypertension (56-81%), ruptured aneurysms, or bleeding from a tumor.

Hemorrhagic CVA Manifestations

• Manifestations depend on the size of the bleed and the location of vascular lesion.
• Vomiting or excruciating headache may occur, leading to an unresponsive state.
• Unresponsive states as a result of massive cerebral edema are usually fatal.

Aneurysms

• Aneurysms results from damage to vessel walls.
• Damage can be caused by congenital abnormalities, trauma, inflammation, or toxins.
• Aneurysms vary in size from 2mm to 3cm.
• 20-25% of cases have more than one aneurysm.
• Aneurysms often occur in the Circle of Willis.
• Aneurysms are usually asymptomatic unless nerve compression or large size is present.
• The first clinical indication typically results from hemorrhage, increased intracranial pressure (ICP), severe headache, photophobia, stiff neck, nausea/vomiting, or loss of consciousness.
• Minor 'leaks' may occur before rupture, draining into CSF.

Diagnosis and Treatment of Aneurysms

• Diagnosis is usually after complaints of severe headaches.
• CT scans identify the extent of the bleed.
• Lumbar puncture identifies blood in CSF.
• Angiography/MRI is used to discover aneurysms, often by accident.
• Treatment involves surgical removal or stabilization with clips.

Meningitis

• Meningitis involves inflammation of the meninges.
• It is caused by pathogens, primarily bacteria, viruses, and fungi.
• Pathogenesis, manifestations, and treatment depend on the infectious agent.
• Meningitis spreads quickly through CSF.
• It can be acute, subacute, or chronic.

Bacterial Meningitis

• Common bacteria include Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.
• Risk factors: age, head trauma, skull fractures, ear/sinus infections, neurosurgery, immunocompromised conditions.
• Bacteria replicate and lyse, releasing endotoxins and inducing inflammatory response.
• Response includes hyperemia and edema.
• CSF thickens due to purulent exudate.
• Purulent CSF interferes with CSF flow.
• It obstructs arachnoid villi, leading to hydrocephalus, cerebral edema, and increased ICP.

Bacterial Meningitis Clinical Manifestations and Diagnosis/Treatment

• Clinical manifestations include fever/chills, throbbing headache, photophobia, neck rigidity, nausea/vomiting, lethargy, drowsiness, confusion, seizures, and skin rash in some cases (meningococcal).
• Diagnosis involves Postural (meningeal signs) due to the resistance of painful stretching of meninges which include: -Flexion of the neck that induces flexion of the hip and knee (Brudzinski's sign) -Resistance to extend the knee while lying with the hip flexed at a right angle (Kernig's sign)
• Lumbar puncture will show purulent CSF with signs of inflammation.
• Treat bacterial meningitis urgently with antibiotics.

Viral Meningitis

• Viral meningitis is the most common type of meningitis.
• It is referred to as aseptic meningitis.
• Viruses like mumps, herpes, West Nile, etc. cause it.
• Routes of entry include hematogenous (most common), neural (herpes viruses), and insect bites (West Nile virus).
• Viral meningitis shares similar manifestations as bacterial meningitis, but it is more mild.
• The mortality rate of viral meningitis is less than 1%.
• Viral meningitis has less edema and is less purulent than bacterial meningitis.
• The main WBC in CSF is lymphocytes.
• There could be long-term effects on children, such as learning disabilities, neuromuscular impairments, and deafness.

Guillain-Barré Syndrome

• Guillain-Barré Syndrome is the most common cause of acute, flaccid paralysis in developed countries.
• It is often severe, ascending, bi-lateral (symmetric).
• Adults are more commonly affected than children.
• The typical age of onset is 20-50 years.
• The syndrome is an acute immune-mediated polyneuropathy.
• A past medical history of acute, influenza-like illness (few weeks prior) or Campylobacter jejuni (food poisoning) may be present.

Guillain-Barré Syndrome - Case Report

• October 5: Tingling in toes.
• October 10: Tingling in fingers.
• October 18: Lower extremity weakness.
• October 24: Inability to stand; then unable to sit then unable to breathe
• This manifests as upright ventilated areflexia,
• Other characteristics of paralysis of respiratory muscles include autonomic nervous system disturbances, arrhythmias, and urinary retention.

Guillain-Barré Syndrome - Mechanism

• There is a cross-reaction of antibodies to myelin (most forms target Schwann cells).
• This leads to demyelination of nerves and poor electrical conduction along the axon.

Guillain-Barré Syndrome - Treatment

• Plasmapheresis is used to remove antibodies.
• High-dose intravenous immunoglobulin therapy is used to saturate binding sites. -Antigens are "presented" on macrophages. -Antigens on myelin attract antibodies.
• There is an 80-90% full and spontaneous recovery in 6-12 months.

Seizure

• A seizure is a sudden, explosive, disorderly depolarization of the cerebral cortex.
• Seizures can result from trauma, infection, or tumor growth.
• Idiopathic cases (e.g., epilepsy) account for 2/3 of cases.

Partial (Focal) Seizure

• The partial (focal) seizure is the most common form of seizure.
• Focal onset: begins locally, usually originating in the cortex.
• Types of seizures: -Simple: occurs in one hemisphere -Complex: begins localized (often in the temporal lobe) and may progress rapidly to both hemispheres

Simple Partial Seizure

• Consciousness is not impaired, but awareness is reduced, and memory remains intact.
• Observed clinical manifestations depend on the area of the brain where the discharge is taking place. -Motor area: typically repeated movement (jerking/ twitching). -Sensory area: no observable manifestations (tingling, crawling). -Special sense: visual, auditory, olfactory. -ANS: flushing, tachycardia, diaphoresis.

Complex Partial Seizure

• Consciousness is impaired/unresponsive during the seizure.
• One is often amnesic, confused, and drowsy after the seizure.
• Ten accompanied by automatisms (repetitive, non-purposeful activities) such as lip smacking, grimacing, or rubbing clothing.
• Hallucinations, déjà vu, and jamais vu have been reported.
• Feelings of fear and detachment, and floods of ideas may be experienced.

Generalized Seizure

• The entire brain is involved with generalized seizures.
• Generalized seizures occur spontaneously or after partial seizures and typically involve multiple foci.
• Generalized seizures begin with a loss of consciousness.
• A tonic stage involves muscle contraction and rigidity.
• A clonic stage involves contraction/relaxation events, salivation, and bowel/bladder incontinence.
• Generalized seizures are followed by confusion and fatigue (sleep).

Seizures

• Prodrome is a manifestation prior to the onset of a generalized seizure (usually hours before, may be days). -Prodrome may include include include headache, nausea, muscle twitching, or changes in sensitivities.
• Aura is a partial seizure (i.e., peculiar visual/auditory sensation) that immediately precedes a generalized form. -It is the actual beginning of the seizure.

Degenerative Diseases

• Degenerative diseases include Alzheimer's Disease, Parkinson's Disease, and Multiple Sclerosis.

Alzheimer's Disease

• Alzheimer's Disease is a form of senile dementia with impairment of memory, abstract thinking, judgment, higher cortical functions, and changes in personality.
• Exact cause unknown and is a diagnosis by exclusion.
• It is the most common cause of severe cognitive dysfunction in older persons.
• There could be a deficiency in an enzyme needed for acetylcholine production.
• There could be a genetic defect such as amyloid plaque formation.
• There may be a virus involved.
• There is a generalized atrophy and loss of neurons in entire cerebral cortex.
• There is a decrease of enzyme responsible for making acetylcholine, which is associated with memory.

Alzheimer's Disease - Features

• The major microscopic features include:
  • Neurofibrillary tangles, made of fibrous, degraded proteins within neurons.
  • Neuritic (senile) plaques, which contain an amyloid core (amyloid beta) and degenerated neurons which disrupt nerve impulses.

Alzheimer's Disease - Manifestations and Prognosis

• It has an insidious (gradual) progression
• Common symptoms: -Lapses of memory (especially short-term) with denial and social withdrawal -Confusion, disorientation (aimless wandering), and language difficulty -Agitation, mood swings, and unpredictable behavior -Eventually, loss of ability to respond to environment (bedridden)
• The general prognosis is 8-10 year survival with death usually resulting from infection (mainly respiratory), and accidents

Alzheimer's Disease - Treatment

• There is no treatment
• Treatments which can be done: -Reinforcing other cognitive functions, maintaining hygiene and health -Some drugs can potentially slow the process.

Parkinson's Disease

• Parkinson's Disease is a degenerative disorder of the basal nuclei (motor and learning functions).
• There is degeneration and deficiency of the dopamine-secreting pathway.
• It affects approximately 55,000 Canadians with the average age of onset is 64 years of age.
• The cause is not known.
• Lewy bodies (round, purple) are hallmark abnormal deposits of brain proteins found through a neuron stained red.

Parkinson's Disease - Manifestations

• Motor Changes: -Bradykinesia (slow) and akinesia (no movement) -Tremor at rest -Difficulty initiating and sustaining smooth movements -Hesitancy, freezing, rigid, jerky, and irregular movements -Slurred speech
• Postural changes: -Flexor posturing (forward leaning position) -Loss of equilibrium and postural reflexes -Shuffling gait -Loss of autonomic functions -Loss of voluntary facial movements

Parkinson's Disease - Treatment

• There is no effective cure, but attempts are made to maintain function.
• Treatment is aimed at restoring brain dopamine levels or activity by administering dopamine precursors (L-dopa).
• Patients may utilize deep brain stimulation.
• Group support, education, daily exercise, and adequate nutrition may be provided.

Multiple Sclerosis

• Multiple Sclerosis is a primary demyelinating disorder of the CNS (does not involve PNS)
• There are multiple areas of demyelination with hardening of tissue. -Lesions (plaques) are macroscopically visible throughout white matter.
• Onset is usually between 15-40 years.
• There are more women than men that get diagnosed with MS. -Women: men = 2:1* (now almost 3)
• Pathogenesis is not known but is suspected to involve the following: -Autoimmune response that kills oligodendrocytes causes demyelination. -Genetic factors.

Multiple Sclerosis - Immune Response and Manifestations

• Immune response resolves leaving diffuse sclerotic plaques and plaques to coalesce (merge).
• Non-synaptic transmission (“short-circuiting”) occurs.
• Clinical manifestations include: -Episodic course (relapses, remissions) following some form of stress -Both sensory and motor symptoms occur -Diffuse pain, fatigue, paresthesia (abnormal sensations, i.e., burning itching, numbness) -Visual disturbances and speech impairment -Balance/coordination impairment -Reduction in muscle strength -Bowel, bladder, and sexual dysfunction -Depression, mood swings, forgetfulness.

Multiple Sclerosis - Diagnosis and Treatment

• Diagnosis is based on history and physical examination with CSF examination and MRI. -Elevated CSF IgG is usually present.
• There is no cure, however treatment focuses on: -exacerbations (with anti-inflammatories) -progression (immunosuppression)
  • supportive rehabilitation.