A. Scope of Problem [1,2,3]

1. In USA, >650,000 per year (total strokes)
   1. >200,000 transient ischemic attacks (TIA)
   2. ~400 per 100,000 population >45 years old annually
   3. Incidence of stroke has decreased over past 50 years [14]
   4. Stroke-related mortality 50-100/100,000 population per year
2. Most are ischemic (~80% or >500,000)
   1. Local athero-thrombotic
   2. Distal source of embolism
   3. Hypoperfusion
3. Prognosis
   1. >25% mortality within a month, >50% mortality by 1 year
   2. 16% institutionalized
   3. ~20% with impaired expression or comprehension of language
   4. ~25% unable to walk without full physical assistance
   5. 70% have decrease in vocational level
4. Survivors of TIA or Minor Stroke [6]
   1. 10 year risk of death ~43%
   2. Age >65 years, diabetes, and claudication have worse prognosis
   3. 10 year risk of any vascular event 44%
   4. These outcomes despite post-event prophylactic agents
5. Second leading cause of death in USA after heart disease
6. Stroke prevention is a critical goal of modern medicine

B. Classification of Stroke

1. Thromboembolic (Occlusive, 90%) [9,38]
   1. Most commonly due to plaque rupture, clot formation, and distal embolization
   2. Three etiologies: large vessel, cardioembolic, lacunar
   3. Carotid stenosis with plaque rupture, thrombosis, distal embolization (~70-80%)
   4. Cardioembolic: pure embolism from cardiac source (~10%)
   5. Patent Foramen Ovale (PFO) is a risk factor for stroke, related to diameter of PFO [59,60]
   6. Lacunar infarctions: 10-20% of occlusive strokes
   7. Emboli typically affect medium arteries, usually middle cerebral or vertebral branches
   8. Spinal arteries can also become occluded and infarction can occur [55]
   9. Complete cardiac and cerebrovascular evaluation must be carried out in all strokes
2. Hemorrhagic (10%) [49]
   1. Includes intracerebral hemorrhage and subarachnoid hemorrhage (SAH)
   2. ICH usually associated with hypertension (HTN) and smaller arteries
   3. Ruptured intracerebral aneurysm or arteriovenous malformation common
3. Large Vessel Disease [9]
   1. Focal deficits such as left or right sided paresis
   2. Mixed forms (sensory AND motor and/or Speech) suggest larger vessels
   3. Usually due to atherothrombotic occlusion
   4. Internal carotid, vertebral or basilar artery usually affected
   5. In symptomatic carotid stenosis with occlusion 70-99%, ~20% of ipsilateral strokes are not due to stenotic (large vessel) disease
   6. In asymptomatic carotid stenosis with occlusion 70-99%, ~45% of ipsilateral strokes are not due to stenotic (large vessel) disease
   7. Thus, carotid stenosis does not prove the etiology of an ipsilateral stroke [9]
4. Cardioembolic Strokes
   1. Usually due to atrial fibrillation (AFib)
   2. Also caused by clot formation in dysfunction left ventricle
   3. AFib also a risk for recurrent stroke [57]
   4. Atrial myxoma with emoblization [16]
5. Lacunar Infarcts
   1. Small infarctions, often asymptomatic or very mild symptoms
   2. Nearly 100% are thought to be caused by blood vessel damage from HTN
   3. Usually multiple, bilateral and asymmetric appearance on CT
   4. More common in Blacks and Asians than in Caucasians
   5. Pure motor or pure sensory symptoms only
   6. White matter involvement
6. Transient Ischemic Attack (TIA) [1,2]
   1. Recovery of function in minutes to within 24 hours
   2. Poor prognosis unless treated: 5% have stroke within 1 day, 5% more within 3 months [46]
   3. TIA is a ~2X risk factor for stroke, ~1.5X for dementia, ~2.5X for vascular death [33]
7. Completed (Infarction) Stroke: some recovery in months or not at all
8. Strokes due to hypotension/hypoperfusion usually affect watershed zones
9. Vasculitis Syndromes [36]
   1. A relatively small number of patients with strokes have CNS vasculitis
   2. These patients are usually younger, present with multifocal or focal disease
   3. Takayasu arteritis is probably most common, occurs in young people
   4. Giant cell arteritis (GCA) occurs in older persons and usually affects the eyes
   5. Isolated CNS vasculitis is an uncommon granulomatous inflammatory disease
   6. Other rheumatologic diseases can include strokes (including systemic lupus)

C. Risk Factors for Stroke

1. TIA is likely the most important risk factor for stroke [5,46]
2. ABCD Risk Score for Stroke within 7 Days after TIA [5]
   1. Six (6) point system for likelihood of stroke after TIA
   2. A=Age >60: 1 point
   3. B=Blood Presusre (systolic >139 or diastolic >89): 1 point
   4. C=Clinical features: unilateral weakness=2, speech problem without weekness=1 point
   5. D=Duration of sympoms (minutes): >59=2, 10-59=1 point
   6. With ABCD scores 0-4, risk of stroke was <95% within 7 days
   7. Diabetes mellitus may also be a risk for stroke after TIA [46]
3. Carotid Stenosis [42]
   1. Symptomatic carotid stenosis is a major risk factor for stroke
   2. Asymptomatic carotid stenoses is also a risk factor for stroke [42]
   3. Atherosclerotic cerebrovascular disease is responsible for >95% of carotid stenosis
   4. Persons with other atherosclerotic vascular disease have increased stroke risk
   5. Asymptomatic stenoses 60-99% are associated with 3.2% annual risk of stroke
   6. Asymptomatic stenoses <60% associated with a 1.6% annual risk of stroke
   7. 45% of strokes in patients with 60-99% stenoses due to lacunes or cardioembolism
4. Other Atherosclerotic Disease
   1. Patient with coronary artery disease (CAD) should be evaluated for carotid stenosis
   2. Peripheral Vascular Disease (PVD)
   3. Aortic atherosclerotic plaques (particularly >4mm size) [11]
   4. Retinal Cholesterol Emboli ~10X risk for stroke
   5. Fabry (lysosomal storage) disease - increased risk, particularly in young people [19]
5. Cholesterol Levels
   1. Poor correlation between total cholesterol levels and stroke
   2. Total fat intake was inversely correlated with ischemic stroke in men
   3. LDL Cholesterol, triglycerides, ApoE, ApoCIII, and ApoB correlate with stenosis
   4. Statins (HMG CoA Reductase Inhibitors) reduce carotid stenosis and stroke risk [10]
   5. Elevated HDL levels in elderly associated with reduced risk of ischemic stroke [50]
6. Smoking
   1. 4-10X increased risk compared with nonsmokers (normotensive patients)
   2. Cessation of smoking reduces risk to 1-2X increase over nonsmokers within 5 years
   3. Smoking greatly increases risk of stroke in users of oral contraceptives
7. HTN
   1. Major risk factor for hemorrhagic stroke
   2. Risk factor for thromboembolic stroke due to accellerated atherosclerosis
   3. Promotes development of left ventricular hypertrophy, another stroke risk factor
   4. Also a major risk factor for thromboembolic stroke and lacunar infarctions
8. Diabetes Mellitus - both Types I and Type II
9. Cardiac Disease
   1. AFib [51]
   2. Post-MI: 44X risk within 30 days, 2-3X over 2-3 years [39]
   3. Mitral Stenosis with left atrial clot and/or aortic regurgitation (sinus rhythm) [56]
   4. Mechanical Heart (or new porcine heart) Valve
   5. PFO - permits right to left shunt, venous clots moving directly into left atrium [59]
10. Sleep Apnea / Hypopnea - risk increased ~3X
11. Surgery [17]
    1. Particularly cardiac and vascular surgeries
    2. Carotid Endarterectomy
    3. Mainly ischemic and embolic types
    4. Carotid stenosis is greatest primary risk factor
12. Age-Related Macular Degeneration (AMD) [8] - 1.9X stroke risk
13. Hormone replacement therapy (HRT) - 1.2X risk in healthy perimenopausal women [46]
14. Oral Contraceptives (OCP)
    1. Moderate and high dose estrogen containing OCP's have <2.8 fold increased risk
    2. Meta-analysis risk of stroke was 1 per year per 24,000 nonsmoking, normotensive women [44]
15. Peripartum Period
    1. Pregnancy associated within increased risk of coagulopathy
    2. Increased thromboembolic and hemorrhagic stroke risk
    3. Spinal artery occlusion also reported [55]
16. Migraine with aura 1.9X risk increase for stroke [24]
17. Alcohol Intake
    1. Moderate (0.3-2 drinks per day) consumption associated with 20-50% stroke risk reduction
    2. Three-fold increased risk of ischemic stroke with >6 drinks per day
    3. Excessive alcohol use increase risk of hemorrhagic stroke [49]
18. Hyperviscosity Syndromes
    1. Monoglonal gammopathy
    2. Polycythemia vera
    3. Essential thrombocythemia
    4. Sickle cell anemia
19. Vasculitis
    1. Cerebral Angiitis
    2. Systemic vasculitides with cerebral vascular involvement
    3. Giant cell arteritis [28]
20. Family History
21. Metabolic Disorders
    1. May cause strokes or TIAs in younger persons
    2. May contribute to risk for strokes
    3. Homocystinuria and/or hyperhomocysteinemia
    4. Organic acid disorders (several)
    5. Orthnithine Transcarbamylase deficiency
    6. Carbohydrate deficient glycoprotein syndromes
    7. MELAS Syndrome
22. Antiphospholipid (Anticardiolipin) Antibodies [20]
    1. Increased risk for stroke and other arterial thromboembolic events
    2. Not a risk for recurrent stroke or other thrombo-occlusive events after initial stroke
23. Late-onset seizures age >60 years may be a risk factor for stroke [21]
24. Phenylpropanoloamine - risk factor for hemorrhagic stroke (drug withdrawn from market) [47]
25. Strokes in Children
    1. Embolism
    2. Premature atherosclerosis
    3. Vasculitis
    4. Congital and acquired heart disease
    5. Hereditary hypercoagulable states

D. Pathophysiology

1. Normal blood flow to brain ~15% of cardiovascular output (~750 mL/min)
   1. Stop blood flow 6 seconds leads to unconsciousness
   2. Irreversible damage occurs in 5-15 minutes
2. Ischemia causes a variety of changes [35,45]
   1. Decreased energy production (mitochondria)
   2. Mitochondrial injury triggers oxygen radicals and apoptosis
   3. Failure of ATP-requiring ionic pumps leads to elevated cellular Na+, Ca2+, Cl-
   4. These ions stimulate internal proteases and phospholipases
   5. Phospholipases stimulate production of prostaglandins and leukotrienes
   6. Proteases stimulate breakdown of cytoskeleton and DNA
   7. Excitotoxic amino acids are released at axon terminals in ischemic area
   8. Leukocytes in ischemic area traverse vasculature and invade brain parenchyma
   9. If blood flow is restored, potential for reperfusion injury occurs as well
   10. Early restoration of blood flow (within 3 hours) is, however, beneficial
3. Release of Excitotoxic Amino Acids [35]
   1. Glutamate is a major contributor here, released shortly after ischemia
   2. Glutamate binds NMDA and AMPA receptors, leading to increased intracellular calcium
   3. Glycine levels also increase progressively in the ischemic focus
   4. Glycine is required for activation of the NMDA channel
   5. Therefore, direct neuron cell death is exacerbated by peri-ischemic glutamate damage
   6. The area directly adjacent to the immediate cell death area is called the "penumbra"
   7. Selective NMDA antagonists have not shown improvement in stroke outcome to date
4. First cells affected by decreased blood flow
   1. Cerebellar Purkinje cell
   2. Hippocampal pyramidal cell
5. Sequence of Events and Responses
   1. No gross pathological abnormalities can be found in brain if death occurs within 6 hours of vascular occlusion
   2. After this, region of infarction becomes edematous, soft and pale
   3. Small, medium thromboembolic infarcts are not visible on CT until 48-72 hours after vascular occlusion
   4. Large thromboembolic strokes are often visible on CT within 6-24 hours
   5. Within 2-10 days swelling subsides
   6. After 10 days, liquefaction and cavitation with thin membrane cover are formed
6. Circulation
   [Figure] 1 "Schematic of the Circle of Willis"
   1. Anterior - internal carotids: supply anterior and middle cerebral arteries
   2. Posterior - vertebral and basilar aa: brainstem, cerebellum, posterior cerebral arteries [22]
   3. The anterior and posterior circulations are connected (sometimes incompletely) via the posterior communicating arteries
   4. These connections form a (incomplete) circle, called "Circle of Willis"

E. Thromboembolic Causes of Stroke

1. Vessel Occlusion (65-80% of strokes)
   1. Atheromatous progressive occlusion (probably most common)
   2. Vessel Trauma
   3. Vessel Dissection
   4. Sickle Cell Disease
   5. Tumor (Abscess) Compression
   6. Hyperviscosity Syndromes
   7. Vasculitis, Diabetes
   8. Fibromuscular dysplasia
   9. Moya Moya Disease
   10. Only invasive angiography is currently effective in evaluating most of these causes
   11. In general, invasive angiography should only be used if surgery is being considered
   12. Magnetic resonance angiography (MRA) may overestimate degree of stenosis (improving)
2. Internal Carotid / Common Carotid
   1. Atherosclerotic plaque breaks off
   2. Thrombus Formation - usually on atherosclerotic (ulcerated plaque)
   3. Carotid Doppler (ultrasound) is recommended for evaluation
3. Cardiac Source
   1. Post-MI or CHF: akinetic, dyskinetic wall, aneurysm
   2. Embolism greatest within 7 days of anterior MI
   3. AFib - high risk particularly with rheumatic heart disease (RHD)
   4. Friable mural (cardiac wall) thrombi are especially common in RHD
   5. Bacterial endocarditis - including infected emboli
   6. Mitral valve prolapse (MVP)
   7. Patent foramen ovale (PFO) - should be investigated in any young person with stroke [60]
   8. Atrial septal defects (ASD)
   9. Transesophageal echocardiography (TEE) is best for evaluation
   10. Sensitivity and specifity of TEE is >97% and is cost effective
4. Causes of Focal Cerebral Infarction
   1. Atherosclerosis (thrombosis) - ulcerated plaque is thrombogenic (Internal carotid, MCA)
   2. Embolism: proximal vessel atherosclerosis, cardiac mural thrombus, valve vegetation
   3. Other embolism: venous thrombous, septal defect
   4. Coagulopathy
   5. Vasculitis
5. Low dose oral contraceptive (OCP) is not a risk factor

F. Symptoms [1,4,7]

1. Symptoms of left hemispheric stroke are significantly more prominant than right sided [4]
2. Middle Cerebral Artery Occlusion
   1. Dominant side: aphasia + right sided weakness
   2. Nondominant side: neglect + left sided weakness
   3. Note: left handed persons may have bilateral language centers
3. Anterior Cerebral Artery
   1. Weakness of leg > arm
   2. Incontinence
   3. Personality change (often depression) [15]
4. Lacunar Syndrome
   1. Weakness on one side with no other findings
   2. Sensory loss on one side with no other findings
   3. Weakness and sensory loss, unilateral, no other findings
5. Posterior Circulation
   1. Isolated homonymous visual field defects - posterior cerebral artery
   2. Bilateral blindness or Diplopia
   3. True vertigo (seen alone, this is rarely associated with stroke)
   4. Cerebellar Signs
   5. Transient weakness with cranial nerve deficits and ataxia - basilar artery
   6. Transient Sensory Changes
   7. Syncope
6. Visual Symptoms
   1. Unilateral vision loss: ophthalmic or branch artery (loss of blood supply to one retina)
   2. Homonymous Hemianopsia or Quadranopsia: Occipital lesion
   3. Internal carotid artery stensosis presents with monocular blindness or TIA or stroke
   4. Transient monocular blindness carries a better prognosis than TIA [52]
7. Amaurosis Fugax
   1. Transient Monocular Blindness
   2. Often described as "shade drawn upward or downward over the eye"
   3. Attacks can be single or multiple
   4. Caused by abrupt, temporary reduction in blood flow to single eye
   5. Most commonly, this is due to arterial occlusion (other causes possible)
   6. Occlusive Arterial Disease: atherosclerosis, thromboemboli, vasculitis
8. Anterior Spinal Artery Occlusion [55]
   1. Sudden lancinating radicular pain
   2. Paresthesia
   3. Selective pain and temperature sensory loss
   4. Preserved tactile sensation
   5. Delayed flaccid paralysis
9. Vertebrobasilar Attacks [22]
   1. Vertigo ~50%
   2. Loss of portion of visual field ~20%
   3. Facial Paresthesia ~20%
   4. Drop Attack ~15%
10. Intracerebral Hemorrhage
    1. Sudden Headache, Nausea and Vomiting
    2. Sometimes triggers vasospasm with possible extension of stroke
    3. Vasospasm may also exacerbate symptoms of a hemorrhagic stroke
    4. Communicating hydrocephalus may develop because of occlusion
    5. Vasospasm and communicating hydrocephalus are much more common with subarachnoid hemorrhage than with brain parenchymal hemorrhage
    6. Electrolyte abnormalities often occur
11. Speech, arms and legs affected: consider very large stroke or subsequent bleeding

G. Diagnosis and Evaluation [2,38,45,53]

1. Must rule out mass lesions as cause of symptoms
   1. Intracranial hemorrhage can present as an acute (hemorrhagic) stroke
   2. Brain tumor (with bleeding into tumor)
   3. Brain abscess
   4. MRI is preferred over CT (improved sensitivity) [13]
   5. Gradient recalled echo (GRE) MRI is most sensitive for detection of acute hemorrhage [40]
2. History and Physical Examination
   1. Focusing on acute facial paresis, arm drift, abnormal speech may improve diagnostic accuracy [12]
   2. Presence of carotid bruits is not sensitive nor specific in a particular patient
   3. Acute onset of focal neurological deficit requires immediate evaluation
   4. Precision based on clinical grounds is very poor in determining stroke type
   5. Level of consciousness is poor prognostic indicator
   6. Change in mental status is an indication for emergent MRI (or CT)
3. Non-Invasive Diagnostic Imaging
   1. Imaging evaluation is critical in all cases to rule out acute hemorrhage [13,26]
   2. Magnetic Resonance Imaging (MRI) is superior to CT for initial diagnosis [13]
   3. Ultrasonography - carotids and cardiac
4. CT Scan
   1. Generally faster and less expensive than MRI
   2. Acute hemorrhage, swelling, midline shift, herniation, radiolucency (wedge shaped)
   3. Vascular distribution, ring enhancement (usually seen in abscess / tumor)
   4. Early ischemic changes on CT scan predict stroke severity but not benefit from TPA [54]
   5. Quantitative CT scanning may provide a tool to predict outcome in stroke prior to thrombolytic therapy [41]
5. Magnetic Resonance Angiography (MRA) and MRI [13,38]
   1. Superior sensitivity versus CT scanning
   2. May provide very early detection of cerebral edema, other ischemic changes
   3. Contrast enhanced MRA superior to other non-invasive methods for detecting >70% carotid stenosis [18,23]
   4. Detection of collateral circulation in setting of carotid occlusion
   5. Diffusion - perfusion weighted MRI scans are able to demarcate ischemic brain regions [45]
   6. GRE MRI is most sensitive method for detection of acute brain hemorrhage [40]
6. Transesphageal Echocardiography
   1. Best method for evaluating cardiac source for thromboembolic stroke
   2. Cost effective and highly sensitive and specific compared with surgical findings
7. Laboratory Diagnostics Acutely [26]
   1. Complete blood count (differential if concern for aspiration or other infection)
   2. Blood glucose level
   3. Serum electrolytes including calcium, magnesium, phosphorus
   4. Renal function: creatinine and blood urea nitrogen
   5. Coagulation Studies: prothrombin and partial thromboplastin times
   6. Urinalysis - including glucose screen, protein
   7. Cardiac enzymes (to rule out MI)
   8. Electrocardiogram (ECG) - baseline is critical
   9. Carotid duplex ultrasound - generally recommended in all patients
   10. Only glucose and platelet count needed prior to tPA (unless on anticoagulation)
8. Brain Specific Protein Markers [37]
   1. Neuron-specific markers S100 and neuron specific enolase released with brain damage
   2. These markers are generally elevated following CABG
9. Plasma Glutamate levels may predict early deterioration (within 48 hours) [27]
   1. Glutamate is an excitatory amino acid released quickly following ischemia (see above)
   2. Glutamate levels in plasma >200µmol/L were associated with poor early outcomes
   3. Glycine levels do not correlate with outcome

H. Overview of Acute Stroke Treatment [1,26,38]

1. Treat as Medical / Neurological Emergency
   1. Stroke care units (SCU) are probably the most important advance in last decade
   2. Management in SCU reduces mortality by >20% and improves functional outcomes
   3. Evaluate immediately with MRI (preferred) or CT to rule out hemorrhage
   4. Lower BP slowly only if diastolic >120mm or systolic >220mm [2]
   5. If no hemorrhage and tPA is not going to be used, give aspirin (ASA) 160-300mg by mouth
   6. Thereafter, 75-160mg ASA daily should be given
   7. ASA + dipyridamole 200mg bid if CVA on ASA alone [2]
2. Supportive Therapy
   1. Prevent aspiration
   2. Give intravenous fluids
   3. Subcutaneous standard or LMW heparin to prevent deep vein thrombosis (DVT)
   4. Graded compression stocking should also be used to prevent DVT
3. Thrombolysis
   1. Thrombolysis with tissue plasminogen activator (TPA) is beneficial up to 3 hours [25,30]
   2. TPA is not effective beyond 4-4.5 hours [26,31]
   3. Risk of bleeding is high, so careful evaluation of imaging study is required
   4. Streptokinase is of no benefit in treatment of stroke [32]
   5. Increase ~10X risk for intracranial hemorrhage and other bleeding within 5-7 days
4. Anti-Coagulation
   1. Only effective when a cardiac embolic source such as AFib is likely
   2. Do not use in large embolic strokes (may cause hemorrhage) until 3-5 days post-stroke
   3. Standard SC heparin has shown no benefit in a large trial [27]
   4. Prophylactic LMW heparin to prevent DVT recommended
   5. Long term anticoagulation for AFib
5. Cardioembolic Source
   1. Anticoagulation is indicated if source known including:
   2. Recent onset AFib, recent MI, carotid plaques, other plaque lesions
   3. Use heparin to prevent further thromboembolic disease (or if posterior stroke)
   4. If no cardioembolic source, then use of heparin is controversial [27]
   5. If stroke is large, may want to wait several days to start anticoagulation
   6. However, this is very controversial, with increasing use of anti-coagulation
6. Stroke in Evolution
   1. Rule out hemorrhage with MRI or CT Scan
   2. Acute anti-coagulation therapy or thrombolysis should be considered
   3. Acute surgery (endarterectomy) may be considered in experienced institutions
   4. Endarterectomy has been effective in major arteries, but only up to primary branches
7. Cerebellar Involvement
   1. Ataxia, loss of coordination; increased drowsiness
   2. Change in mental status: consider increased edema or cerebral hemorrhage
   3. Must consider possibility of bleed with rapid progression (surgical emergency)
   4. Compression on 4TH ventricle leads to CSF Outflow Obstruction and elevated ICP
   5. May progress rapidly to death (emergent CT scan essential)
8. Treatment using existing modalities within 1 day (versus usual 3-20 days) after TIA or minor stroke reduces risk of recurrent stroke at 90 days from 10.3% to 2.1% [61]

I. Improvement in Symptoms Following Stroke

1. Collateral Circulation
   1. Thrombolytics have been shown to improve regional blood flow
   2. Vasodilating agents have not improved outcomes
2. Edema reduction permits more normal function
3. Return of function to partially ischemic areas bordering infarction (called "penumbra") often associated with improved outcome
4. In fact, restoration of blood flow to penumbra neurons should be a major focus of early therapies
5. Neural regeneration can occur in adult brains after stroke (focus of much research) [58]

J. Worsening of Symptoms Following Stroke

1. Infarction extends
2. Hemorrhage occurs
3. Edema, swelling can lead to herniation syndromes (especially cerebellar infarcts)
4. CT or MRI indicated acutely if symptoms worsen
5. Consider anti-coagulation if hemorrhage is not present

K. Common Medical Complications

1. Aspiration
2. Sepsis
3. Hypoxia
4. Hypoglycemia or Hyperglycemia - glucose control is critical during recovery phase
5. Syndrome of Inappropriate Anti-Diuretic Hormone (mainly with SAH)
6. Cardiac: Arrhythmias, Infarction, heart failure
7. DVT ± Pulmonary Embolism
8. Depression [15]
9. Recurrent Stroke

L. Syndromes Associated With Stroke

1. Multi-infarct Dementia
   1. Vascular disease is likely the second most common cause of stroke
   2. LDL cholesterol levels correlate with development of dementia in the setting of stroke
2. Post-Stroke Depression [43]
   1. Originally believed to be more prevalent after anterior left hemisphere lesions
   2. However, review has shown location of brain lesion does not affect risk of depression
3. Other Behavioral Changes
4. Wallenberg's Syndrome
   1. Lateral Medullary Syndrome (infarction)
   2. Due to thromboembolism vertebral artery > posterior inferior cerebellar artery [22]
   3. Loss of pain sensation on ipsilateral face (Descending CN V) and contralateral body
   4. Vertigo (CN VIII), Ataxia (Cerebellar), Dysarthria (CN IX and X), Horner's Syndrome
5. Other characteristic deficits with specific arterial occlusions

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