Stroke

Sean Barber, Jaime Gasco, Remi Nader, and Aaron Dumont

What is a stroke?

A neurological deficit resulting from poor perfusion of a portion of the brain or brainstem

What is the mechanism by which poor perfusion leads to neuronal injury and death?

An inability to undergo aerobic glycolysis and oxidative phosphorylation leads to:

• Deficiency of ATP and failure of the Na⁺/K⁺ ATPase (resulting in cell swelling)

• Failure of the Ca²⁺,Mg²⁺ ATPase (leading to an influx of Ca²⁺)

• Reduced protein synthesis (which requires ATP)

• Activation of phospholipases, proteases, and endonucleases (by the increased intracellular Ca²⁺)

• Accumulation of free radicals (leading to membrane lipid peroxidation, DNA fragmentation, and protein cross-linking and fragmentation)

• Accumulation of glutamate and other excitatory neurotransmitters (leading to excitotoxic damage)

What are the three types of stroke?

• Ischemic infarct: most common (87% of strokes)1

• Hemorrhagic stroke (10% of strokes)¹

• Venous infarct

What are some modifiable risk factors for stroke?

Hypertension, tobacco smoking (doubles the risk of ischemic stroke²), heavy alcohol consumption, diabetes, dysrhythmia, pregnancy, physical inactivity, low HDL cholesterol

What EEG changes are typically seen in the penumbra region?

Isoelectric silence

Which brain regions are most susceptible to global cerebral ischemia (“watershed zones”)?

Those regions at the most distal fields of arterial irrigation. The border zone between ACA and MCA distributions is at greatest risk. A stroke in this watershed region may be seen as a “sickle-shaped” necrotic band a few centimeters lateral to the interhemispheric fissure in the setting of hypotensive episodes.

What inflammatory conditions can lead to vessel occlusion and cerebral infarcts?

Arteritis

• Infectious

• Polyarteritis nodosa

• Primary (granulomatous) angiitis of the CNS

What is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)?

A hereditary condition leading to stroke. Caused by mutations in the Notch3 gene. Characterized by recurrent strokes and dementia. Diagnosis is by demonstration of basophilic, PAS-positive granules in walls of affected vessels as well as in skin and muscle.3

What is cerebral amyloid angiopathy (CAA)?

A condition (may be sporadic or familial) in which an amyloidogenic peptide (Aβ₄₀) is deposited in the walls of meningeal and cortical vessels, weakening vessel walls and resulting in an increased risk of hemorrhage⁴

Where do emboli causing embolic strokes typically originate?

• Cardiac mural thrombi (e.g., in atrial fibrillation, MI, valvular disease)

• Paradoxical thrombi in patients with cardiac anomalies or patent foramen ovale

• Emboli from carotid artery atheromatous plaques

Which artery is most frequently occluded by embolic strokes?

MCA^5,6

What is the most common underlying cause of spontaneous (nontraumatic) intra cerebral (intraparenchymal) hemorrhage (ICH)?

Hypertension (>50% of ICHs). Other causes include systemic coagulopathy, neoplasms, amyloid angiopathy, vasculitis, aneurysms, vascular malformations, drugs (e.g., cocaine)

Where are the most common sites for hypertensive intra-cerebral hemorrhage?

Putamen (50–60%), thalamus, pons, cerebellum (especially dentate nuclei)

Fig. 53.1 Axial CT scan revealing right putaminal hemorrhage in a hypertensive patient.

What are lacunar infarcts?

Small, cavitary (lacunar = “lake-like”) areas of tissue loss (<15 mm wide) occurring in the lenticular nucleus (most common), caudate, thalamus, pons, internal capsule, and deep white matter (least common) due to hypertensive changes and resultant infarction of the deep penetrating arteries and arterioles that supply these structures.

What is a transient ischemic attack (TIA)?

Transient (<24 hours) neurological deficit resulting from poor perfusion of a region of the brain or brainstem

What is the risk of stroke after TIA?

5% of TIA patients will have a stroke within 48 hours,⁷ and 10% will have a stroke within 90 days^1,7

How long after initial stroke symptoms can an ischemic stroke typically be visualized on CT?

Most strokes can be seen as a low density by 24 hours. Some ischemic strokes may reveal early (hyperacute, <6 hours) signs that may confer a worse prognosis (particularly in MCA strokes).⁸

What are some early (<6 hours) signs of ischemic stroke that may be seen on CT or MRI?

• CT often normal9

• Loss of gray-white interface

• Mass effect (effacement of sulci, midline shift)^10,11

• Enhancement⁹

• Hyperdense artery sign (intraarterial clot leads to increased arterial density on noncontrast CT)

• Insular ribbon sign: loss of the normally striated appearance of the insular cortex due to edema in the distribution of the lenticulostriate arteries¹⁰

What is the National Institutes of Health Stroke Scale (NIHSS)?

A scale (based on the Cincinnati stroke scale) designed to assess stroke severity in suspected stroke patients. Higher scores indicate more widespread deficits (likely due to occlusion or larger and/or more proximal vessels).^12,13

How are ischemic strokes treated?

• Airway, ventilator support, and supplemental oxygen

• Maintenance of normothermia, normotension, and normoglycemia

• Close monitoring of vitals (cardiac monitoring), neuro status, and laboratories (e.g., CBC, electrolytes)¹⁴

• Aspirin, anticoagulation

• Steroids (for steroid-responsive vasculitis)

• Mannitol (for mass effect)

• Keep patient supine with modest head elevation (to maximize CBF)

• Correction of anemia

In cases where the patient presents within a 4.5-hour window thrombolytic therapy (IV or IA tPA) may be indicated. Other procedures potentially indicated in early stages include mechanical embolectomy and reduction of mass effect (e.g., in the presence of brainstem compression as in cerebellar stroke)

What is the time window during which IV tPA may be indicated for treatment of ischemic stroke?

Up to 4.5 hours following onset of symptoms (4.5 hours from the time the patient was last seen without symptoms). This window was formerly set at 3 hours, but was increased to 4.5 hours in select patients (age <80, baseline NIHSS score <25, no prior stroke history if diabetic) due to the results of the 2009 European Cooperative Acute Stroke Study (ECASS) III.^15,16

What are some of the absolute contraindications to IV tPA?

• ICH on admission CT or history of ICH

• Clinical signs of SAH

• Known intracranial aneurysm, neoplasm, or AVM

• Hypodensity of more than one third of the cerebral hemisphere on CT (multilobar infarction)

• Active internal bleeding or acute trauma

• Coagulopathy (INR >1.7 or PT >15 seconds, platelet count <100,000, heparin in last 48 hours)

• Hypertension (SBP >185 mm Hg or DBP >110 mm Hg) not controlled with nicardipine or IV labetalol

• Intracranial or intraspinal surgery, serious head trauma, or previous stroke within last 3 months 17,18

How long should anticoagulation and antiplatelet drugs be held following IV tPA treatment?

24 hours^17,18

What is the primary risk associated with the use of IV tPA?

Intracranial hemorrhage (seen in 6.4 to 8.8% of patients receiving IV tPA compared with 0.6 to 3.4% receiving placebo)^19,20

What are the indications for endovascular treatment of ischemic stroke (intraarterial tPA or mechanical embolectomy)?

Failure of IV tPA, time window 4.5 to 6 hours (ineligibility for IV tPA due to time criteria)

True or false: Hypertension should be treated aggressively in stroke patients.

False. Hypertension may be needed in stroke patients to maintain cerebral blood flow and should be treated cautiously. Blood pressure should be monitored every 15 minutes in post IV-tPA patients, and SBP >180 or DBP >105 should be treated with IV labetalol, nicardipine infusion, or sodium nitroprusside as per American Heart Association (AHA) guidelines.²¹

When is anticoagulation indicated in stroke patients?

Heparin therapy is rarely indicated in acute ischemic stroke.²² High-intensity warfarin therapy has been proven beneficial in acute ischemic stroke in the setting of antiphospholipid antibody syndrome.²³

When is decompressive craniectomy indicated in stroke patients?

Suboccipital craniectomy may reduce mortality in patients with cerebellar stroke and progressive neurological deterioration/deficit due to brainstem compression.24–26

Early (<24 hours) decompressive hemicraniectomy has been shown to reduce mortality and improve functional outcome in select patients with large hemispheric infarctions (e.g., malignant MCA territory infarction).^27–29

When is carotid endarterectomy indicated in stroke patients?

When high-grade carotid stenosis (50–99%) is demonstrated ipsilateral to a neurological deficit³⁰

What neurological deficits are associated with occlusion of the MCA?

• Contralateral (CL) bodily weakness (UE > LE)

• CL weakness of lower face

• CL sensory loss (UE, LE, and face)

• CL neglect

• Ipsilateral (IL) gaze preference

• CL homonymous hemianopsia

In cases where dominant hemisphere is involved:

• Aphasia (receptive and/or expressive)

• Gerstmann syndrome

What is Gerstmann syndrome?

Neurological deficits resulting from damage (e.g., due to infarct, mass) of dominant parietal lobe, including:

• Agraphia (inability to write)

• Left-right confusion

• Digit agnosia (inability to identify finger by name)

• Acalculia (inability to perform rudimentary mathematics)

What neurological deficits are associated with occlusion of the ACA?

CL weakness (LE > UE), abulia, aphasia

What neurological deficits are associated with occlusion of the PCA?

• CL homonymous hemianopsia (macular sparing present due to redundant supply from MCA)

• Balint syndrome: poor hand-eye coordination, oculomotor apraxia (poor voluntary guidance of eye movements), simultanagnosia (inability to simultaneously perceive two objects)

• Anton-Babinski syndrome: “cortical blindness,” the patient is blind but does not admit to blindness and may confabulate or appear unaware of the deficit

• Alexia (inability to read)

• Dejerine-Roussy syndrome (thalamic pain syndrome)

What neurological deficits are associated with occlusion of the vertebral artery?

Lateral (Wallenberg) or medial (Dejerine) medullary syndrome

What is Wallenberg syndrome?

Also known as lateral medullary syndrome. A syndrome classically attributed to occlusion of PICA, although occlusion of the vertebral artery is more commonly (80–85%) the cause.31,32 Symptoms include:

• IL facial pain and sensory loss (due to damage to the descending tract and nucleus of V)

• IL Horner’s syndrome (due to damage to the descending sympathetic tract)

• Hoarseness and dysphagia (due to damage to the nucleus ambiguous)

• Possible vertigo, nystagmus, diplopia, and IL cerebellar deficits, e.g., ataxia (due to damage to the inferior cerebellar peduncle and vestibular nuclei)

• CL loss of bodily pain and temperature sensation (due to damage to the spinothalamic tract)

• Palatal myoclonus may be seen due to disruption of the central tegmental tract.

What symptoms are expected with medial medullary syndrome (Dejerine syndrome)?

• Contralateral hemiparesis (due to damage to the ipsilateral pyramid)

• Contralateral sensory deficits (due to damage to the medial lemniscus)

• Ipsilateral paralysis and atrophy of tongue muscles (due to damage to the hypoglossal nucleus and/or nerve)

What neurological deficits are associated with occlusion of AICA?

Lateral pontine syndrome, also known as Marie-Foix syndrome. Symptoms include:

• CL loss of pain and temperature (due to damage to the spinothalamic tract)

• IL weakness of lower face, with or without decreased salivation and lacrimation, with or without loss of taste to anterior two thirds of tongue (due to damage to the facial nerve and nucleus)

• Nystagmus, vertigo (due to damage to the spinal trigeminal nucleus and tract)

• IL hearing loss (due to damage to the cochlear nuclei)

• IL cerebellar signs (due to damage to the middle and inferior cerebellar peduncles)

• IL Horner’s syndrome (due to damage to the descending sympathetic fibers)

What neurological deficits are associated with occlusion of the anterior choroidal artery?

Damage to posterior limb of IL internal capsule. Symptoms include:

• CL weakness (corticospinal pathway)

• CL sensory loss (dorsal columnar pathway)

• CL homonymous hemianopsia (visual pathway)