Basic Anatomy

• The anterior circulation, consisting of the paired internal carotid arteries and their branches (ophthalmic, anterior cerebral, and middle cerebral arteries), supplies most of the cerebral hemispheres and the deep cortical gray matter.
• The anterior cerebral artery (ACA) supplies the parasagittal cerebral cortex, which includes portions of the motor and sensory cortex related to the contralateral lower limb and the so-called bladder inhibitory or micturition center.
• The middle cerebral artery (MCA) supplies most of the remainder of the cerebral hemisphere, and deep cortical structures.
• The cortical branches of the MCA include the superior division, which supplies the entire motor and sensory cortical representation of the face, and upper limb; and the expressive language (Broca’s) area of the dominant hemisphere.
• The inferior division supplies the visual radiations, the region of visual cortex related to macular vision, and the receptive language (Wernicke’s) area of the dominant hemisphere.
• Lenticulostriate branches supply the basal ganglia, as well as motor fibers related to the face, hand, arm, and leg.
• The posterior circulation, consisting of the paired vertebral arteries, the basilar artery, and their branches—the posterior inferior cerebellar (PICA), anterior inferior cerebellar (AICA), superior cerebellar, and posterior cerebral arteries—supplies the brainstem, cerebellum, thalamus, and the medial aspects of the occipital and temporal lobes.
• The anterior and posterior circulations join via the posterior communicating arteries to form the circle of Willis at the base of the skull.

Clinicoanatomic Correlation

• Anterior Circulation
• Anterior circulation strokes rarely have associated symptoms; neurologic deficits accompanied by headache, nausea, and vomiting are more suggestive of intracerebral hemorrhage or posterior circulation stroke.
• Clinical syndrome of ACA occlusion
• Contralateral weakness and sensory loss affecting the lower limb.
• Confusion and impaired cognition.
• Urinary incontinence.
• Clinical syndrome of MCA occlusion
• Superior division stroke results in contralateral weakness and sensory deficit in the face and upper limb.
• If the dominant hemisphere is involved, Broca’s aphasia occurs (impaired language expression with normal comprehension).
• Inferior division stroke results in marked impairment of contralateral cortical sensory functions, contralateral homonymous hemianopsia, and contralateral neglect.
• If the dominant hemisphere is involved, Wernicke’s aphasia occurs (impaired comprehension and recall, with fluent—but often nonsensical—speech).
• An acute confusional state may indicate involvement of the nondominant hemisphere.
• Occlusion at the bifurcation or trifurcation of the MCA combines the features of superior and inferior division stroke.
• Posterior Circulation
• Posterior circulation strokes frequently present more of a diagnostic challenge. In addition, complications of cerebellar infarcts, such as edema compressing brainstem structures, may cause rapid deterioration (i.e., within hours).
• Symptoms associated with vertebrobasilar infarcts include syncope, dizziness and vertigo, nystagmus, dysphagia, dysarthria, facial sensory disturbance, ataxia, depressed consciousness or confusion, and incontinence.
• Clinical syndrome of posterior cerebral artery (PCA) occlusion
• Contralateral homonymous hemianopsia.
• Ocular abnormalities (including oculomotor (III) nerve palsy and internuclear ophthalmoplegia).
• With involvement of the dominant hemisphere, patients may be unable to name objects or to read but retain the ability to write.
• Clinical syndrome of basilar artery occlusion
• Thrombosis is often incompatible with survival.
• Basilar artery thrombosis affects the pons and may be confused with pontine hemorrhage.
• Coma is common.
• Hemiplegia or tetraplegia is usually present.
• The pupils are constricted but reactive.
• Involvement of the dorsal portion of the pons (i.e., the tegmentum) produces unilateral or bilateral abducens (VI) nerve palsy; vertical nystagmus may be present.
• Infarction of the ventral portion of the pons with sparing of the tegmentum causes tetraplegia in a patient who remains conscious (referred to as the locked-in syndrome). Voluntary eye opening, vertical eye movements, and ocular convergence are preserved.
• Emboli usually stop at the top of the basilar artery, at the bifurcation into the PCAs.
• Immediate loss of consciousness (or depressed LOC) is caused by impaired blood flow to the reticular activating system.
• Hemiplegia or tetraplegia with decerebrate or decorticate posturing.
• Ipsilateral or bilateral oculomotor (III) nerve palsies.
• Clinical syndrome of PICA occlusion
• Results in lateral medullary (Wallenburg’s) syndrome
• Symptoms may include vertigo, nausea, vomiting, dysphagia, dysarthria, hoarseness (due to vocal cord paralysis), and hiccup.
• Neurologic exam may reveal nystagmus; ipsilateral Horner’s syndrome, paralysis of the soft palate and posterior pharynx, and limb ataxia; and impaired pain/ temperature sensation in the ipsilateral face and contralateral limbs.
• The motor system is spared.
• Clinical syndrome of AICA occlusion
• Produces ipsilateral facial weakness, gaze palsy, deafness, and tinnitus.
• Clinical syndrome of superior cerebellar artery occlusion
• Hypertropia (deviation of the eyes in opposite directions equally).
• Contralateral sensory disturbance.
• Lacunar Infarction
• These infarcts occur in the deep gray and white matter structures (e.g., basal ganglia and internal capsule); the onset may be subacute with symptoms developing over hours or days.
• Headache is absent or minor; there is no impairment in level of consciousness.
• Pure motor hemiparesis: uniformly affects the contralateral face and limbs.
• Pure sensory stroke: contralateral hemisensory loss (may be associated with paresthesia).
• Dysarthria-clumsy hand syndrome: includes dysarthria, dysphagia, and contralateral facial and hand weakness and clumsiness.
• Ataxic hemiparesis: consists of cerebellar ataxia and leg > arm > face weakness.

Scope of the Problem

• Disruption in the flow of blood to the brain results in ischemia and cell death. The central area of infarction is surrounded by a region of salvageable tissue, referred to as the penumbra.
• Mechanisms of ischemia include embolism, thrombosis, and hemorrhage. Identifying the etiology of the patient’s symptoms is critical for determining therapy.
• Massive cerebral infarcts are typically associated with cerebral edema, which peaks 3 to 5 days after onset. Patients with such swelling are at risk for herniation.

• Vascular Disorders
• Atherosclerosis
• Diastolic or isolated systolic hypertension
• Hyperlipidemia (hypercholesterolemia)
• Cigarette smoking
• Oral contraceptive use
• Diabetes mellitus
• Hereditary predisposition (i.e., family history of ischemic vascular disease at age <60)
• Excessive alcohol use
• Physical inactivity
• Age
• Male gender
• Ethnicity
• Carotid or vertebral artery dissection
• Signs and symptoms of carotid dissection may include jaw or neck pain, visual changes similar to those that accompany migraine headaches, and Horner’s syndrome.
• Vertebral or basilar artery dissection is associated with headache, posterior neck pain, and acute brainstem dysfunction.
• Venous or sinus thrombosis
• Patients with this disease process usually have a predisposing condition, such as contiguous infection (e.g., otitis, sinusitis), hypercoagulable state, or dehydration.
• Clinical manifestations include headache, papilledema, depressed level of consciousness, seizures, and focal neurologic deficits.
• Inflammatory disorders
• Giant cell arteritis, systemic lupus erythematosis, polyarteritis nodosa, granulomatous angiitis (primary angiitis of the CNS), syphilitic arteritis, AIDS
• Drug abuse
• Cocaine, amphetamines, and heroin
• Infective endocarditis caused by IV drug abuse may lead to embolic stroke.
• Other forms of drug abuse are postulated to cause vasospasm, vasculitis, or rupture of preexisting aneurysms or vascular malformations.
• Migraine
• Fibromuscular dysplasia
• Cardiac Disorders
• Mural thrombus
• Generally associated with myocardial infarction (MI) or cardiomyopathy.
• Rheumatic heart disease
• Arrhythmias
• Atrial fibrillation and bradycardia-tachycardia (sick sinus) syndrome
• Endocarditis
• Mitral valve prolapse: small increase in risk of stroke; massive strokes are rare
• Paradoxic embolus
• Embolic material from the systemic circulation may gain access to the brain through a pathologic communication between right and left sides of heart (e.g., ASD, patent foramen ovale).
• Atrial myxoma
• Prosthetic heart valves
• Hematologic Disorders
• Thrombocytosis, polycythemia, sickle cell disease, leukocytosis (i.e., leukemia), hypercoagulable states

Diagnosis
History

• Attempt to identify, as accurately as possible, the onset, course, and type of symptoms, as well as the patient’s activity at onset.
• Determine the patient’s stroke risk factors, other potential causes for the patient’s symptoms, and any contraindications to thrombolytics or other agents.
• Neurologic deficits that occur abruptly, and are maximal at onset, suggest an embolic stroke. Stepwise, incremental deficits are more indicative of thrombosis.
• Hemorrhagic strokes often have a rapid onset. Maximum deficit may be present immediately but worsening may occur. Consciousness may be impaired.
• Subarachnoid hemorrhage (SAH) is characterized by symptoms of variable onset and progression; severe headache and neck stiffness; and often impaired consciousness.

• Hypotension may be the underlying cause of a stroke; markedly elevated blood pressure is suggestive but not diagnostic of a hemorrhagic stroke.
• An irregular cardiac rhythm may indicate chronic or new-onset atrial fibrillation and an embolic source.
• Increased ICP may be accompanied by bradycardia.

Physical Examination

• Focus on searching for an underlying systemic cause, especially a treatable one.
• HEENT
• Note any signs of trauma. Palpate the temporal arteries.
• Fundoscopic exam may reveal evidence of embolization. Papilledema indicates increased ICP. Retinal hemorrhages may be noted in SAH.
• Determine patency of the airway and ensure the airway is protected.
• Neck: evaluate the carotid pulses and check for carotid bruits, Neck stiffness may or may not be present in SAH.
• Cardiac exam: note any arrhythmias or evidence of valvular disease (i.e., murmurs).
• Neurologic exam
• The initial neurologic exam should be a brief search for signs of increased ICP or impending transtentorial herniation (e.g., dilated pupil, depressed consciousness, or posturing).
• Neurologic deficits that do not conform to the distribution of any single cerebral artery suggest a hemorrhagic or mass lesion.
• Assess the level of consciousness and mental status. Determine whether the patient has aphasia (expressive or receptive?) or dysarthria.
• Evaluate cranial nerve function, with special attention paid to pupils, extraocular movements, visual fields, facial symmetry, gag reflex and corneal reflex.
• The presence of a gaze palsy may help localize the lesion. A patient with a cerebral hemispheric stroke will typically gaze toward the side of the insult; a brainstem infarct will cause the patient to gaze away from the side of the lesion.
• Motor exam: the most sensitive indicator of upper extremity weakness is the presence of a pronator drift. Whenever possible, lower extremity strength should be assessed by observing the patient’s gait.
• Sensory exam: peripheral sensation (light touch, pinprick, and vibration/position sense). Double simultaneous stimulation: assess sensation on both sides of the body simultaneously; patients with cortical infarcts will only notice the unaffected side.
• Cerebellar exam: look for nystagmus, ataxia, or poor coordination.
• Reflexes: recent stroke is accompanied by hyporeflexia (and flaccidity). Search for pathologic reflexes (e.g., presence of a Babinski reflex indicates an upper motor neuron disorder).

Evaluation

• Pulse Oximetry
• Rapid determination of oxygen saturation may reveal impending respiratory failure and the need for mechanical ventilation. Supplemental oxygen may suffice.
• Laboratory
• Bedside glucose testing is crucial to exclude hypoglycemia as a cause of focal neurologic deficits.
• A complete blood count may reveal an underlying hematologic disorder presenting as a stroke.
• Prothrombin time (PT) and partial thromboplastin time (PTT) are helpful in excluding coagulopathy.
• Baseline serum electrolytes are recommended.
• An elevated ESR may suggest giant cell arteritis or other vasculitis.
• Blood for type and cross match (patients with SAH)
• Consider a toxicology screen in patients suspected of drug abuse (although the results seldom change the patient’s acute management).
• Pregnancy test in females of child-bearing age.
• Lumbar puncture (LP) is indicated when CNS infection or SAH is suspected. In the case of SAH, LP is performed after a negative CT scan. LP may also suggest a venous or sinus thrombosis (CSF pressure is typically increased and pleocytosis may occur), or granulomatous angiitis (CSF pleocytosis occurs).
• EKG
• May detect cardiac ischemia, or cardiac arrhythmias which predispose to stroke (e.g., atrial fibrillation). In addition, multiple abnormalities are described in patients with subarachnoid hemorrhage, including peaked or symmetric, deeply inverted T waves; shortened PR intervals; and tall U waves.
• Chest radiograph
• In selected patients, chest X-ray (CXR) may reveal an infectious process, malignancy, or evidence of heart failure. In intubated patients, CXR is used to confirm placement of the endotracheal tube.
• Imaging
• Noncontrast CT scan is the emergency radiologic study of choice when evaluating patients with suspected stroke, TIA, or SAH. CT is able to distinguish between ischemic and hemorrhagic strokes, and will detect blood in more than 90% of cases of aneurysmal rupture. In addition, early signs of cerebral edema are identified with noncontrast CT scanning.
• When available, MRI is useful for early ischemic infarcts. MRI may also be more sensitive for ischemic strokes in the brainstem or cerebellum, as well as in detecting thrombotic occlusion of venous sinuses.
• Electroencephalogram (EEG) is rarely useful in the acute evaluation of stroke. It may, however, help to differentiate between seizure disorder and TIA, or between lacunar and cortical infarcts.

Differential Diagnosis

• Vascular Disorder
• Intracerebral hemorrhage, SAH
• Subdural or epidural hematoma
• Hypertensive encephalopathy
• Complicated migraine
• Arterial embolism to an extremity
• Air embolism
• Structural Lesion
• Abscess, neoplasm
• Multiple sclerosis
• Metabolic Process
• Hypoglycemia, hyperosmolar nonketotic hyperglycemia
• Infectious Process
• Encephalitis, meningitis
• Peripheral Nerve Disorder
• Bells palsy, other peripheral nerve palsies
• Peripheral vertigo
• Other
• Acute angle closure glaucoma
• Seizure with postictal (Todd’s) paralysis

Treatment

• General Management Issues
• As with all emergent conditions, evaluation of the patient with a neurologic deficit begins with airway, breathing, and circulation. Patients with severely depressed mental status and patients with an unprotected airway may require intubation and mechanical ventilation.
• All patients should be placed on continuous pulse oximetry and cardiac monitoring, and have peripheral intravenous access established.
• Patients noted to have signs of increased ICP should be aggressively managed.
• Oxygen
• Supplemental oxygen may be required to maintain oxygen saturation >95%. However, in the absence of hypoxia, supplemental oxygen has not been shown to affect outcome.
• Blood Pressure Control
• In the first few hours following acute stroke, mild to moderate hypertension is commonly observed. Over the next few hours to days, the blood pressure generally declines spontaneously. The ischemic penumbra may be dependent upon a moderately increased blood pressure for adequate perfusion; thus, use of antihypertensive agents may exacerbate the patient’s condition.
• Cautious blood pressure control—with easily titratable, short-acting parenteral medications—is recommended in the following situations: (1) hypertensive encephalopathy; (2) cardiac ischemia or aortic dissection; (3) intracerebral hemorrhage; (4) when thrombolytic therapy is considered (see exclusion criteria below); and (5) the mean arterial pressure (MAP) is >130, or the SBP is >220.
• Anticoagulants
• Heparin has been shown to benefit patients at risk for cardioembolic stroke (especially patients with ischemic or rheumatic heart disease). In addition, patients with venous sinus occlusion benefit from heparin use.
• Antiplatelet Agents
• Aspirin has been shown to reduce the rate of nonfatal recurrent stroke and death after acute stroke (versus placebo). Aspirin is recommended in patients who are not candidates for thrombolytics or other anticoagulants.
• Ticlopidine inhibits the ADP pathway of platelet aggregation; it also reduces blood fibrinogen levels. In patients with TIA or minor stroke, ticlopidine results in significant risk reduction in stroke recurrence or death versus aspirin. However, the hematologic side effects (TTP, thrombocytopenia, and neutropenia) have limited its recommended use to patients who have a contraindication to aspirin and who can be closely monitored in this setting; clopidogrel is preferred by many practitioners.
• Clopidogrel is similar in action and effect to ticlopidine. It is recommended for aspirin-intolerant patients and has a significantly lower rate of TTP than ticlopidine.

Specific Treatment
Acute Ischemic Stroke

• Intravenous Thrombolytics (IV rt-PA)
• In the NINDS rt-PA stroke study, patients treated with rt-PA within 3 h of symptom onset were at least 30% more likely (than patients given placebo) to have minimal or no disability at 3 mo on various clinical scales. However, 6.4% of patients in the treatment arm had a symptomatic ICH within 36 h of stroke onset, compared with 0.6% of patients given placebo. Mortality was similar in both groups. Based on these results, the FDA approved the use of IV rt-PA in acute ischemic stroke within 3 h of symptom onset. In addition, the AHA and the American Academy of Neurology have issued practice guidelines recommending the use of intravenous thrombolysis.
• Other studies have failed to show improvement in outcome over placebo. For this reason, the use of thrombolytics in stroke remains controversial. However, because this modality is now being described by certain groups as the standard of care, the inclusion and exclusion criteria are included here. It is important to note that both ACEP and ABEM have developed position statements which indicate that further studies are necessary before thrombolytics become a community standard of care.
• Dosing for IV rt-PA is as follows: 0.9 mg/kg total dose, with 10% given over 1 min as a bolus; the remainder is infused over 1 h.
• Consultation with a neurologist is strongly recommended prior to the initiation of IV rt-PA. Patients with very severe deficits, as well as those over age 75, are probably at increased risk for ICH. Accurate informed consent is critical.
• Inclusion criteria
• Age >18 yr
• Ischemic stroke with a clearly defined time of onset within 3 h of initiation of treatment
• Neurologic deficit measurable on the NIHSS
• Baseline CT scan of the brain with no evidence of intracranial hemorrhage
• Exclusion criteria
• Patient history
• Stroke or serious head trauma within the preceding 3 mo
• Major surgery (or biopsy of a parenchymal organ) within the past 14 days
• Prior intracranial hemorrhage; history of CNS neoplasm, aneurysm, or AVM
• Arterial puncture at a noncompressible site within the past 7 days
• Gastrointestinal or urinary tract hemorrhage within the previous 21 days
• Lumbar puncture within the past 7 days
• Recent myocardial infarction
• History of known hereditary or acquired abnormal hemostasis
• Pregnant or lactating female
• Clinical features
• Systolic BP >185 mm Hg or diastolic BP >110 mm Hg, or aggressive treatment is required to reduce blood pressure to the specified limits Rapidly improving or minor symptoms
• Symptoms suggestive of subarachnoid hemorrhage (SAH)
• Seizure at the onset of stroke
• Clinical presentation consistent with acute MI or post-MI pericarditis
• Diagnostic studies
• Major hypodensity or effacement of cerebral sulci in more than one-third of the territory of the MCA
• Received heparin within 48 h of stroke onset, with elevated PTT
• Prothrombin time (PT) >15 seconds
• Platelet count <100,000/mm3
• 50 > glucose >400 mg/dL

TIA

• In the past, patients with neurologic symptoms that resolved within 24 h were said to have had a transient ischemic attack (TIA). However, recent evidence indicates that evidence of infarction is seen on CT of patients whose symptoms last more than 1 h.
  For this reason, many neurologists are describing symptoms that persist for more than 1 h as an acute stroke. In addition, the majority of TIAs resolve within minutes.
• Patients with TIAs are at increased risk for subsequent stroke and death.
• Aspirin, ticlopidine, and clopidogrel have all been shown to reduce the risk of future TIAs, strokes, and death.
• Anticoagulation is recommended for patients with cardiac embolus as a cause of their TIA symptoms.

  Table Grading of patients with subarachnoid hemorrhage

  Grade	Mental Status	Neurologic Deficits	Surgical Candidate
  I	Normal	None	Yes
  II	Mildly altered	Minimal, focal	Yes
  III	Confused Mild,	focal	Yes
  IV	Stuporous	Moderate to severe	No
  V	Coma	Decerebrate posturing	No

Hemorrhagic Stroke

• Cautious blood pressure control is recommended. Various guidelines exist, ranging from keeping the diastolic blood pressure at approximately 100 mm Hg to basing the target systolic and diastolic levels on the patient’s premorbid blood pressure.
• Look for and aggressively treat early signs of increased ICP with head-of-bed elevation, diuretics (furosemide, mannitol), and hyperventilation.
• Although most cases of ICH are not amenable to neurosurgical intervention, some patients benefit from surgical drainage. Potential surgical candidates are those with neurologic deterioration, superficial cerebral hemorrhages causing mass effect, and cerebellar hematomas. Neurosurgical consultation is recommended in all patients with intracerebral hemorrhage.

Subarachnoid Hemorrhage

• SAH frequently results from rupture of an aneurysm or AVM. Preventing rerupture, by maintaining adequate blood pressure control, is the mainstay of treatment. Elevation of the head of the bed, mild sedation, and analgesics (for headache) may suffice.
  The blood pressure should be reduced to approximately 160/100 mm Hg, using rapidly titratable, parenteral medications if necessary.
• Nimodipine, a calcium channel blocker, is indicated for the prevention of cerebral vasospasm in order toprevent subsequent ischemia; the dose is 60 mg enterally every 4 h.
• A prophylactic anticonvulsant is recommended; consider corticosteroids.
• Prompt neurosurgical consultation is recommended. The timing and outcome of surgical intervention are determined by the patient’s clinical grade and medical stability, among other factors.
• Grading of patients with SAH (Table 4E.1).

• Acute Stroke Syndromes
• Patients with acute intracerebral hemorrhage require admission to an ICU or step-down unit for close monitoring.
• All patients with acute ischemic strokes should be hospitalized for medical stabilization and evaluation of their functional independence as well as their rehabilitation potential. Patients who receive thrombolytics should be admitted to the ICU within 3 h.
• Patients with multiple previous strokes may not require admission if they are medically stable and social support is adequate.
• TIA
• Current recommendations are that patients with new TIAs be admitted for workup and initiation of treatment.