Cerebral Ischemia and Ischemic Stroke

Overview


Roughly 2 per 1,000 persons per year sustain an ischemic stroke; the incidence of stroke rises markedly with age. Women are less commonly affected than men up to age 80, and equally commonly afterward.


Cerebral ischemia is critically impaired perfusion in an area of the brain.


Cerebral ischemia can be classified by




  • Etiology: ischemia is mostly caused by the blockage of arteries by emboli (arterio-arterial emboli from atherosclerotic stenoses, as well as cardiogenic emboli), macroangiopathy (arteriosclerotic vascular occlusion), or microangiopathy (occlusion of smaller vessels by fibrinoid necrosis, also called “lipohyalinosis”). Impaired venous outflow is a less common cause.



  • Course: transient ischemic attack (TIA) versus progressive or completed stroke.



  • Type of infarction: territorial, watershed, border zone, lacunar.



  • The affected vessel and the resulting vascular syndrome (e.g., middle cerebral artery [MCA] syndrome, posterior cerebral artery syndrome, basilar artery syndrome). Depending on the extent of tissue injury caused by ischemia, the ensuing neurologic deficits may be either transient or permanent.


Every ischemic event calls for thorough diagnostic evaluation to determine the cause, so that recurrences can be prevented. Moreover, appropriate treatment must be given immediately (above all, hemodynamic stabilization and surveillance, thrombolytic treatment where indicated, and recurrence prophylaxis). The diagnosis and treatment of stroke in a specialized institution (a so-called stroke unit or stroke center) is associated with a markedly better outcome.


6.5.2 Anatomy and Pathophysiology


Arterial Blood Supply of the Brain


To understand how the localization and extent of cerebral infarcts depends on the particular artery that is occluded, one must know the anatomy of the territories of the individual vessels, as well as their numerous anastomoses. The anastomotic arterial circle of Willis, at the base of the brain, provides a connection between the carotid and vertebral circulations and between the blood supplies of the right and left cerebral hemispheres ( ▶ Fig. 6.19). The territories of the major cerebral arteries are shown in ▶ Fig. 6.20.



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Fig. 6.19 Arteries of the base of the brain. (Reproduced from Bähr M, Frotscher M. Duus’ Topical Diagnosis in Neurology. 4th ed. Stuttgart: Thieme; 2005.)



9783131364524_c006_f020.eps


Fig. 6.20 Territories supplied by the individual arteries of the brain.


The Regulation of Cerebral Perfusion


Glucose is the brain’s nearly exclusive source of energy. The brain accounts for only approximately 2% of body weight but receives approximately 15% of the cardiac output. Regulatory mechanisms ensure that the cerebral perfusion remains constant despite fluctuations in the arterial blood pressure, as long as the latter remains within a certain range. Thus, if the arterial blood pressure should fall, a compensatory dilatation of the cerebral arteries occurs to maintain cerebral perfusion, which is significantly reduced only when the systolic blood pressure falls below 70 mm Hg (or below 70% of the baseline value in hypertensive individuals). Hyperventilation and intracranial hypertension lessen cerebral perfusion, while hypoventilation (i.e., an elevated partial pressure of CO2) increases it.


Consequences of Cerebral Hypoperfusion


Relative ischemia and penumbra Normal cerebral perfusion is approximately 58 mL per 100 g of brain tissue per minute. Signs and symptoms of ischemia begin to appear when the perfusion falls below 22 mL per 100 g per minute. In this stage of relative ischemia, the functional metabolism of the affected brain tissue is impaired, but the infarction threshold has not yet been crossed and the tissue can regain its normal function as soon as the perfusion renormalizes. The longer the relative ischemia lasts, however, the less likely it is that normal function will be regained. The zone of tissue in which the local cerebral perfusion lies between the functional threshold and the infarction threshold is called the ischemic penumbra (“partial shadow”). Within the penumbra, brain perfusion is linearly related to the arterial blood pressure.




Note



The penumbra is of major importance in the diagnostic evaluation of stroke, as well as in therapeutic decision-making and prognostication:




  • Within the penumbra, perfusion is reduced, but diffusion is still normal (perfusion–diffusion mismatch). Thus, imaging studies (above all, MRI) can distinguish it from tissue that has already undergone infarction.



  • If the occluded vessel is promptly recanalized, the tissue in the penumbra can largely survive and regain its normal function. The penumbra thus represents the tissue at risk for further stroke that may be salvageable by revascularization. Imaging of the penumbra is an important aid to clinical decision-making.


The ischemic penumbra in a patient with an acute MCA occlusion is shown in ▶ Fig. 6.21. A normal cerebral angiogram was presented in an earlier chapter (see ▶ Fig. 4.12). An occlusion of the MCA is seen in ▶ Fig. 6.24.



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Fig. 6.21 Visualization of the ischemic penumbra with diffusion-weighted (a) and perfusion-weighted MRI (b). The patient is a 55-year-old man with acute left hemiparesis due to occlusion of the main stem of the right middle cerebral artery. For comparison, diffusion-weighted (c) and perfusion-weighted MRI scans (d) of a 58-year-old man with acute hemianopsia are also shown. (a) The diffusion-weighted image reveals a mottled hyperintense signal in the posterior portion of the right middle cerebral artery territory; most of the territory, however, has a normal diffusion signal. (b) The perfusion-weighted image is based on the time to peak uptake of contrast medium, which is delayed throughout the entire right middle cerebral artery territory. The penumbra is the area of tissue in which perfusion is diminished, but diffusion is normal. If the occluded vessel can be reopened early enough, bringing blood back into the hypoperfused area, the tissue in the penumbra will largely survive and regain its function. (c) Diffusion-weighted MRI for comparison. (d) Perfusion-weighted MRI for comparison. In this case, the area of abnormality is nearly congruent to that seen in (c); thus, there is no penumbra, i.e., the infarction is complete and no brain tissue can now be saved by recanalization.


Total ischemia causes irreversible structural damage of the affected region of the brain. If the blood supply of the entire brain is cut off, unconsciousness ensues in 10 to 12 seconds and cerebral electrical activity, as demonstrated by electroencephalogram (EEG), ceases in 30 to 40 seconds ( ▶ Fig. 6.22). Cellular metabolism collapses, the sodium/potassium pump ceases to function, and interstitial fluid—that is, sodium and water—flows into the cells. The resulting cellular swelling is called cytotoxic cerebral edema. Later, when the blood–CSF barrier collapses, further plasma components, including osmotically active substances, enter the brain tissue; a net flow of fluid from the intravascular space into the intercellular and intracellular spaces then produces vasogenic cerebral edema. In a vicious circle, these two varieties of edema lead to additional compression of brain tissue, thereby impairing the cerebral perfusion still further.


6.5.3 The Classification of Cerebral Ischemia by Severity


The severity of cerebral ischemia is correlated with its clinical course if untreated. Standardized scales and scores are available for its assessment. The most commonly used scale is the National Institutes of Health Stroke Scale (NIHSS, ▶ Table 6.14).
















































































































































Table 6.14 NIHSS (National Institutes of Health Stroke Scale)


Findings


0


1


2


3


4


Points


1a


Level of consciousness


Awake


Somnolent


Stupor


Coma



1b


Orientation questions: Age? Month?


2 correct


1 correct


0 correct




1c


Commands open and close (1) the eyes and (2) the nonparetic hand


2 correct


1 correct


0 correct




2


Gaze paresis


None


Partial


Complete




3


Visual field


Normal


Partial hemianopsia


Complete hemianopsia


Bilateral hemianopsia/blindness



4


Central facial palsy


None


Mild


Complete lower half of the face


Complete upper and lower halves of the face



5a


Left arm motor function


No sinking when held up for 10 s


Sinks but does not touch underlying surface


Sinks onto underlying surface


No antigravity activity


No movement at all


5b


Right arm motor function


6a


Left leg motor function


6b


Right leg motor function


7


Limb ataxia


None


One limb affected


Two limbs affected




8


Sensation


Normal


Partially impaired


Markedly impaired or lost




9


Language


Normal


Moderate aphasia, communication possible


Severe aphasia, communication impossible


Global aphasia, mute



10


Dysarthria


None


Slurred but intelligible speech


Unintelligible speech (or the patient is mute)




11


Neglect, inattention


None


In one modality


In more than one modality




Total = NIHSS score



9783131364524_c006_f022.eps


Fig. 6.22 Time course of cerebral ischemia. Diagram of the effect of sudden total deprivation of blood supply to the brain on tissue metabolism, consciousness, the EEG, neuronal morphology, and tissue glucose concentration.




Practical Tip



The term “minor stroke” is commonly used to designate a stroke with only mild motor and/or sensory deficits, with an NIHSS score of 3 points at most (no more than 1 point on any item). Patients with a minor stroke are generally fully awake and alert and neuropsychologically intact. They have a good prognosis.


A stroke with an NIHSS score of more than 15 points has a poor prognosis if untreated and is classified as a “severe stroke.”


6.5.4 Etiology, Risk Factors, and Primary Prophylaxis


Etiology


Ischemic stroke has multiple causes ( ▶ Fig. 6.23). Embolic events and atherosclerotic stenoses of the major extra- and intracranial arteries play important roles, but there can also be hypertension-induced atherosclerotic changes of the midsized arteries or fibrinoid necrosis (lipohyalinosis) of the small arteries.


A simplified classification by etiology divides ischemic strokes into five classes:




  • Macroangiopathy: atherosclerosis of large extra- and intracranial vessels, leading to thrombosis in the region of an atherosclerotic plaque, hemodynamic insufficiency in the poststenotic circulation, or arterio-arterial embolism.



  • Cardiogenic and aortogenic embolism, mainly due to atrial fibrillation, but also as a complication of myocardial infarction, valve replacement, endocarditis, or cardiomyopathy.



  • Microangiopathy: cerebral small-vessel disease/arteriolosclerosis, usually due to hypertension, most commonly seen in the elderly.



  • Other etiologies, for example, vasculopathy, dissection, arteritis, coagulopathy, paradoxical embolism, right-to-left shunt.



  • Undetermined etiology.


▶ Table 6.15 may be a useful aid to the systematic search for the cause of stroke.


































































































Table 6.15 Etiologic classification of ischemic stroke

Cause


Atherosclerosis




  • Major extra- and intracranial vessels, including aortic arch: thrombosis, arterio-arterial embolism, hemodynamic insufficiency




  • Aorta




  • Small vessels: lacunar infarction


Cardiogenic embolism


Mural thrombus due to myocardial infarction, cardiomyopathy, myocardial aneurysm


Valvular heart disease including rheumatic heart-valve disease, bacterial and nonbacterial endocarditis, prosthetic valves


Arrhythmia including atrial fibrillation, sick sinus syndrome, brady- and tachyarrhythmias


Atrial myxoma


Paradoxical embolism through an open foramen ovale or atrial septal defect


Atrial thrombus in aneurysm of the atrial septum


Venous and venous sinus thrombosis


Septic sinus thrombosis


Coagulopathy (e.g., polycythemia, antithrombin deficiency), pregnancy, drugs (oral contraceptives, glucocorticoids)


Bland, i.e., without identifiable cause


Hematologic diseases


Thrombophilia due to protein C, protein S, or antithrombin-III deficiency, antiphospholipid antibodies, anticardiolipin antibodies, paroxysmal nocturnal hemoglobinuria


Hemoglobinopathy, e.g., sickle-cell anemia, thalassemia


Hyperviscosity syndrome due to polyglobulia, thrombocytosis, leukocytosis, macroglobulinemia, myeloma, polycythemia vera, myeloproliferative syndromes


Vasculitis


Primary CNS vasculitis, granulomatous angiitis of the CNS


Systemic necrotizing vasculitis with CNS involvement, e.g., in periarteritis nodosa, Churg–Strauss syndrome, giant-cell arteritis (polymyalgia rheumatica, temporal arteritis), Takayasu’s arteritis, Wegener granulomatosis, lymphomatoid vasculitis, hypersensitivity vasculitis


Connective-tissue diseases and collagenoses with CNS involvement, e.g., systemic lupus erythematosus, scleroderma, rheumatoid arthritis, Behçet disease, mixed connective tissue disease


Infectious vasculitis, e.g., due to HIV, tuberculosis, borreliosis, neurosyphilis, fungi, mononucleosis, CMV infection, herpes zoster, hepatitis B, rickettsia, bacterial endocarditis


Toxins


Illicit drugs, e.g., cocaine (also as crack), amphetamines, LSD, heroin


Medications, e.g., sympathomimetic drugs, ergotamines, triptans, intravenous immunoglobulins


Nonatherosclerotic vascular diseases


Dissections of the extra- or intracranial arteries supplying the brain or of the aorta, spontaneous or due (e.g.) to trauma, Marfan syndrome, or fibromuscular dysplasia


Posttraumatic thrombosis or avulsion of arteries supplying the brain


Vasospasm after subarachnoid hemorrhage


Arteriovenous malformations


Hereditary vascular diseases, e.g., Osler–Weber–Rendu disease (hereditary telangiectasia), moyamoya,a CADASIL, and other familial cerebral vasculopathies; fibromuscular dysplasia in neurofibromatosis


Pulmonary venous thrombosis


Dolichoectasiab


Amyloid angiopathy (β-amyloid deposition in the walls of cerebral blood vessels)


Various other causes


Vasospasm, e.g., in migraine, reversible cerebral vasoconstriction syndrome


Metabolic diseases, e.g., homocystinuria, hyperhomocysteinemia, Fabry disease (lysosomal storage disease with ceramide trihexoside deposition in blood vessels), MELAS, and other mitochondrial encephalomyopathies


Other sources of emboli, e.g., fat and air emboli, pseudovasculitic syndrome with cholesterol emboli, tumor emboli, distal emboli from giant aneurysms


Collagenoses (e.g., in neurofibromatosis)


Other pulmonary diseases


Iatrogenic stroke


Angiography and surgery on the carotid arteries, aorta, and heart


Injection of steroid crystals, fat embolism, etc.


Liposculpturing (liposuction and reinjection of adipose tissue)


Stroke of no identifiable cause


Abbreviations: CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy; CNS, central nervous system; HIV, human immunodeficiency virus; LSD, lysergic acid diethylamide; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.


aA rare disease, most prevalent in Japan but also seen elsewhere, involving stenosis of the cerebral vessels due to fibrosis of the intima of the distal portion of the carotid artery. Collateral vessels form, resulting in the typical angiographic appearance of a puff of smoke (in Japanese, “moyamoya”).


bDilated macroangiopathy with widening and tortuosity of the cerebral blood vessels.



9783131364524_c006_f023.eps


Fig. 6.23 The causes of stroke. (a) The most important causes of stroke. (Reproduced from Mattle H, Mumenthaler M. Neurologie. Stuttgart: Thieme; 2013.) (b) A paradoxical embolus through a patent foramen ovale.

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Dec 28, 2017 | Posted by in NEUROLOGY | Comments Off on Cerebral Ischemia and Ischemic Stroke
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