Cerebral Edema Associated With Large Hemispheric Infarction

Abstract

Large hemispheric infarction (LHI) is a severe form of is-chemic stroke affecting the majority of or complete middle ce-rebral artery (MCA) distribution area with or without anterior cerebral artery and posterior cerebral artery involvement and characterized by the development of life-threatening cerebral edema. 1 LHI stroke pathogenesis is typically due to cardio-embolism; in younger patients, cervical artery dissection may be the precipitating event. 2,3 Moreover, different pathogeneses may secondarily lead to LHI after subarachnoid hemorrhage. 4 Diverse definitions for LHI have been employed in clinical trials, generally based on a combination of neurological signs or symptoms. 1,5-14 A small percentage (≤10%) of acute ischemic strokes become LHI 15-18 ; yet LHI is associated with substantial morbidity and mortality. More than 50% of patients experiencing an LHI will develop malignant cerebral edema (MCE) and rapid neurological decline within 2 to 3 days of symptom onset. 11,19 The pathophysiologic pathways subsequently leading to MCE, however, are still not fully understood. 7,20-23 Undoubtedly, blood-brain barrier (BBB) breakdown and predominantly vasogenic edema formation represent key mechanisms for the development of MCE. 9,23,24 The mortality rate in LHI patients with severe MCE receiving standard medical treatment is ≈40% to 80% compared with 5% to 25% in stroke patients without severe MCE. 8,25-27 Clarifying terminology for LHI was recently introduced by the Neurocritical Care Society/German Society for Neuro-Intensive Care and Emergency Medicine 12 and the American Heart Association/American Stroke Association 1 to distinguish between the infarction and the resulting edema. The most common guideline-supported definition of LHI refers to "a large ischemic stroke affecting the total or subtotal territory of the MCA, involving the basal ganglia at least partially, with or without involvement of the adjacent territories" (Figure 1). 12 This definition of LHI is supported using flumazenil positron emission tomography and an irreversibly damaged neuronal tissue volume >95 mL, 8 or diffusion-weighted magnetic resonance imaging (DWI) and a lesion volume >82 mL on DWI. 25 Ischemic strokes resulting from internal carotid artery or proximal MCA occlusion are significantly larger than other cerebral strokes, affecting the total or subtotal MCA territory. Because of the size and location of the occlusion, patients with LHI are uniquely at risk for MCE. 28 However, because of the complex pathophysiology involved in the development of LHI, more than volume alone should be considered in the prediction of MCE. 20 In LHI, acute interruption of blood flow below the minimum threshold for basic metabolic maintenance results in an infarcted ischemic core within minutes. 29 The remaining areas affected by the occlusion are marginally perfused from collateral arteries and may remain viable for several hours. However, if perfusion is not reestablished to the penumbra within an individually defined critical time window, collateral circulation is often inadequate to maintain functional demand, and this tissue becomes irreversibly infarcted. 29 In addition to bedside neurological examination, various assessments are recommended for the evaluation of neurolog-ical impairment and disability. 30 The National Institutes of Health Stroke Scale-a 15-item neurological deficit score that provides an ordinal nonlinear measure of acute stroke-related injury by assigning numerical values to various aspects of neurological function-is highly predictive of long-term functional outcome and is widely used in clinical stroke trials and clinical practice; however, certain aspects have been shown to not correlate robustly with infarct volume. 31 Most stroke units include the National Institutes of Health Stroke Scale as part of their standard of care, making it one of the best assessments to gauge the patient deterioration, often associated with LHI. 31a