ORIGINAL ARTICLE Massive Cerebral Infarction Suresh Subramaniam, MD, MSc,* and Michael D. Hill, MD, MSc, FRCPC*† severely disabled with poor quality of life. The incidence is Background: Massive cerebral infarcts cause brain edema with 1 midline shifts and impingement on vital structures producing coma estimated at 2 to 10% of all ischemic stroke. and death. The mortality rate is estimated at 80% with standard Massive cerebral infarction may be managed both medi- medical treatment. Surgical decompression with hemicraniectomy cally and surgically, with little available evidence from random- has proved to be life saving, but the impact on functional outcomes ized controlled studies to guide the choice. Numerous develop- is largely unknown. The focus of this review is to discuss the ments have occurred in the medical and surgical management of treatment options for massive cerebral infarcts. patients with massive cerebral infarction in the recent past. This Review Summary: Neurologic deterioration following massive article presents a narrative review of the literature concerning the cerebral infarct needs to be recognized early enough for medical and surgical interventions. Medical management includes monitoring in clinical course and medical and neurosurgical management of a neurologic intensive care unit, hyperosmolar agents, and hyper- massive cerebral infarction, highlighting specific areas in which ventilation. Surgical management includes decompressive hemi- developments are occurring rapidly. craniectomy and duraplasty with resection of infarcted tissue in some instances. Conclusion: Hemicraniectomy is emerging as a promising treat- ment of patients with massive cerebral infarcts, but only select patients benefit from this procedure. Further information from ran- Malignant middle cerebral artery (MCA) domized controlled trials is required to elucidate the best treatment options for this kind of stroke. infarction is a form of massive cerebral Key Words: massive cerebral infarcts, hemicraniectomy, infarction that is used to describe complete hypothermia, malignant middle cerebral artery infarct MCA territory infarction resulting in significant (The Neurologist 2005;11: 150–160) space-occupying effect. assive cerebral infarct is one of the most catastrophic Mforms of ischemic stroke with no proven treatment. METHODS Malignant middle cerebral artery (MCA) infarction is a form The literature was searched from 1970 using MEDLINE of massive cerebral infarction that is used to describe com- and EMBASE with keywords massive cerebral infarcts, hemi- plete MCA territory infarction resulting in significant space- craniectomy, malignant MCA infarct, and hypothermia. Articles occupying effect. The resulting depression of consciousness unavailable for translation were not retrieved. Theoretically, terminates in coma and brain death within 2 to 5 days in massive cerebral infarcts are large hemispheric infarcts associ- almost 80% of patients treated with conservative medical ated with edema and tissue displacements. Only the salient therapy alone. The survivors of this form of stroke are features of management are reviewed here. From the *Calgary Stroke Program, Department of Clinical Neurosciences, and the †Departments of Medicine and Community Health Sciences, University of Calgary, Alberta, Canada. Complete middle cerebral artery (MCA) territory Reprints: Michael D. Hill, MD, MSc, FRCPC, Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Foothills infarction is invariably caused by occlusion of Hospitals, Room 1242A, 1403 29th Street NW, Calgary, Alberta, T2N the distal internal carotid artery and the 2T9 Canada. E-mail: [email protected]. Copyright © 2005 by Lippincott Williams & Wilkins proximal MCA trunk. ISSN: 1074-7931/05/1103-0150 DOI: 10.1097/01.nrl.0000159987.70461.d7 150 The Neurologist • Volume 11, Number 3, May 2005 The Neurologist • Volume 11, Number 3, May 2005 Massive Cerebral Infarction CLINICAL COURSE AND PREDICTORS OF than a global increase in intracranial pressure (ICP). Regional CLINICAL DETERIORATION differences in ICP and cerebral perfusion pressure (CPP) play a The clinical course of massive cerebral infarction is major role in the exacerbation of cerebral ischemia. A focal determined by the location of vascular occlusion, intrinsic increase in ICP in areas of impaired autoregulation around the tissue susceptibility, and duration of ischemia. Complete infarction can cause paradoxic reduction in cerebral perfusion MCA territory infarction is invariably caused by occlusion of pressure, resulting in ischemia. Focal ICP can lead to focal the distal internal carotid artery and the proximal MCA trunk ischemia when ICP is greater than 20 mmHg, and global (commonly referred to as a T-occlusion or L-occlusion).1 The ischemia occurs when ICP is greater than 50 mmHg. Patients at etiology of malignant MCA infarction is almost always em- risk for ischemic brain edema are those with large hemispheric bolic, either from a proximal cardiac source or carotid disease strokes involving more than 50% of the MCA territory (Fig. 1). (dissection, atheroembolic). Anatomic factors such as an The clinical predictors of early deterioration have been largely incomplete circle of Willis and impaired collateral circulation derived from numerous case reports. Headache, nausea, vomit- play a critical role in determining the extent of infarction. The ing, early somnolence. and respiratory disturbances occur in hemodynamic effects of collateral circulation are important in approximately 50% of patients with malignant MCA infarction maintaining perfusion to penumbral regions. The extent of as early as 3 hours after stroke onset and may herald mass effect infarction is also determined by brain tissue susceptibility to from significant brain edema and early deterioration. These ischemia. For example, susceptibility is augmented by diabe- symptoms ideally warrant neurologic intensive care unit (ICU) tes mellitus. Diabetes mellitus enhances apoptosis induced by admission and monitoring. Mass effect with edema usually cerebral ischemia in rodent models.2 Reperfusion injury may occurs 1 to 5 days following the ictus, leading to herniation of be another important component cause of massive MCA brain tissue through dural spaces. This can produce subfalcine, infarction. Reperfusion of irreversibly damaged brain may transtentorial, uncal, and tonsillar herniation, often resulting in enhance edema formation and result in rapid development of rapid death.1,6–8 swelling (within 24 hours), with hemorrhagic transformation leading to mass effect. These factors commonly result in a fatal outcome. There is a mortality rate of 80% with standard 3 medical treatment alone. Mass effect with edema usually occurs 1 to 5 Clinically, carotid T-occlusion produces ischemia of the frontoparietal regions, leading to hemianopia and flaccid days following the ictus, leading to herniation hemiplegia. Often, these patients have head turning and gaze of brain tissue through dural spaces. deviation to the affected hemisphere secondary to involve- ment of frontal eye fields. Global aphasia due to involvement of the dominant hemisphere or hemispatial neglect from nondominant hemisphere involvement can all be highly dis- abling.1,4,5 Early identification of patients susceptible for Neuroimaging is an invaluable tool for identifying pa- malignant MCA infarction is crucial for appropriate selection tients at risk for developing ischemic brain edema. Neurologic of medical and surgical interventions. deterioration correlates with horizontal displacement of the an- terior septum and pineal gland on computed tomographic (CT) scan rather than with ICP elevation. The presence of low-density infarction and edema on CT scan that occupies more than 50% of MCA territory is a reliable predictor of subsequent edema The clinical symptoms of worsening neurologic formation following a large hemispheric infarct. von Kummer et status following a large hemispheric infarct are al9 have shown that early (Ͻ6 hours) CT scan changes of greater than 50% MCA hypodensity or local brain swelling (effacement mainly due to focal ischemic brain edema and of sulci, compression of lateral ventricle) are associated with focal displacement of brain rather than a fatal outcomes in 85% of patients (94% specificity and 61% sensitivity). In addition, hemorrhagic transformation of large global increase in intracranial pressure (ICP). hemispheric infarcts may worsen the brain edema and tissue shifts. Barber et al10 proposed the use of early radiologic signs on follow-up CT scans performed within 48 hours of stroke onset in predicting mortality at 30 days. The CT parameters The clinical symptoms of worsening neurologic status anteroseptal shift (Ͼ5 mm), pineal shift (Ͼ2 mm), hydroceph- following a large hemispheric infarct are mainly due to focal alus, temporal lobe infarction, and the presence of other vascular ischemic brain edema and focal displacement of brain rather territory infarction were predictive of fatal outcomes.10 Case © 2005 Lippincott Williams & Wilkins 151 Subramaniam and Hill The Neurologist • Volume 11, Number 3, May 2005 TREATMENT CONSIDERATIONS Management options for massive cerebral infarction can be classified into medical and surgical. Currently, there are no strict guidelines available from randomized controlled trials. Patients susceptible to the development of massive cerebral infarction should be admitted to a neuro-ICU setting with facilities available