References for this Review were identified through searches of PubMed with the search terms “hemicraniectomy”, “malignant MCA infarction”, and “decompressive surgery” from 1970 until July, 2009. References selected were limited to core clinical journals. Articles were also identified through searches of the authors' own files. Only papers published in English or German were reviewed.
ReviewMalignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives
Introduction
Although space-occupying, malignant middle cerebral artery (MCA) infarction has not been defined as a distinct disorder, its definition is usually based on clinical presentation, typical clinical course, and neuroradiological findings.1 Patients with subtotal or complete MCA infarctions typically present with hemiparalysis, severe sensory deficits, head and eye deviation, hemi-inattention, and, if the dominant hemisphere is involved, global aphasia.2, 3 Patients with malignant MCA infarctions show a progressive deterioration of consciousness over the first 24–48 h and commonly have a reduced ventilatory drive, requiring mechanical ventilation.4, 5 Malignant MCA infarctions constitute between 1% and 10% of all supratentorial ischaemic strokes,4 and treatment of this disorder has been a major unsolved problem in neurocritical care.6, 7 Several pharmacological treatment approaches, such as osmotic therapy, steroids, hyperventilation, barbiturates, and trishydroxymethylaminomethane (THAM) buffers, have been proposed to reduce cerebral oedema formation, but so far none of these therapeutic strategies has been supported by adequate evidence of efficacy from clinical trials.8, 9, 10 Between 2007 and 2009, data from randomised trials were published that provided evidence of a substantial decrease in mortality of patients who underwent decompressive surgery (hemicraniectomy) for treatment of space-occupying MCA infarction.5, 11, 12 Meta-analyses supported this finding;5, 13 however, as some primary outcome measures were neutral, there are fundamental questions about trial design and interpretation and about the benefits of this surgery on functional outcome in surviving patients. Moreover, although the survival benefit from hemicraniectomy is undisputed, the functional outcome of surviving patients treated with this procedure is variable and often poor, raising important ethical considerations.
In this Review, we briefly outline the epidemiology, clinical characteristics, and imaging findings in malignant MCA infarctions. We then assess the evidence for current treatment strategies, with a particular focus on hemicraniectomy and the implications of the recent trials. Questions about the individual indication for hemicraniectomy in specific patients with malignant MCA infarction are discussed and we give our perspective on future clinical studies.
Section snippets
Epidemiology and clinical features
Generally, subtotal or complete MCA infarctions are found in up to 10% of patients with supratentorial ischaemia.4, 15 The yearly incidence of a malignant acute ischaemic stroke is between about 10 and 20 per 100 000 people.4, 16, 17 Compared with other patients with ischaemic stroke, substantially fewer of those who have malignant MCA infarction have a history of ischaemic stroke and women are more likely to be affected.16, 18 Moreover, patients with malignant MCA infarction seem to be younger
Imaging and prediction of a malignant course
Cranial CT is widely used for the diagnosis and monitoring of patients with malignant MCA infarction (figure 2).1, 3, 33, 34 However, as repeated CT imaging up to the first 3 days after stroke onset might be necessary to determine the definite area of infarction and the extent of any associated brain swelling and midline shift, several studies have focused on identifying variables that allow an early prediction of a malignant course by use of multi-slice CT, CT angiography, CT perfusion, and
Pharmacological approaches
Patients with large, space-occupying MCA infarctions require immediate intensive care on a specialised neurocritical care unit. Sedation, intubation, and mechanical ventilation are often indicated early, and even electively once the malignant course of the disease has been verified, to prevent aspiration and to allow invasive treatment to be started.9, 41 There are many pharmacological approaches to the prevention and management of the developing brain oedema.9 Treatment with osmotic compounds,
Surgical techniques
Decompressive surgery is based on a hemicraniectomy in combination with a duraplasty.55 After incision of the skin in the shape of a question mark, a bone flap that has a diameter of at least 12 cm is removed, including parts of the frontal, parietal, temporal, and occipital squama.56, 57 The removed bone flap must be of a sufficient size to prevent additional ischaemic lesions.58 After opening of the dura, a dural patch is inserted, which usually consists of homologous periosteum or a temporal
Conclusions
Malignant MCA infarction was associated with high mortality for many years. The three European prospective randomised trials and the pooled analyses have revealed a substantial increase in survival with decompressive surgery. However, there are several clinical and ethical questions that need to be resolved in future studies. These questions regard the timing of surgery (before or after the 48-h time window), particularly as oedema formation often peaks after this time; the definition of a
Search strategy and selection criteria
References (101)
- et al.
Stroke
Lancet
(2008) - et al.
Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial
Lancet Neurol
(2009) - et al.
Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials
Lancet Neurol
(2007) - et al.
Reassessment of the HAMLET study
Lancet Neurol
(2009) - et al.
Middle cerebral artery territory infarction and early brain swelling: progression and effect of age on outcome
Mayo Clin Proc
(1998) Cerebral ischemia: the microcirculation as trigger and target
Prog Brain Res
(1993)- et al.
Prospective evaluation of malignant middle cerebral artery infarction with blood-brain barrier imaging using Tc-99m DTPA SPECT
Brain Res
(2006) - et al.
Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome
Lancet
(1996) - et al.
Early external decompressive craniectomy with duroplasty improves functional recovery in patients with massive hemispheric embolic infarction: timing and indication of decompressive surgery for malignant cerebral infarction
Surg Neurol
(2004) - et al.
Assessing the benefits of hemicraniectomy: what is a favourable outcome?
Lancet Neurol
(2007)
Hemicraniectomy for hemispheric infarction and the HAMLET study: a sequel is needed
Lancet Neurol
Ultra-early decompressive craniectomy for malignant middle cerebral artery infarction
Surg Neurol
Is decompressive craniectomy for malignant middle cerebral artery territory infarction of any benefit for elderly patients?
Surg Neurol
Long-term outcome after hemicraniectomy for space occupying right hemispheric MCA infarction
Clin Neurol Neurosurg
Predictors of life-threatening brain edema in middle cerebral artery infarction
Cerebrovasc Dis
Hemicraniectomy for middle cerebral artery infarction
Curr Neurol Neurosci Rep
‘Malignant’ middle cerebral artery territory infarction: clinical course and prognostic signs
Arch Neurol
Brain edema after stroke. Clinical syndrome and intracranial pressure
Arch Neurol
Large hemispheric infarction, deterioration, and intracranial pressure
Neurology
Treatment of space-occupying cerebral infarction
Crit Care Med
Antiedema therapy in ischemic stroke
Stroke
Clinical review: therapy for refractory intracranial hypertension in ischaemic stroke
Crit Care
Sequential-Design, Multicenter, Randomized, Controlled Trial of Early Decompressive Craniectomy in Malignant Middle Cerebral Artery Infarction (DECIMAL trial)
Stroke
Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial
Stroke
Large infarcts in the middle cerebral artery territory. Etiology and outcome patterns
Neurology
Massive cerebral infarction with severe brain swelling: a clinicopathological study
Stroke
Space-occupying cerebral infarct
Nervenarzt
Mechanisms and timing of deaths from cerebral infarction
Stroke
Predictors for malignant middle cerebral artery infarctions: a postmortem analysis
Neurology
Anatomy and functionality of leptomeningeal anastomoses: a review
Stroke
Early clinical and radiological predictors of fatal brain swelling in ischemic stroke
Stroke
Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass
N Engl J Med
Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under conservative intensive care
Intensive Care Med
Predictors of fatal brain edema in massive hemispheric ischemic stroke
Stroke
Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction
J Neurol Neurosurg Psychiatry
Extracellular concentrations of non-transmitter amino acids in peri-infarct tissue of patients predict malignant middle cerebral artery infarction
Stroke
Identification and clinical impact of impaired cerebrovascular autoregulation in patients with malignant middle cerebral artery infarction
Stroke
The prediction of malignant cerebral infarction by molecular brain barrier disruption markers
Stroke
Spreading depolarizations occur in human ischemic stroke with high incidence
Ann Neurol
Acute cerebral infarct: physiopathology and modern therapeutic concepts
Radiologe
Computed tomographic parameters predicting fatal outcome in large middle cerebral artery infarction
Cerebrovasc Dis
Multiphasic helical computed tomography predicts subsequent development of severe brain edema in acute ischemic stroke
Arch Neurol
Accuracy of perfusion-CT in predicting malignant middle cerebral artery brain infarction
J Neurol
Prediction of malignant middle cerebral artery infarction by diffusion-weighted imaging
Stroke
Prediction of malignant middle cerebral artery infarction by early perfusion- and diffusion-weighted magnetic resonance imaging
Stroke
Prediction of malignant course in MCA infarction by PET and microdialysis
Stroke
Patterns and predictors of blood-brain barrier permeability derangements in acute ischemic stroke
Stroke
Mechanical ventilation in patients with hemispheric ischemic stroke
Crit Care Med
Barbiturate coma in severe hemispheric stroke: useful or obsolete?
Neurology
Treatment options for large hemispheric stroke
Neurology
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