Elsevier

The Lancet Neurology

Volume 8, Issue 10, October 2009, Pages 949-958
The Lancet Neurology

Review
Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives

https://doi.org/10.1016/S1474-4422(09)70224-8Get rights and content

Summary

Space-occupying, malignant middle cerebral artery (MCA) infarctions are still one of the most devastating forms of ischaemic stroke, with a mortality of up to 80% in untreated patients. An early diagnosis is essential and depends on CT and MRI to aid the prediction of a malignant course. Several pharmacological strategies have been proposed but the efficacy of these approaches has not been supported by adequate evidence from clinical trials and, until recently, treatment of malignant MCA infarctions has been a major unmet need. Over the past 3 years, results from randomised controlled trials and their pooled analyses have provided evidence that an early hemicraniectomy leads to a substantial decrease in mortality at 6 and 12 months and is likely to improve functional outcome. Hemicraniectomy is now in routine use for the clinical management of malignant MCA infarction in patients younger than 60 years of age. However, there are still important questions about the individual indication for decompressive surgery, particularly with regard to the ideal timing of hemicraniectomy, a potential cut-off age for the procedure, the hemisphere affected, and ethical considerations about functional outcome in surviving patients.

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 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.

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