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(Stroke. 2003;34:1899.)
© 2003 American Heart Association, Inc.

Original Contributions

Editorial Comment—Can We Predict Massive Space-Occupying Edema in Large Hemispheric Infarctions?

Christine A.C. Wijman, MD, Guest Editor

Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford Stroke Center, Palo Alto, California

Approximately 10% of large hemispheric infarctions are associated with massive, so-called malignant, space-occupying cerebral edema resulting in neurological deterioration due to brain tissue shifts, leading to herniation and often death. Increase in intracranial pressure is a late phenomenon that typically does not occur until after clinical signs of herniation have developed.¹ Space-occupying edema is the leading cause of death within the first week of stroke. Mortality rates derived from intensive care unit–based series are as high as 79% despite aggressive medical therapy, and survivors have a poor neurological outcome.² These data should be interpreted with caution because of possible selection bias.

There is currently no universally accepted treatment modality for patients who deteriorate as a result of space-occupying hemispheric infarction.³ Hemicraniectomy with dural patch enlargement has been proposed as a life-saving measure and might be the most promising therapeutic option. The goal of surgery is to reverse mass effect and brain tissue shifts, decrease increased intracranial pressure, improve cerebral perfusion pressure, and prevent secondary neural injury. Laboratory studies of hemicraniectomy for large hemispheric infarction in rats have shown a decrease in mortality and, when performed very early, reduction in infarct volume as well as improved neurological outcome.⁴ Data in humans have been largely derived from case series and 2 open, nonrandomized, controlled studies. In 1 study 32 patients with clinical deterioration, midline shift, and uncal herniation or obliteration of the cisterns underwent hemicraniectomy, and 21 controls received medical treatment alone.⁵ Mean time between symptom onset and surgery was 39 hours. Mortality was 34% in the surgically treated group compared with 78% in the control group. A subsequent study from the same investigators included 31 patients who underwent early hemicraniectomy at a mean of 21 hours after symptom onset.⁶ Mortality was reduced to 16%, and functional outcome in the survivors in the surgical group in both studies was improved compared with historic controls. Although these data suggest a potential substantial benefit of decompressive surgery, they cannot be readily translated into clinical practice. Most importantly, nonrandomized enrollment resulted in a control group with older and sicker patients. Furthermore, it remains unclear whether the quality of life in survivors is acceptable enough to advocate surgery as a beneficial treatment, particularly in elderly patients and perhaps in those with dominant hemispheric strokes.

While controversy remains over the beneficial effect of hemicraniectomy in space-occupying hemispheric stroke, randomized controlled trials are presently under way that should provide some more objective efficacy data. The final data of HeADDFIRST, a multicenter pilot study funded by the National Institute of Neurological Disorders and Stroke, are expected to be available in 6 to 12 months. In Europe the HAMLET study is currently randomizing patients with massive space-occupying hemispheric infarctions to decompressive surgery or medical treatment to assess differences in mortality and functional outcome at 1 year.

Can we predict massive space-occupying edema in large hemispheric infarctions? If hemicraniectomy proves to be beneficial in patients with life-threatening edema from stroke, it stands to reason that early surgery will result in the best clinical outcomes. Conversely, unnecessary surgical procedures with their associated risks should be avoided. Thus, early and accurate prediction of malignant hemispheric infarction might become crucial in the management of these patients.

Various studies have reported on clinical predictors of malignant middle cerebral artery (MCA) infarction (MMI), including the following: high NIHSS score on admission, history of hypertension or heart failure, increased baseline white blood cell count, early nausea/vomiting, and early elevated blood pressure. However, since the unfavorable course of MMI is primarily determined by a large space-occupying lesion with mass effect and tissue shifts, it seems logical that imaging prognosticators will improve predictive accuracy. Indeed, several studies have found that early CT hypodensity involving >50% of MCA territory, involvement of additional vascular territories, early attenuated corticomedullary contrast on CT, and MCA trunk or carotid-T occlusion increase the chance of malignant cerebral edema. Total infarct volume appears to be of particular importance. A prospective study of ^99mtechnetium-ethyl-cysteinate-dimer single-photon emission CT within 6 hours of symptom onset in 108 patients with MCA infarction predicted mortality with 82% sensitivity and 98% specificity.⁷ A prospective study of 53 patients with MCA occlusion showed that hypodensity on CT covering >50% of MCA territory within 6 hours had an 85% positive predictive value for fatal outcome with 94% specificity.⁸ Horizontal displacement of the pineal gland of 4 mm on CT within 48 hours of stroke is also associated with high mortality.⁹ A small retrospective MRI study of 28 patients with MCA or carotid-T occlusion found that a DWI lesion >145 cm³ within 14 hours of stroke onset predicted MMI with 100% sensitivity and 94% specificity.¹⁰ Prediction was further improved by combining DWI lesion volume with ADC measurements.

In the accompanying article, Thomalla et al report on the predictive value of DWI and PWI within 6 hours of stroke onset in 37 patients with MCA stroke and proximal vessel occlusion. MMI was defined as a decline in consciousness demonstrated as at least 1 point on the level of consciousness item on the NIHSS, in conjunction with a large space-occupying infarct and compression of ventricles or midline shift. The authors found in their analysis that ADC_<80% >82 mL was the most accurate MRI prognosticator, predicting MMI with 87% sensitivity and 91% specificity. Admission NIHSS score had a higher sensitivity than any single MRI prognosticator but had only moderate (72%) specificity. Three patients were misclassified as MMI with use of the 82 mL ADC_<80% cutoff. Multivariate analysis could not be performed because of the small sample size.

In conclusion, the study of Thomalla et al contributes unique data on early prediction of space-occupying hemispheric infarction by MRI prognosticators in the 6-hour time window. However, before these parameters can be used in clinical practice, they will need to be validated in a well-designed, prospective study with a larger sample size.

	References

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This Article Full Text (PDF) All Versions of this Article: 34/8/1899    most recent 01.STR.0000081986.02572.D5v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wijman, C. A.C. Search for Related Content PubMed PubMed Citation Articles by Wijman, C. A.C.