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ObjectiveTo determine the impact of infarct volume before hemicraniectomy in malignant middle cerebral artery infarction (MMI) as an independent predictor for patient selection and outcome prediction, we retrospectively analyzed data of 140 patients from a prospective multicenter study.MethodsPatients from the Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY) Registry who underwent hemicraniectomy after ischemic infarction of >50% of the middle cerebral artery territory were included. Functional outcome according to the modified Rankin Scale (mRS) was assessed at 12 months. Unfavorable outcome was defined as mRS score of 4 to 6. Infarct size was quantified semiautomatically from CT or MRI before hemicraniectomy. Subgroup analyses in patients fulfilling inclusion criteria of randomized trials in younger patients (age ≤60 years) were predefined.ResultsAmong 140 patients with complete datasets (34% female, mean [SD] age 54 [11] years), 105 (75%) had an unfavorable outcome (mRS score >3). Mean (SD) infarct volume was 238 (63) mL. Multivariable logistic regression identified age (odds ratio [OR] 1.08 per 1-year increase, 95% confidence interval [CI] 1.02–1.13, p = 0.004), infarct size (OR 1.27 per 10-mL increase, 95% CI 1.12–1.44, p < 0.001), and NIH Stroke Scale score (OR 1.10, 95% CI 1.01–1.20, p = 0.030) before hemicraniectomy as independent predictors of unfavorable outcome. Findings were reproduced in patients fulfilling inclusion criteria of randomized trials in younger patients. Infarct volume thresholds for prediction of unfavorable outcome with high specificity (94% in overall cohort and 92% in younger patients) were >258 mL before hemicraniectomy.ConclusionOutcome in MMI depends strongly on age and infarct size before hemicraniectomy. Standardized volumetry may be helpful in the process of decision-making concerning hemicraniectomy.

Objective: To assess, by Rankin scale, the functional disability of patients who had a malignant middle cerebral artery (MCA) ischemic stroke, who underwent decompressive craniotomy (DC) within the first 30 days. Methods: A cross-sectional study in a University hospital. Between June 2007 and December 2014, we retrospectively analyzed the records of all patients submitted to DC due to a malignant MCA infarction. The mortality rate was defined during the hospitalization period. The modified outcome Rankin score (mRS) was measured 30 days after the procedure, for stratification of the quality of life. Results: The DC mortality rate was 30% (95% CI 14.5 to 51.9) for the 20 patients reported. The mRS 30 days postoperatively was ≥ 4 [3.3 to 6] for all patients thereafter. Conclusion: DC is to be considered a real alternative for the treatment of patients with a malignant ischemic MCA infarction.Keywords: craniotomy; cerebral infarction; intracranial hypertension. RESUMO Objetivo: Avaliar a capacidade funcional de pacientes com acidente vascular cerebral isquemico no territorio da arteria cerebral media (ACM) submetidos a craniotomia descompressiva (CD) no periodo de 30 dias pela escala de Rankin. Metodos: Estudo transversal em um hospital universitario. Entre junho de 2007 e dezembro de 2014, analisados retrospectivamente os registros de todos os pacientes submetidos a CD devido a enfarte maligno na ACM. A taxa de mortalidade foi definida durante o periodo de internacao. O resultado da estratificacao da qualidade de vida foi atraves da escala Rankin modificado (mRS) mensurado em 30 dias apos o procedimento. A taxa de mortalidade CD Resultados: foi de 30% (IC 95% 14,5-51,9) para os 20 pacientes relatados. A mRS 30 dias de pos-operatorio foi => 4 [3,3-6] para todos os pacientes. Conclusao: CD deve ser considerada uma alternativa real para o tratamento de pacientes com enfarte isquemico no territorio da ACM.Palavras-chave: craniotomia; infarto cerebral; hipertensao intracraniana.

Introduction: Malignant middle cerebral artery (MCA) stroke has a disproportionately high mortality due to the rapid development of refractory space-occupying cerebral edema. Animal models are essential in developing successful anti-edema therapies; however to date poor clinical translation has been associated with the predominately used rodent models. As such, large animal gyrencephalic models of stroke are urgently needed. The aim of the study was to characterize the intracranial pressure (ICP) response to MCA occlusion in our recently developed ovine stroke model. Materials and Methods: 30 adult female Merino sheep (n = 8-12/gp) were randomized to sham surgery, temporary or permanent proximal MCA occlusion. ICP and brain tissue oxygen were monitored for 24 hours under general anesthesia. MRI, infarct volume with triphenyltetrazolium chloride (TTC) staining and histology were performed. Results: No increase in ICP, radiological evidence of ischemia within the MCA territory but without space-occupying edema, and TTC infarct volumes of 7.9+/-5.1% were seen with temporary MCAO. Permanent MCAO resulted in significantly elevated ICP, accompanied by 30% mortality, radiological evidence of space-occupying cerebral edema and TTC infarct volumes of 27.4+/-6.4%. Conclusions: Permanent proximal MCAO in the sheep results in space-occupying cerebral edema, raised ICP and mortality similar to human malignant MCA stroke. This animal model may prove useful for pre-clinical testing of anti-edema therapies that have shown promise in rodent studies. Refereed/Peer-reviewed

Early decompressive craniectomy (DC) has been shown to reduce mortality in malignant middle cerebral artery (MCA) infarction, whereas efficacy of DC on functional outcome is inconclusive. Here, we performed a meta-analysis to estimate the effects of DC on malignant MCA infarction and investigated whether age of patients and timing of surgery influenced the efficacy. We systematically searched PubMed, Medline, Embase, Cochrane library, Web of Science update to June 2014. Finally, A total of 14 studies involved 747 patients were included, of which 8 were RCTs (341 patients). The results demonstrated that early DC (within 48 h after stroke onset) decreased mortality (OR = 0.14, 95%CI = 0.08, 0.25, p3) (OR = 0.38, 95%CI = 0.20, 0.73, p = 0.004) for 12 months follow-up. In the subgroup analysis stratified by age, early DC improved outcome both in younger and older patients. However, later DC (after 48h after stroke onset) might not have a benefit effect on lowering mortality or improving outcome in patients with malignant infarction. Together, this study suggested that decompressive surgery undertaken within 48 h reduced mortality and increased the number of patients with a favourable outcome in patients with malignant MCA infarction.

Background: In order to determine the impact of the severity of ischemia on malignant edema formation, we investigated various degrees of perfusional deficit by 11C-flumazenil PET in patients with large middle cerebral artery (MCA) infarction. Methods: 17 patients with large MCA stroke were included. Cerebral blood flow (CBF) was measured 15.9 ± 6.4 h after the ictus. Patients were divided into a malignant (n = 9) and a benign group (n = 8) as a function of their clinical courses and edema. Edema was measured as maximal midline shift on follow-up CTs. Total hypoperfusion volume was divided into different subvolumes according to the degree of CBF reduction. Results: Subvolumes of severe ischemia relative to total ischemic area were significantly larger in the malignant group than in the benign group and were significantly correlated with edema formation. The highest correlation and best predictive values for edema formation with a sensitivity, specificity, and a positive and negative predictive value of 100% were found for subvolumes with severe ischemia. Correlation coefficients and prediction decreased for subvolumes with less severe perfusional deficit, pointing to the risk of misclassifying patients when relying on the volume of total perfusional deficit alone. Conclusions: Malignant MCA infarction seems to be determined more by the volume of severe perfusional deficit than that of total perfusional deficit. Assessment of severely ischemic areas allows prediction of malignant edema formation and might help to select candidates for hemicraniectomy.

Malignant middle cerebral infarction is defined as a clinicaldeterioration from hemispheric swelling and is named‘‘malignant’’ because it is rapidly injurious to the patient.Recommendations for early decompressive hemicraniec-tomy (DHC) in malignant middle cerebral artery infarction(mMCAI)intheclinicalroutineare based ondata fromthreeEuropean randomised controlled trials (DECIMAL, DE-compressive Craniectomy In MALignant middle cerebralartery infarcts [1]; DESTINY, DEcompressive Surgery forthe Treatment of malignant Infarction of the middle cerebralartery [2]; and HAMLET, Hemicraniectomy After Middlecerebral artery infarction with Life-threatening Edema Trial[3]) and two pooled meta-analyses [3, 4]. The results clearlydemonstrated that DHC is more than just an optional inter-vention in mMCAI as mortality was consistentlysignificantlylowerinpatientswho underwentsurgery acrossall three trials, as compared with controls. None of the trialsormeta-analyses were abletoshow significant improvementin functional outcome with DHC when the predefineddichotomization between a modified Rankin scale score(mRS) of 0–3 and 4–6 was used [3, 5]. However, a post hocmeta-analysis of the pooled data including totally 109patients indicates that early surgery ( 4 (6 months: 31.2 vs. 92.3 %; 1 year: 37.5 vs.100 %). Based on those findings, the authors come to theoptimistic conclusion that DHC is beneficial for patientsaged 61–80 years although there seems to be an increasedlikelihood for those patients to survive with moderatelysevere disability (mRS 4).As Zhao et al. state in the discussion of their article,those results are ‘‘exciting,’’ providing the first outcome