Surgical aspects of decompression craniectomy in malignant stroke: review.

BACKGROUND: Space-occupying malignant stroke of the middle cerebral artery (MCA) is associated with a high mortality rate of up to 80% under conservative treatment. Although there is convincing evidence that decompression craniectomy can significantly reduce mortality rate and improve neurological outcome in young patients (<60 years), many surgeons are still hesitant to recommend hemicraniectomy for stroke patients. SUMMARY: This review addresses some major issues that appear to be an obstacle to decompression craniectomy, in particular, indicating surgery for patients >60 years or with infarcts of the dominant hemisphere. Furthermore, it emphasizes technical issues such as timing and size of the craniectomy, additional temporal lobectomy, and resection of the temporal muscle, as well as duraplasty and cranioplasty. According to the current literature, decompression craniectomy in older patients can increase survival without most severe disabilities, although, most survivors need assistance in most bodily needs. Involvement of the dominant hemisphere results in aphasia that might partly recover in younger patients, although, considering the neuropsychological deficits caused by infarctions of the nondominant hemisphere, involvement of the dominant hemisphere does not pose as a contraindication for decompression craniectomy. Furthermore, there is convincing evidence that surgery should be performed within 48 h after the onset of symptoms and the size of the craniectomy should be at least 12 cm as a minimum. An additional lobectomy or the resection of the temporal muscle, however, can only be part of individual treatment options. Conceding the weak evidence, it is recommended to close the dura by some form of a duraplasty avoiding cerebrospinal fluid leakages or scarring between the cortex and the scalp leading to injuries during reimplantation of the bone-flap. Complications associated with decompression surgery (hemorrhages, infections, 'sinking skin-flap syndrome', cerebrospinal fluid leakages, hydrocephalus, seizures), with the infarction itself, or with those that occur during the ICU course (cardiac and pulmonary complications) appear acceptable and are mostly treatable, especially considering the fatal course of conservative treatment. Key Message: This review summarizes the current state of the literature about decompression craniectomy of patients with malignant stroke addressing, in particular, critical surgical issues, and thus, help surgeons to make decisions confidently for/or against performing surgery.

Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: A prospective multicenter observational study.

OBJECTIVE: Early identification of patients at risk of space-occupying "malignant" middle cerebral artery (MCA) infarction (MMI) is needed to enable timely decision for potentially life-saving treatment such as decompressive hemicraniectomy. We tested the hypothesis that acute stroke magnetic resonance imaging (MRI) predicts MMI within 6 hours of stroke onset. METHODS: In a prospective, multicenter, observational cohort study patients with acute ischemic stroke and MCA main stem occlusion were studied by MRI including diffusion-weighted imaging (DWI), perfusion imaging (PI), and MR-angiography within 6 hours of symptom onset. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. RESULTS: Of 140 patients included, 27 (19.3%) developed MMI. The following parameters were identified as independent predictors of MMI: larger acute DWI lesion volume (per 1 ml odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06; p < 0.001), combined MCA + internal carotid artery occlusion (5.38, 1.55-18.68; p = 0.008), and severity of neurological deficit on admission assessed by the National Institutes of Health Stroke Scale score (per 1 point 1.16, 1.00-1.35; p = 0.053). The prespecified threshold of a DWI lesion volume >82 ml predicted MMI with high specificity (0.98, 95% CI 0.94-1.00), negative predictive value (0.90, 0.83-0.94), and positive predictive value (0.88, 0.62-0.98), but sensitivity was low (0.52, 0.32-0.71). INTERPRETATION: Stroke MRI on admission predicts malignant course in severe MCA stroke with high positive and negative predictive value and may help in guiding treatment decisions, such as decompressive surgery. In a subset of patients with small initial DWI lesion volumes, repeated diagnostic tests are required.

Association of Infarct Volume Before Hemicraniectomy and Outcome After Malignant Infarction.

OBJECTIVE: To 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. METHODS: Patients 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. RESULTS: Among 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. CONCLUSION: Outcome in MMI depends strongly on age and infarct size before hemicraniectomy. Standardized volumetry may be helpful in the process of decision-making concerning hemicraniectomy.

Therapy of acute basilar artery occlusion: intraarterial thrombolysis alone vs bridging therapy.

BACKGROUND AND PURPOSE: While intravenous recombinant tissue plasminogen activator (rt-PA) has been approved for acute stroke therapy within 3 hours, the optimum management of basilar artery occlusion (BAO) is still a matter of debate. We compared intraarterial thrombolysis with the combined bridging approach of intravenous abciximab and intraarterial thrombolysis with rt-PA (bridging therapy) in an observational, longitudinal, monocenter study. METHODS: Between 1998 and 2006, information for 106 patients with acute BAO were prospectively entered into a local database. Patients eligible for treatment received either intraarterial thrombolysis with rt-PA alone (intraarterial thrombolysis) or were treated with intravenous abciximab and intraarterial rt-PA (bridging therapy). Outcome parameters were recanalization of the basilar artery according to Trial in Myocardial Infarction criteria, survival, and reduction of severe disability and death at 3 months. Logistic regression was used to identify independent predictors for recanalization, survival, and clinical outcome. RESULTS: Of a total of 106 patients with confirmed BAO, 87 patients underwent subsequent angiography. Among those, 75 patients were identified who received the full treatment protocol. Patients in the bridging group had a better recanalization rate (83.7% vs 62.5%; P=0.03), a higher survival rate (58.1% vs 25%; P=0.01), and a better chance for an outcome with no or only mild to moderate disability (modified Rankin Scale score, 0-3; 34.9% vs 12.5%; P=0.02). Symptomatic intracerebral hemorrhage rates were comparable in both groups (14% in the bridging group vs 18.8%; P=0.41). Independent predictors for recanalization were age (OR, 0.95; 95% CI, 0.91-0.99), atrial fibrillation (OR, 6.53; 95% CI, 1.14-37.49), and bridging therapy (OR, 3.37; 95% CI, 1.02 to 11.18). Independent prognostic factors for outcome were Glasgow coma scale score at presentation (OR, 1.24; 95% CI, 1.03-1.45) and the combination of bridging therapy with successful recanalization (OR, 3.744; 95% CI, 1.04-13.43). CONCLUSIONS: Bridging therapy for acute BAO with intravenous abciximab and intraarterial rt-PA appears to be safe and yields higher recanalization and improved survival rates, as well as an overall improved chance for a better outcome.

Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials.

BACKGROUND: Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned. METHODS: Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0-4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0-3 and 4 to death. Data analysis was done by an independent data monitoring committee. FINDINGS: 93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS

Comparison of ABC/2 estimation technique to computer-assisted planimetric analysis in warfarin-related intracerebral parenchymal hemorrhage.

BACKGROUND AND PURPOSE: The ABC/2 formula is a reliable estimation technique of intracerebral hematoma volume. However, oral anticoagulant therapy (OAT)-related intracerebral hemorrhage (ICH) compared with primary ICH is based on a different pathophysiological mechanism, and various shapes of hematomas are more likely to occur. Our objective was to validate the ABC/2 technique based on analyses of the hematoma shapes in OAT-related ICH. METHODS: We reviewed the computed tomography scans of 83 patients with OAT-associated intraparenchymal ICH. Location was divided into deep, lobar, cerebellar, and brain stem hemorrhage. Shape of the ICH was divided into (A) round-to-ellipsoid, (B) irregular with frayed margins, and (C) multinodular to separated. The ABC/2 technique was compared with computer-assisted planimetric analyses with regard to hematoma site and shape. RESULTS: The mean hematoma volume was 40.83+/-3.9 cm3 (ABC/2) versus 36.6+/-3.5 cm3 (planimetric analysis). Bland-Altman plots suggested equivalence of both estimation techniques, especially for smaller ICH volumes. The most frequent location was a deep hemorrhage (54%), followed by lobar (21%), cerebellar (14%) and brain stem hemorrhage (11%). The most common shape was round-to-ellipsoid (44%), followed by irregular ICH (31%) and separated and multinodular shapes (25%). In the latter, ABC/2 formula significantly overestimated volume by +32.1% (round shapes by +6.7%; irregular shapes by +14.9%; P ANOVA <0.01). Variation of the denominator toward ABC/3 in cases of irregularly and separately shaped hematomas revealed more a precise volume estimation with a deviation of -10.3% in irregular and +5.6% in separately shaped hematomas. CONCLUSIONS: In patients with OAT-related ICH, >50% of bleedings are irregularly shaped. In these cases, hematoma volume is significantly overestimated by the ABC/2 formula. Modification of the denominator to 3 (ie, ABC/3) measured ICH volume more accurately in these patients potentially facilitating treatment decisions.

Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most serious and potentially fatal complication of oral anticoagulant therapy (OAT). Still, there are no universally accepted treatment regimens for patients with OAT-ICH, and randomized controlled trials do not exist. The aim of the present study was to compare the acute treatment strategies of OAT-associated ICH using vitamin K (VAK), fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs) with regard to hematoma growth and outcome. METHODS: In this retrospective study, a total of 55 treated patients were analyzed. Three groups were compared by reviewing the clinical, laboratory, and neuroradiological parameters: (1) patients who received PCCs alone or in combination with FFP or VAK (n=31), (2) patients treated with FFP alone or in combination with VAK (n=18), and (3) patients who received VAK as a monotherapy (n=6). The end points of early hematoma growth and outcome after 12 months were analyzed including multivariate analysis. RESULTS: Hematoma growth within 24 hours occurred in 27% of patients. Incidence and extent of hematoma growth were significantly lower in patients receiving PCCs (19%/44%) compared with FFP (33%/54%) and VAK (50%/59%). However, this effect was no longer seen between PCC- and FFP-treated patients if international normalized ratio (INR) was completely reversed within 2 hours after admission. The overall outcome was poor (modified Rankin scale 4 to 6 in 77%). Predictors for hematoma growth were an increased INR after 2 hours, whereas administration of PCCs was significantly protective in multivariate analyses. Predictors for a poor outcome were age, baseline hematoma volume, and occurrence of hematoma growth. CONCLUSIONS: Overall, PCC was associated with a reduced incidence and extent of hematoma growth compared with FFP and VAK. This effect seems to be related to a more rapid INR reversal. Randomized controlled trials are needed to identify the most effective acute treatment regimen for lasting INR reversal because increased levels of INR were predisposing for hematoma enlargement.

Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials.

BACKGROUND AND PURPOSE: We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials. METHODS: Patients were examined by perfusion-weighted and diffusion-weighted imaging < or =6 hours. Within 3 hours, patients were treated according to Second European-Australasian Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA was performed based on MRI findings. Favorable outcome was assessed after 90 days using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral bleeding complications were assessed on follow-up MRI or computed tomography. Data were compared with the pooled placebo and pooled tPA patients of the ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke (NINDS) tPA trials. RESULTS: From 174 MRI-selected tPA patients, 62% (n=108) were treated in < or =3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40% [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI-selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and 1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392). CONCLUSIONS: This study supports that it is safe and effective to expand the time window for IV-tPA up to 6 hours in patients with tissue at risk as defined by MRI.

Nuclear factor-kappaB contributes to infarction after permanent focal ischemia.

BACKGROUND AND PURPOSE: Activation of transcription factor nuclear factor-kappaB (NF-kappaB) may induce expression of either proinflammatory/apoptotic genes or antiapoptotic genes. Because a considerable number of middle cerebral artery occlusions (MCAOs) in humans are not associated with reperfusion during the first 24 hours, the role of NF-kappaB after permanent MCAO (pMCAO) was investigated. METHODS: Mice transgenic for a NF-kappaB-driven beta-globin reporter were exposed to pMCAO, and the expression of the reporter gene was quantified with real-time polymerase chain reaction. Mice lacking the p50 subunit of NF-kappaB and wild-type controls were exposed to pMCAO with or without treatment with pyrrolidinedithiocarbamate (PDTC), an NF-kappaB inhibitor. Brain sections of human stroke patients were immunostained for the activated NF-kappaB. RESULTS: pMCAO increased NF-kappaB transcriptional activity to 260% (36.9+/-4.5 compared with 14.4+/-2.6; n=10; P<0.01) in the brain; this NF-kappaB activation was completely blocked by PDTC (17.2+/-2.6; n=9; P<0.05). In p50-/- mice, pMCAO resulted in 41% (18+/-3.2 mm3; n=12) smaller infarcts compared with wild-type controls (32.9+/-3.8 mm3; n=9; P<0.05), which was comparable to the protection achieved with PDTC in wild-type mice (19.6+/-4.2 mm3; n=8). Pro-DTC, a PDTC analogue that does not cross the blood-brain barrier, had no effect, even though Pro-DTC and PDTC were equally protective in vitro. During the first 2 days of human stroke, NF-kappaB was activated in neurons in the penumbral areas. CONCLUSIONS: NF-kappaB is induced in neurons during human stroke, and activation of NF-kappaB in the brain may contribute to infarction in pMCAO.

A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume.

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.

The speed of ultraearly hematoma growth in acute intracerebral hemorrhage.

OBJECTIVE: The prognostic importance of the speed of early hematoma growth in acute intracerebral hemorrhage (ICH) has not been well established. We aimed to determine the association between the rate of increase in hematoma volume and major clinical outcomes in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. The effects of early intensive blood pressure (BP) lowering according to the speed of hematoma growth were also investigated. METHODS: Pooled analyses of the INTERACT1 (n = 404) and INTERACT2 (n = 2,839) studies-randomized controlled trials of patients with spontaneous ICH with elevated systolic BP, randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. The speed of ultraearly hematoma growth (UHG) was defined as hematoma volume (mL)/onset-to-CT time (hours). Primary outcome was death or major disability (modified Rankin Scale score of 3-6) at 90 days. RESULTS: Among a total of 2,909 patients (90%) with information on UHG and outcome, median speed of UHG was 6.2 mL/h. There was a linear association between UHG and outcome: multivariable-adjusted odd ratios 1.90 (95% confidence interval 1.50-2.39) for 5-10 mL/h and 2.96 (2.36-3.71) for >10 mL/h vs the <5 mL/h group. There were no clear differences in the effects of intensive BP lowering according to 3 speeds of UHG on outcome (p = 0.75 for homogeneity). CONCLUSIONS: The speed of UHG in patients with ICH was continuously associated with increased risks of death or major disability, and from lower levels than previously reported (≥5 mL/h). The benefits of intensive BP lowering appear to be independent of the speed of bleeding.

Combining magnetic resonance imaging within six-hours of symptom onset with clinical follow-up at 24 h improves prediction of 'malignant' middle cerebral artery infarction.

BACKGROUND: A large diffusion-weighted imaging lesion ≤six-hours of symptom onset was found to predict the development of 'malignant' middle cerebral artery infarction with high specificity, positive predictive value, and negative predictive value, but sensitivity was low. HYPOTHESIS: We tested the hypothesis that sensitivity can be improved by adding information from clinical follow-up examination after 24 h. METHODS: We analyzed data from a prospective, multicenter, observational cohort study of patients with acute ischemic stroke and middle cerebral artery occlusion studied by stroke magnetic resonance imaging ≤six-hours of symptom onset. We used the National Institutes of Health Stroke Scale to assess severity of symptoms after 24 h. We used the Classification and Regression Trees analysis to define the optimal thresholds of diffusion-weighted imaging lesion volume and the National Institutes of Health Stroke Scale after 24 h in patients developing 'malignant' middle cerebral artery infarction. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for two simple predictive models based on acute diffusion-weighted imaging lesion volume alone and acute diffusion-weighted imaging lesion volume together with the National Institutes of Health Stroke Scale after 24 h. RESULTS: Of 135 patients, 27 (20%) developed a 'malignant' middle cerebral artery infarction. The Classification and Regression Trees analysis identified acute diffusion-weighted imaging lesion ≥78 ml and the National Institutes of Health Stroke Scale score after 24 h ≥22 as optimal cut-offs. Inclusion of the National Institutes of Health Stroke Scale score after 24 h in a simple two-step decision tree increased sensitivity from 0·59 to 0·79, while specificity, positive predictive value, and negative predictive value remained largely unchanged. CONCLUSION: Clinical follow-up examination after 24 h helps identify patients at risk of 'malignant' middle cerebral artery infarction that are missed by predictive algorithms based on early diffusion-weighted imaging lesion volume alone.

Cooling in intracerebral hemorrhage (CINCH) trial: protocol of a randomized German-Austrian clinical trial.

BACKGROUND: Intracerebral hemorrhage accounts for up to 15% of all strokes and is frequently associated with poor functional outcome and high mortality. So far, there is no clear evidence for a specific therapy, apart from general stroke unit or neurointensive care and management of secondary complications. Promising experimental and pilot clinical data support the use of therapeutic hypothermia after intracerebral hemorrhage. AIMS: The study aims to determine if therapeutic hypothermia improves survival rates and reduces cerebral lesion volume after large intracerebral hemorrhage compared with conventional treatment. MATERIAL AND METHODS: The Cooling in IntraCerebral Hemorrhage trial is a prospective, multicenter, interventional, randomized, parallel, two-arm (1 : 1) phase II trial with blinded end-point adjudication. Enrolment: 50 patients (age: 18 to 65 years) with large (25 to 64 ml on cranial computertomography), primary intracerebral hemorrhage of the basal ganglia or thalamus within 6 to 18 h after symptom onset are randomly allocated to therapeutic hypothermia for eight-days or conventional temperature management. In the therapeutic hypothermia group, a target temperature of 35.0°C is achieved by endovascular catheters and followed by slow controlled rewarming. Data analysis is based on the intent-to-treat population. The primary outcome measure of the study is the development in total lesion volume on cranial computertomography (intracerebral hemorrhage plus perihemorrhagic edema on day 8 ± 0.5 and day 1 ± 0.5 after intracerebral hemorrhage) and the mortality after 30 days. Secondary end-points are the in-hospital mortality, mortality, and functional outcome (modified Rankin Scale and Barthel-Index) after 90 and 180 days. Safety measures include any adverse events associated with therapeutic hypothermia. DISCUSSION: In the face of a lack of evidence-based therapies for patients with large intracerebral hemorrhage, new promising approaches are desperately needed, but need evaluation in randomized controlled trials. CONCLUSION: The results of Cooling in IntraCerebral Hemorrhage trial are believed to directly influence future therapy of large intracerebral hemorrhage.

Short period of early reperfusion aggravates blood-brain barrier dysfunction during permanent focal ischemia in rats.

Unintentional reperfusion is considered a complication in various experimental models of focal brain ischemia. In the present study, we evaluated whether short intermittent reperfusion affects ischemic brain damage and blood-brain barrier (BBB) integrity in a model of permanent focal ischemia. Focal brain ischemia was induced in male Sprague-Dawley rats using the filament method. A 20-s reperfusion period was allowed 0.5, 2, or 10 min after thread occlusion of the middle cerebral artery. In control animals, the transient reperfusion episode was omitted. The infarct volume and extent of swelling was examined 24 h after permanent thread occlusion. Immunohistochemical staining for thrombin extravasation was performed. Transient reperfusion early after thread occlusion augmented brain swelling (control, 12.4 ± 8.5%; reperfusion after 0.5 min, 24.7 ± 7.0%*; after 2 min, 36.7 ± 4.8%*; after 10 min, 33.8 ± 4.9%*; *p < 0.01 vs. control) and significantly enhanced leakage of the plasma protein thrombin, whereas the ischemic volume was unaffected. Early intermittent reperfusion may be responsible for increased BBB disruption in permanent ischemia. Similar reperfusion episodes during early ischemia sequelae in patients-due to incomplete adherence or distal movements of a clot-may be causative for increased BBB damage, more severe edema, and potentially hemorrhagic transformation.

The role of surgery in ischemic stroke: decompressive surgery.

PURPOSE OF REVIEW: This review gives an integrated view on the current status of decompressive surgery in space-occupying hemispheric brain infarction with a focus on new developments based on the available data of recent clinical trials, also including preliminary data from randomized trials reported at international stroke conferences in 2006. RECENT FINDINGS: The treatment of ischemic brain infarction with life-threatening space-occupying edema is, because of a lack of prospective studies, one of the major controversial issues within neurocritical care medicine today. Only a few years ago, massive cerebral infarctions were regarded an untreatable disease with fatal outcome. The introduction of decompressive surgery (hemicraniectomy) has completely changed this point of view. Most of the reports, however, are retrospective with low numbers of patients. There are only few prospective trials that suggest a substantial benefit of decompressive surgery to significantly reduce mortality as compared to maximal conservative treatment alone. The control groups in these studies, however, consist of patients with higher age and higher rates of co-morbidities. Also, in most studies information on long-term outcome is insufficient. In 2006 long expected preliminary data from randomized trials of hemicraniectomy have been reported at international stroke conferences. They yield very positive results. SUMMARY: Decompressive surgery appears to be a promising treatment option for patients with space-occupying hemispheric brain infarction.