Background and Purpose-Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6-and 12-month functional outcomes from the DESTINY trial. Methods-DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end pointϭmodified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. Results-A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (Pϭ0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (Pϭ0.23). Conclusions-DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.

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on behalf of the CONSCIOUS-1 InvestigatorsBackground and Purpose-This randomized, double-blind, placebo-controlled, dose-finding study assessed efficacy and safety of 1, 5, and 15 mg/h intravenous clazosentan, an endothelin receptor antagonist, in preventing vasospasm after aneurysmal subarachnoid hemorrhage. Methods-Patients (nϭ413) were randomized to placebo or clazosentan beginning within 56 hours and continued up to 14 days after initiation of treatment. The primary end point was moderate or severe angiographic vasospasm based on centrally read, blinded evaluation of digital subtraction angiography at baseline and 7 to 11 days postsubarachnoid hemorrhage. A morbidity/mortality end point, including all-cause mortality, new cerebral infarct from any cause, delayed ischemic neurological deficit due to vasospasm, or use of rescue therapy, was evaluated by local assessment. Clinical outcome was assessed by the extended Glasgow Outcome Scale at 12 weeks. Results-Moderate or severe vasospasm was reduced in a dose-dependent fashion from 66% in the placebo group to 23% in the 15 mg/h clazosentan group (risk reduction, 65%; 95% CI, 47% to 78%; PϽ0.0001). No significant effects were seen on secondary end points. Post hoc analysis using a centrally assessed morbidity/mortality end point that included death and rescue therapy but only cerebral infarcts and delayed ischemic neurological deficit due to vasospasm on central review showed a trend toward improvement with clazosentan (37%, 28%, and 29% in the 1, 5, and 15 mg/h groups versus 39% in the placebo group, nonsignificant). Clazosentan was associated with increased rates of pulmonary complications, hypotension, and anemia. Conclusions-Clazosentan significantly decreased moderate and severe vasospasm in a dose-dependent manner and showed a trend for reduction in vasospasm-related morbidity/mortality in patients with aneurysmal subarachnoid hemorrhage when centrally assessed. Overall, the adverse effects were manageable and not considered serious. (Stroke. 2008;39:3015-3021.)

Bilateral and unilateral laminotomy allowed adequate and safe decompression of lumbar stenosis, resulted in a highly significant reduction of symptoms and disability, and improved health-related quality of life. Outcome after unilateral laminotomy was comparable with that after laminectomy. In most outcome parameters, bilateral laminotomy was associated with a significant benefit and thus constitutes a promising treatment alternative.

The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2. The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter.

Subarachnoidal release of inflammatory cytokines (interleukin (IL)-1 , IL-6, and tumour necrosis factor (TNF)-) was characterised in 35 patients with subarachnoid haemorrhage (SAH) and control subjects and compared with development of complicating haemodynamic abnormalities in basal cerebral arteries and clinical outcome. Serial analysis allowed the observation of a subacute response profile of these key mediators of inflammation in the subarachnoidal space. This compartmentalised inflammatory host response was closely associated in time and extent with development of increased blood flow velocities in the basal cerebral vessels as recorded by transcranial Doppler sonography. Moreover, intrathecal secretion of inflammatory cytokines was significantly increased in patients with poor clinical outcome. Together, these findings suggest a role of excessive compartmentalised inflammatory host response in pathogenesis of cerebrovascular complications after SAH. (J Neurol Neurosurg Psychiatry 2001;70:534-537) Keywords: subarachnoid haemorrhage; inflammatory cytokines; cerebral blood flow; vasospasm; cerebral ischaemia Subarachnoid haemorrhage (SAH) most commonly occurs when an aneurysm in a basal cerebral artery ruptures. Among patients who survive this event, the leading cause of death and disability is subsequent constriction of the large cerebral arteries causing delayed cerebral ischaemia, the "second stroke". 1 2 Monitoring of cerebral blood flow velocities (CBFVs) in the large pial arteries identifies patients with SAH with raised risk for ischaemic complications. [3][4][5][6] In SAH, it has been shown in multiple studies that CBFVs on transcranial Doppler sonography are inversely related to vessel diameters on angiography. [3][4][5][6] The noninvasive character of this technique enables serial investigations of developing haemodynamic abnormalities in an individual patient.Earlier studies described inflammatory changes in SAH-that is, subarachnoidal and perivascular leucocytic infiltrates in the subarachnoidal space 7-9 in relation to development of cerebral vasospasms. 8 9 Moreover, the proinflammatory cytokines interleukin (IL)-1 , IL-6, and tumour necrosis factor (TNF)-that orchestrate the cascade of inflammatory host response to infection and tissue damage 10 11 have been detected in the CSF of patients with SAH. [12][13][14][15][16] These earlier findings suggest an inflammatory pathogenesis of vasospasms in SAH. In this study, we tested the hypothesis that the extent and pattern of secretion of key mediators of inflammation IL-1 , IL-6, and TNFare associated with development of haemodynamic abnormalities in basal cerebral arteries and with clinical outcome. Patients and methods PATIENTS AND CONTROL SUBJECTSThirty five patients (21 women and 14 men), aged between 23 and 76 (median 56) years with SAH caused by aneurysmal rupture and presenting within 48 hours after onset of first symptoms were studied. Hunt and Hess scores to classify disease severity were 1 in 9%, 2 in 11%, 3 in 32%, 4 in 29%, and...

This study indicates that clazosentan reduces the frequency and severity of cerebral vasospasm following severe aneurysmal SAH with the incidence and severity of adverse events comparable to that of placebo.

Although there was a significant decrease in midline shift after craniectomy, this did not translate into decompressive craniectomy demonstrating a beneficial effect on patient outcome.