Patients with aneurysmal subarachnoid hemorrhage (SAH) who experience delayed cerebral ischemia (DCI) have an increased risk of poor outcome. Delayed cerebral ischemia is considered to be caused by vasospasm. However, not all patients with DCI have vasospasm. Inversely, not all patients with vasospasm develop clinical symptoms and signs of DCI. In the past, treatments aiming at vasospasm were not successful in preventing ischemia. The purpose of this review is to give an overview of clinical data showing that DCI cannot always be attributed to vasospasm, and to present an in-depth analysis of clinical and autopsy studies on the role of microthrombosis in the pathogenesis of DCI. Clinical studies show that DCI is associated with an activation of the coagulation cascade within a few days after SAH, preceding the time window during which vasospasm occurs. Furthermore, impaired fibrinolytic activity, and inflammatory and endotheliumrelated processes, lead to the formation of microthrombi, which ultimately result in DCI. The presence of microthrombi is confirmed by autopsy studies. Insight in the pathophysiology of DCI is crucial for the development of effective therapies against this complication. Because multiple pathways are involved, future research should focus on drugs with pleiotropic effects.

Recently, two randomized controlled phase II studies showed that acute initiation of statin treatment directly after aneurysmal subarachnoid hemorrhage (SAH) decreases the incidence of radiologic vasospasm and clinical signs of delayed cerebral ischemia (DCI), and even reduces mortality. It was hypothesized that the beneficial effect resulted from pleiotropic effects of statins. The purpose of this study was to investigate the biologic effects of acute statin treatment in patients with SAH. We performed an exploratory single-center, prospective, randomized, double-blind, placebo-controlled trial. Patients were randomized to simvastatin 80 mg or placebo once daily. A total of 32 patients were included. There were no statistically significant differences in clinical baseline characteristics. With regard to primary outcomes, there were significant differences by treatment group for total cholesterol and low-density lipoprotein (LDL) cholesterol (P < 0.0001), but not for parameters of coagulation, fibrinolysis, endothelium function, and inflammation. With regard to secondary outcomes, no differences were observed in the incidence of transcranial Doppler vasospasm, clinical signs of DCI, and poor outcome. We conclude that both the primary and secondary outcome results of this study do not support a beneficial effect of simvastatin in patients with SAH (ISRCTN45662651).

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Certain posterior circulation aneurysm locations (PCA, VA-PICA, and BA-VBJ) represent separate disease entities affecting patients at different ages with distinct patterns of presentation, treatment options, and outcomes. Favorable overall long-term outcome can be achieved in 90% of patients with PCA aneurysms, in 60% of those with VA-PICA aneurysms, and in 39% of those with BA-VBJ aneurysms when using endovascular and surgical techniques. The natural history of the disease was poor in patients with incomplete aneurysm thrombosis after treatment.

Background and Purpose-Hyperglycemia may worsen outcome after aneurysmal subarachnoid hemorrhage. We performed a systematic review to investigate the relation between admission hyperglycemia and outcome after aneurysmal subarachnoid hemorrhage. Methods-We included cohort studies or clinical trials of patients with aneurysmal subarachnoid hemorrhage admitted within 72 hours that documented admission glucose levels or the rate of hyperglycemia. Outcome had to be assessed prospectively after 3 or more months. The overall mean glucose level was calculated by weighting for the number of patients included in each study. To calculate the effect size, we pooled the ORs and 95% 95% CIs of poor clinical outcome in patients with or without hyperglycemia. Results-We searched MEDLINE, EMBASE, Science Citation Index, and the bibliographies of relevant studies. We included 17 studies totaling 4095 patients. The mean admission glucose level was 9.3 mmol/L (range, 7.4 to 10.9 mmol/L; 14 studies, 3373 patients) and the median proportion of patients with hyperglycemia was 69% (range, 29 to 100; 16 studies, 3995 patients; cutoff levels of hyperglycemia, 5.7 to 12.0 mmol/L). The pooled OR (8 studies, 2164 patients) for poor outcome associated with hyperglycemia was 3.1 (95% CI, 2.3 to 4.3). Cutoff points for defining hyperglycemia varied across studies (6.4 to 11.1 mmol/L), but this had no clear effect on the observed OR for poor outcome. Conclusions-After aneurysmal subarachnoid hemorrhage, admission glucose levels are often high and hyperglycemia is associated with an increased risk of poor clinical outcome. A randomized clinical trial is warranted to study the potential benefit of glycemic control after aneurysmal subarachnoid hemorrhage. (Stroke. 2009;40:e424-e430.)

Background and Purpose— Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage. If clinical signs of DCI occur, induced hypertension is a plausible but unproven therapeutic intervention. There is clinical equipoise if the use of hypertension induction is useful or not with the consequence that this strategy is irregularly used. We explored the effect of blood pressure augmentation in preventing cerebral infarction in patients with clinical signs of DCI. Methods— We performed a retrospective observational study, totaling 1647 patients with aneurysmal subarachnoid hemorrhage admitted at 3 academic hospitals in the Netherlands between 2006 and 2015. To study the primary outcome DCI related cerebral infarcts, we only included patients with no cerebral infarct at the time of onset of clinical signs of DCI. Cox regression was used to test the association between induced hypertension after onset of clinical signs of DCI and the occurrence of DCI related cerebral infarcts. Logistic regression was used to relate hypertension induction with poor outcome after 3 months, defined as a modified Rankin score >3. Results were adjusted for treatment center and baseline characteristics. Results— Clinical signs of DCI occurred in 479 (29%) patients of whom 300 without cerebral infarction on computed tomography scan at that time. Of these 300 patients, 201 (67%) were treated with hypertension induction and 99 were not. Of the patients treated with hypertension induction, 41 (20%) developed a DCI related cerebral infarct compared with 33 (33%) with no induced hypertension: adjusted hazard ratio, 0.59; 95% CI, 0.35 to 0.99. Hypertension induction also prevented poor outcome: adjusted odds ratio, 0.27; 95% CI, 0.14 to 0.55. Conclusions— Hypertension induction seems an effective strategy for preventing DCI related cerebral infarcts if not already present at the time of onset of clinical signs of DCI. This may lead to a reduction in poor clinical outcome.

Objective To prevent complications following decompressive craniectomy (DC), such as sinking skin flap syndrome, studies suggested early cranioplasty (CP). However, several groups reported higher complication rates in early CP. We studied the clinical characteristics associated with complications in patients undergoing CP, with special emphasis on timing. Methods A single-center observational cohort study was performed, including all patients undergoing CP from 2006 to 2018, to identify predictors of complications. Results 145 patients underwent CP: complications occurred in 33 (23%): 18 (12%) epi/subdural hemorrhage, 10 (7%) bone flap infection, 4 (3%) hygroma requiring drainage, and 1 (1%) post-CP hydrocephalus. On univariate analysis, acute subdural hematoma as etiology of DC, symptomatic cerebrospinal fluid (CSF) flow disturbance (hydrocephalus) prior to CP, and CP within three months after DC were associated with higher complication rates. On multivariate analysis, only acute subdural hematoma as etiology of DC (OR 7.5; 95% CI 1.9-29.5) and symptomatic CSF flow disturbance prior to CP (OR 2.9; 95% CI 1.1-7.9) were associated with higher complication rates. CP performed within three months after DC was not (OR 1.4; 95% CI 0.5-3.9). Pre-CP symptomatic CSF flow disturbance was the only variable associated with the occurrence of epi/ subdural hemorrhage. (OR 3.8; 95% CI 1.6-9.0) Conclusion Cranioplasty has high complication rates, 23% in our cohort. Contrary to recent systematic reviews, early CP was associated with more complications (41%), explained by the higher incidence of pre-CP CSF flow disturbance and acute subdural hematoma as etiology of DC. CP in such patients should therefore be performed with highest caution.

Small retrospective case series suggest that decompressive hemicraniectomy can be life saving in patients with cerebral venous thrombosis (CVT) and impending brain herniation. Prospective studies of consecutive cases are lacking. Thus, a single centre, prospective study was performed. In 2006 we adapted our protocol for CVT treatment to perform acute decompressive hemicraniectomy in patients with impending herniation, in whom the prognosis with conservative treatment was considered infaust. We included all consecutive patients with CVT between 2006 and 2010 who underwent hemicraniectomy. Outcome was assessed at 12 months with the modified Rankin Scale (mRS). Ten patients (8 women) with a median age of 41 years (range 26–52 years) were included. Before surgery 5 patients had GCS < 9, 9 patients had normal pupils, 1 patient had a unilaterally fixed and dilated pupil. All patients except one had space-occupying intracranial hemorrhagic infarcts. The median preoperative midline shift was 9 mm (range 3–14 mm). Unilateral hemicraniectomy was performed in 9 patients and bilateral hemicraniectomy in one. Two patients died from progressive cerebral edema and expansion of the hemorrhagic infarcts. Five patients recovered without disability at 12 months (mRS 0–1). Two patients had some residual handicap (one minor, mRS 2; one moderate, mRS 3). One patient was severely handicapped (mRS 5). Our prospective data show that decompressive hemicraniectomy in the most severe cases of cerebral venous thrombosis was probably life saving in 8/10 patients, with a good clinical outcome in six. In 2 patients death was caused by enlarging hemorrhagic infarcts.