The CHESS may become a valuable diagnostic tool for early estimation of shunt dependency after SAH. Further evaluation and external validation will be required in prospective studies.

The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas.

Background Miscoding mutations of the TET2 gene, which encodes the a-ketoglutarate-dependent enzyme that catalyses the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, thus producing DNA demethylation, have been detected in 10e25% of acute myeloid leukaemias lacking IDH1/2 mutations. Most low-grade diffuse gliomas carry IDH1/2 mutations (>85%), but molecular mechanisms of pathogenesis in those lacking IDH1/2 mutations remain to be elucidated. Methods Miscoding mutations and promoter methylation of the TET2 gene were screened for in 29 low-grade diffuse gliomas lacking IDH1/2 mutations. Results Single-strand conformational polymorphism followed by direct sequencing showed the absence of miscoding mutations in TET2. Methylation-specific PCR revealed methylation of the TET2 promoter in 5 of 35 cases (14%). In contrast, none of 38 low-grade diffuse gliomas with IDH1/2 mutations had TET2 promoter methylation (p¼0.0216). Conclusion Results suggest that TET2 promoter methylation, but not TET2 mutation, may be an alternative mechanism of pathogenesis in a small fraction of low-grade diffuse gliomas lacking IDH1/2 mutations.

OBJECTIVE The complete clipping of a cerebral aneurysm usually warrants its sustained occlusion, while clip remnants may have far-reaching consequences. The aim of this study is to identify the risk factors for clip remnants requiring retreatment and/or exhibiting growth. METHODS All consecutive patients with primary aneurysm clipping performed at University Hospital of Essen between January 1, 2003, and December 31, 2013, were eligible for this study. Aneurysm occlusion was judged on obligatory postoperative digital subtraction angiography and the need for repeated vascular control. The identified clip remnants were correlated with various demographic and clinical characteristics of the patients, aneurysm features, and surgery-related aspects. RESULTS Of 616 primarily clipped aneurysms, postoperative angiography revealed 112 aneurysms (18%) with clip remnants requiring further control (n = 91) or direct retreatment (n = 21). Seven remnants exhibited growth during follow-up, whereas 2 cases were associated with aneurysmal bleeding. Therefore, a total of 28 aneurysms (4.5%) were retreated as clip remnants (range 1 day to 67 months after clipping). In the multivariate analysis, the need for retreatment of clip remnant was correlated with the aneurysm's initial size (> 12 mm; OR 3.22; p = 0.035) and location (anterior cerebral artery > internal carotid artery > posterior circulation > middle cerebral artery; OR 1.85; p = 0.003). Younger age with a cutoff at 45 years (OR 33.31; p = 0.004) was the only independent predictor for remnant growth. CONCLUSIONS The size and location of the aneurysm are the main risk factors for clip remnants requiring retreatment. Because of the risk for growth, younger individuals (< 45 years old) with clip remnants require a long-term (> 5 years) vascular follow-up. Clinical trial registration no: DRKS00008749 (Deutsches Register Klinischer Studien).

Female sex, higher age, arterial hypertension, smoking, and familial IA are major risk factors for MIA. In addition, MIA patients are at risk for enhanced IA formation. Further studies are needed to evaluate rupture risk and the role of ethnicity, especially in the context of increased MIA identification with improved neurovascular imaging.

ObjectiveDelayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts.MaterialsData from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score >2) at 6 months follow-up was analyzed.ResultsThe final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt & Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], p < 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, p < 0.0001) of EVT. The rates of DCI (20.8% vs 29%, p = 0.0001) and unfavorable outcome (44% vs 50.6%, p = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome.ConclusionsA preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in patients with SAH and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH.Classification of evidenceThis study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.

Background and Purpose-Loss of movement coordination is the main postacute symptom after cerebellar infarction.Although the course of motor recovery has been described previously, detailed kinematic descriptions of acute stage ataxia are rare and no attempt has been made to link improvements in motor function to measures of neural recovery and lesion location. This study provides a comprehensive assessment of how lesion site and arm dysfunction are associated in the acute stage and outlines the course of upper limb motor recovery for the first 4 months after the infarction. Methods-Sixteen adult patients with cerebellar stroke and 11 age-matched healthy controls participated. Kinematics of goal-directed and unconstrained finger-pointing movements were measured at the acute stage and in 2-week and 3-month follow-ups. MRI data were obtained for the acute and 3-month follow-up sessions. A voxel-based lesion map subtraction analysis was performed to examine the effect of ischemic lesion sites on kinematic performance. Results-In the acute stage, nearly 70% of patients exhibited motor slowing with hand velocity and acceleration maxima below the range of the control group. MRI analysis revealed that in patients with impaired motor performance, lesions were more common in paravermal lobules IV/V and affected the deep cerebellar nuclei. Stroke affecting the superior cerebellar artery led to lower motor performance than infractions of the posterior cerebellar artery. By the 2-week-follow-up, hand kinematics had improved dramatically (gains in acceleration up to 86%). Improvements between the 2-week and the 3-month-follow-ups were less pronounced. Conclusion-In the acute stage, arm movements were mainly characterized by abnormal slowness (bradykinesia) and not dyscoordination (ataxia). The motor signs were associated with lesions in paravermal regions of lobules IV/V and the deep cerebellar nuclei. Motor recovery was fast, with the majority of gains in upper limb function occurring in the first 2 weeks after the acute phase. (Stroke. 2010;41:2191-2200.)

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