Using ATECO MRV and a novel grading system for quantifying sinovenous stenoses, the authors can identify IIH patients with sensitivity and specificity of 93%.

Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative risk [RR] 1·08, 95% CI 0·76–1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58–2·52; p=0·52). Interpretation This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury. Funding National Institute of Neurological Disorders and Stroke.

The presence of contrast enhancement in a brain tumor is often regarded as a sign of malignancy. The authors identified 314 patients with malignant and low-grade supratentorial glial neoplasms in an unselected population, 58 of which lacked contrast enhancement on preoperative neuroimaging. Nonenhancing gliomas were malignant in approximately one third of cases, especially in older patients. Histologic confirmation of the diagnosis is therefore important in all patients suspected of harboring a primary glial neoplasm.

An autosomal recessive syndrome of nonprogressive cerebellar ataxia and mental retardation is associated with inferior cerebellar hypoplasia and mild cerebral gyral simplification in the Hutterite population. An identity-by-descent mapping approach using eight patients from three interrelated Hutterite families localized the gene for this syndrome to chromosome region 9p24. Haplotype analysis identified familial and ancestral recombination events and refined the minimal region to a 2-Mb interval between markers D9S129 and D9S1871. A 199-kb homozygous deletion encompassing the entire very low density lipoprotein receptor (VLDLR) gene was present in all affected individuals. VLDLR is part of the reelin signaling pathway, which guides neuroblast migration in the cerebral cortex and cerebellum. To our knowledge, this syndrome represents the first human lipoprotein receptor malformation syndrome and the second human disease associated with a reelin pathway defect.

Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development.