News & Views in 2018

A new study has identified key differences between women and men with regard to the nature and burden of Alzheimer disease (AD) pathology in the brain. In addition to highlighting possible sex differences in AD pathophysiology, the findings could have important implications for the diagnosis and management of this condition.

A nationwide German study of prescription data has demonstrated that switching to an antiepileptic drug from a different manufacturer increases the risk of seizure relapse. This finding sparks a debate about the reason for seizure worsening after switching and whether or not it is a pharmacological issue.

Amyotrophic lateral sclerosis (ALS) is a progressive motor disorder, and many patients also show non-motor symptoms including executive, behavioural and language dysfunction. A new study demonstrates a robust relationship between progression of these non-motor symptoms and declining motor disease in patients with ALS, providing important insights into mechanisms of ALS pathogenesis.

New research indicates that most patients with epilepsy exhibit cyclic (24 h or multi-day) seizure patterns. The findings could have important implications for the design of antiseizure drug regimens.

A committee has developed a guideline on prolonged disorders of consciousness. Caution in prognostication is advocated because patients who have been unconscious or barely conscious for a long time might improve. The new guideline voices concern about persistent vegetative state as a clinical diagnosis but also rejects several unsupported therapies.

The TOLEDO study provides new evidence to support the use of subcutaneous apomorphine infusion to control motor fluctuations in patients with advanced Parkinson disease. The findings should encourage neurologists to consider implementing apomorphine infusion or other device-aided therapies earlier in the disease course, before the emergence of troublesome dyskinesias.

A new study has shown that peritoneal dialysis and isochronic parabiosis can clear misfolded tau proteins from mouse brain. The findings add to our understanding of how Alzheimer disease-associated proteins can be therapeutically removed by peripheral interventions.

A new publication from the Whitehall study confirms earlier findings that light to moderate alcohol drinkers have a reduced risk of dementia compared with abstainers and heavy drinkers. Importantly, the study follows a cohort from middle age, whereas most previous research on this topic has focused on older adults.

During cluster headache attacks, plasma levels of calcitonin gene-related peptide (CGRP) increase, and trigeminal nerve activation leads to pain. A new study shows that CGRP infusion can induce cluster headache attacks in some patients, with important implications for the investigation of CGRP-targeted therapies in cluster headache.

Multimodal imaging in neurodegenerative disorders can provide insights on structural, functional and neurochemical alterations that might not be possible via clinical testing alone. New findings on multimodal imaging in idiopathic REM sleep behaviour disorder (iRBD) have implications for the relationship between iRBD, the clinical phenotype of Parkinson disease and the underlying substrate of Lewy body disease, particularly for understanding the pathophysiology and designing disease-modifying therapies.

Patent foramen ovale (PFO) is prevalent among young patients with cryptogenic stroke, and PFO closure reduces the risk of recurrent stroke in these individuals. A new study confirms that PFO is also frequent in patients with cryptogenic stroke aged >60 years, but the optimal management of such patients remains unresolved.

In a recent study, rivaroxaban was not superior to aspirin for secondary prevention of stroke and systemic emboli after an initial embolic stroke of undetermined source (ESUS) but was associated with a higher risk of bleeding. What does that mean for the concept of ESUS and for future trials?

Moderate and severe traumatic brain injuries (TBIs) have long been recognized as risk factors for dementia, but the relationship between mild TBI (mTBI) and dementia is unclear. New research demonstrates that even an mTBI without loss of consciousness is associated with a twofold increase in the risk of dementia.

Eteplirsen, a compound designed to restore dystrophin in patients with Duchenne muscular dystrophy, controversially received approval by the FDA in 2016. Owing to limited clinical data, the approval was based on eteplirsen’s effect on dystrophin expression. Now, the dystrophin quantification results have been published, and although low levels of dystrophin expression are shown, the quantification remains debatable.

Tackling intertumoural and intratumoural heterogeneity is one of the most important challenges in the study and treatment of glioblastoma. A new anatomical transcriptional atlas of human glioblastoma associates established anatomical features with distinct molecular subclasses and provides open access to these well-annotated data for drug target validation and data-mining projects.

Following on from a recent European Academy of Neurology guideline on pharmacological treatment of multiple sclerosis (MS), the American Academy of Neurology has issued an updated practice guideline on disease-modifying therapies (DMTs) for MS. The guideline provides 30 general recommendations for initiating, switching and stopping DMTs, and indicates future research directions.

The WHO’s revised classification system for CNS tumours now incorporates genetic features, including the mutation status of isocitrate dehydrogenase (IDH) genes. A new article proposes that mutational status of CDKN2A and CDKN2B should also be included to facilitate grading of IDH-mutated gliomas with both prognostic and clinical relevance.

In a recent study, individuals with brain amyloid-β accumulation but no cognitive impairment were classified as being at risk of Alzheimer disease, yet amyloid-β is widely considered to be a pathological biomarker of Alzheimer disease rather than a risk factor — it cannot be both.

An incomplete grasp of how the G₄C₂ repeat expansion in C9orf72 leads to amyotrophic lateral sclerosis and frontotemporal dementia has hindered progress in treatment development. Now, a study has combined unbiased genetic screens and CRISPR–Cas9 gene editing to validate known molecular pathways and identify novel therapeutic targets involved in G₄C₂ repeat pathogenesis.

New research has found that anaesthesia and surgery are associated with increased blood levels of two markers of neuronal injury — neurofilament light (NFL) and tau. The findings highlight the neurotoxic effects of anaesthesia and surgery and indicate that tau and NFL could present useful biomarkers for postoperative neurocognitive disorders.