Volume 15 Issue 1, January 2019

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.

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.

Early diagnosis of Alzheimer disease (AD) is crucial for efficient selection of clinical trial participants for drug development and ultimately for timely treatment of individuals with AD. Here, Claire Murphy examines the potential for olfactory and other sensory impairments as very early indicators of AD and considers the important questions that remain to be answered.

Impairment of cerebral autoregulation after traumatic brain injury (TBI) is associated with poor outcomes, but the reasons underlying this association are poorly understood. This Review highlights genetic polymorphisms that might be linked to cerebrovascular function after TBI that might promote improved understanding of the pathogenic mechanisms underlying impaired vascular reactivity and offer potential targets for new therapies.

Pathogenic variants in POLG, which encodes the catalytic subunit of DNA polymerase γ, cause a spectrum of overlapping disease phenotypes. This Review describes the clinical features, pathophysiology, natural history and treatment of POLG-related disorders, focusing particularly on the neurological manifestations.

The development of treatment for multiple sclerosis over the past 25 years is a success of translational medicine. In this Timeline article, Tintore et al. chart major developments and discuss the implications for current and future patient management.