Reviews & Analysis

As yet, no clear strategy has been developed for discontinuation of disease-modifying therapy in multiple sclerosis. A recent observational study adds new information, but the most informative patient groups are still to be assessed comprehensively, and several questions need to be addressed in prospective studies.

Guide RNA-mediated CRISPR–Cas nucleases are a powerful technology for the engineering of mammalian genomes. CRISPR–Cas9-dependent editing of mutated genes that cause Huntington disease and fragile X syndrome was recently achieved in cell-based models, heralding the first step towards developing this technology into viable therapeutics for neurological diseases.

A new systematic review detected strong evidence of unreliable results via use of statistical and logical analyses of 33 randomized clinical trials. Our outrage at these rare occurrences of potential fraud could be rooted in our disdain at our failures in peer review, given that this special effort was required to detect long-running potential fraud.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease predominantly affecting upper and lower motor neurons. Here, the authors outline previous and current efforts to characterize genes that are associated with ALS, and describe what is currently known about the genetic architecture of ALS.

The majority of patients who receive radiotherapy for brain tumours go on to develop disability, but the pathophysiological mechanisms of radiation-associated cognitive decline remains poorly understood. Here, Makale and colleagues review animal model and patient data on the mechanisms of radiotherapy-associated CNS damage and posit that early damage — occurring before 6 months after irradiation — contributes to long-term cognitive disability.

Rett syndrome (RTT) is a rare, progressive neurodevelopmental disorder that almost exclusively affects girls, and is caused by a mutation in theMECP2gene. The authors highlight major milestones in RTT over the past 50 years, and acknowledge the international collaborations that are driving this research programme.

Lifestyle and environmental factors, some which are potentially modifiable, have important roles in the risk of multiple sclerosis (MS), and some of these risk factors, such as Epstein–Barr virus infection, smoking and obesity in adolescence, interact with genetic risk factors. Here, Olsson and colleagues summarize recent data on modifiable environmental and lifestyle factors in MS, with a focus on gene–environment interactions.

Cryptococcal meningitis is a major cause of morbidity and mortality in immunocompromized individuals, and, even in apparently immunocompetent individuals, carries a high risk of mortality. Treatment in immunocompromized patients is challenging because these patients are at risk of immune reconstitution inflammatory syndrome (IRIS). This Review summarizes the diagnosis and treatment of cryptococcal disease in various disease.

A cross-sectional community-based study shows that strictly lobar cerebral microbleeds are associated with cognitive impairment, and might be a surrogate marker for early small-vessel injury. The anatomical distribution of cerebral microbleeds suggests that cerebral amyloid angiopathy (with or without Alzheimer disease) might have a key role in early cognitive impairment.

2016 has marked 100 years since the landmark description of what we now know as Guillain–Barré syndrome (GBS). Goodfellow and Willison chart the great progress we have made in understanding the pathogenesis of GBS, and developing established and emerging therapies.

Neuroinflammation is central in many neurological conditions, and 'big data' have the potential to elucidate the complexity of inflammatory processes. This Review considers how the drive to collect and analyse big data is increasing our understanding of neuroinflammation in disease, and how these data can be used to improve clinical management.

The recently revised 5th edition of the WHO classification of brain tumours 'blue book' will have a major impact in stratifying diagnosis and treatment. However, low-grade neuroepithelial tumours (LEATs), which present with early-onset focal epilepsy, lack integrated clinicopathological and molecular genetic diagnostic tools. The Neuropathology Task Force of the International League against Epilepsy will critically discuss this issue, as well as offer perspectives on how to decipher and validate clinically meaningful LEAT entities using the current WHO approach.

A randomized placebo-controlled phase III trial of adjuvanted herpes zoster subunit vaccine has shown a substantial improvement in vaccine efficacy in adults aged ≥70 years compared with the currently used, live attenuated vaccine. The finding has profound implications for reducing illness burden, although the duration of vaccine protection needs further evaluation.

The central vein sign (CVS) has been proposed as a novel MRI biomarker to improve the accuracy and speed of multiple sclerosis (MS) diagnosis. This Consensus Statement from the NAIMS Cooperative provides a roadmap to help radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS.

Unruptured intracranial aneurysms (UIAs) have a prevalence of 3% in the adult population. Currently, there is a large variability in how patients with UIAs are managed. Here, the authors review the latest human data on the formation, progression and rupture of intracranial aneurysms, as well the risks associated with preventive treatment.

In a randomized, sham-controlled trial, transcranial focused ultrasound thalamotomy was shown to benefit patients with medication-refractory essential tremor, although the technique has limitations and the long-term benefits are unclear. Nevertheless, the work suggests that focused ultrasound thalamotomy will become an alternative to other surgical procedures for refractory essential tremor.

Analysis of data from a large number of deep brain stimulation (DBS) recipients in North America has revealed a higher rate of revisions and removals of DBS leads than was previously reported. Hardware malfunction, lead infection and malpositioning were the most frequent reasons for revision or removal.

The primary headache disorders are among the most common diseases worldwide. Nathaniel Schuster and Alan Rapoport discuss new and emerging preventive and acute treatments that have the potential to address unmet needs of patients with headache disorders, and to help treat and reduce headache-associated disability.

Opportunistic infections of the CNS, such as cryptococcal meningitis, cerebral toxoplasmosis, and tuberculous meningitis, are a major cause of morbidity and mortality in HIV-positive individuals. This Review provides an update on diagnosis and treatment of opportunistic infections, as well as management of immune reconstitution inflammatory syndrome in the setting of HIV-associated CNS infections.

The earliest stages of Parkinson disease (PD) offer the best opportunity to intervene, but detecting early disease is difficult. In this Review, Postuma and Berg provide an overview of established and potential markers of prodromal PD, and consider how these markers can be combined to identify patients who have prodromal PD and could benefit from treatment.