Review Articles in 2017

Reliable biomarkers for frontotemporal dementia (FTD) are required for accurate discrimination between dementia types, prediction of clinical progression and tailoring of pharmacological interventions. This Review discusses the increasing number of available biomarkers for FTD — including novel imaging modalities and fluid biomarkers — and the future challenges in their implementation.

Autologous haematopoietic stem cell transplantation has produced striking results in patients with aggressive multiple sclerosis in small trials. In this Review, Muraro et al. provide an overview of the procedure, detail evidence for its high efficacy in multiple sclerosis, and provide recommendations for its clinical use and future trials.

Chronic pain presents a major health burden, affecting more than 20% of adults worldwide, but currently available analgesics lack efficacy and/or are associated with severe adverse effects. Here, Ellen Niederberger and colleagues discuss epigenetic modulation as a new opportunity in pain-relief therapy, and consider the future challenges for the clinical development of these drugs.

Effective drug treatments for intracerebral haemorrhage (ICH) are still lacking. However, therapies that target microglial phenotype switching might soon become available for affected patients. Here, Wang and colleagues summarize key advances in understanding of microglial function after ICH, including modulators of microglial function and interactions with other cells.

Determining how the incidence and prevalence of dementia changes over time requires population-based studies that use consistent methods over time. In this Review, the authors discuss the results of 14 worldwide studies that have attempted this approach. The findings consistently indicate that the incidence and prevalence of dementia, at least in Western countries, is stable or declining.

In the past few years, paradigms for the treatment of low-grade glioma have shifted, owing to new diagnostic criteria and new clinical trial evidence. Here, Jan Buckner and colleagues discuss how molecular markers are challenging previous assumptions about low-grade glioma, and examine how new data will affect diagnostic testing, surgery, chemotherapy and radiation therapy for individuals with these tumours.

This Review presents an overview of vaccine-based immunotherapies for human glioma. Although efficacy remains unproven for the vaccines in clinical development, Weller and colleagues highlight promising strategies for antagonizing glioma-associated immunosuppression and boosting immune responses in vaccinated patients. Ultimately, such approaches might help to control the growth of human gliomas.

Nonsystemic vasculitic neuropathy (NSVN) is an under-recognized single-organ vasculitis of peripheral nerves. In this Review, Collins and Hadden provide an update on the classification, diagnosis and treatment of NSVN, and propose definitions and an up-to-date differential diagnosis of multifocal neuropathy.

Central vestibular disorders, including vestibular migraine, account for around 25% of cases of vertigo and dizziness. In this Review, the authors present the key signs and symptoms of central vestibular disorders, and they also consider higher vestibular dysfunctions, which involve more than one sensory modality as well as cognitive domains.

Clinical recognition of autoimmune encephalitis is vital in order for effective early treatment to be provided. Here, van Sonderen and colleagues describe the syndromes associated with antibodies against LGI1, Caspr2 and voltage-gated potassium channels and highlight the importance of determining the molecular identity of patient antibodies for diagnosis and treatment.

Human induced pluripotent stem cells (hiPSCs) enable researchers to recapitulate an individual's neural development in a dish, with the potential to provide unique insight into the pathogenic mechanisms of neurodevelopmental disorders. Here, the authors provide an overview of disease modelling with hiPSCs and discuss existing hiPSC models of neurodevelopmental disorders.

MRI has become the standard method for diagnosis and monitoring of patients with brain tumours, but conventional MRI sequences have important limitations. This Review summarizes the clinical role of the rapidly developing field of amino acid PET and advanced MRI techniques in adults with brain tumours, and provides an outlook for future developments in PET and MRI.

In this Review, Krismer and Wenning discuss the risk factors for and the clinical presentation and neuropathology of multiple system atrophy (MSA) — a devastating and fatal neurodegenerative disorder. They provide an overview of ongoing trials and international efforts to improve care in patients with MSA.

Although our understanding of the biological mechanisms of stroke have advanced considerably in animal models, this progress has not been translated into improvements to restorative therapies following stroke in humans. Here, Nick Ward discusses the reasons behind this lack of benefit, and the prospects for understanding poststroke plasticity in humans, with a focus on the development of biomarkers that can reconcile preclinical and human studies.

Gasparotti et al. provide an overview of new and emerging technologies for assessing a variety of peripheral neuropathies, including magnetic resonance neurography, diffusion tensor imaging and ultrasonography for large-fibre neuropathies, and corneal confocal microscopy, evoked potentials and microneurography for small-fibre neuropathies.

Dementia is commonly encountered in advanced stages of Parkinson disease (PD), but evidence is accumulating that cognitive decline can manifest much earlier in the disease course. Aarsland and colleagues review current knowledge regarding cognitive impairment in patients with PD, focusing on cerebrospinal fluid and imaging biomarkers as potential predictors of cognitive decline in this population.

Altered brain network connectivity might underlie the deficits in social cognition that characterize autism spectrum disorders (ASD). Here, Modi and Sahin discuss the use of event-related potentials (ERPs) evoked by sensory and social stimuli to assess network connectivity in humans with ASD and in animal models, and consider the potential for ERPs to provide a translational biomarker of social dysfunction.

Stroke is associated with an increased risk of dementia, but efforts to develop treatments that prevent dementia in survivors of stroke have thus far been unsuccessful. Here, Mok and colleagues review the mechanisms underlying early-onset and delayed-onset poststroke dementia, and highlight promising future strategies for the development of preventive treatments.

Neuroinflammation can cause acute secondary injury after traumatic brain injury (TBI), and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, the authors propose a new framework for targeted immunomodulation after TBI.

Research into the mechanisms of diabetic neuropathy have focused on neurons, but evidence is accumulating that Schwann cells have a central role. In this Review, the authors consider how Schwann cell dysfunction and the interactions of these cells with neurons and microvessels contribute to the pathogenesis of neuropathy in diabetes.