Reviews & Analysis

Since 2005, we have made substantial progress in understanding the pathophysiology and natural history of movement disorders such as Parkinson disease and Huntington disease. However, disease-modifying therapies for these conditions have proved elusive and, as a consequence, treatments remain largely symptomatic.

In the past 10 years, the realization that migraine is a brain disorder rather than a vascular disorder has facilitated development of various treatments, ranging from innovative immunopharmaceuticals through to neurostimulation. Many clinical trials have been successful, and such considerable progress holds promise for the coming decade of migraine treatment.

Parkinson disease is defined by its motor symptoms, but onset of nonmotor symptoms, including constipation, can start much earlier. In this Review, Klingelhoefer and Reichmann present the evidence that the pathogenesis of Parkinson disease starts in the gut and is transferred to the CNS via trans-synaptic cell-to-cell transport that initiates a cascade of α-synuclein aggregation. They also consider how this process might be triggered by environmental factors, and how these earliest stages of pathogenesis might be targeted to delay or prevent disease progression.

Since the launch ofNature Clinical Practice Neurologyin 2005, we have seen remarkable progress in many areas of neurology research, but what does the future hold? For this special Viewpoint article, we invited a panel of Advisory Board members and other journal contributors to outline their research priorities and predictions for the next 10 years.

Recent decades have seen a dramatic reduction in age-adjusted stroke-related mortality, presumably owing to better control of vascular risk factors, use of antithrombotic agents and improvements in acute stroke care. Here, we highlight a few developments in stroke prevention and acute care that have particularly influenced the care of patients.

The risk factors for cardiovascular disease are largely the same as those that harm brain health, and—importantly—these shared risk factors are modifiable. This Perspectives article discusses how the conceptual shift from avoiding vascular risk factors to promoting brain health creates opportunities for reducing morbidity and mortality associated with poor brain health.

The past decade has yielded a host of important conceptual advances in epilepsy, along with some promising findings related to diagnostics and therapeutics. We are on an upswing where precise identification of the cause of a patient's seizure disorder can be matched to therapy that has a high likelihood of success.

In my personal view, the past decade in dementia research has been marked by remarkable discoveries in the field of frontotemporal dementia, accompanied by steady scientific consolidation tinged with therapeutic disappointments related to Alzheimer disease.

The term 'preclinical Alzheimer disease (AD) treatment' refers to interventions that are initiated in cognitively unimpaired at-risk individuals, and are intended to postpone, reduce the risk of, or prevent the clinical onset of AD. In this article, the authors review emerging strategies for the accelerated evaluation of preclinical AD treatments, and discuss the work that has set the stage for implementing these strategies. In particular, they highlight the role of the Collaboration for Alzheimer's Prevention (CAP)—an initiative that is designed to help stakeholders advance AD prevention research in a coordinated, transparent and effective way.

Monoamine neurotransmitters are involved in many neurological functions, and defects in their synthesis, metabolism and transport leads to a variety of disorders with subtly different clinical manifestations that make them difficult to diagnose. The authors of this Review outline the clinical features, diagnosis and management of monoamine neurotransmitter disorders, and consider recent and future advances in knowledge and therapeutic options.

The diagnosis and monitoring of multiple sclerosis (MS) still relies largely on clinical manifestations and imaging. Blood-based or cerebrospinal fluid biomarkers to facilitate prognostic evaluation, staging and subtyping of MS, as well as to predict treatment response and adverse effects, are sorely needed. This comprehensive Review by Charlotte Teunissen and colleagues provides an update on advances in biomarker development and validation in MS, focusing on the clinical applications of MS biomarkers.

A large study from the USA suggests that epilepsy in pregnant women elevates the risk of adverse events both to the mother and the fetus, including an 11-fold increase in the risk of death of the mother at delivery. Although the data are intriguing, the study has caveats that call for cautious interpretation.

A new study describes a biomarker profile based on cerebrospinal fluid (CSF) tau and amyloid-β_1–42 in a uniquely large population with a variety of dementia diagnoses. This study confirms the differential diagnostic value of CSF biomarkers and further highlights the important neuropathological overlap between dementia aetiologies.

Cognitive dysfunction is frequently observed in patients with multiple sclerosis (MS), and can have a substantial impact on daily activities and quality of life. In this Review, Fielding and colleagues discuss how ocular motor measures in patients with MS might be used to characterize disruption to wide-ranging networks that support cognitive function, and to track disease progression and responses to novel therapies in these individuals.

In the second part of the MAGNIMS network's evidence-based guidelines, Wattjes and colleagues discuss the use of MRI in prognostication and follow-up in patients with multiple sclerosis. The group recommend several techniques that are useful for monitoring disease activity and treatment efficacy, and identify those techniques that require further study.

Blood-derived biomarkers for gliomas would facilitate diagnostic and prognostic evaluation and assessment of treatment response. Extracellular vesicles, in particular, could be valuable, because they contain a variety of microRNAs, tumour DNA and metabolic markers that reflect the heterogeneous composition of the tumour. Here, Westphal and Lamszus provide an overview of the state of the art, prospects and challenges in development of circulating biomarkers for gliomas.

The ABCD2 score was developed to triage patients with transient ischaemic attack according to the risk of experiencing a stroke in the next few hours or days. However, a new systematic review and meta-analysis on the ABCD2 score gives us considerable cause to rethink its value for clinical situations.

The results of a futility trial, which used the PPAR-γ receptor agonist pioglitazone in an attempt to modify disease progression in Parkinson disease, do not support initiation of further trials. However, although this trial was well designed and conducted, we question whether it is time to fully shut the door on pioglitazone.

Dysregulation of the type I interferon pathway has been implicated in the pathogenesis of a spectrum of neuroinfectious and neuroinflammatory disorders. McGlasson et al. review the range of neurological diseases associated with type I interferon underactivity and overactivity, highlighting advances in our understanding of the molecular and cellular pathogenesis of these conditions. They also discuss the potential utility of type I interferon as a biomarker and therapeutic target in neuroinflammatory disease.

After an ischaemic or haemorrhagic stroke, microglial activation and the release of cell death products initiate a chain of inflammatory events that lead to vascular damage and oedema. Here, Shi and colleagues discuss the similarities between acute stroke and multiple sclerosis, and review past attempts to limit poststroke inflammation via immunotherapy. The authors then highlight gaps in our knowledge about the immune system's reaction to stroke, and discuss how best to move forward with this line of research.