Review Articles in 2017

Amyloid-β (Aβ) and tau come in a variety of forms and assembly states, not all of which are toxic. In this Review, Polanco and colleagues explain the clinical and therapeutic implications of this new understanding while highlighting the physiological and pathogenetic roles of Aβ and tau.

Two decades after antisense oligonucleotides (ASOs) were initially identified as agents capable of modulating RNA processing and protein expression, the first antisense oligonucleotide (ASO) therapies have now been approved for the treatment of neurological disease. Here, Rinaldi and Wood discuss our current understanding of ASO pharmacology, and the future prospects for ASO-mediated treatment of neurological disease

Idiopathic rapid eye movement (REM) sleep behavioural disorder (RBD) is now recognized as an early marker of α-synucleinopathies. Here, Högl and colleagues review potential biomarkers for RBD and summarize the evidence for a prodromal stage, which might enable disease-modifying intervention. In light of these advances, they reconceptualize idiopathic RBD as isolated RBD.

Inadequate remyelination is central to degeneration and disability in patients with multiple sclerosis (MS); however, all currently approved therapies for MS are primarily immunomodulatory. Here, Martin Stangel and colleagues review our current knowledge of remyelination in MS, discuss results from clinical trials of remyelination-enhancing therapies, and evaluate the opportunities for future regenerative treatments.

The causes of migraine remain unknown despite the high prevalence and societal burden of this disorder. Here, the authors highlight how advances in imaging and genetic studies of migraine provide insights into the underlying mechanisms of this disorder; furthermore, they discuss the potential for genetic and imaging biomarkers to improve our ability to prevent and treat migraine attacks.

Exercise and physical therapy are important adjunct interventions to improve gait and balance impairments in patients with Parkinson disease (PD), as these features are inadequately treated by current pharmacological and surgical treatments. Here, Mak and colleagues discuss the long-term effects of exercise and physical therapy for PD, possible risks, recommendations for clinical practice, and emerging treatment approaches.

Fatigue, defined as extreme and persistent mental and/or physical tiredness, weakness or exhaustion, frequently occurs as a challenging symptom or comorbidity in many neurological diseases. In this Review, Penner and Paul discuss the definitions and manifestations of fatigue, focusing on its pathophysiological background, assessment strategies, and current treatment options.

PET is a versatile imaging technique that is advancing our understanding of cerebrovascular disease and intracerebral pathophysiology. In this Review, Evans and colleagues describe mechanistic insights from PET studies relating to the metabolic pathophysiology of carotid atherosclerosis, salvageable penumbra after stroke, and neuroinflammatory changes associated with small vessel disease and vascular cognitive impairment.

In the ongoing search for new and better migraine treatments, human models have a key role in the discovery of novel targets for antimigraine drugs. This Review summarizes existing experimental models of migraine in humans, and describes the development and use of these models in the identification of key molecular pathways, biomarkers and drug targets.

Genome engineering tools, including targeted gene editing and gene regulation, are becoming available to correct the mutations that cause neuromuscular disorders such as muscular dystrophy, spinal muscular atrophy and myotonic dystrophy. This Review summarizes the genome engineering strategies that are under preclinical evaluation for the treatment of degenerative neuromuscular disorders, focusing on the tools that show the greatest potential for clinical translation.

Increasing evidence suggests that Alzheimer disease (AD) is not simply a CNS disorder, but involves interactions between systemic and brain-related factors. Wang and colleagues review the role of amyloid-β (Aβ) in AD, highlighting systemic abnormalities linked to Aβ metabolism and discussing how these abnormalities might influence central pathways of Aβ production and clearance.

Although the most common neuropathy associated with diabetes mellitus is distal symmetric polyneuropathy, inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) can also occur, and might be amenable to treatment. In this Review, Rajabally et al. consider the features of CIDP in diabetes, how this condition can be differentiated from other neuropathies, and management options for CIDP and other inflammatory neuropathies in diabetes.

Tuberculous menigitis (TBM) presents a major health burden around the world, especially in individuals with concomitant HIV infection, in whom mortality is nearly 50%. Here, members of the TBM International Research Consortium summarize our current understanding of TBM pathogenesis, diagnosis and management, and discuss key avenues for future research.

Cerebral venous thrombosis (CVT) is a prominent cause of stroke, particularly in young adults. Knowledge of this condition has greatly increased in the past two decades, primarily owing to new data from international patient registries. This Review provides an overview of the epidemiology, pathophysiology, diagnosis and treatment of CVT, with a focus on new advances in the field.

Deep brain stimulation is used to treat a variety of neurological conditions, including Parkinson disease, dystonia and intractable pain, but the mechanisms underlying its therapeutic effects remain unclear. Drawing on clinical and experimental data, the authors examine hypotheses that have been proposed to explain the effects of DBS, and present the case for a change in terminology to 'deep brain neuromodulation'.

The prevalence of stroke in women is predicted to increase rapidly in the near future. Yet, despite the presence of numerous female-specific risk factors for stroke, women remain under-represented in stroke clinical trials. Here, members of the Women Initiative for Stroke in Europe (WISE) group summarize new advances and future research priorities in the research of stroke in women.

Accumulation of misfolded protein in neurons is a common feature of many neurodegenerative diseases. In this Review, Hetz and Saxena discuss the latest advances in our understanding about the mechanisms by which protein misfolding causes neurodegeneration, and look at novel insights into the role of cellular responses to protein misfolding in synaptic function and in inflammatory and mechanical injury in the nervous system.

The process of phenotyping and classification of dementia has improved over decades of careful clinicopathological correlation, and through the discovery ofin vivobiomarkers of disease. Elahi and Miller review the salient features of the most common dementia subtypes, emphasizing neuropathology, epidemiology, risk factors, and signature signs and symptoms.

The discovery that IgG4 autoantibodies against node of Ranvier proteins are linked to distinct subsets of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represents a key advance in our understanding of the chronic inflammatory neuropathies (CINs). Here, Querol and colleagues discuss the clinical implications of these autoantibodies in patients with CIDP and other immune-mediated neuropathies.

Despite intensive investigation, the genetic basis of chemotherapy-induced peripheral neurotoxicity (CIPN) remains elusive. In this critical update, Argyriou and colleagues highlight strategies for overcoming the methodological flaws of pharmacogenetic studies and the inadequacy of current tools for assessing CIPN. As yet, however, genetic profiling cannot identify patients at risk of CIPN or guide their management.