Reviews & Analysis

From the interruption of clinical trials by shelter-in-place orders to the challenges involved in safely collecting biofluid samples, drug development for neurological disease was hit hard by the COVID-19 pandemic this year. However, the field has responded with innovative solutions, and 2021 could see the therapeutic pipeline flowing again.

The identification of pathogenic targets in amyotrophic lateral sclerosis means that effective therapies are increasingly likely. In this Review, Kiernan et al. discuss advances towards therapy and the innovations needed in clinical trials to facilitate the translation into treatments for patients.

In this Review, Wolf et al. provide an overview of the hypomyelinating leukodystrophies and discuss how identification of the genes involved in these disorders have provided insight into the clinical presentations of these disorders and into myelin biology.

In this Review, the authors discuss recent progress in the detection and prediction of recovery of consciousness in patients with disorders of consciousness caused by severe brain injuries. They describe the ongoing development of pharmacological and electrophysiological therapies designed to enhance recovery.

Accumulating evidence indicates important roles for microglial activation and neuroinflammation in Alzheimer disease (AD). Here, Leng and Edison describe the interplay between microglial activation and AD-related pathologies and discuss how microglial priming and activation might influence the trajectory of AD.

In this Perspective, the authors discuss the mechanisms underlying the complex relationship between lesion size and functional recovery after spinal cord injury, highlighting various complications that can limit the accuracy of outcome prediction in patients and in animal models.

Many neurologists have used telemedicine during the COVID-19 pandemic. Studies have shown that videolinks in acute care can save personal protective equipment and protect staff. Furthermore, the telephone can provide supra-hospital care in Parkinson disease and manage patients with amyotrophic lateral sclerosis well. The primacy of face-to face care has been dented.

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation and has become a standard of care in a range of movement disorders. This Review discusses the evolution and current status of DBS technology and anticipates future advances.

In this Review, Cortese et al. provide an overview of the pathobiology and evolving presentations of progressive multifocal leukoencephalopathy and other diseases caused by JC virus, and discuss emerging immunotherapeutic approaches that could increase survival.

Although common, post-traumatic headache remains poorly understood and poorly treated. New data have implicated calcitonin gene-related peptide and the trigeminovascular system in this disorder, opening up new avenues for research into its pathophysiology and treatment.

A genome-wide association study has identified the first risk factors for sporadic prion disease other than mutations of PRNP, which encodes prion protein. These hits could open up new fronts in prion biology, risk prediction, and drug development.

In this Review, the authors discuss how technological advances are enabling clinical genetic testing for various dementia disorders. Additionally, they consider which types of test are appropriate for which patients and address the ethical issues that can be raised by genetic testing in these disorders.

Current medications used for pain management can have dose-limiting adverse effects. In this Review, Waxman et al. discuss compounds designed to target peripheral sodium channels for pain relief and highlight the challenges and future potential of this therapeutic strategy.

Focused ultrasound (FUS) offers the ability to non-invasively and precisely intervene in key circuits that underlie common and challenging brain disorders. This Review provides a comprehensive update of FUS applications in the brain, including thermoablation, blood–brain barrier opening and neuromodulation.

The anti-seizure medications used to treat patients with epilepsy can improve symptoms but do not address the underlying cause of the condition. In this Review, the authors discuss the ongoing shift towards personalized treatments for specific epilepsy aetiologies.

In this Review, the authors discuss how new therapies are changing the field of spinal muscular atrophy. They consider the effects of treatment at different stages of the disease, what treatment effects tell us about the disease and the challenges facing the field in the treatment era.

In this Review, Dalakas et al. discuss the complement system, the role it plays in autoimmune neurological disease and neurodegenerative disease, and provide an overview of the latest therapeutics that target complement and that can be used for or have potential in neurological disorders.

Drug repositioning and repurposing can enhance traditional drug development efforts and could accelerate the identification of new treatments. In this Review, Ballard and colleagues highlight priority compounds for repurposing for the treatment of Alzheimer disease.

B cell-depleting agents are emerging as important disease-modifying drugs for multiple sclerosis, but their effectiveness in relation to established treatments remains uncertain. To cast light on this issue, several studies have provided head-to-head comparisons of the anti-CD20 antibody rituximab with natalizumab, fingolimod and dimethyl fumarate in patients with multiple sclerosis.

With the advent of disease-modifying therapies for spinal muscular atrophy, prenatal and extra-neural alterations associated with the condition have garnered increasing attention as potential determinants of the therapeutic window and efficacy of novel drugs. Two recent studies highlight the impact of spinal muscular atrophy on prenatal bone and organ development.