Reviews & Analysis

In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the endocannabinoid system and the expanded endocannabinoid system and discuss the involvement of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease.

Amyloid-β deposition underlies the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD), but the disease pathways differ. Here, Greenberg et al. consider the interactions between CAA and AD, the factors that determine which disease pathway transpires, and the implications for therapeutic development.

Some individuals with post-stroke language impairment, or aphasia, will spontaneously recover partial language function. In this Review, the authors propose that existing hypotheses about this recovery from aphasia can be considered as examples of two principles: degeneracy and variable neuro-displacement.

Two new studies show that gliomas can manipulate normal elements of neuronal development and plasticity to create neuron–glia synapses, activation of which leads to glioma proliferation. Interventions that target the AMPA receptor could slow down tumour growth by altering this synaptic transmission.

Artificial intelligence algorithms are well suited to the fast decision making needed in the management of large vessel occlusive stroke. In a new study, a fully automated CT angiography algorithm identified large vessel occlusions with impressive sensitivity, but the work highlights the need for high reporting standards to maximize translatability.

Spinal cord injury leads to disruption of neural circuitry and connectivity, resulting in permanent neurological disability. Hutson and Di Giovanni assess the clinical potential of emerging strategies that are designed to augment neuroplasticity and promote sensorimotor recovery after spinal cord injury.

In this Review, David et al. discuss the ability of advanced quantitative MRI techniques to identify secondary degenerative changes induced by spinal cord injury and assess the suitability of these techniques for predicting patient outcome.

A new study provides direct biological evidence for a prodromal phase of multiple sclerosis (MS), with implications for studying disease aetiology and underscoring the limitations of therapies that solely target inflammation. The findings also suggest an opportunity to apply secondary prevention strategies at the very earliest stages of the disease.

In this Perspectives article, Jan Lünemann and colleagues discuss the potential of immune reconstitution therapies to induce remission in individuals with multiple sclerosis. They highlight our limited understanding of the mechanisms underlying this remission and suggest future areas of research.

A new study shows that the monoclonal antibody fremanezumab is effective for migraine prophylaxis, even in patients who have failed to respond to multiple preventive treatments. However, not all patients benefit from this treatment, and detailed investigation of non-responders could help to identify additional pharmacological targets and increase the number of responders.

In this Review, the authors describe the evidence for abnormalities in energy metabolism and mitochondrial function in migraine, consider the potential mechanisms and highlight treatments that affect metabolism. They conclude that migraine is a conserved adaptive response that helps to restore brain energy homeostasis.

Charcot–Marie–Tooth disease (CMT) encompasses a group of inherited neuropathies that exhibit phenotypic and genetic heterogeneity. The authors discuss the application of next-generation sequencing (NGS) to the diagnosis of CMT and present a method for incorporating NGS into CMT clinical practice.

Axonal transport is the process whereby motor proteins navigate microtubules to deliver diverse cargoes from one end of the axon to the other. In this Review, Schiavo and colleagues explore the link between perturbations in axonal transport and neurological disease.

In this Consensus Statement, Leonhard et al. provide a globally applicable guideline for the diagnosis and management of Guillain–Barré syndrome, including information on early recognition of the disease, prediction of clinical course and outcome, and management of complications and sequelae.

A new study — unique in its size, scope and collaborative nature — has identified genetic variants that are associated with progression of Parkinson disease (PD). However, limitations of the study highlight the need for large-scale, phenotype-harmonized, multi-ethnic, longitudinal studies to characterize PD subtypes and develop individualized therapies.

This Review discusses the contribution of adverse early-life experiences to aberrant brain maturation, which might underlie vulnerability to cognitive brain disorders. The authors suggest that fragmented and unpredictable environmental and parental signals comprise a novel and potent type of adversity.

Post-traumatic headache (PTH) is a common disabling consequence of mild traumatic brain injury. In this Review, Ashina et al. discuss possible pathogenic mechanisms of PTH, the research needed to improve our understanding, and drugs for prevention and treatment of persistent PTH.

In this Review, Dong and Yong summarize the mechanisms and consequences of T cell–microglia interactions in multiple sclerosis, discuss therapeutic approaches that affect these interactions and consider the challenges of translating preclinical knowledge in this area to humans.

Outdated knowledge of arterial perfusion territories still guides clinical decisions and management in acute and chronic stroke. In a new study, application of machine learning techniques provides more detail than ever before, laying the foundation for improved stroke management and new research.

Understanding the heterogeneity of typical Alzheimer disease (AD) is of increasing importance for the development of new and effective treatments. A new study in patients with AD described two robust cognitive subtypes with different pathology distributions, genetic backgrounds and clinical trajectories.