Reviews & Analysis

In this Review, Brennan and Henshall discuss how microRNAs determine and control neuronal and glial functions, how this process is altered in states associated with hyperexcitability, and the prospects for microRNA targeting for the treatment of epilepsy.

In 2018, the Discovery and Validation of Biomarkers to Develop Non-Addictive Therapeutics for Pain workshop convened to discuss strategies to facilitate the development of biomarkers and end points for pain. The outcomes of this workshop are outlined in this Consensus Statement.

Smeland and colleagues examine the evidence for a polygenic architecture of schizophrenia. This new knowledge of schizophrenia pathobiology has important implications for understanding its genetic overlap with other traits and disorders, which could influence future disease classifications and mechanistic research.

The COVID-19 pandemic has added an additional layer of complexity to endovascular treatment (EVT) for acute ischaemic stroke. Drawing on recently published guidelines, this article provides a conceptual framework for EVT in the COVID-19 era, outlining key principles for ensuring safe and timely EVT while minimizing the risk of infectious exposure for health-care workers and patients.

Antibodies to glutamic acid decarboxylase (GAD) are associated with several neurological syndromes but their importance and role are controversial. In this Review, Graus et al. propose criteria for assessing the association between GAD antibodies and neurological syndromes and discuss the pathogenicity of GAD antibodies.

Zoonotic and vector-borne parasites are important preventable risk factors for epilepsy. The authors explore the pathophysiological basis of the link between parasitic infections and epilepsy and consider preventive and therapeutic approaches to reduce the epilepsy burden associated with parasitic disorders.

In this Review, the authors discuss the treatment and management of cognitive impairment in people with multiple sclerosis. They describe the theoretical rationales, challenges and advances in cognitive rehabilitation and exercise training for treating multiple sclerosis-related cognitive impairment, and discuss future directions for research in this field.

A recently published consensus statement from the European Academy of Neurology provides new guidance on the diagnosis and management of monogenic cerebral small vessel diseases. Despite a lack of high-quality evidence, the recommendations are likely to be useful to all clinicians involved in the diagnosis and treatment of these conditions.

In this Review, Tan et al. provide an overview of the clinical and preclinical evidence that immune system dysfunction is involved in Parkinson disease, and discuss how increasing knowledge of the underlying mechanisms is driving development of immune-based therapeutic approaches.

In this Review, Montaner and colleagues summarize how proteomics, genomics, transcriptomics and metabolomics are contributing to the discovery and development of biomarkers in stroke, and how bringing them together with integromics could provide new biomarkers and therapeutic opportunities.

Most research into blood-based biomarkers for neurodegenerative disorders has so far focused on Alzheimer disease. In this Review, Aarsland and colleagues give an overview of the current status of blood-based biomarkers for the non-Alzheimer disease neurodegenerative disorders.

Disorders of consciousness (DOCs), including vegetative and minimally conscious states, represent a financial, medical and ethical conundrum. Recently published guidelines for the diagnosis, prognosis and treatment of DOCs should lead us to reconsider our management strategies for these challenging disorders.

An understanding of the biochemical processes underlying Parkinson disease (PD) will be essential for the development of disease-modifying therapies. In a recent study, a novel biochemical phenotype of the disease was identified from analysis of inducible pluripotent stem cell-derived dopaminergic neurons from individuals with young-onset PD.

In this Review, Panza and colleagues provide an overview of the current understanding of pathogenic mechanisms of frontotemporal dementia spectrum disorders and discuss how this knowledge is driving the development of potential disease-modifying drugs.

In this Review, Peng et al. summarize the evidence for cell-to-cell transmission of pathological proteins in neurodegenerative diseases such as Alzheimer disease and Parkinson disease, and identify key questions for future investigation.

Muscle imaging is increasingly important in the management of neuromuscular diseases, and techniques are becoming ever more sophisticated. Three new studies demonstrate the advances being made in diagnostic and quantitative muscle imaging, including the incorporation of artificial intelligence for image analysis.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that has proved difficult to study owing to its rarity. A recent report from a large Spanish registry has provided new insights into the clinical features and management of MG, particularly in individuals aged ≥65 years.

Mortality from neurodegenerative disease is high among professional soccer players, potentially associated with repeated head impacts during routine gameplay. New data suggest that the apolipoprotein E ε4 allele might exacerbate the effects of soccer ball heading on cognition. However, genotyping of athletes to determine their dementia risk remains a distant prospect.

In 2019, the Alzheimer’s Association International Conference featured a debate on the role of infections in AD pathogenesis. Here, participants from that debate discuss the evidence regarding the infectious theory of AD and suggest avenues for future investigation.

In this Review, Karimy et al. discuss the mechanisms by which inflammation can contribute to the pathogenesis of acquired hydrocephalus and highlight targets for therapeutic intervention.