Review Articles

Many autoimmune and genetic causes of sporadic late-onset cerebellar ataxia (SLOCA) can now be identified, but some individuals remain categorized as having idiopathic SLOCA. Wirth and colleagues discuss advanced genomic techniques that might identify additional ‘missing’ SLOCA causes, potential prognostic biomarkers and progress towards effective treatments.

Myotonic dystrophy type 1 (DM1) is the most prevalent muscular dystrophy in adulthood and among the most clinically diverse monogenic diseases. This Review summarizes the latest insights into the molecular underpinnings of DM1, highlighting the implications for therapy development.

Non-invasive brain stimulation (NIBS) shows considerable promise as a therapeutic strategy for neurological and psychiatric disorders. This Review explores the role of NIBS techniques, including repetitive transcranial magnetic stimulation and transcranial electrical stimulation, for treating cognitive impairments, speech and language difficulties, and motor control deficits in people with neurodegenerative or brain lesion disorders.

This Review considers the aetiology of health disparities in neurology at an individual, interpersonal, community and societal level, and suggests practical interventions to address the multifactorial issues.

Management of autoimmune neuropathies has remained unchanged for much of the past 30 years, but recent advances are changing the rate of progress. In this Review, the authors summarize the latest developments, including discoveries in disease mechanisms, new diagnostic guidelines, identification of new biomarkers and the status of promising clinical trials.

The neuronal ceroid lipofuscinoses, or Batten disease, are a group of fatal inherited neurodegenerative lysosomal storage disorders. Despite having defined genetic causes, the underlying disease mechanisms remain poorly understood and treatments are limited. Cooper and colleagues highlight recent advances in understanding the cell biology and disease pathogenesis, which could inform future therapeutic development.

Spreading depolarization is widely accepted as the cause of migraine aura, but its relationship with migraine headache is less clear. In this Review, Harriott and Ayata review the evidence that links spreading depolarization with the headache phase of migraine with aura, and consider the potential of therapeutic targeting of spreading depolarization in migraine.

Neurodegenerative diseases such as Alzheimer disease, Parkinson disease, frontotemporal lobar degeneration and multiple system atrophy are characterized pathologically by deposition of specific proteins in the brain. This article reviews the latest advances in the development of PET radiotracers for neurodegenerative proteinopathies and highlights the diagnostic and therapeutic applications of this technology.

Low-income and middle-income countries bear a high burden from dementia that is not reflected in research. This Review outlines the reasons for this disparity and explores the challenges and opportunities of dementia research in low-income and middle-income countries.

Here, Rafii and Aisen review recent progress surrounding the approvals of amyloid-targeting monoclonal antibodies, the first disease-modifying therapies for Alzheimer disease. The Review highlights key factors that affect the integration of these treatments into clinical practice and explores future directions.

In this Review, the authors describe perturbations in neuroimmune, metabolic and oxidative pathways in major depressive disorder and explore how imbalances in each of these pathways can contribute to the acute phase of the disease.

Chimeric antigen receptor (CAR) T cells provide an effective treatment option for advanced haematological malignancies, but neurological adverse effects of CAR T cell therapies are common. This article reviews current knowledge regarding the mechanisms that contribute to neurological toxicities following CAR T cell therapy and highlights current and emerging management strategies.

This Review considers how DNA methylation-based biomarkers can be used to monitor brain ageing and stratify neurological disease risk. The authors focus on epigenetic clocks, which can be applied across multiple tissues to estimate biological ageing, and blood-based epigenetic scores, which can track brain-based phenotypes and risk factors for neurological disease.

In this Review, Taddei and Duff consider the concepts of synapse vulnerability and resilience, and how an understanding of the mechanisms that underlie these states could identify novel strategies to mitigate the cognitive dysfunction associated with dementias.

Sex and gender influence the entire healthcare ecosystem of Alzheimer disease (AD). In this Review, Castro-Aldrete et al. present a holistic view of sex and gender in AD, and discuss how these factors affect research and policy efforts to improve AD prevention, diagnosis and treatment.

Brain cell-derived extracellular vesicles (EVs) in the blood, carrying diverse cargoes, represent a valuable source of predictive, diagnostic, prognostic, disease-monitoring and treatment-response biomarkers for neurological disorders. This Review summarizes key aspects of EV biology and provides a critical overview of EV biomarker research and therapeutic development in neurology.

Near-death experiences (NDEs) are episodes of disconnected consciousness that typically occur in actual or perceived life-threatening situations. This Review discusses the mechanisms that might underlie the rich conscious experience in NDEs and proposes a model that encompasses a cascade of concomitant psychological and neurophysiological processes within an evolutionary framework.

The complement system has important roles in a variety of physiological processes, but it can also contribute to neurodegenerative diseases such as Alzheimer disease through excessive synaptic pruning and neuroinflammation. In this Review, the authors explore the therapeutic potential of targeting specific complement components for the treatment of Alzheimer disease.

Epidemiological evidence has demonstrated associations between sleep and epilepsy, but we lack a mechanistic understanding of these associations. In this Review, Sheybani et al. consider the associations between epilepsy and sleep at the cellular, network and system levels, the mechanistic underpinnings of these associations and their clinical relevance to the management of epilepsy.

Friedreich ataxia (FRDA) is a rare multisystem disorder and is the most common early-onset hereditary ataxia in populations of European, Arab and Indian descent. This article reviews the milestones in FRDA translational and clinical research over the past 10 years and outlines the priorities for future FRDA research.