Perspectives

This Perspective centres on alterations in the fatty acid-ome as the critical feature of lipid aberration in α-synucleinopathies, specifically Parkinson disease. Here, the authors explain the biological and genetic basis for their hypothesis, with an emphasis on the transient binding of α-synuclein to fatty acids of various lipids.

Deep brain stimulation (DBS) is a highly effective treatment option for movement disorders and is also being explored for other brain disorders. This Perspective proposes a unified framework, termed adaptive circuit targeting, which combines adaptive and connectomic DBS to enable decoding of symptom severity from brain signals and activation of relevant symptom-response circuits.

Earlier this year, the Nav1.8 channel inhibitor suzetrigine became the first new pain therapeutic to be approved in 20 years. Here, Waxman et al. discuss the challenges of improving Nav1.8-targeted relief for acute pain and the translation to chronic pain.

This Perspective article explores the efficacy of multimodal lifestyle interventions to tackle the rising incidence of dementia in low- and middle-income countries. The authors discuss a contextual adaptation of the Finnish FINGER trial, Africa-FINGERS, which is pioneering a culturally relevant, multidomain approach to dementia risk reduction for African settings.

Racial and ethnic disparities in MS susceptibility and outcomes are often attributed to immutable factors such as genetic ancestry. In this Perspective, however, the authors argue that structural racism can lead to biological changes by shaping environmental exposures and lived experiences — a phenomenon termed ‘embodiment’.

Genetic studies in Africa can provide a unique window into hereditary neurological diseases (HNDs). This Review highlights the benefits and challenges of conducting genetic research in Africa and summarizes the insights into HNDs gained from previous studies on the continent.

The development of α-synuclein biomarkers has raised debate as to whether Parkinson disease dementia and dementia with Lewy bodies should fall under a single biological diagnosis. Here the authors discuss the similarities and differences in symptoms, neuropathology and biomarkers of the two dementias, highlighting potential important divergent biological mechanisms.

In this Perspective, the authors provide a detailed description of rare autoimmune encephalitic conditions that present with recurrent seizures that are resistant to immunotherapy, grouped under the term autoimmune encephalitis-associated epilepsy. The article considers the clinical characteristics and pathophysiological mechanisms of these conditions, alongside current knowledge of treatment and outcomes.

Autoimmunity in multiple sclerosis (MS) is generally considered to be directed against components of myelin or oligodendrocytes. However, this Perspective argues that an immune attack on the ion and water homeostasis machinery in astrocytic endfeet is the primary event in MS and that myelin damage results from astrocyte dysfunction.

Evidence suggests that anthropogenic climate change is accelerating, with serious consequences for human health. This Perspective explores how the effects of climate change, such as extreme temperatures, altered weather patterns and increased air pollution, interact with the brain, and discusses how neurologists can respond constructively to the climate crisis.

The importance of active involvement of people living with diseases in various aspects of medicine, including disease management and follow-up, regulatory issues, health advocacy and clinical research, is increasingly recognized. This Perspective reviews the current status of patient involvement in neurological and other medical research, highlighting the role of patient experts.

Evidence for the effects of sex hormones on inflammation, myelination and neurodegeneration has implications for both cisgender and gender-diverse individuals with multiple sclerosis. Here, the authors summarize what is known about the effects of endogenous and exogenous sex hormones, and they highlight the need for future research inclusive of gender-diverse individuals.

In this Perspective, the authors present the Digitized Memory Clinic, a new framework for the diagnostic pathway of neurodegenerative dementias that incorporates digital health technologies with currently available assessment tools, such as fluid and imaging biomarkers, in an interplay with the physician.

In this Perspective, the authors discuss how our understanding of coeliac disease could provide insights into the mechanisms of multiple sclerosis, the involvement of Epstein–Barr virus and the possibility of antiviral treatment against the virus as a therapy for multiple sclerosis.

In this Perspective, the authors propose a new classification system for amyotrophic lateral sclerosis and related neurodegenerative disorders that recognizes, in parallel, the clinical syndromes and the underlying biology of disease. The framework emerged from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023).

Alzheimer disease is a complex and multifactorial condition. The authors of this Perspective suggest that its lack of a singular common pathogenesis prevents it from being regarded as a straightforward ‘disease’ and that treatment will therefore require a multifaceted approach.

In this Perspective, the authors discuss the need for neurologists to assist in court cases involving criminal behaviour that was potentially influenced by a neurological disorder. The authors review evidence linking neurological disorders with criminal activity, and advocate for the development of forensic neurology as a subspecialty of the field.

In this Perspective, Zech and Winkelmann outline multidimensional strategies for genetic diagnosis in patients with rare movement disorders and highlight community-driven data-sharing and case-matchmaking platforms designed to foster the discovery of new genotype–phenotype relationships.

This Perspective proposes a tripartite model involving the amygdala, hippocampus and striatum as key structures underlying cognitive dysfunction in Parkinson disease. The authors explore the anatomical and functional relationships of the structures and summarize evidence of their involvement in the cognitive aspects of the disease.

Here, the authors offer their perspective on the roles of cell states in sustaining health and counteracting disease, and examine how cellular ageing might set the stage for pathological fate loss and neurodegeneration.