Current Opinion in Neurology最新文献

Purpose of review: Recent advances in the capabilities and usability of artificial intelligence (AI) architectures coupled with increased availability of neuroimaging datasets has fuelled a rapid expansion in AI applications to epilepsy neuroimaging. This review summarizes the main applications of AI in epilepsy neuroimaging and suggests future directions for the field.

Recent findings: A range of different machine learning approaches, from multi-layer perceptrons to volumetric and graph-based convolutional neural networks, have been utilized for prediction of whether people will have epilepsy, detection of structural epilepsy lesions, localization of seizure onset zones, segmentation of resection cavities after epilepsy surgery as well as for image enhancement.

Summary: AI in epilepsy neuroimaging research has primarily focussed on lesion detection and localization, with a number of open and validated tools now available for evaluation across diverse settings. Additional applications of AI in epilepsy neuroimaging are either at earlier stages of development or emerging as new challenges. As these tools and their supporting evidence mature, further work addressing the hurdles of clinical integration is required.

Purpose of review: To review progress in developing new pharmacological treatments for epilepsy, focusing on agents in clinical development.

Recent findings: Over 30 different treatments are currently in clinical development, including novel small molecules, nucleic acid-based therapies, stem cells, microbiome-targeting bacteria, and repurposed drugs originally approved for other indications. Most of these treatments target rare epilepsies, particularly the developmental and epileptic encephalopathies, reflecting a development shift from common epilepsies to rare drug-resistant syndromes where unmet therapeutic needs are greatest. Most compounds are still in early development, and publicly accessible data consist mainly of conference reports and congress abstracts. For only two compounds (the K v 7 activator azetukalner and the inhaled emergency treatment Staccato alprazolam) has evidence of efficacy been obtained from relatively large, well designed randomized placebo-controlled trials.

Summary: New paradigms in drug discovery have brought to development innovative treatments with diverse targets and mechanisms of action. Many of these treatments are etiology-targeting and have the potential for disease-modifying effects. Although high-quality evidence is awaited, there is hope that over the next few years much needed life-changing therapies will be widely available for millions of people with disabling, drug-resistant epilepsies.

Purpose of review: Blood-based biomarkers (BBMs) for Alzheimer's disease are beginning to enter clinical practice. As this integration advances, it is essential to critically examine their strengths, limitations, and readiness for broader clinical application.

Recent findings: Evidence increasingly supports the utility of BBMs for clinical management of Alzheimer's disease, with phosphorylated tau species, Aβ42/40 ratio, GFAP, and NfL among the most studied. Plasma p-tau forms have emerged as the most promising markers, showing strong correlations with amyloid plaque deposition and predictive value for disease progression. The WHO and the Global CEO Initiative have outlined minimum performance criteria for clinical use. While no BBM meets these benchmarks with a single cutpoint, adopting a two-cutpoint approach by introducing an intermediate category has enabled some assays to achieve the required accuracy. Several assays are now commercially available, and two have recently received FDA clearance to assist in confirming or ruling out amyloid-beta pathology.

Summary: BBMs could transform Alzheimer's disease diagnostics by enabling scalable, minimally invasive approaches for early detection and monitoring. As implementation advances, assay harmonization, assessment of demographic and physiological influences, and real-world validation across diverse populations remain essential to ensure reliability and equitable access.

Purpose of review: One in five patients with epilepsy has idiopathic generalized epilepsy (IGE). Novel definitions of seizure types, recent data on pharmacotherapy, and new studies on psychiatric and cognitive comorbidities will be critically discussed.

Recent findings: Epileptic seizures have been re-classified by the International League Against Epilepsy (ILAE), acknowledging absence-to-tonic-clonic seizures and generalized negative myoclonic seizures. Differing from the classical ILAE definition of IGE subtypes, current evidence underlines that IGEs represent rather a neurobiological continuum than separate syndromes. Valproate is still the most efficacious compound to suppress myoclonic and tonic-clonic seizures, but novel data confirm the high risk for both anatomical and neurodevelopmental teratogenicity. However, switching from valproate to other antiseizure medications commonly results in seizure recurrence or worsening. As compared to the general population, persons with IGE have a two- to fourfold increased risk of psychiatric disorders, the lifetime risk is 30-50%. Bidirectional associations between IGE and psychiatric conditions suggest that the latter are integral components of a broader IGE endophenotype.

Summary: Valproate continues to be the most efficacious treatment for IGE but also the most teratogenic, leaving women who plan to become pregnant in a dilemma. Psychiatric comorbidities are frequent in IGE and thus require special attention and a holistic treatment approach.

Purpose of review: This review explores Alzheimer's disease (AD) in individuals with Down syndrome (DS), a genetically defined population with near-universal development of AD neuropathology by age 40. We examine the genetic basis of DS-AD, epidemiology, biomarker trajectories, and clinical trial innovations, highlighting how insights from DS research inform broader AD pathogenesis, early detection, and therapeutic strategies.

Recent findings: Advances in biomarker research, including longitudinal studies such as ABC-DS, have mapped predictable trajectories of amyloid, tau, and neurodegeneration in DS-AD, aligning closely with clinical staging. Plasma and CSF biomarkers (Aβ42, p-tau, NfL, GFAP) and neuroimaging modalities (amyloid/tau PET, MRI) demonstrate early and sequential changes decades before dementia onset. Revised AD diagnostic criteria now classify DS individuals as Stage 0 from birth, acknowledging genetic determinism and enabling earlier intervention. Comparative analyses between DS-AD, autosomal-dominant AD, and sporadic AD reveal shared pathological features but distinct timing and distribution of amyloid and tau. Clinical trials targeting amyloid and APP pathways in DS are underway, leveraging predictable disease progression to accelerate therapeutic development.

Summary: Studying AD in DS provides a unique lens into the natural history of Alzheimer's disease, offering critical insights into genetic drivers, biomarker evolution, and therapeutic opportunities. The genetically defined and biologically concordant nature of DS-AD enables precise staging and early intervention strategies that can be translated to sporadic and familial AD. Continued investment in DS research will advance biomarker validation, refine clinical trial design, and inform personalized treatment approaches for the broader AD population.

Purpose of review: This review highlights the latest advances in the genetics of multiple sclerosis (MS). While earlier research defined the polygenic architecture of disease susceptibility, recent efforts have focused on unraveling the genetics of disease progression and dissecting the interplay between host genetics and environmental triggers.

Recent findings: The discovery of the first locus associated with MS severity (DYSF-ZNF638) revealed central nervous system (CNS)-intrinsic mechanisms of progression distinct from immune-mediated susceptibility. Recently, a multi-ancestry genome-wide association studies confirmed most of the previously identified susceptibility loci (most of which are involved in immune biology) and identified 4 additional associations. Mounting evidence on EBV-host genetic convergence highlights critical gene-environment interactions in disease etiopathogenesis.

Summary: Advances in genetics are broadening the conceptual framework of MS pathogenesis, separating the immunological triggers of disease susceptibility from distinct, CNS-specific drivers of disease progression. Future efforts leveraging longitudinal, deeply phenotyped cohorts and functional validations will empower translational applications for prevention, prognostication, and treatment.

Purpose of review: Pediatric headache not only impacts an individual's psychosocial, physical, and academic functioning, but also imposes a burden on their broader systems (e.g. healthcare, financial systems). Literature regarding the bidirectional nature of the socioecological burden of pediatric headache has yet to be synthesized. This is crucial, given the importance of identifying next steps for health-policy, advocacy, research, and intervention development for pediatric headache.

Recent findings: Globally, rates of pediatric headache have risen, with incidence and prevalence varying by geographical location and headache type. Healthcare system and family financial burden of headache suggests increases in healthcare utilization and costs, and parental loss of wages due to missed work. Psychosocial and academic impacts of headache on youth include poorer school attendance, higher rates of stress, internalizing symptoms, and externalizing disorders.

Summary: The burden of pediatric headache is clear across several domains of functioning and affects the broader systems supporting the impacted individual. Nuanced relationships between psychosocial functioning and pediatric headache have emerged, demonstrating the need for future research to consider specific factors (e.g. headache type, age, and gender) as moderators of disability-related outcomes and psychosocial functioning, and the clinical development of biopsychosocial interventions tailored to address domains of disability.

Purpose of review: Cluster headache is a disorder which has been shown to have both a circadian and a circannual pattern. This review gives an overview of the chronobiology of cluster headache summarizing recent findings on structural variations with a focus on the hypothalamus and the implication of the molecular clock and circadian and circannual variations in gene expression.

Recent findings: Recent imaging studies using high-resolution structural and functional MRI have highlighted subtle hypothalamic alterations in cluster headache, specifically at the microstructural and connectivity level rather than clear macrostructural changes. Diffusion-based measures reveal altered fractional anisotropy and diffusivity in the hypothalamus, suggesting modified neuronal connectivity that may relate to attack frequency. In parallel, experimental data suggest significant differences in pain perception between day and night, which correlate to circadian oscillations of gene expression, and several drugs used for cluster headache have been reported to alter the molecular clock.

Summary: The striking circadian and circannual phenotype of cluster headache opens for the possibility of clock-modulating therapy. The potential to pharmacologically target the molecular clock mechanism is supported by experimental data from mice demonstrating substantial effects of standard cluster headache treatments on the molecular clock.

Purpose of review: Headache disorders are the leading cause of neurological disability globally, yet their management remains marked by profound inequities in access to diagnosis, evidence-based treatment, specialist care, and policy prioritization. This review examines current regional disparities in headache care delivery and highlights emerging system-level approaches aimed at reducing the global treatment gap.

Recent findings: High-income regions in Western and Northern Europe, East Asia, and North America have developed advanced care models but continue to face inequities related to socioeconomic gradients, insurance coverage, and fragmented care pathways. In contrast, Eastern Europe, South and Central Asia, Latin America, and much of Africa experience substantial limitations in workforce capacity, diagnostic infrastructure, and medication availability, with population-based surveys indicating high prevalence but minimal health-system readiness. Transitional health systems, including Türkiye and the MENA region, demonstrate increasing awareness and partial integration of structured headache pathways, though coverage remains insufficient. Across regions, telemedicine, digital health tools, community-based initiatives, and workplace programs have shown promise in expanding access, reducing stigma, and improving continuity of care, while reinforcing the central role of primary care.

Summary: Collectively, these developments signal a shift toward more coordinated and equity-oriented headache service models. Sustainable progress will require strengthened global collaboration, integration of AI-supported decision tools, expansion of cross-border registries and real-world data platforms, and the systematic inclusion of headache disorders within national noncommunicable disease frameworks to ensure high-quality care across diverse populations.