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[2025 Round-up] Multiple sclerosis research in 2025: earlier diagnosis and halting progression

In 2025, substantial breakthroughs were made with respect to earlier diagnosis, improved mechanistic understanding, and new hope for delaying progression of multiple sclerosis. Over successive refinements, the McDonald criteria have enabled earlier diagnosis of multiple sclerosis, with the 2017 update allowing diagnosis at the initial clinical event.1 The newly revised 2024 criteria allow for identification of asymptomatic disease with biological and radiological biomarkers.2 Because optic neuritis is the initial clinical event in about 25% of people with multiple sclerosis, inclusion of the optic nerve as a fifth anatomical location for demonstrating dissemination in space, incorporation of optical coherence tomography, visual evoked potentials, and orbital MRI as supportive paraclinical tests are welcome additions to the diagnostic criteria.

[2025 Round-up] Movement disorders in 2025: advances in early diagnosis and personalised treatment

Important advances occurred in the field of movement disorders in 2025. The surge of wet biomarkers over the past few years has now led to biological definitions of neurodegenerative diseases. However, the main breakthroughs have been driven by technological advances in neuroimaging, neuromodulation, cell and gene therapy, digital biomarkers, deep learning, and artificial intelligence.

[2025 Round-up] Epilepsy research in 2025: sudden unexpected death in epilepsy, artifical intelligence and seizure classification

Epilepsy is a dynamic, multidisciplinary field that rapidly adopts technological innovation. Reflecting this dynamism, 2025 saw substantial scientific, clinical, and technical advances in multiple domains of epilepsy research. Among the most influential advances were identification of risk markers for sudden unexpected death in epilepsy (SUDEP), applications of artificial intelligence (AI) to predict treatment response and data interpretation, and the new epileptic seizure classification from the International League Against Epilepsy (ILAE).

[2025 Round-up] Major advances in traumatic brain injury research in 2025

2025 marked a turning point in traumatic brain injury (TBI) research, with studies now showing that TBI is a chronic condition characterised by prolonged biomarker elevations and long-term comorbidities, fundamentally shifting clinical management from acute intervention to lifelong monitoring and care. A new TBI classification framework was developed that captures the heterogeneity of TBI, which will allow for personalised treatment and targeted clinical trials. In parallel, emerging therapeutic approaches offer renewed hope for better outcomes.

[Comment] Unravelling the role of the microbiome in Parkinson's disease

Evidence for the involvement of the microbiome in Parkinson's disease continues to accumulate, contributing to an increasingly multidimensional picture of the interactions of the brain with other organs. The trillions of microorganisms—bacteria, fungi, viruses, and other microbes—that inhabit the human body, particularly those residing in the gut, are now recognised as key modulators of brain function and dysfunction. This recognition has led to the emergence of research into a distinct microbiome–gut–brain axis.

[Comment] The role of the exposome in Parkinson's disease

The term exposome has been widely used to describe the environmental exposures an individual encounters throughout their lifetime, and the effects these exposures could have in relation to health and disease. In the past decade, the concept of the exposome has gained increasing attention across multiple disciplines, with its scope broadening to include biological responses to these exposures.1 External exposome factors include pollution, chemicals, and radiation, lifestyle factors such as physical activity and diet, and climate change.

[Comment] Advances in understanding sudden unexpected death in people with drug-resistant epilepsy

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death, affecting 1·00–1·14 per 1000 people with epilepsy annually.1 Identifying those at high risk or low risk of SUDEP is necessary for counselling and targeted intervention. Population-based case–control studies have identified risk factors, such as poorly controlled tonic–clonic seizures, nocturnal seizures, medication non-adherence, and solitary living, and how they interact to inform risk stratification.2,3 However, medical record data do not provide the detailed phenotypic and mechanistic insights needed to refine risk prediction and identify intervention targets.

[Comment] Exploring immunomodulation with azathioprine in Parkinson's disease

Neuroinflammation has been recognised as a characteristic feature of Parkinson's disease for decades.1 Early observations of activated microglia in affected brain regions, most notably the substantia nigra, were initially viewed as a reaction to neurodegeneration rather than a contributor to Parkinson's disease pathogenesis. Interpretation of these neuropathological observations has since shifted due to mounting evidence implicating immune dysregulation in the disease process. This evidence includes in-vivo PET imaging studies showing microglial activation early in the disease course,2 and experimental models demonstrating microglial activation, which can be induced by α-synuclein, contributing to neuronal loss in the substantia nigra.

[Editorial] Turning policy into action for brain health

Neurological disorders are among the leading causes of disability worldwide, yet millions of people still lack access to effective care, particularly in low-income and middle-income countries (LMICs). A pivotal step to address these gaps was the adoption of the Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022–31 (IGAP) by the 75th World Health Assembly in May, 2022. This comprehensive roadmap aims to achieve measurable progress and enhance the quality of life for people affected by neurological conditions by 2031.

Type 2 Diabetes Genetic Risk and Type 1 Diabetes Heterogeneity and Progression

Insulin secretion varies widely in preclinical type 1 diabetes. To understand the pathogenesis of this metabolic heterogeneity, we asked whether genetic predisposition to type 2 diabetes, quantified by a type 2 diabetes genetic risk score (T2D-GRS), modulates β-cell function and disease progression in individuals at risk of type 1 diabetes. We analyzed 4,324 islet autoantibody–positive TrialNet Pathway to Prevention participants with genome-wide genotyping and oral glucose tolerance testing. Both T2D-GRS and the type 1 diabetes genetic risk score 2 (T1D-GRS2) differed significantly across five previously described groups defined by C-peptide area under the curve (AUC; a measure of insulin secretion). The highest C-peptide AUC group, compared with the lowest, had significantly higher T2D-GRS, lower T1D-GRS2, higher BMI z- score, greater insulin resistance, older age, and lower prevalence of male participants; multiple islet autoantibody positivity; and IA-2 or insulin autoantibody positivity. Progression to clinical (stage 3) type 1 diabetes was significantly associated with T1D-GRS2 across all groups and with T2D-GRS in all but the lowest C-peptide AUC group. In conclusion, type 2 diabetes genetic burden shapes metabolic heterogeneity and accelerates progression in preclinical type 1 diabetes. These results support the evaluation of type 2 diabetes–related mechanisms as targets to improve the prediction and prevention of type 1 diabetes. Article Highlights Heterogeneity in β-cell function is a barrier to precision medicine in type 1 diabetes. We asked whether type 2 diabetes–associated genes influence insulin secretion and progression to clinical type 1 diabetes in autoantibody-positive individuals. A type 2 diabetes genetic risk score was associated with higher C-peptide area under the curve (AUC) and increased clinical type 1 diabetes risk in all but the lowest C-peptide AUC subgroup. Addressing type 2 diabetes mechanisms could improve type 1 diabetes prediction and prevention.

[Position Paper] Absolute neutrophil count and adverse drug reaction monitoring during clozapine treatment: consensus guidelines from a global Delphi panel

Despite its superior effectiveness for treatment-resistant schizophrenia, clozapine has a high burden of adverse drug reactions (ADRs), which require monitoring and treatment. This global Delphi study has established consensus guidelines for absolute neutrophil count (ANC) thresholds for consideration of clozapine cessation and provided monitoring protocols for ADR management. Recommendations include lowering ANC thresholds for consideration of clozapine cessation to 1·0 × 109 cells per L (0·5 × 109 cells per L for Duffy antigen receptor for chemokines-null individuals) and discontinuing routine ANC monitoring after 2 years.

[Review] Programmes for people who are homeless and have severe mental illness in low-income and middle-income countries: a systematic review

Homelessness and severe mental illness are inter-related issues, the co-occurrence of which leads to poor outcomes for affected individuals. Evidence for effective interventions in high-income countries is accruing, but little is known about how to intervene in the diverse sociocultural contexts of low-income and middle-income countries (LMICs). The aim of this systematic review was to synthesise peer-reviewed and grey literature on programmes for people experiencing homelessness and severe mental illness in LMICs.

[Articles] Comparison of antidepressant deprescribing strategies in individuals with clinically remitted depression: a systematic review and network meta-analysis

In remitted depression, slow tapering plus psychological support is as effective as antidepressant continuation in preventing relapse and superior to abrupt or rapid discontinuation. In remitted anxiety, despite consistent population characteristics and effect estimates, limited evidence warrants cautious generalisation. Guidelines should promote individualised deprescribing with gradual tapering and structured psychological support.

[Articles] Joint detection of risk for psychotic disorders or bipolar disorders in clinical practice in the UK: development and validation of a clinical prediction model

This study shows that the transdiagnostic clinical prediction model can identify patients at risk of developing psychotic disorders or bipolar disorders and displayed excellent performance. Such a novel approach would enable systematic early detection of young people at risk of psychotic disorders or bipolar disorders, advancing preventive care in real-world clinical practice.

Heidi Taipale: a curiosity-driven approach to data

“Clinical trials often operate under ideal conditions with highly motivated participants, but real-world patients are more diverse and face different challenges. Our registry-based studies reflect this reality.” Since 2017, Heidi Taipale and her colleagues have been using the Nordic registries—a large data source on individual-level and population-level health from Denmark, Finland, Iceland, Norway, and Sweden—to conduct groundbreaking psychiatric pharmacoepidemiology studies. With resounding results in relation to clozapine and schizophrenia treatment, Taipale has become a leading figure within the field.