Artificial intelligence (AI) applications in neurology have reached an inflection point. Despite US Food and Drug Administration approval of numerous algorithms in neuroimaging, neurophysiology, genetics and chatbots, their real-world impact remains limited. This disconnect between research promise and clinical reality represents a gap in understanding how to translate AI algorithms into clinical benefit for patients globally. In this Perspective, we examine the challenges that prevent clinical AI use in neurology moving beyond pilot studies towards meaningful clinical impact. We consider the steps required in the process of translation, including research, validation of AI models, regulatory approval pathways and clinical implementation. We discuss implementation of AI models as stand-alone products versus embedded platforms, and the requirements for sustainable deployment. Beyond traditional clinical decision support tools, we examine paraclinical applications of AI, including chatbots and ambient voice documentation. We recommend expanding capacity for prospective validation and scaling by implementing and validating technologies across multiple sites and countries, which requires infrastructure from long-term partnerships. Neurology must shift from asking whether AI can work to understanding how to use it safely at scale.
BACKGROUND: The application of chaos theory has positive results in different fields of science. Its nonlinear modeling properties and its vision of dynamic systems have enabled it to capture complex relationships in fields such as physics, financial econometrics, social systems and mathematical demography. This paper reviews the implication of chaos theory in the medical sciences. METHODOLOGY: We carried out a systematic literature review under Cochrane’s international standards. A search strategy was executed with indexed terms (MeSH, DeCS and Emtree) that varied according to each database (Embase, MEDLINE, SciELO, LILACS). The PROSPERO registration number was CRD42023491407. FINDINGS: In total, 2598 articles were retrieved, of which 20 were included. Algorithmic applications of chaotic systems were diverse. The medical fields with the largest studies were cardiology, neurology and oncology. The most used software was Matlab, however, in all cases, except one, we did not find open-source codes related to the studies. INTERPRETATION: We found a wide heterogeneity in the studies reviewed, and this was reflected in the scope of research results. While some papers focus on proving the existence of chaotic behavior or understanding the nature of the phenomena being studied, others propose practical implications, such as in prescribing medicines and organizing health units. CLINICAL TRIAL NUMBER: Not applicable.
The so-called Someya's sinew string is a linear structure observed in the buccal mucosa distal to the mandibular second molar and is primarily recognized in Japanese prosthodontic practice. Although previous studies have described its prevalence and clinical importance, particularly during impression procedures for removable prostheses, its anatomical basis remains unclear, and it is not formally defined in standard anatomical terminology. This study reviews the existing literature and reexamines the nature of this structure from anatomical and surgical perspectives. Based on clinical observations and previously reported findings, we propose that Someya's sinew string may represent postoperative scar tissue following mandibular third molar extraction rather than a distinct anatomical entity. Its location, linear morphology, low prevalence, and frequent asymmetry support this interpretation. Additionally, none of the cases observed in our experience exhibited intact mandibular third molars. Although this hypothesis remains unverified, it provides a coherent explanation consistent with current clinical and structural observations. Importantly, regardless of its origin, this structure remains clinically relevant and should be recognized in prosthodontic practice, particularly during impression procedures. Further studies, including histological and imaging analyses, are warranted to clarify its biological nature.
Migraine is a chronic neurological disorder and a leading cause of disability worldwide. In India, it poses a significant public health challenge, with prevalence estimates ranging from 14% to 28.7%. The objective of the work was to assess the epidemiological burden of migraine in India and critically examine clinical, social, and infrastructural challenges impacting its management and policy support. A narrative review of peer-reviewed literature published between 2015 and 2025 was conducted using PubMed, Scopus, and Web of Science, focusing on migraine diagnosis, treatment advances, and policy frameworks. Searches included terms such as "early diagnosis," "medication overuse headache," "policy support," and "novel migraine therapies," prioritizing systematic reviews and meta-analyses. Expert insights were also incorporated through thematic analysis of discussions from a dedicated migraine session at the 69 th Annual National Conference of the Indian Public Health Association (March 2025, Belagavi). The results demonstrate that migraine affects over 213 million individuals in India, disproportionately impacting women and working-age populations. Current therapeutic approaches lack personalization, and access to innovative treatments remains limited due to regulatory and insurance gaps. Policy neglect and sociocultural stigma exacerbate disease burden. This report highlights the debilitating nature of Migraine and the associated economic loss in India, which remains under-recognized in policy and insurance frameworks. A multidisciplinary, patient-centered approach integrating clinical innovation, policy reform, and mental health support is found to be the need of the hour.
This scoping review aims to identify, map, and synthesize evidence on the sexual and reproductive health (SRH) information needs of youth 15-24 years living with epilepsy, congenital heart disease (CHD), or systemic lupus erythematosus (SLE) in the USA and Canada, and identify barriers and facilitators to access to SRH information and services. Youth and young adults with chronic health conditions face elevated and condition-specific reproductive risks. Among youth with epilepsy, interactions between seizures, antiseizure medications, hormones, and hormonal contraceptives increase the risk of unintended pregnancy. For youth with congenital heart disease, a substantial proportion of pregnancies are associated with cardiac complications, and contraceptive counseling is often delayed or inconsistently delivered. In systemic lupus erythematosus, limited contraceptive options and teratogenic therapies further heighten reproductive risk, with active disease associated with significantly increased risks of preterm birth and pre-eclampsia. Despite these well-documented risks, youth with chronic conditions frequently report unmet SRH information needs related to contraception, medication safety, fertility, and pregnancy planning. Evidence remains fragmented across specialties and largely focused on pregnancy outcomes rather than youth-centered informational needs and access to services. Our preliminary search did not identify a comprehensive scoping review that maps sexual and reproductive health (SRH) information needs, barriers, and facilitators across these three chronic conditions among young people in North America. Given the anticipated heterogeneity in study designs, populations, and outcomes, a scoping review is appropriate for characterizing the breadth and nature of the evidence base. Eligible sources will include empirical studies from the USA and Canada involving youth aged 15-24 years diagnosed with epilepsy, CHD, or SLE. Studies must address SRH information needs and/or barriers and facilitators to accessing SRH information or services. Youth-reported needs will be distinguished from caregiver or provider perspectives, which will be included only when directly relevant to youth experiences. All primary qualitative, quantitative, and mixed-methods designs, as well as empirical grey literature, will be considered. This review will follow Joanna Briggs Institute (JBI) methodology for scoping reviews and will be reported in accordance with the PRISMA-ScR guidelines. A three-step search strategy will be implemented across MEDLINE, Embase, CINAHL, PsycINFO, Scopus, Web of Science, CENTRAL, and targeted grey literature sources from the inception of each database to the final search date. Two reviewers will independently screen records and extract data using a piloted standardized tool. Results will be synthesized descriptively and analyzed using manifest-level content analysis to categorize SRH information needs, barriers, and facilitators. Findings will be mapped across socio-ecological levels and developmental stages (15-19 and 20-24 years), where data permit. This protocol is registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/5SWTY).
Monoclonal antibodies (mAbs) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway are safe and effective treatments for migraine prevention. However, the high cost of these novel therapies has led to reimbursement policies requiring patients to try multiple traditional preventives before access. Here, we evaluate the real-world effectiveness of onabotulinumtoxinA (BoNT-A) as first-line treatment and describe the sequential transition to anti-CGRP monoclonal antibodies in patients who did not achieve sufficient response, within the Polish chronic migraine treatment program. In this retrospective cohort study, we included 94 patients with chronic migraine who received BoNT-A treatment according to the PREEMPT protocol every 3-4 months for 12 months as first-line treatment. Headache diaries and documentation were used to evaluate reductions in monthly headache days (MHD) and MIDAS scores. Patients were divided into two subgroups based on their response after three BoNT-A administrations: insufficient response (≤ 50% reduction in MHD) and sufficient response (> 50% reduction in MHD). We included 94 patients (93.62% female, age range 22-66 years). Following three BoNT-A injection cycles, 70 patients (74.47%) did not achieve the ≥ 50% response threshold and were sequentially transitioned to fremanezumab per programme protocol. In the insufficient response group, MHD decreased from 18.26 ± 4.46 to 13.90 ± 4.64 days (t(69) = 15.49, p < 0.001), representing a 23.9% reduction, while MIDAS scores decreased from 93.77 ± 41.80 to 61.69 ± 35.56 (t(69) = 10.22, p < 0.001, 34.2% reduction). In the sufficient response group (n = 24, 25.53%), MHD decreased from 17.83 ± 1.95 to 7.83 ± 1.83 days after 3 injections (56.1% reduction, t(23) = 31.97, p < 0.001), and further to 4.13 ± 1.77 days after 5 injections (76.7% reduction, t(22) = 32.59, p < 0.001). Pearson's correlation analysis revealed moderate positive correlation between MHD and MIDAS after 3 injections (r = 0.392, p < 0.001), which weakened substantially after 5 injections (r = 0.082, p = 0.691). Baseline MIDAS scores were numerically higher in the sufficient response group (116.62 ± 61.12 vs. 93.77 ± 41.80, t(92) = 2.04, p = 0.044); however, given the outcome-dependent nature of group allocation, this difference should not be interpreted causally or as a prognostic marker. For patients who did not experience sufficient improvement after the third BoNT-A administration, treatment was changed to fremanezumab. Our real-world data demonstrate that 74.47% of patients with chronic migraine did not achieve the ≥ 50% MHD reduction threshold after three onabotulinumtoxinA injections, supporting the current Polish therapeutic algorithm that allows sequential transition to anti-CGRP monoclonal antibodies for insufficient responders.
Sharing serious information (SSI) is a critical communication skill for physicians. Existing frameworks vary in their teaching and application, and many physicians desire better training. This study aimed to develop a theory-informed framework and cognitive aid for sharing serious information (SSI) through a multiphased development process involving a systematic review and expert focus groups. A multiphased approach was used: (1) a systematic review of four databases (1983-2024) to identify core components of SSI; and (2) twelve multidisciplinary focus groups (2022-2024) using the nominal group technique to integrate these components into a structured framework. A modified PICO/PEO approach (Population, Exposure/Intervention, Outcomes) guided study selection, and the AMSTAR2 tool was only used for quality appraisal of systematic reviews. From 4,892 titles/abstracts, 52 were selected for inclusion. Thematic synthesis identified eight themes for optimal SSI: (1) limiting delay between diagnosis and SSI, (2) preparation time for meetings, (3) patient-centered communication, (4) discussion of emotions, (5) verifying understanding, (6) affirmation of treatment options, (7) offering a confidant, and (8) providing information resources. These themes, interpreted cautiously across heterogeneous evidence sources, informed the development of the MEET & MAKE CleaR PROCESS framework, encompassing preparation (MEET), sharing (MAKE), clarification (CleaR), and ongoing plan (PROCESS). The MEET & MAKE CleaR PROCESS framework and its cognitive aid aim to equip educators and clinicians with a structured approach to instructing and managing SSI encounters especially with simulation-based education. We believe this up-to-date framework could minimize the negative impact of SSI on patients, relatives, and physicians.
Pain is a critical yet frequently underestimated component in the care of patients with acquired brain injury (ABI) and disorders of consciousness (DoC). Because these individuals often lack the ability to communicate verbally or purposefully, clinicians face substantial challenges in recognizing and managing pain, despite its profound influence on autonomic stability, behavioural responsiveness, rehabilitation engagement and overall prognosis. This position paper synthesizes current knowledge on the multidimensional nature of pain and reviews the main behavioural, autonomic and neurophysiological tools available to assess nociception and pain-related processing in non-communicative patients. By integrating evidence from standard clinical scales with advanced physiological markers and neuroimaging findings, we highlight how preserved activity within the so-called pain matrix challenges traditional assumptions about pain absence in DoC populations. The paper argues for a shift toward multimodal, patient-centred approaches that combine behavioural observation with objective physiological indicators to improve diagnostic accuracy and ensure ethically responsible care. Practical guidance is provided on selecting appropriate assessment tools, interpreting behavioural and physiological signs of nociception, and implementing more effective pain management strategies. Accurate pain assessment is essential not only to promote recovery and facilitate rehabilitation but also to uphold the central ethical principle of safeguarding the dignity of patients with disorders of consciousness. Understanding pain in Disorders of Consciousness (DoC) is a major clinical and ethical challenge, as residual nociceptive processing may be underestimated. This study advances a multidimensional framework integrating behavioural and neurophysiological evidence, moving beyond simple detection toward interpretation of pain meaning. It has direct implications for improving pain assessment, guiding personalized management and supporting more accurate and ethically grounded care in non-communicative patients.
Disease-modifying therapies for degenerative ataxias, including emerging gene therapies, are in the clinical trial pipeline. Sensitive outcome measures are urgently needed for treatment monitoring and participant selection to improve trial feasibility in these rare diseases. In hereditary ataxias, the ability to identify people who carry disease-causing mutations before symptom onset also raises the possibility of enrolment into trials before symptom manifestation, but biomarker data are key for participant selection and outcome monitoring in such preventive trials. Quantitative neuroimaging readouts have emerged as viable candidate biomarkers of ataxia pathology and progression that could supplement traditional clinical outcome assessments as clinical trial end-points. In this Consensus Statement, the Ataxia Global Initiative MRI Biomarkers Working Group critically reviews candidate MRI end-points for trials in the most common spinocerebellar ataxias (SCA1, SCA2 and SCA3) and Friedreich ataxia and provides evidence-based, disease-specific recommendations for the selection of MRI end-points for trials in these diseases. Recommendations are also provided for further research to address remaining knowledge gaps.
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Life expectancy is a key indicator of population health and an important guide for health policy1,2. Although Asia represents approximately 60% of the global population, studies of longitudinal trends in life expectancy and their underlying drivers across Asian countries remain limited, with most previous research focused on western or high-income settings3-6. Here we provide a comprehensive analysis of life expectancy, cause-specific mortality and risk factors in 1990-2023 across 34 Asian countries and territories, utilizing data from the Global Burden of Disease Study 20231,7. Life expectancy increased in all countries and territories between 1990 and 2023, with the largest annual gains observed in South Asia and the smallest annual gains in high-income Asia Pacific countries and territories. Reductions in cardiovascular disease mortality were the primary contributors to life expectancy gains in Central Asia, East Asia and high-income Asia Pacific, whereas declines in diarrhoeal diseases and tuberculosis contributed most in South and Southeast Asia. In 2019-2023, life expectancy declined in several Asian regions, largely driven by the COVID-19 pandemic, with a nearly two-year loss in the first year of the pandemic. The causes of changes in life expectancy and the contributing risk factors varied across regions and countries/territories. Therefore, under the principles of proportional universalism, proactive and effective policies at both regional and national levels are essential to reduce premature mortality and reduce life expectancy inequalities across Asia.
People with Lewy body disease exhibit heterogeneous clinical symptoms, diverse patterns of neurodegeneration on imaging and variable Lewy body pathology at post-mortem. The brain-first versus body-first (BvB) model provides a unifying framework that may account for much of this variability. According to the BvB model, Lewy pathology originates either in autonomic nerves of the gut or other peripheral neurons (body first) or in the olfactory bulb with subsequent spread to the limbic system (brain first). Both subtypes are thought to begin largely outside the CNS, possibly triggered by exogenous factors such as infectious agents or toxins. The model is supported by several observations. First, some individuals develop autonomic dysfunction and sleep disorders years before diagnosis, whereas other individuals experience these symptoms only after diagnosis. Second, in people with prodromal sleep disorders, cardiac sympathetic denervation precedes nigrostriatal degeneration by approximately a decade, whereas in individuals without sleep disorders, these systems degenerate in the opposite sequence. Third, post-mortem studies often reveal bottom-up or top-down gradients of Lewy pathology, consistent with body-first versus olfactory-first origins. This Review provides a critical appraisal of the BvB model, highlighting supporting evidence and current limitations. The article also considers implications for diagnostics, therapy and prevention, and outlines key avenues for future research.
Post-COVID-19 condition (PCC), also known as long COVID, is a heterogeneous condition marked by persistent symptoms following acute SARS-CoV-2 infection. As approximately 6% of people who have experienced acute COVID-19 are estimated to develop PCC, the potential population is vast. Many of the key symptoms of PCC reflect involvement of the nervous system, ranging from cognitive impairment ('brain fog'), headaches and fatigue to anxiety and depression. This Review summarizes the spectrum of neurological and psychological symptoms that occur following acute SARS-CoV-2 infection, with a particular focus on the international consensus-based core outcome set for PCC. We also explore the proposed underlying mechanisms, including evidence for immune system dysregulation, microvascular dysfunction and volumetric changes on neuroimaging. In addition, we review ongoing and completed large-scale treatment trials. Growing evidence suggests a bidirectional interaction between symptoms traditionally considered neurobiological in origin, such as cognitive deficits and headache, and those within the purview of psychiatry, such as anxiety and depression. PCC represents an opportunity to better understand the long-term consequences of acute infection and improve management strategies and outcomes, not only for people with the condition but also for those with other post-viral syndromes that affect brain health.
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The neural extracellular matrix (ECM) in the CNS is a dynamic network of proteins and glycans that exists in multiple forms, including perineuronal nets, perisynaptic ECM and periaxonal coats. Together with the diffuse interstitial ECM, these components regulate synaptic stability, plasticity and network excitability. Behavioural studies highlight the crucial roles of ECM in shaping memory engrams and cognitive flexibility, positioning ECM as a promising therapeutic target for cognitive interventions across neurological diseases. ECM remodelling is a shared hallmark across multiple CNS diseases, yet it manifests in condition-specific patterns, from robust scar formation in trauma and stroke to more subtle and broadly distributed, but functionally substantial, ECM changes in chronic neurological disorders. Mechanistically, ECM remodelling is driven by multiple factors, including neuronal activity, neuromodulation and neuroinflammation. Diverse ECM-targeting treatments have shown efficacy in preclinical models of CNS diseases and provide attractive options for further optimization, repositioning and clinical translation. Furthermore, innovative biochemical and imaging technologies are emerging to provide further insight into ECM composition and dynamics, paving the way for novel ECM-targeting therapeutic strategies and biomarkers for diagnosis and monitoring.
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All physicians will experience challenging history taking encounters, where communication is impaired and negatively impacts the diagnostic process. The aims of this systematic review were to (1) undertake a meta-analysis of the frequency of challenging encounters; (2) collate adverse outcomes of challenging encounters; (3) identify underlying causes of challenging encounters; (4) identify strategies to deal with different challenges; and (5) align these strategies with our published phenomenological framework of history taking challenges. This was a systematic review and meta-analysis of prevalence data adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses and the Meta-analyses of Observational Studies in Epidemiology guidelines. A literature search in MEDLINE, Embase and Cochrane databases was performed on 12 July 2020, and updated on 4 August 2025, focusing on challenging history taking encounters in any clinical setting. Articles reporting on the frequency, adverse outcomes, causative factors or strategies used to address challenges in the history taking process in any clinical area of medicine. Factors associated with challenging history encounters (causative or consequential) were categorised using inductive coding and referenced to a phenomenological framework. Meta-analysis was used to estimate the prevalence of history taking encounters using a restricted maximum likelihood model with τ 2 and I 2 as tests for heterogeneity and funnel plot with Egger's test for publication bias. 73 articles were included in the analysis. The overall prevalence of challenging history taking encounters was 19.5% (95% CI 14.2% to 24.7%). Adverse outcomes of patient dissatisfaction (level 1 evidence) and diagnostic uncertainty (level 3 evidence) were identified. Factors associated with (n=22) and strategies to mitigate challenging encounters (n=13) were categorised. Correlation of factors and strategies with a phenomenological approach created a framework to assist novice history takers in approaching such circumstances. Challenging history taking encounters are common. Little is known of the relative importance of factors associated with challenging history taking encounters or the impact of suggested strategies. Many of the suggested strategies to facilitate meaningful communication in these situations involve a departure from standard history taking. More research is required to better define the nature of challenges encountered in history taking with a view to develop better educational models for trainee physicians.
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