European Journal of Neurology最新文献

{"title":"Epidemiology of Progressive Supranuclear Palsy in Navarre, Spain: A Population-Based Study","authors":"P. Arrondo Gómez,&nbsp;E. Vicente,&nbsp;G. Martí-Andrés,&nbsp;J. Sánchez Ruiz de Gordoa,&nbsp;I. Gastón,&nbsp;P. Clavero,&nbsp;R. Valentí,&nbsp;J. Delfrade,&nbsp;M. E. Erro","doi":"10.1111/ene.70592","DOIUrl":"10.1111/ene.70592","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epidemiological studies carried out on progressive supranuclear palsy (PSP) provide heterogeneous data. Our aim has been to analyze incidence, point prevalence, survival, and time to diagnosis of PSP in Navarre, a northern Spanish region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a population-based observational retrospective study from 2010 to 2022. Data from various sources of health information were reviewed to identify all potential diagnoses of PSP, validated through medical records reviews. Patients were included if they fulfilled the 2017 Movement Disorder Society (MDS) criteria and were classified into the different PSP phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 226 prevalent PSP cases were identified. Age-standardized point prevalence rate at January 1, 2023, was 7.52/100,000 inhabitants, and age-standardized annual incidence rate (IR) for the period was 2.41/100,000 person-years. PSP-Richardson syndrome (RS) phenotype showed significantly higher prevalence and incidence rates compared to PSP non-RS phenotypes. Joinpoint regression for overall incidence showed a significant increase until 2018 and thereafter a significant steep decline. Joinpoint regression for prevalence showed a statistically significant annual decline from 2018 onwards. Mortality rate experienced a peak in 2020. Median time to diagnosis was 37 months, and the median survival from clinical symptom onset was 89 months. PSP-RS was associated with reduced time to diagnosis and reduced survival compared to the PSP non-RS phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study represents the first population-based epidemiological study of PSP in Spain and the first with application of the new MDS diagnostic criteria in Europe, providing detailed incidence, prevalence, and mortality data that are in accordance with other European studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reappraisal of the Diagnostic Significance of Transcranial Magnetic Stimulation and Triple Stimulation in Amyotrophic Lateral Sclerosis","authors":"Birgit Andersen,&nbsp;Christian Krarup","doi":"10.1111/ene.70560","DOIUrl":"10.1111/ene.70560","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To reassess the importance of transcranial magnetic stimulation (TMS), including the triple stimulation technique (TST), to detect upper motor neuron (UMN) involvement in amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this single-center prospective study, 144 consecutive patients suspected of having motor neuron disease were included over 5 years at the time of diagnosis. All patients were examined clinically and with EMG to assess UMN and lower motor neuron (LMN) involvement, and survival was ascertained 2 years after inclusion of the last patient. Our TMS protocol consisted of TST in both arms and conventional motor evoked potentials (MEP) in arms and legs to assess central motor conduction time (CMCT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The TST could be performed in 142 patients who showed central conduction failure in 63%, which was often markedly asymmetrical, and 50% had prolonged CMCT in the legs. Combining TST in the arms and conventional MEP in the legs showed central abnormalities in 77%. In 62 patients with only signs of LMN involvement at clinical and EMG assessment, the TST amplitude ratio was reduced in 45%, and combined TST to the arms and conventional MEP to the legs disclosed a central abnormality in 61%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The main clinical significance was the subclinical corticospinal involvement at TMS with TST in a large proportion of patients without clinical UMN involvement. TMS with TST is a sensitive, non-invasive electrophysiological method to detect corticospinal dysfunction in ALS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Sensitivity of Neuropsychological Scales Hinder Detection of Potential Benefit of Treatments in Alzheimer's Disease: A Position Paper","authors":"Simona Luzzi,&nbsp;Julie S. Snowden","doi":"10.1111/ene.70590","DOIUrl":"10.1111/ene.70590","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite the advent of Disease Modifying Therapies (DMTs) for Alzheimer's Disease (AD), the approval and commercialization of anti-amyloid monoclonal antibodies has been slow and contentious, particularly in Europe. The primary source of debate is the discrepancy between robust biological effects—namely, effective β-amyloid clearance—and modest clinical improvements, which, although statistically significant, often fail to reach the minimal clinically important difference (MCID) compared to placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This paper highlights a confounding factor in the interpretation of the results of clinical trials: limited sensitivity of neuropsychological outcome measures. These tools, developed in the 1980s and only marginally updated, are not suited to detect subtle but meaningful cognitive changes in early disease stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ADAS-Cog, the most commonly used cognitive endpoint, suffers from a substantial ceiling effect, impairing its ability to capture cognitive decline over short durations in prodromal populations. Likewise, functional scales such as the CDR-SB are inherently insensitive in mild cognitive impairment (MCI), as functional independence is, by definition, preserved. Moreover, the use of composite multidomain scales with high baseline scores may mask domain-specific improvements, further limiting a drug's capacity to reach MCID thresholds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Methodological limitations risk undervaluing the therapeutic impact of treatment, particularly in trials targeting early or preclinical phases where changes are subtle and domain-specific. Urgent reconsideration of outcome measures is necessary to ensure accurate assessment of clinical efficacy and to avoid prematurely discarding potentially beneficial therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythrocyte Fragility in Progressive Multiple Sclerosis.","authors":"Carmen Jacob, Thomas E Williams, Charlotte M Stuart, Aviva Witkover, Simon Hametner, Hans Lassmann, Charles R M Bangham, Jeremy Chataway, Ian Galea","doi":"10.1111/ene.70595","DOIUrl":"https://doi.org/10.1111/ene.70595","url":null,"abstract":"<p><strong>Background: </strong>Aberrant iron homeostasis is increasingly recognized as a key pathological feature in progressive multiple sclerosis (MS). Although the source of excess brain iron remains unclear, haemoglobin is one possible source. To test this hypothesis, we conducted a case-control study to determine whether erythrocytes are more fragile in people with progressive MS (PwPMS) and examined associations between erythrocyte fragility and brain atrophy.</p><p><strong>Methods: </strong>PwPMS and control individuals were recruited from two centres. Two measures of erythrocyte fragility were assessed at baseline: the Median Corpuscular Fragility (MCF) and haemolysis curve slope. A subset of PwPMS in one centre underwent MR imaging at the same time as osmotic fragility testing and annually for three years thereafter.</p><p><strong>Results: </strong>A total of 174 participants were included (75 PwPMS, 99 controls), with MRI data available for 44 PwPMS. No significant differences in the MCF were observed between PwPMS and controls in either the full or age-matched cohorts. However, the haemolysis curve slope in PwPMS was less steep than healthy controls (median PwPMS = -24.76, controls = -28.73, p = 0.017), consistent with a subpopulation of fragile erythrocytes, with a similar trend in the age-matched subset (p = 0.056). Erythrocyte fragility was associated with normalized whole brain volume at the time of osmotic fragility testing and up to three years thereafter.</p><p><strong>Conclusions: </strong>Extracellular haemoglobin from lysis of an erythrocyte subpopulation may contribute to neurodegeneration in progressive MS. Further research is warranted to elucidate the interplay between erythrocyte health, inflammation and neurodegeneration, which may open avenues for novel therapeutic strategies.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":"e70595"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migraine Patients Treated With Erenumab and the Risk of Hypertension: A Registry-Based Real-World Study.","authors":"Christian Lampl, Reem Suliman, Viktoria Tischler-Strasser, Antoinette MaassenVanDenBrink, Taoufik Alsaadi","doi":"10.1111/ene.70597","DOIUrl":"10.1111/ene.70597","url":null,"abstract":"<p><strong>Background: </strong>Recent post-marketing studies have indicated a possible association between anti-CGRP receptor monoclonal antibodies (anti-CGRP-mAbs) used for migraine prophylaxis and an increased risk of hypertension (HT).</p><p><strong>Methods: </strong>We performed a retrospective real-world exploratory study, including individuals with a confirmed diagnosis of migraine who were treated with erenumab, an anti-CGRP receptor (r)-mAb, for at least 12 months. Inclusion was limited to individuals with complete clinical records and regular follow-up, with at least one visit every 3 months and data available to assess treatment outcomes. Patients were excluded if they had previously received anti-CGRP mAbs or gepants for migraine prevention before starting the current therapy, were on any concomitant baseline migraine preventive treatment, or did not complete the 12-month follow-up visits.</p><p><strong>Results: </strong>One hundred twenty-five participants were eligible and included in the analysis. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were compared between baseline and follow-up visits, conducted every 3 months for up to 24 months while the patient was on treatment. Individuals treated with erenumab initially received 70 mg, administered subcutaneously every 4 weeks. Throughout the 12-month treatment period, blood pressure (BP) measurements remained stable and within normal physiological ranges, indicating no significant hypertensive effect. Analysis across multiple visits showed that SBP ranged from 118 to 121 mmHg, while DBP stayed between 78 and 80 mmHg. Erenumab treatment over 24 months in 54 patients demonstrated stable BP with no notable hypertensive effects.</p><p><strong>Conclusions: </strong>This study did not find sufficient evidence that treatment with erenumab leads to the development of HT.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":"e70597"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13062758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Criteria and Management of MELAS and Stroke-Like Episodes: Consensus-Based Statements.","authors":"Michelangelo Mancuso, Marcello Bellusci, Valerio Carelli, Irenaeus de Coo, Daria Diodato, Felix Distelmaier, Omar Hikmat, Michio Hirano, Rita Horvath, Amel Karaa, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Chiara La Morgia, Piervito Lopriore, Mika Henrik Martikainen, Robert McFarland, Olimpia Musumeci, Robert D S Pitceathly, Guido Primiano, Shamima Rahman, Fernando Scaglia, Andrew Schaefer, Manuel Schiff, Luisa Semmler, Costanza Lamperti, Serenella Servidei","doi":"10.1111/ene.70588","DOIUrl":"10.1111/ene.70588","url":null,"abstract":"<p><strong>Background and purpose: </strong>Mitochondrial Encephalomyopathy, Lactic acidosis and Stroke-like episodes (MELAS) is a rare multisystem mitochondrial disorder with clinical heterogeneity. Diagnostic criteria and management strategies for MELAS and mitochondrial stroke-like episodes (SLE) remain inconsistent. This work provides international consensus recommendations on the definition, diagnosis, and management of MELAS and SLE in pediatric and adult populations.</p><p><strong>Methods: </strong>An international Delphi consensus process was conducted within the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD), in collaboration with the US Mitochondrial Medicine Society, the ERN for Hereditary Metabolic Disorders (MetabERN), and patient representatives. Following a systematic literature review, 54 statements addressing diagnostic definitions and management of MELAS were evaluated. Statements not reaching consensus were revised and re-evaluated during a face-to-face meeting.</p><p><strong>Results: </strong>Consensus supported defining MELAS as a clinical syndrome characterized by one or more SLE in the context of mitochondrial dysfunction caused by a pathogenic mitochondrial DNA variant, particularly m.3243A>G in MT-TL1. The use of terms such as \"MELAS-like\" or \"MELAS spectrum\" was discouraged. The panel agreed that the efficacy of L-arginine, L-taurine, L-citrulline, coenzyme Q₁₀, vitamins, and other supplements remains unproven and requires validation in clinical trials. Antiseizure medications should be initiated promptly when seizures are suspected during SLE, and intravenous corticosteroids may be beneficial acutely. Multidisciplinary management of neurological, neuropsychiatric, and systemic complications was endorsed.</p><p><strong>Conclusions: </strong>This international consensus provides updated definitions and practical guidance for the diagnosis and management of MELAS and SLE, aiming to harmonize clinical practice and inform future evidence-based research.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":"e70588"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features and Prognosis of SEPTIN9-Related Hereditary Neuralgic Amyotrophy.","authors":"Julian Theuriet, Isabelle Quadrio, Frédéric Fer, Pauline Monin, Adrien Bohic, Alice Gravier-Dumonceau, Vianney Poinsignon, Emilien Delmont, Emmanuelle Salort-Campana, Shahram Attarian, Sylvain Nollet, Philippe Petiot, Solène Ronsin, Stéphane Peysson, Pierre Lozeron, Françoise Bouhour, Philippe Corcia, Antoine Pegat, Tanya Stojkovic","doi":"10.1111/ene.70603","DOIUrl":"10.1111/ene.70603","url":null,"abstract":"<p><strong>Background: </strong>Neuralgic amyotrophy (NA) causes acute episodes of neuropathic pain in the upper limbs, followed by weakness and atrophy. NA can be idiopathic (INA) or hereditary (HNA). The SEPTIN9 gene has been linked to HNA. This study aimed to characterize the clinical and prognostic features of patients with SEPTIN9-related HNA.</p><p><strong>Methods: </strong>This retrospective multicenter study included all adult patients diagnosed with SEPTIN9-related HNA in France from January 2012-June 2025. INA patients were included as controls.</p><p><strong>Results: </strong>Twelve patients with SEPTIN9-related HNA and 25 with INA were included. A family history of NA (75%) and dysmorphic features (50%) were reported exclusively in the SEPTIN9 group. The median age at neurological episode was significantly lower in the SEPTIN9 group (26.0 years) than in the INA group (38.5 years; p < 0.01). Multiple episodes were more frequent in the SEPTIN9 group (75%) than in the INA group (24%; p < 0.01). Distal upper-limb nerves were more frequently affected in SEPTIN9-related HNA episodes than in INA episodes. Sensory symptoms were significantly more frequent in SEPTIN9-related HNA episodes (57%) than in INA episodes (22%; p < 0.01). A higher proportion of SEPTIN9-related HNA patients had a modified Rankin Scale score ≥ 2 (42%) compared with INA patients (16%), although this difference did not reach statistical significance (p = 0.12).</p><p><strong>Conclusions: </strong>While not completely sensitive or specific, certain features may prompt clinicians to suspect a SEPTIN9-related form when assessing a patient with NA: young age, dysmorphic features, a family history of NA, repeated episodes, sensory symptoms, and distal nerve involvement affecting the upper limbs.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":"e70603"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Patients with Myasthenia Gravis in the French Rare Disease Registry.","authors":"Jean-Philippe Camdessanche, Andoni Echaniz-Laguna, Guilhem Solé, Cécile Blein, Mariana Ciumas, Claude Messiaen, Anne-Sophie Jannot, Shahram Attarian","doi":"10.1111/ene.70604","DOIUrl":"https://doi.org/10.1111/ene.70604","url":null,"abstract":"<p><strong>Background: </strong>The French National Rare Diseases Registry (BNDMR) was established in 2007 to ensure access to optimal care standards for all patients with rare diseases in dedicated reference centres. The objective of this retrospective cohort study was to describe patients with myasthenia gravis (MG) in the BNDMR.</p><p><strong>Methods: </strong>All patients aged ≥ 18 years in the BNDMR with a confirmed diagnosis of MG visiting a reference centre at least once between 2007 and 2021 (inclusive) were included. Diagnosis was defined through ORPHA:589 or ORPHA:391490 disease codes. Patients were followed for ≥ 12 months until 31 December 2022 (or until death). Data were collected on demographics and disease history. Mortality was estimated using Kaplan-Meier survival analysis. Healthcare resource utilisation at the reference centre was documented.</p><p><strong>Results: </strong>Overall, 3963 patients were analysed. Mean follow-up duration was 6.1 ± 3.8 years. The median interval between diagnosis and inclusion was 3.8 months [IQR: 1.5-7.5] and the median age at symptom onset was 52.0 [IQR: 34.0-69.0] years. Survival probability was 82.7% at 10 years, and higher in women than men (p < 0.001; logrank test). The mean interval between visits was 4.1 months. The mean number of overnight or day hospitalisations per patient was 2.6 ± 3.4 and the mean number of physician consultations per patient per year was 1.7 ± 1.1.</p><p><strong>Conclusion: </strong>This national registry study provides reference data for patients in France with a confirmed diagnosis of MG. However, all patients with MG are still not managed in dedicated reference centres.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":"e70604"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kappa Free Light Chains Reflect Treatment Response and Progression Independent of Focal Inflammation in Multiple Sclerosis.","authors":"Igal Rosenstein, Markus Axelsson, Magnus Johnsson, Clas Malmeström, Hlin Kvartsberg, Henrik Zetterberg, Jan Lycke, Lenka Novakova","doi":"10.1111/ene.70602","DOIUrl":"https://doi.org/10.1111/ene.70602","url":null,"abstract":"<p><strong>Background: </strong>Cerebrospinal fluid (CSF) kappa free light chains (KFLC) is a sensitive marker of intrathecal immunoglobulin synthesis and is incorporated into the 2024 McDonald criteria for multiple sclerosis (MS). How disease-modifying therapies (DMTs) influence KFLC dynamics and their association with treatment response remains unclear.</p><p><strong>Objective: </strong>To determine whether intrathecal KFLC synthesis changes during DMT and whether these changes are associated with clinical outcomes.</p><p><strong>Methods: </strong>Patients with treatment-naïve relapsing-remitting MS were prospectively enrolled at the Sahlgrenska MS Center (Gothenburg, Sweden). Paired CSF and serum samples were collected at baseline and after 12 months of treatment with dimethyl fumarate (DMF) or natalizumab (NTZ). KFLC index was calculated as [(CSF KFLC/serum KFLC)/(CSF albumin/serum albumin)]. Treatment response was assessed using no evidence of disease activity-3 (NEDA-3) and progression independent of relapse and MRI activity (PIRMA⁺).</p><p><strong>Results: </strong>Forty-eight patients were included (DMF n = 26, NTZ n = 22). NTZ reduced KFLC index from a median 117.4 (63.6-171.9) at baseline to 78.8 (39.4-104.0) at 12 months (adjusted p = 0.003), corresponding to a median decline of -51.0 (IQR -82.1 to -24.7), whereas DMF produced no meaningful change. In NTZ-treated patients maintaining NEDA-3 or without PIRMA⁺, KFLC index declined markedly (both p < 0.01). Change in KFLC index predicted outcomes, yielding an AUC of 1.0 for NEDA-3 and 0.79 for non-PIRMA⁺.</p><p><strong>Conclusions: </strong>Natalizumab appears to reduce intrathecal KFLC synthesis, and a decline in KFLC index may reflect effective suppression of CNS humoral immunity. ΔKFLC index could serve as a sensitive biomarker of treatment response and disease stability in MS.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":"e70602"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mood and Age Predict Cognitive Complaints in Memory Clinic Patients: A Machine-Learning and Linear Modeling Approach.","authors":"Florian W Sander, Marie Pittet, Valeria Manera, Christine Krebs, Esther Brill, Andrea Brioschi-Guevara, Philippe Ryvlin, Joaquin A Anguera, Adam Gazzaley, Philippe Robert, Stefan Klöppel, Jean-François Démonet, Giulia Binarelli, Arseny A Sokolov","doi":"10.1111/ene.70583","DOIUrl":"https://doi.org/10.1111/ene.70583","url":null,"abstract":"<p><strong>Introduction: </strong>Cognitive complaints are often considered early indicators of Alzheimer's disease (AD) and commonly lead to memory clinic consultations. Prior studies suggest stronger associations between cognitive complaints and mood than with objective cognition, but this interplay remains poorly understood. Using a machine learning-supported approach, we aimed to (1) identify key predictors of cognitive complaints, and (2) compare the value of gamified versus standard neuropsychological testing in detecting subtle deficits.</p><p><strong>Methods: </strong>In this international multi-center study, 98 participants (57 females; mean age 71.9, range 55-86) from three memory clinics completed the Cognitive Failures Questionnaire (CFQ), mood and apathy questionnaires, the tablet-based gamified Adaptive Cognitive Evaluation Explorer (ACE-X), and standard neuropsychological tests. Predictors of CFQ scores were examined using elastic net regression and the Boruta algorithm, followed by linear mixed-effects modeling.</p><p><strong>Results: </strong>Greater mood symptoms were associated with more cognitive complaints, whereas increasing age was linked to fewer complaints. Study center accounted for additional variance. The final model explained a substantial proportion of variance (conditional R² = 0.48, marginal R² = 0.33). Participants had lower z-scores on ACE-X compared to standard testing, but neither predicted the severity of cognitive complaints.</p><p><strong>Discussion: </strong>Mood and age were main predictors of cognitive complaints in memory clinic patients. Although ACE-X yielded lower normative scores than standard tests, neither cognitive measure was linked to complaints. These findings highlight the importance of systematically assessing mood, adopting personalized approaches when evaluating subjective and objective cognition, and the potential value of gamified assessments for screening populations at risk of AD.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 4","pages":"e70583"},"PeriodicalIF":3.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}