BACKGROUND:Plasma and cerebrospinal fluid (CSF) protein biomarkers in amyotrophic lateral sclerosis (ALS) may provide insight into disease mechanisms and yield clinically useful biomarkers. METHODS:Overall, 363 proteins in plasma and CSF from 198 patients with ALS and 125 matched controls were profiled using Olink assays. Associations with disease status, survival, and functional decline, as well as longitudinal biomarker stability across the disease course were assessed, together with network and enrichment analyses. ALS risk-associated biomarkers were externally validated in the UK Biobank (UKB). RESULTS:Overall, 125 proteins were significantly associated with at least one outcome (i.e., case status, risk, survival, or functional decline), and 21 were associated with three or more outcomes. NEFL was the most robust biomarker in plasma and CSF, alongside TNFRSF12A in plasma and CSF, EDA2R in plasma, and FABP4 in plasma and CSF. Most biomarkers remained stable longitudinally across the disease course. ALS risk-associated biomarkers were replicated in UKB, in which > 3000 plasma proteins were measured in 52,990 participants, including 298 with ALS. Network and enrichment analyses highlighted their roles in immune response and extracellular-matrix remodeling, and their enrichments in the brain and T-cell subsets. Construction of an ALS risk-prediction model achieved an ROC-AUC of 0.72 in the UKB validation cohort. CONCLUSIONS:These findings suggest candidate protein biomarkers for ALS risk stratification, early detection, and clinical therapeutic monitoring.
BACKGROUND:Migraine's economic burden is mostly due to reduced work productivity, which is underestimated by commonly used patient-reported outcome measures (PROMs). In this prospective, multicentric, real-world study, we used the HEADWORK questionnaire (HWq), a disease-specific work-related PROM, to assess the impact of anti-calcitonin gene receptor peptide (anti-CGRP) monoclonal antibodies (mAbs) on work-related limitations. METHODS:Migraine patients eligible for treatment with anti-CGRP mAbs were enrolled from three headache centers: IRCCS C.Besta, Mondino Foundation and Policlinico Campus Bio-Medico. Migraine days per month (MMDs), monthly acute medications (MAMs), and HWq were collected every 3 months up to 12 months of follow-up. A GLM design was used to address change in HWq scales' score (primary endpoint), MAMs and MMDs; we also tested whether change in HWq differed across responders' group and defined minimum clinically important difference (MCID) for HWq. RESULTS:Out of 175 patients (130 females, mean age 48.9 ± 8.8) 152 completed the study. Among them: 37 (24.3%) were non-responders, 69 (45.4%) were responders, and 46 (30.3%) were super-responders. A reduction in all endpoints was observed since the first 3 months of treatment and maintained up to 12-month follow-up. Time*group interaction showed a superior effect, both in HWq scales and MAMs, with super-responders achieving the best outcome. CONCLUSIONS:A significant reduction in MMDs and MAMs and an improvement in both HWq scales in patients under mAbs treatment was found from the 3-month follow-up onwards. The positive impact on work-related disability should be taken into consideration in planning cost-effectiveness evaluations and drug policy strategy.
BACKGROUND AND PURPOSE:While the estimation of the climate change effects is dependent on the models used, there is a growing consensus that emissions of greenhouse gases (GHG) cause global warming, resulting in the acceleration of climate change. The degree to which climate change is going to affect the nervous system of healthy individuals and how it may lead to an increase in the prevalence and burden of neurological disorders is presently incompletely understood and studied. It is imperative that the neurological community increases its awareness about climate change and strives for a clear evidence-based consensus on the relationship between climate change and the negative consequences on brain health and neurological disorders. METHODS:Part I provides a narrative overview of climate change in neurology, whereas Part II focuses on climate change action in neurology. RESULTS:We provide clinicians and neuroscience stakeholders with tools to understand key concepts at the interface between climate change, neurological disorders, and brain health. Moreover, this paper states priorities in this field for the European Academy of Neurology, through the work of the Environmental Influences in Neurology Task Force, presenting 10 operational areas adapted from the WHO operational framework for building climate-resilient and low-carbon health systems. CONCLUSION:In the frame of its Brain Health Mission, the European Academy of Neurology is committed to supporting a neurology that is able to understand the impact of climate change and become a climate-resilient neurology to promote health in general and brain health specifically.
INTRODUCTION:Lack of standardised methodologies and secure processing environments for intracerebral EEG (iEEG) data creates critical barriers to international collaboration and reproducibility in clinical neuroscience. Within the framework of the Human Brain Project and EBRAINS, we have developed a specific platform, the Human Intracerebral EEG Platform (HIP), to address this challenge. METHODS:The specifications considered to develop the HIP included: (1) secure access to sensitive datasets; (2) standardised data organisation following the BIDS for iEEG (BIDS-iEEG) to ensure interoperability; (3) controlled access via a secure web-based interface; (4) provision of software needed to analyse iEEG; (5) a structured governance model enabling institutional participation through formal data sharing agreements; and (6) alignment with FAIR principles. RESULTS:HIP was implemented as a cloud-based Trusted Research Environment (TRE), with a first operational release in 2023. It provides private spaces for each participating institution and researchers, as well as collaborative spaces to share data. The HIP operates many software packages, including 3DSlicer, Brainstorm, HiBoP, etc., and CiCLONE, a tool specifically designed to coregister and visualise electrodes and recording leads on MRI and brain atlas. So far, the HIP hosts 34 institutions and 10 ongoing projects, including that on heartbeat potentials that show promising findings toward a better understanding of central autonomic dysfunction in persons with epilepsy. CONCLUSIONS:The HIP addresses key barriers to large-scale iEEG research by combining secure governance, standardised data management, and collaborative analysis within a dedicated TRE, facilitating reproducible multi-centre research.
BACKGROUND:Artificial intelligence (AI) is rapidly transforming clinical neurology, offering significant potential to enhance diagnosis, treatment, and disease management. Despite this transformative promise, AI adoption in neurology remains limited due to a lack of a reliable evidence base to support its use, as well as educational, ethical, methodological, and regulatory barriers. Furthermore, currently, there is no standardized educational framework for the application of AI in clinical neurology across Europe. METHODS:To address this gap, the European Academy of Neurology (EAN) has established a dedicated multidisciplinary Task Force (TF) on AI in Clinical Neurology. This TF involves neurologists, neurology trainees, medical students, computer and data scientists, ethicists, patient representatives, and regulatory experts. RESULTS:The AI TF has designed a modular curriculum covering technical AI foundations and models, clinical applications, ethical implications, and regulatory compliance. Planned educational resources include e-learning modules, podcasts, masterclasses, and interactive sessions at EAN congresses. Also, a recently conducted Europe-wide survey supported the TF in identifying current knowledge levels and educational and systemic barriers, informing the design of targeted interventions. In parallel, the TF will formulate recommendations addressing the ethical and regulatory implications of AI use in neurology, tailored to the specific needs of clinicians. CONCLUSIONS:The EAN TF on AI in Clinical Neurology represents a strategic initiative to enable responsible AI integration through multidisciplinary collaboration. By closing educational gaps, establishing clear ethical standards, and facilitating stakeholder engagement, the TF aims to empower neurologists to confidently and ethically adopt AI technologies, ultimately improving patient care across Europe.
BACKGROUND AND AIM:Brain-derived tau (BD-tau) is a predominantly CNS-derived form of tau protein detectable in blood that reflects brain injury and has emerged as a potential biomarker in ischemic stroke for assessing neuronal damage, monitoring infarct progression, and predicting functional outcome. However, its temporal profile and the optimal timing for correlation with infarct volume remain unclear. METHODS:This prospective cohort study included patients with ischemic stroke, with venous blood samples collected daily during the first week and at 3 months after symptom onset. Infarct volume was assessed by MRI at 48-72 h. Plasma BD-tau concentrations were measured using a Simoa assay. Linear mixed-effects models were used to analyze changes in biomarker levels. The optimal time point for correlation between BD-tau and infarct volume was identified using a 24-h moving-window Pearson correlation analysis. RESULTS:Fifty-four patients (median age 78 years, 50% female) contributed 285 plasma samples. Plasma levels of BD-tau followed a parabolic trajectory reaching a peak approximately 5 days after symptom onset. After 90 days, the concentration of BD-tau was lower than in the last measurement of the first week. The strongest correlation between BD-tau and infarct volume occurred at 105 h (4.4 days) (r = 0.89, 95% CI: 0.78-0.95) after symptom onset. CONCLUSIONS:Plasma BD-tau exhibits a distinct temporal profile after ischemic stroke, with peak levels and maximal correlation with infarct volume occurring around Day 4-5. These findings have important implications for interpreting BD-tau levels and optimizing sampling strategies in clinical studies. TRIAL REGISTRATION:Clinicaltrials.gov NCT03812666.
BACKGROUND:Amyotrophic lateral sclerosis (ALS) is one of the most devastating fatal motor neuron diseases, characterized by progressive degeneration of motor neurons in the brain and spinal cord. A significant advance in ALS therapy was achieved with the recent European Medicines Agency approval of Tofersen, the first antisense oligonucleotide (ASO) specifically targeting SOD1 mRNA, a key genetic determinant of the disease. Yet, despite its clinical relevance, data on SOD1-ALS in Central Eastern Europe remain scarce. METHODS:Here, we present a multicentric study across six countries-Austria, Czechia, Poland, Hungary, Slovakia, and Slovenia-representing approximately 16% of the European Union's population. We report all pathogenic, likely pathogenic, and uncertain SOD1 variants, along with the phenotypic features, including heritability, age, site of onset, and survival. We also assessed the availability of genetic testing, counseling, and access to Tofersen therapy across the region. RESULTS:Out of 1200 patients with confirmed ALS, we identified 24 distinct pathogenic SOD1 variants in a total of 67 patients (median age at onset 47 [40-55] years), of whom 65.7% had familial ALS (fALS) and 34.3% had sporadic ALS (sALS). We characterized the associated phenotypes and reported that 42 patients are currently receiving Tofersen therapy. CONCLUSION:This study provides the first comprehensive overview of SOD1-ALS in Central Eastern Europe. Our findings underscore the importance of genetic testing and counseling, as well as equitable access to targeted therapies such as Tofersen to advance patient-specific care in this region.
BACKGROUND:Cerebral hypoperfusion, an acute manifestation of intracranial arterial stenosis (ICAS), is particularly concerning among older East Asian adults given its high prevalence. Systemic inflammation triggered by PM2.5 exposure has been linked to cerebrovascular diseases, yet evidence on its specific components of hypoperfusion in this vulnerable group remains limited. We explore associations between PM2.5 and its components exposure with cerebral hypoperfusion, and assess mediation by inflammatory indicators. METHODS:We analyzed 967 patients with symptomatic ICAS at the First Affiliated Hospital of Soochow University. Hypoperfusion was evaluated using multimodal CT imaging and quantified with MIStar software. Three-year exposure to PM2.5 and its components was estimated using the TAP database. Associations were evaluated using generalized additive models and restricted cubic spline regression, while weighted quantile sum regression assessed mixture effects. Mediation analysis quantified inflammatory markers' roles in these relationships. RESULTS:PM2.5 was significantly association with cerebral hypoperfusion (OR = 4.344, 95% CI: 3.323-5.734), with black carbon (BC) showing the strongest association (OR = 4.396, 95% CI: 3.327-5.869), followed by sulfate (SO4 2-) (OR = 4.359), organic matter (OM) (OR = 4.278), nitrate (NO3 -) (OR = 3.552), and ammonium (NH4 +) (OR = 3.313). OM (44.2%) and BC (42.2%) contributed 86% of the total mixture effect. Neutrophils mediated 5.37% of the total effect between PM2.5 and cerebral hypoperfusion, whereas leukocytes (4.30%) and monocytes (2.73%) demonstrated significant mediation effects. CONCLUSION:Prolonged exposure to PM2.5 and its components, particularly OM and BC, was associated with increased cerebral hypoperfusion risk, partially mediated by inflammatory responses. These findings highlight the need for component-targeted air quality policies to reduce cerebrovascular risk in vulnerable populations.
BACKGROUND:Myasthenia gravis (MG) is increasingly concentrated in older adults, and age may shift the balance of benefit and risk for MG therapies. This study seeks to evaluate the effect of age on treatment efficacy in clinical trials of MG. METHODS:PubMed and Cochrane Library were searched and clinical trials enrolling adults with MG that reported the quantitative myasthenia gravis (QMG) score and the myasthenia gravis activities of daily living (MG-ADL) scale were included. Of 2214 records identified, 18 trials met inclusion criteria. Random-effects meta-analysis was used to pool treatment effects, and random-effects meta-regression evaluated trial-level mean baseline age as a modifier of treatment efficacy. RESULTS:Eighteen trials published from 2017 to 2025 included 1823 participants (982 assigned to treatment and 841 to control). Pooled effects favored treatment over control for the QMG (MD -2.402; 95% CI, -3.099 to -1.706; I 2 = 60.7%) and MG-ADL scores (MD, -1.591; 95% CI, -1.874 to -1.309; I 2 = 0.0%). In meta-regression, higher mean trial age was associated with attenuation of treatment benefit on the QMG scale (β per 10 years, 1.21; 95% CI, 0.02 to 2.42; p = 0.047). This effect was most pronounced for FcRn inhibitors. No association was observed for the MG-ADL score (β per 10 years, 0.08; 95% CI, -0.50 to 0.66; p = 0.779). CONCLUSIONS:In this meta-analysis, older trial populations showed smaller treatment-related improvements in the QMG but not in the MG-ADL score. These findings suggest that age may contribute to differences in treatment effects across MG trials.
BACKGROUND:Intravenous thrombolytic therapy (IVT) is recommended for patients with acute ischemic stroke (AIS) and disabling deficits, regardless of National Institutes of Health Stroke Scale (NIHSS) score. The benefit of IVT in patients with mild AIS was, however, not documented in recent trials. The aim of this study was to evaluate the effectiveness of IVT in mild AIS in a nationwide registry-based study. METHODS:AIS patients from the Norwegian Stroke Registry (2016-2022) with a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 at admission were included. Using 1:1 propensity score matching, 1736 IVT-treated patients were matched with 1736 controls. Primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 90 days. Secondary outcomes included mRS 0-2, a favorable mRS shift (range 0-6), and death within 28 and 90 days. Data on symptomatic intracerebral hemorrhage (sICH) were available only for the IVT group. RESULTS:At 90 days, 68.4% of IVT-treated patients and 61.2% of controls achieved mRS 0-1 (OR 1.39; 95% CI 1.20-1.60). IVT was associated with a higher probability of achieving excellent functional outcome in patients with NIHSS 4-5 (OR 1.53; 95% CI 1.06-2.21) and NIHSS 2-3 (OR 1.64; 95% CI 1.32-2.03), but not NIHSS 0-1 (OR 1.14; 95% CI 0.89-1.44). No significant differences in overall mortality were observed. SICH occurred in 3.7% of IVT-treated patients. CONCLUSION:IVT was associated with favorable functional outcomes for mild AIS, but not in patients with NIHSS 0-1.
BACKGROUND:Neuro-Behçet syndrome (NBS) is a heterogeneous inflammatory disorder in which venous involvement is well recognized, while intracranial arterial pathology remains insufficiently characterized. Conventional luminal imaging methods are limited in detecting early or isolated arterial wall abnormalities. Vessel wall imaging (VWI) may provide additional insights into arterial involvement in NBS. METHODS:Thirty-nine NBS patients (27 men, 12 women; mean age 38.52 ± 9.54 years) underwent intracranial VWI; 16 were imaged during the attack period and 23 during the attack-free period. A total of 1170 artery segments were systematically evaluated for wall thickening patterns and contrast enhancement. VWI findings were analyzed in relation to imaging timing, radiological subtype, MR angiography findings, and EDSS. RESULTS:Vessel wall involvement was found in 16 patients (41%), mainly in the posterior circulation (81%). Concentric wall thickening without enhancement was the most common pattern (80.48%). Vessel wall involvement was significantly more frequent in patients imaged during the attack period compared with those imaged in the attack-free period (68.8% vs. 21.7%; p = 0.007). Vessel wall enhancement was present only in the attack period (p = 0.022). Notably, higher EDSS scores were significantly associated with multisegmental posterior circulation involvement, particularly when ≥ 3 segments were affected (p = 0.015; p = 0.024). CONCLUSION:Intracranial arterial wall involvement is detectable by VWI in a substantial proportion of NBS patients, predominantly in the posterior circulation with a concentric thickening pattern. These findings suggest that arterial wall pathology may be more common than previously recognized and that VWI provides complementary diagnostic information beyond conventional luminal imaging.
BACKGROUND:Reproductive health is a critical component of care for women with multiple sclerosis (MS), yet standardized interdisciplinary approaches remain limited. OBJECTIVES:This Delphi consensus aimed to develop an interdisciplinary, evidence-informed care model tailored to the Italian healthcare system. RESULTS:A two-round Delphi process was conducted in Italy (June-July 2025), involving MS experts (Round 1: 107, Round 2: 95), including neurologists, gynecologists, pediatricians, nurses, and patient representatives. Participants evaluated key aspects of the reproductive care pathway, from preconception counseling to postpartum follow-up, to identify priorities and areas of agreement across disciplines. Strong consensus was achieved on the importance of early counseling, coordinated interdisciplinary management, and individualized treatment planning across the reproductive continuum. The central role of nurses in patient education was also emphasized. Divergence emerged regarding the continuation of specific therapies during pregnancy and the role of neonatal immunological monitoring following exposure to depleting agents, reflecting areas of ongoing uncertainty and limited evidence. CONCLUSIONS:This consensus proposes the first interdisciplinary framework for reproductive care in MS within the Italian context. It emphasizes patient-centered decision-making, collaboration across specialties, and the integration of reproductive health into routine MS management. By identifying both shared priorities and unresolved challenges, it provides a foundation for more harmonized, evidence-informed clinical practice and future research.
BACKGROUND:Lewy body diseases (LBDs) are heterogeneous, and this variability is already evident in the prodromal phase. Several frameworks propose that prodromal heterogeneity reflects distinct phenotypic and biological subtypes, supported by differences in clinical profiles, imaging, and α-synuclein biomarkers. We provide a detailed clinical characterization of two enriched prodromal cohorts: isolated REM Sleep Behavior Disorder (iRBD) and Hyposmia with Dopamine Transporter Deficit. METHODS:This cross-sectional study included 360 participants with iRBD, 1101 with hyposmia and abnormal dopamine transporter imaging and 283 healthy controls from the Parkinson's Progression Markers Initiative. Using the earliest assessments available, we compared the Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease Autonomic Dysfunction (SCOPA-AUT) and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III. Group differences were assessed using age and sex-adjusted permutation testing. Secondary descriptive analysis identified the individual items contributing most to between-group differences. RESULTS:Both prodromal cohorts had significantly worse scores than healthy controls in all assessments. Compared with hyposmia, iRBD was associated with higher SCOPA-AUT and MDS-UPDRS Part I scores, driven mainly by constipation and urinary symptoms. CONCLUSION:In prodromal Lewy body disease, iRBD is associated with a statistically significant excess of autonomic symptom burden compared with hyposmia with dopamine transporter deficit, with the largest item-level differences in urinary and constipation measures.
BACKGROUND:CVT-301 (Inbrija) has demonstrated its effectiveness in treating OFF periods in people with Parkinson's disease (PwP). However, its effect on non-motor symptoms (NMS) and quality of life has not been researched yet. Our aim was to analyze the change observed in health-related quality of life (HRQoL) and, as a secondary exploratory analysis, NMS associated with OFF episodes in PwP treated with CVT-301. METHODS:INLEVO-LIFE PD (an open-label study of the effect of INhaled LEVOdopa on quality of LIFE and non-motor symptoms in Parkinson's Disease) is a prospective open-label study conducted in five centers in Spain. The change from baseline (V0) to the end of the observational period (12 ± 2 weeks) (V12w) in the 39-item Parkinson's Disease Quality of Life Questionnaire (PDQ-39) total score was the primary efficacy measure. RESULTS:Forty PD patients (age 62.3 ± 9.2 years; 55% males) were included between March/2024 and November/2025. At 12 weeks, 34 patients were using CVT-301 and completed the follow-up (85%). The PDQ39 total score decreased from 43.6 ± 24.2 at V0 to 31.4 ± 20.6 at V12w (p < 0.0001). A significant decrease was observed in the mean score of 4 domains of the PDQ39. NMS burden was reduced at v12w from the OFF state to 30, 60, and 90 min after using CVT-301 (p < 0.0001). Mean daily OFF time decreased by 1.6 ± 1.9 h (p < 0.0001). Adverse events related to CVT-301 were reported in 35% of the patients. CONCLUSION:HRQoL and NMS associated with OFF episodes improved in PwP after 12 weeks using CVT-301.
INTRODUCTION:Migraine is a common neurological disorder and a non-traditional risk factor for ischaemic stroke. Its relationship with specific stroke subtypes and post-stroke outcomes remains unclear. We evaluated the association between migraine (with and without aura), stroke aetiology, functional outcomes, and cardiovascular risk profiles in young patients with ischaemic stroke or TIA. METHODS:Patients aged ≤ 55 years enrolled in the STROKE-CARD long-term follow-up study underwent structured face-to-face headache interviews by headache specialists using ICHD-3 criteria. A predefined protocol collected demographic, clinical, neuroimaging, aetiological, and cardiovascular risk data. RESULTS:Among 289 young stroke patients (median age 48.0 [41-52] years; 36.3% women), 92 (31.8%) had a history of migraine (51.1% with aura). Migraine was more common in women, associated with younger age at stroke onset and more frequent headache at stroke onset, but not with traditional vascular risk factors. PFO was more prevalent in patients with migraine with aura (68.9% vs. 36.9% no migraine, p < 0.001). No significant differences were observed in stroke territory or stroke pattern. Stroke severity (NIHSS) and functional outcome (mRS) at discharge were more favourable in migraineurs (p ≤ 0.001). In multivariable analysis, migraine without aura was independently associated with good functional outcome (OR 7.21, 95% CI 1.93-26.93, p = 0.003). CONCLUSION:In young adults with ischaemic stroke, migraine-particularly with aura-was associated with younger age at stroke onset and a higher prevalence of PFO, while traditional vascular risk factors and stroke characteristics were similar across groups. Despite comparable stroke patterns, patients with migraine experienced more favourable short-term outcomes. TRIAL REGISTRATION:Post-Stroke Disease Management-Stroke Card: NCT02156778; Stroke Card Long-term Follow-Up NCT04205006.
BACKGROUND:Acute ischemic stroke is a leading cause of death and disability. Despite strong evidence supporting reperfusion therapies and Stroke Unit care, access and quality of stroke services remain heterogeneous across Europe. Although national stroke registries provide valuable real-world data, fragmentation, limited interoperability, and data protection constraints have restricted multinational analyses and benchmarking. METHODS:The Federating European REgistries for Stroke (FERES) initiative establishes a GDPR-compliant federated framework for secondary use of stroke registry data. FERES harmonizes heterogeneous datasets through a stroke-specific Common Data Elements (CDE) model and performs analyses locally within each registry using the Medical Informatics Platform, sharing only aggregated, non-identifiable outputs. To validate the framework, a predefined showcase analysis comparing anterior versus posterior circulation acute ischemic stroke was executed in both centralized and federated modes using an identical harmonized dataset. RESULTS:FERES connected five national registries from Austria, Greece, Ireland, Italy, and Switzerland within a unified federated infrastructure. At the time of analysis, 149,772 patient events from two registries were accessible for federated querying, with three additional registries technically integrated and in advanced onboarding. The harmonized ontology comprised 945 standardized variables spanning the stroke care pathway. Federated execution reproduced centralized pooled-data results across descriptive statistics, hypothesis testing, effect sizes, and multivariable regression models with only minimal numerical discrepancies. CONCLUSIONS:FERES demonstrates that large-scale, multinational stroke research and benchmarking can be conducted in Europe using a privacy-preserving federated approach, providing a scalable foundation for cross-border real-world evidence generation and quality improvement.
BACKGROUND:Diagnosing chronic inflammatory demyelinating polyneuropathy (CIDP) relies on clinical and electrodiagnostic features. In 2021, the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) revised the CIDP guideline, superseding the 2010 European Federation of Neurological Societies (EFNS)/PNS guideline. This study compares the diagnostic accuracy of both guidelines and evaluates the impact of specific criterion changes and nerve conduction study (NCS) extensiveness. METHODS:Patients with CIDP were included if they fulfilled the 2010 EFNS/PNS electrodiagnostic criteria for at least possible CIDP or had a presumptive clinical CIDP diagnosis with objective treatment response. Matched controls were patients with suspected chronic immune-mediated neuropathy who received a diagnosis other than CIDP. Diagnostic accuracy was evaluated using two thresholds: one including possible CIDP and one restricted to (probable/definite) CIDP. The impact of electrodiagnostic criteria changes and NCS extensiveness on diagnostic performance was assessed. RESULTS:We included 339 patients and 339 matched controls. Sensitivity of the 2010 EFNS/PNS guideline was 92% when including possible CIDP and 91% for probable/definite CIDP, with specificities of 67% and 78%, respectively. For the 2021 EAN/PNS guideline, sensitivity was 94% when including possible CIDP and 83% for CIDP, with specificities of 66% and 86%, respectively. Differences were due to sensory criteria and changes in conduction block criteria. Unilateral NCS would miss 77 possible CIDP diagnoses. CONCLUSION:Sensitivity and specificity were comparable when including possible CIDP, but the 2021 EAN/PNS guideline showed lower sensitivity and higher specificity for CIDP alone. Modifying criteria, including removal of sensory abnormalities, and more extensive NCS enhanced accuracy.
BACKGROUND:Acquired demyelinating syndromes (ADS) in children include multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD), and other seronegative disorders. We previously reported an increased incidence of overall paediatric ADS and MS between 2007 to 2010 and 2011-2016 (from 0.66 to 0.80 and 0.15 to 0.26 per 100,000 person-years, respectively). Environmental factors, including viral exposure, may influence these rates. Comparing a recent period that includes the COVID-19 pandemic provides an opportunity to study temporal patterns. METHODS:Children < 18 years with a first demyelinating event between January 2017 and June 2025 were prospectively included in the nationwide PROUDkids 2.0 study or referred to the Dutch Paediatric MS Centre. Diagnoses followed international criteria, and incidence rates were calculated using national population data. RESULTS:Among 257 included children, 111 (43%) had MS, 93 (36%) MOGAD, 5 (2%) AQP4+ NMOSD, and 48 (19%) seronegative ADS. Overall ADS incidence was 0.91 per 100,000 person-years, with MS 0.40, MOGAD 0.33, AQP4+ NMOSD 0.02, and seronegative ADS 0.16 per 100,000 person-years. Compared with 2011-2016 (0.26 per 100,000), MS incidence increased, whereas other ADS rates remained stable. MS incidence declined after COVID-19 restrictions, particularly among adolescents, while MOGAD incidence rose modestly in younger children during the COVID restrictions. CONCLUSIONS:Paediatric MS incidence continues to rise in the Netherlands, whereas the incidence of other ADS remains stable. Temporal variations in the incidence of MS and MOGAD during and after the COVID-19 pandemic may reflect the influence of viral exposure in their pathogenesis.
BACKGROUND:This study aimed at identifying neuropsychological sub-phenotypes in amyotrophic lateral sclerosis (ALS) within the mild cognitive impairment (MCI) and mild behavioral impairment (MBI) frameworks. METHODS:We used individual task-/item-level data from the cognitive and behavioral sections of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) from 901 non-demented ALS to derive neuropsychological sub-phenotypes pursuant to classical MCI and MBI frameworks and in accordance with an expanded version of Strong's criteria, which also addressed memory and visuo-spatial measures. RESULTS:The prevalence of MCI and MBI was 39% and 37%, respectively in this retrospective review. The following MCI sub-phenotypes were identified: dysexecutive MCI-single- and multiple-domain (dMCI-sd: 63%; dMCI-md: 24%, respectively); non-dysexecutive MCI-single- and multiple-domain (ndMCI-sd: 12%; ndMCI-md: 1%, respectively). MBI was classified as follows: apathetic MBI-single- and multiple-domain (aMBI-sd: 40%; aMBI-md: 20%, respectively); apathetic-disinihibited/perseverative MBI-multiple domain (ad/pMBI-md: 21%); disinihibited/perseverative MBI-multiple domain (d/pMBI-md: 7%); psychotic MBI-single- and multiple-domain (psyMBI-sd: 2%; psyMBI-md: 3%, respectively); unclassifiable MBI-multiple domain (uMBI-md: 1%). 143 (16%) of patients exhibited mild cognitive and behavioral impairment (MCBI). CONCLUSIONS:This study delivers a provisional, ECAS-based classification for the neuropsychological sub-phenotyping of non-demented ALS patients, which, with further validation, might be useful for both research and clinical purposes.
