Multiple sclerosis (MS) is characterized by large-scale brain network dysfunctions. EEG microstate analysis may track these dynamics. We investigated whether microstates could distinguish patients with MS from healthy volunteers, and cognitively impaired from cognitively preserved (CP) patients. For this cross-sectional observational study, we recruited participants from the Policlinico Umberto I Multiple Sclerosis Center (Rome). We compared microstates of patients with relapsing-remitting MS (Expanded Disability Status Scale [EDSS] score <3, no relapses within 30 days) with those of age-matched and sex-matched healthy volunteers. We also compared cognitively impaired and preserved patients. Group comparisons were performed on microstate temporal parameters and topographies (topographic analysis of variance). Classification used stepwise linear discriminant analysis (LDA). We enrolled 88 patients with MS (60 women, mean age 42.75 years) and 46 healthy volunteers (23 women, mean age 33.7 years). Compared with healthy volunteers (n = 45, 23 women, mean age 33.7 years), patients with MS (n = 46, 25 women, mean age 34.6 years) showed greater explained variance (p < 0.001), occurrence (p < 0.001), and coverage (p < 0.001) of class B (visual network) and reduced mean duration (MD) of classes F (salience network, p = 0.014) and G (sensorimotor network, p = 0.009). Topographic differences were found between cognitively impaired (n = 57, 20 women, mean age 35.5 years) and preserved (n = 31, 40 women, mean age 46.7 years) patients for classes C, F, and G (p < 0.05). Patients with cognitive impairment exhibited significantly reduced explained variance of class F (p = 0.003). Class A was associated with longer disease duration (explained variance, p = 0.006; MD, p = 0.042; coverage, p = 0.007), higher EDSS scores (MD, p = 0.013), and poorer ambulation (explained variance, p = 0.049). Class D inversely correlated with EDSS scores (occurrence, p = 0.011; coverage, p = 0.036), whereas class B inversely correlated with information processing speed (explained variance, p = 0.025; occurrence, p = 0.018; coverage, p = 0.028). Stepwise LDA identified classes B and D as discriminators between patients with MS and healthy volunteers (77% accuracy, p < 0.001), and class F as a discriminator between CP and impaired participants (64.8% accuracy, p = 0.007). EEG microstates reveal behaviorally relevant alterations in patients with MS, supporting their utility as sensitive markers of large-scale functional network reorganization associated with clinical disability.

Sport-related head exposure characteristics (i.e., concussion history, sport contact classification, and total years of sport participation) are suggested to be associated with short-term and long-term health outcomes in competitive athletes. However, their relationship with intermediate health outcomes (specifically within 5 years of collegiate sport retirement) remains unknown. Therefore, we examined associations between sport-related head exposure characteristics and physical, mental, cognitive, and behavioral health measures among former collegiate athletes. Former collegiate athletes who completed a baseline evaluation between 2018 and 2021 and were evaluated within 5 years of collegiate graduation were included. Primary predictors included lifetime concussion history (0 [referent], 1-2, 3+), sport contact classification (unexposed [ref.], low, high), and total years of sport participation (continuous). Outcome measures collected included the Alcohol Use Disorders Identification Test, Brief Symptom Inventory-18 (BSI-18), Neuro-Quality of Life cognitive domain (Neuro-QoL), Patient Health Questionnaire (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), Sport Concussion Assessment Tool (SCAT) symptom inventory, 12-Item Short Form Survey (SF-12), and Satisfaction with Life Scale. Twelve multivariable linear regression models with bootstrapping were constructed, with adjusted unstandardized beta coefficients (BAdj) and standard errors (SEs) estimated. Overall, 3,910 former collegiate student-athletes were examined; 48.6% were female, 73.0% attended a Division I school, 36.2% self-reported ≥1 lifetime diagnosed concussion, 38.1% participated in a high-exposure sport, and the median years since college graduation to assessment was 5.0. Independently, scores of BSI anxiety (BAdj = 1.24, SE = 0.36), BSI depression (BAdj = 0.88, SE = 0.37), global severity index [GSI] (BAdj = 2.66, SE = 0.91), PHQ-9 (BAdj = 1.34, SE = 0.40), PSQI (BAdj = 0.69, SE = 0.29), SCAT total symptom severity (BAdj = 5.14, SE = 1.31), and SF-12 mental composite score (BAdj = -3.39, SE = 0.83) were worse in athletes with 3+ concussions compared with athletes without a history of concussion. Athletes with 1-2 concussions vs no concussion history similarly had worse scores independently for BSI-18 GSI (BAdj = 0.88, SE = 0.35), anxiety (BAdj = 0.40, SE = 0.15), Neuro-QoL (BAdj = -0.97, SE = 0.36), PHQ-9 (BAdj = 0.77, SE = 0.19), PSQI (BAdj = 0.27, SE = 0.13), SCAT total symptom severity (BAdj = 2.13, SE = 0.55), and SF-12 mental composite score (BAdj = -1.80, SE = 0.41). Lifetime concussion history was the most common predictor of adverse self-reported health outcomes compared with other exposure characteristics, within 5 years of collegiate sport retirement. Despite the associations, most former athletes remained within normal clinical levels during this early postretirement period.

Background and ObjectivesPrevious studies, including large cohort analyses comparing vaccinated and unvaccinated adults, suggest that routine immunizations such as inactivated influenza vaccines (IIVs) may reduce Alzheimer dementia (AD) risk. Whether AD risk differs after high-dose IIV (H-IIV) vs standard-dose IIV (S-IIV) remains unexamined. We hypothesized that AD risk would be lower among adults ≥65 years after H-IIV compared with S-IIV.MethodsThis retrospective cohort study analyzed data spanning 2014–2019 from IQVIA PharMetrics Plus for Academics, a US health care claims database. Eligible participants were ≥65 years with ≥2 years of continuous medical and pharmaceutical coverage and no previous diagnostic or pharmacotherapeutic indicators of cognitive impairment. Vaccinations were identified by name and Current Procedural Terminology codes. Participants were followed for up to 3 years postvaccination. Incident AD was defined using International Classification of Diseases codes and AD medication dispenses (anticholinesterase inhibitors, memantine). We emulated a target trial using sequential nested trials to align eligibility, treatment assignment, and time-zero with vaccination dates, preventing immortal time bias. Inverse probability weighting adjusted for measured confounding, emulated randomization, and mitigated selection bias. Effects were estimated as risk difference, number needed to treat (NNT), risk ratio; 95% CIs were obtained via bootstrapping. Secondary analyses examined potential effect modifiers such as sex.ResultsThe H-IIV group included 120,775 unique participants (185,183 person-trials; mean age 74.4 years, SD 5.5; 57.3% female), and the S-IIV group included 44,022 participants (53,918 person-trials; mean age 73.0, SD 6.1; 56.4% female). H-IIV was associated with significantly lower AD risk during months 1–25 postvaccination (minimum NNT = 185.2 at 25 months). After sex stratification, risk reduction persisted longer among women (months 1–13, minimum NNT = 416.7) than men (months 17–24, significant only in intention-to-treat analysis, minimum NNT = 232.6).DiscussionHigh-dose influenza vaccination is associated with reduced AD risk compared with standard-dose vaccination in adults ≥65 years, with a stronger effect among women. Significant study limitations included duration of follow-up (≤3 years) and lack of sociodemographic, lifestyle, biomarker, and mortality data. Further research is needed to clarify whether the observed difference reflects protection against influenza infection or non-infection–related mechanisms.Classification of EvidenceThis study provides Class II evidence that treatment with H-IIV vs S-IIV was associated with decreased incident dementia in individuals ≥65 years of age captured in this US health care claims database.

Background and ObjectivesThe mechanisms underlying tremor generation in Parkinson disease (PD) remain unclear. Previously, we demonstrated a connection between rest tremor amplitude and higher dopamine transporter (DAT) binding in the ipsilateral striatum among the Parkinson Progression Markers Initiative cohort. Here, we investigated the association of parkinsonian motor symptoms with striatal DAT binding in a sizable and clinically representative sample of patients with parkinsonian signs to validate the previously observed ipsilateral relationship in PD.MethodsThis observational cross-sectional study included right-handed patients referred for [123I]FP-CIT SPECT because of clinically uncertain parkinsonism or tremor at Turku University Hospital and the Helsinki and Uusimaa Hospital District, Finland. Each patient underwent a comprehensive clinical evaluation and follow-up (median 3.0 years [interquartile range (IQR) 2.5]). Associations between striatal tracer binding and symptoms were investigated using voxel-wise linear models, adjusting for age, sex, motor symptom severity, and medication. The primary outcome measure was the association between rest tremor amplitude and striatal DAT binding.ResultsAt the end of the follow-up period, of the 414 patients included (median age 68 years [IQR 14], 49.4% female), 148 were evaluated to have PD and 79 other forms of parkinsonism with striatal DAT deficit. In total, 187 patients had normal binding. Among the patients with PD, left and right rest tremor amplitudes were positively associated with ipsilateral striatal DAT binding (β = +0.12 [95% CI +0.05, +0.19] and +0.10 [+0.05, +0.15] specific binding ratio [SBR] per point; pFWE + Bonf. < 0.05, respectively). Left and right bradykinesia (β = −0.16 [−0.22, −0.09] and −0.18 [−0.25, −0.10] SBR per 5 points, pFWE + Bonf. < 0.05, respectively) and rigidity (β = −0.07 [−0.08, −0.04] and −0.08 [−0.11, −0.05] SBR per point, pFWE + Bonf. < 0.05, respectively) mainly showed a negative association with contralateral striatal DAT binding. No consistent associations were observed in non-PD groups.DiscussionThese findings confirm the positive association between rest tremor amplitude and ipsilateral striatal DAT binding in a clinical sample of PD patients. However, the non-PD groups were diagnostically heterogeneous, limiting conclusions about disease specificity.

Clinical phenotypes of neuropathies associated with contactin-associated protein-1 (CASPR1) or isolated CASPR1/contactin-1 (CNTN1)-complex-IgG are not well characterized, and we aimed to describe the same. Patient sera positive for CASPR1 or CASPR1/CNTN1-complex-IgG by cell-based assay (CBA) at Mayo Clinic Neuroimmunology Laboratory (January 1, 2010-May 31, 2024) was identified retrospectively and prospectively. Clinical and paraclinical data were collected. CASPR1/CNTN1-complex-IgG-positive sera were tested using tissue indirect immunofluorescence assay, murine teased nerve fibers, and ELISAs for CASPR1 and CNTN1 to elucidate antigenic targets. Patients were compared with CNTN1-IgG and NF155-IgG4 autoimmune nodopathy cohorts. Among 17 CASPR1 or isolated CASPR1/CNTN1-complex-IgG-seropositive patients identified, 14 had clinical data (CASPR1-IgG = 8 [50% males, median age 50 years], CASPR1/CNTN1-complex-IgG = 6 [67% males, median age 42 years]). Neuropathic pain was more common in CASPR1-IgG (88% vs 33%), while sensory ataxia was more frequent in CASPR1/CNTN1-complex-IgG cases (100% vs 75%). All showed primarily demyelinating electrophysiology (1 CASPR1/CNTN1-complex-IgG case presented as chronic inflammatory sensory polyradiculopathy). Intravenous immunoglobulin (IVIg) refractoriness occurred in 63% of CASPR1-IgG and 40% of CASPR1/CNTN1-complex-IgG. Rituximab was effective in 6 of 7 (86%) treated patients. One patient with CASPR1/CNTN1-complex-IgG who was refractory to multiple immunotherapies underwent allogenic hematopoietic stem cell transplant after which she was off immunotherapies and is in sustained remission for the past 10 years. CASPR1-IgG patients progressed faster to nadir than NF155-IgG4 (p = 0.003). CASPR1/CNTN1-complex-IgG patients had more frequent asymmetric onset (p = 0.009) and greater long-term disability than NF155-IgG4 (p = 0.035). Five of the 7 CASPR1-IgG patients had IgG4 antibodies, compared with 2 of the 5 CASPR1/CNTN1-complex-IgG patients. Four isolated CASPR1/CNTN1-complex-IgG sera tested positive by tissue immunofluorescence assay; 3 also bound paranodes on teased nerve fibers. CASPR1-IgG cases had higher titers compared with CASPR1/CNTN1-complex-IgG cases by CBA. Three of the 5 CASPR1/CNTN1-complex-IgG cases had CASPR1-IgG reactivity by ELISA, while the other 2 were negative by both CASPR1 and CNTN1 ELISA. CASPR1-IgG and CASPR1/CNTN1-complex-IgG neuropathies, though rare, usually have a rapidly progressive course. Both are frequently IVIg-refractory and respond to rituximab. Compared with NF155-IgG4 nodopathies, CASPR1-IgG exhibits faster progression, while some CASPR1/CNTN1-complex-IgG nodopathies can cause greater long-term disability.

Neonatal encephalopathy (NE)-including hypoxic-ischemic encephalopathy (HIE)-is associated with significant morbidity and mortality worldwide. While data registries provide hypothesis-generating data, aid in quality improvement, and track management/outcomes over time, we recently demonstrated that only 4 of 1,281 (0.3%) variables were collected by all 22 international NE/HIE registries: birth weight, gestational age, and 1- and 5-minute Apgar scores. In response, our team set out to develop a set of common inpatient data elements to enable future harmonization of NE/HIE registry data. Using a modified Delphi method, a panel of 14 international NE experts voted to separate the 1,281 variables from our previous study into "core elements," "supplemental elements," or those that "do not need to be collected." Based on the anonymous survey results, we created draft lists of core and supplemental common data elements (CDEs). These lists were further revised through group consensus meetings and external feedback from global registry leaders and attendants at 2 international conferences. The final data forms include 164 core elements and 225 supplemental elements stratified into 11 domains: demographics; pregnancy, labor, and delivery; delivery room; transport; acid-base; therapeutic hypothermia; neuromonitoring and seizures; neuroimaging; laboratory values (other than acid-base); hospital course; and discharge. The CDEs are the first of several important steps to further standardize research and reporting of NE/HIE investigations to perform more efficient and powerful clinical research in the field moving forward. Future studies need to establish a clinical and research definition of HIE and develop CDEs for collecting long-term, family-centered follow-up data postdischarge.

Previous studies have indicated an increased risk of cerebrovascular and coronary events shortly after cancer diagnosis. However, whether cancer affects mortality outcomes after stroke and myocardial infarction (MI) remains unclear. We aimed to investigate the relationship between cancer diagnosis and mortality after stroke and MI. Using linked nationwide databases from Taiwan, we conducted a population-based cohort study including 3 cohorts of patients with first-time ischemic stroke, hemorrhagic stroke, and MI between 2011 and 2019. The primary outcome was 90-day mortality, with follow-up beginning at the index stroke (for ischemic and hemorrhagic stroke cohorts) and MI (for the MI cohort) event date for all patients. Odds ratios (ORs) of 90-day mortality associated with all cancers combined and 15 cancer types were estimated through propensity score matching for potential confounding variables. Excess mortality rates (between patients with cancer and matched controls) were analyzed across time intervals after cancer diagnosis, stratified by age group, cancer stage, and cancer type. Overall, 440,664, 159,606, and 228,993 patients were included in ischemic stroke (mean age, 70.1 years; 40.7% female), hemorrhagic stroke (mean age, 65.4 years; 36.5% female), and MI (mean age, 67.8 years; 29.7% female) cohorts, respectively. Compared with matched controls, patients with cancer had higher risks of 90-day mortality in ischemic stroke (OR 2.71, 95% CI 2.63-2.79), hemorrhagic stroke (OR 2.20, 95% CI 2.11-2.29), and MI (OR 1.63, 95% CI 1.57-1.69). Across 3 cohorts, substantial variations existed among cancer types, with aggressive malignancies (e.g., pancreatic cancer) consistently presenting the highest risks. Excess mortality rates were highest during the first postdiagnosis year and declined progressively thereafter. This temporal pattern was consistent across age groups and cancer stages, with excess mortality rates highest among patients aged 18-59 years and those with stage 4 disease. Despite variability among cancer types, excess mortality typically peaked within 2 years. This population-based study showed that patients with cancer had higher risks of mortality after stroke and MI, with substantial variations by cancer type, although cause-specific mortality data were lacking. Excess mortality rates peaked shortly after diagnosis, particularly for early-onset cancer and advanced disease.

A 51-year-old man presented with a 3-month history of progressive lower extremity weakness and numbness, starting distally and progressing proximally, accompanied by mild gait difficulty but no bowel/bladder symptoms.Examination revealed mild hypoesthesia starting at T10 and grade 4/5 lower extremity weakness suggesting a spinal lesion.Thoracolumbosacral MRI revealed longitudinally extensive edema from T8 to the conus medullaris (CM) with prominent vascular flow voids on the spinal cord surface; and magnetic resonance angiography (MRA) revealed a dilated intradural vein from the S1 level to the CM, concerning for a sacral dural arteriovenous fistula ([DAVF]; Figure 1, A-C).Spinal angiography confirmed a sacral DAVF