Background: Depression is a common mental health comorbidity among individuals with seizure disorders. The emergence of depression results from the complex interplay of clinical, psychological and social factors. Objectives: To identify clusters of risk factors associated with depressive symptoms in adults with seizure disorders. This study uses exploratory factor analysis (EFA) to model a range of variables and investigate their interactions and influence on depressive symptoms. Design: Cross-sectional observational study. Methods: A retrospective examination of medical records identified 121 patients with seizures and moderate depressive symptoms. Demographic, clinical and psychosocial data were extracted and modelled using EFA. Factor structure was determined by adhering to standard fit criteria: CFI ⩾0.90, TFI ⩾0.90, RMSEA ⩽0.08 and latent factor loadings ⩾0.4. Results: The mean age of the cohort was 31.3 ± 10.0 years (range of 18–64), comprising 68 males (56.2%) and 53 married individuals (43.8%). Qataris constituted the largest nationality at 48 (39.7%), and the most prevalent diagnosis was right temporal lobe epilepsy (28.9%). Moderate depressive symptoms were the most common PHQ-9 classification (42.1%), with an average score of 14. EFA yielded a three-factor solution (χ 2 = 71.9, df = 52, RMSEA = 0.06, CFI = 0.96, TFI = 0.92) with the first latent factor incorporating age and social variables, the second encompassing medications and cognitive abilities, and a final factor encapsulating seizure-related items. Conclusion: Exploratory factor analysis elucidates the intricate relationships between variables that impact depressive symptoms in individuals with seizure disorders. It highlights how clusters of variables emerge, providing insight into how depressive symptoms develop in this population. These findings offer new potential avenues for the management and treatment of depression in people experiencing these debilitating events.
Background Natalizumab is a disease-modifying therapy for patients with relapsing-remitting multiple sclerosis (RRMS). In addition to its original intravenous (IV) formulation, a subcutaneous (SC) route of administration (RoA) was approved in 2021. Subsequently, the observational SISTER study was initiated in Germany and Austria to generate real-world data on the utilization, patient preferences, safety, and effectiveness of natalizumab in everyday clinical practice. Objectives The primary objective was to compare patients’ preference of RoA and satisfaction with SC vs. IV natalizumab at baseline and up to 12 months of treatment. Secondary objectives included drug utilization, effectiveness outcomes, safety, and treatment satisfaction with natalizumab. Design SISTER was a prospective, multicenter, observational study on RRMS patients who were allocated to 3 parallel treatment cohorts: Patients switching from IV to SC natalizumab (SC switcher) and patients starting natalizumab on either the SC or IV route (starter SC/IV). Methods The final study analyses were based on 310 patients (220 switchers, 44 SC starters, 46 IV starters) with an observation period of 10.8±3.1 months. Results Patient preference for the initial RoA at baseline was 95.1% among SC starters and 77.5% among IV starters (p=0.045). More IV starters than SC starters or SC switchers at baseline and Month 6 wished to change the initial RoA. Disease activity remained low in all cohorts, and the AE pattern was consistent with the known safety profile of natalizumab. The procedure duration was distinctly shorter on SC treatment than on IV treatment. Conclusions The final SISTER results suggest a patient preference for the SC vs. IV route and support the outcomes of the NOVA Part 2 trial, in which the preference of the SC route over IV was demonstrated in a cross-over design. The SC route allowed relevant time savings, and its good safety and tolerability argues for possible self-administration of SC natalizumab.
Background: Natalizumab (NTZ) is a highly effective disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS), originally administered intravenously (IV). A subcutaneous formulation (SC_NTZ) became available in Switzerland in 2021, offering potential advantages. Objective: To investigate satisfaction and convenience of use of SC_NTZ in MS patients. Design: Swiss, prospective, multicenter study. Methods: Consecutive RRMS patients treated with either ⩽6 (starters) or > 6 (long-term users) SC_NTZ injections completed the Treatment Satisfaction Questionnaire with Medication-II (TSQM-II, higher scores indicating greater satisfaction) and the Patient Satisfaction Questionnaire (PSQ) at baseline (Visit 1, V1). Starters were reassessed at the 9th SC_NTZ dose (Visit 2, V2). Non-parametric tests were applied to compare long-term users with starters at V1, and changes from V1 to V2 in starters. Results: One hundred six patients (73.6% female, median age 39.6 years, prior IV_NTZ 81.1%) were enrolled, including 79 long-term users and 27 starters. At V1, in the overall group the median (IQR) TSQM-II effectiveness, side effects, convenience and global satisfaction scores were 83 (67–100), 100 (92–100), 83 (72–89) and 83 (75–100), respectively. On the PSQ, the most commonly cited benefit was short administration time (80.2%). SC_NTZ treatment “never” affected work attendance in 54/87 (62.1%) employed patients. Seventy-nine percent participants reported spending ⩽1 h for SC_NTZ administration. Nonetheless, 76/86 (88.4%) of switchers from IV_NTZ found opportunities for discussions with healthcare professionals to be “similar”/”improved,” and 78 (90.7%) preferred SC_NTZ. Findings were consistent across subgroups and time points. Conclusion: This real-world, multicenter Swiss study supports SC_NTZ as a well-tolerated, highly accepted, and patient-preferred alternative to IV_NTZ.
Background: Disorders of consciousness (DoC) have limited effective therapies. Implantable vagus nerve stimulation (VNS) is established for epilepsy but remains underexplored for DoC with comorbid epilepsy. Objectives: To evaluate whether VNS is associated with improved consciousness recovery in DoC patients with epilepsy and to explore factors related to response. Design: Retrospective propensity score-matched cohort study. Methods: Ninety DoC patients with epilepsy received implantable VNS or conservative management. The primary outcome was clinically meaningful improvement at 1 year (Coma Recovery Scale-Revised (CRS-R) increase ⩾3 points). Propensity score matching (1:1) balanced baseline characteristics (23 per group). Longitudinal CRS-R trajectories were assessed using linear mixed-effects models with Type III ANOVA. Logistic regression within the VNS cohort explored factors associated with responder status; adverse events were extracted from operative and follow-up records. Results: The 1-year responder rate was higher with VNS than with conservative management (34.78% vs 4.35%; two-sided Fisher’s exact test, p = 0.022). Longitudinal analyses showed a significant group × time interaction (χ 2 = 43.535, p < 0.001) with greater CRS-R gains from 3 months onward in the VNS group. Within the VNS cohort, responder status was associated with baseline minimally conscious state (aOR = 9.750, 95% confidence interval (CI) 1.592–59.695; p = 0.014) and better seizure control (McHugh classification; aOR = 22.667, 95% CI 3.140–163.629; p = 0.002). Traumatic etiology was not associated with 12-month net CRS-R improvement after adjustment for baseline CRS-R (β = 0.893, 95% CI −1.583 to 3.369; p = 0.466). Five patients reported stimulation-related hoarseness/dysphonia, and two had surgical-site complications; no device removal occurred. Conclusion: Implantable VNS was associated with higher 1-year clinically meaningful improvement and greater longitudinal CRS-R gains than conservative management in DoC patients with epilepsy. Prospective controlled studies are warranted.
Background: The association between body mass index (BMI) and cognition, disability, and quality of life (QoL) is controversial in multiple sclerosis (MS). Objectives: We investigated the association between BMI and cognitive function, disability, and QoL in MS. Methods: A cross-sectional secondary analysis of the DISCOMS trial was performed to study the association between BMI and cognition, disability, and QoL. Cognitive function was measured by the symbol digit modalities test (SDMT) and disability was measured based on the expanded disability status scale (EDSS) and patient determined disability steps (PDDS). QoL markers were measured by the Quality of Life in Neurological Disorders. Descriptive and inferential statistics were used to analyze the association between BMI and cognition, disability, and QoL. Results: The study included 253 participants, mostly female (83.8%) and white (89.3%). Their mean BMI was 27.27 (SD = 5.6), and 62% were overweight, obese, or very obese. Controlling for age, gender, and disease-modifying therapy duration, BMI as a continuous or as a categorical variable was not associated with cognitive function as measured by the SDMT or disability as measured by the EDSS and/or the PDDS. EDSS as a dichotomous variable was associated with BMI; 1-unit increase in BMI was associated with a 5.7% increase in the odds of having an EDSS score greater than 4 (β = 0.055, p = 0.045). Higher continuous BMI was associated with physical domains dysfunction; worse fatigue ( p = 0.009), and worse lower extremities function ( p = 0.008), while the very obese group had a higher risk of physical and emotional domain dysfunction than the normal BMI group. Conclusion: The lack of observed associations between BMI and cognitive function or disability in this older MS cohort suggests that the relationship between BMI and clinical outcomes may vary across domains. Nevertheless, the associations identified between BMI and QoL measures emphasize the potential importance of weight management in supporting overall health and well-being among individuals with MS. Trial registration of the primary DISCOMS study: ClinicalTrials.gov NCT03073603.
Background: Siponimod is approved in Europe for active secondary progressive multiple sclerosis (SPMS), but real-world data on its treatment patterns and outcomes in people with SPMS (pwSPMS) is limited. Objective: To assess the demographic and clinical characteristics, effectiveness, and safety of siponimod in pwSPMS in a real-world setting. Design: Non-interventional/observational, retrospective, multicenter study (28 centers). Methods: Patients (⩾18 years) with active SPMS treated with siponimod in routine care were included. Retrospective clinical, radiological, and laboratory data were collected for patients up to 24 months before and 12 months after siponimod treatment. Results: In total, 210 participants were included (mean age: 52.5 ± 8.6 years; females: 71.0%). At treatment initiation, the mean Expanded Disability Status Scale (EDSS) score was 5.7 ± 1.2. The mean time since multiple sclerosis diagnosis and the median time since active SPMS diagnosis were 16.7 ± 8.9 years and 1.3 (0.3; 4.4) years, respectively. Common comorbidities included psychiatric disorders and dyslipidemia (20.6%, each). Regarding working status, 55.9% with available information showed incapacity for work. Prior to siponimod, 44.3% received highly effective therapies: fingolimod (20.5%), rituximab (9.5%), ocrelizumab (5.2%), natalizumab (4.8%), and alemtuzumab (2.4%). After 1 year, 82.8% of the patients remained stable in terms of disability progression, 94.3% were free of relapses, and 85.7% did not present radiological disease activity; 46.2% experienced adverse events, 8.6% experienced serious adverse events, and 26 (12.4%) patients discontinued permanently. Conclusion: In the study cohort, pwSPMS had high disability scores and comorbidities; more than half were unable to work, and over 40% had previously received high-efficacy therapies. After 1 year of siponimod treatment, most pwSPMS showed no signs of disease activity, with stabilized EDSS scores and relapses and new T2 or gadolinium-T1 lesions, as well as a favorable safety profile.
Background: Delirium affects 10–30% of acute stroke patients, is associated with poor outcomes and places a substantial burden on healthcare staff. Evidence-based prevention and treatment strategies are limited, resulting in heterogeneous and poorly standardised delirium management in acute stroke care. Objectives: We aimed to describe real-world delirium management in German and Austrian stroke units (SUs) and to delineate the extent of practice variation in prevention and treatment. Design: We conducted a cross-sectional, web-based survey of stroke neurologists working at SUs in Austria and Germany. Methods: The 30-item questionnaire assessed professional background, delirium prevention and pharmacological treatment approaches. Descriptive statistics and exploratory subgroup analyses were performed. Results: Seventy responses from 63 SUs were analysed (median physician SU experience, 14.5 years). Delirium was estimated to affect 20% of patients and was perceived as highly burdensome for both physicians and nurses (median score, 9/10 each). Delirium prevention measures were established in 42 (67%) SUs but routinely applied to all patients in only 12 (19%), mainly due to staffing shortages (nurses, 48%; physicians, 25%). Pharmacological delirium treatment was reported by all respondents. Benzodiazepines were preferred for alcohol withdrawal delirium (60%) and antipsychotics for hyperactive or mixed delirium (59%). α2-Agonists were the most common escalation therapy across these subtypes (46%–67%). Conclusion: Delirium management in German and Austrian SUs is highly heterogeneous, limited by staffing constraints and strongly relies on non-evidence-based pharmacological strategies. These findings highlight critical gaps in care and call for enhanced staffing and stroke-specific trials to inform evidence-based delirium management.
Background In recent years, marine-derived drugs for Alzheimer’s disease (AD) have attracted growing attention, but their comparative cognitive efficacy and safety remain uncertain because of inconsistent findings across studies. Objectives To compare the efficacy and safety of marine-derived interventions for Alzheimer’s disease. Design Systematic review and Bayesian network meta-analysis of randomized controlled trials conducted in accordance with PRISMA 2020. Data sources and methods We systematically searched PubMed and the Cochrane Library for randomized controlled trials (RCT) of marine-derived drugs in patients with AD. Continuous outcomes were synthesized as mean differences (MD) in change-from-baseline, and dichotomous outcomes were synthesized as odds ratios (OR), each with 95% credible intervals (CI). Results A total of 16 eligible RCTs involving 4,158 patients were included. For the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), GV-971 (vs placebo; MD -1.85, 95% CI -2.89 to -0.82) and tramiprosate (vs placebo; MD -0.83, 95% CI -1.63 to -0.02) significantly improved cognitive function. For the Mini-Mental State Examination (MMSE), rifampicin (vs placebo; MD 1.90, 95% CI 0.25 to 3.56) was associated with greater improvement in MMSE scores, whereas tramiprosate (vs placebo; MD -2.40, 95% CI -4.67 to -0.09) was associated with poorer cognitive performance. No statistically significant differences among drugs were observed for the Clinical Dementia Rating-Sum of Boxes (CDR-SB) or for the incidence of adverse events. Overall, treatment effects were outcome-dependent, with significant benefits observed mainly in ADAS-Cog and MMSE, whereas no intervention demonstrated consistent superiority across all cognitive outcomes. Conclusion Marine-derived drugs showed generally acceptable safety and potential cognitive benefits in selected outcomes. GV-971 and tramiprosate improved ADAS-Cog scores, while rifampicin therapy showed a possible MMSE benefit. However, no intervention was consistently superior across cognitive outcomes, and the antibiotic finding was based on a single small trial. Current evidence is therefore insufficient to identify the optimal marine-derived therapy for AD, highlighting the need for larger, adequately powered RCTs.
Background Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis presents relapse risk and potential functional impairment, with no established maintenance treatment guidelines. Objectives The study aimed to uncover prognostic signatures, and identify predictors of relapse and poor outcome using real-world evidence. Design This multicenter retrospective study included anti-LGI1 encephalitis patients from five tertiary hospitals in Eastern China between January 2015 and January 2024, with ≥ 24-month follow-up. Methods Relapse was defined as the presence of new or worsening clinical features after at least 3 months of stability or improvement. Poor outcome was defined as a modified Rankin Scale score > 2 at last follow-up. Results A total of 104 patients were included (median age 56.5 years, 60.6% male). Following the acute phase, the majority (66.3%) received prolonged corticosteroid treatment (≥6 months) without steroid-sparing maintenance immunotherapy (SSMI), whereas 16.3% received SSMI. Twelve patients (11.5%) experienced relapse. Hyponatremia at diagnosis was more common in relapsing patients ( p = 0.017), and was significantly associated with an increased risk of relapse in Cox regression (hazard ratio = 4.67, 95% confidence interval [CI] = 1.41–15.53, p = 0.012). Poor outcome was observed in 17 patients (16.3%), with male sex (odds ratio [OR] = 5.12, 95% CI = 1.27–34.48, p = 0.041) and hyponatremia (OR = 4.69, 95% CI = 1.54–15.47, p = 0.008) as potential risk factors. Conclusion This study suggests that hyponatremia is associated with an increased risk of relapse and poor outcome in anti-LGI1 encephalitis. These findings may facilitate individualized risk stratification, but further validation in larger prospective cohorts is needed.
Background Vagus nerve stimulation (VNS) has emerged as a promising adjunctive approach for stroke rehabilitation. However, current clinical applications are predominantly limited to invasive VNS implantation or unilateral transcutaneous auricular nerve stimulation (taNS), often characterized by small sample sizes and a primary focus on upper limb motor recovery. Although emerging evidence suggests that bilateral taNS (BtaNS) may confer superior neuromodulatory effects compared with conventional left-sided unilateral taNS (LtaNS), its efficacy and safety profile for comprehensive post-stroke limb motor rehabilitation remain largely unexplored. Objectives To evaluate the efficacy and safety of BtaNS combined with routine rehabilitation in promoting motor recovery in post-stroke patients with hemiplegia. Design A prospective, double-blinded, three-arm randomized controlled trial. Methods Patients with subacute or chronic stroke were recruited from the Department of Rehabilitation Medicine at the First Affiliated Hospital of Nanchang University between January 2025 and December 2025. Participants were randomly assigned to one of three groups: BtaNS, LtaNS, or a control group. All patients received routine rehabilitation therapy targeting both upper and lower limb motor function. Additionally, patients in the taNS groups received either LtaNS or BtaNS (stimulation parameters: 20 Hz frequency, 300 µs pulse width, intensity individually adjusted within a range of 0.5–1.0 mA) for 30 minutes twice daily, six days per week, over a four-week period. The primary outcome measures included the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Fugl-Meyer Assessment for Lower Extremities (FMA-LE) and the Wolf Motor Function Test (WMFT). Secondary outcomes encompassed the Berg Balance Scale (BBS), the Modified Barthel Index (MBI), and low-frequency oscillations measured via functional near-infrared spectroscopy (fNIRS). Adverse events were monitored to assess safety throughout the treatment period. Results A total of 111 patients were enrolled in this study, of whom 5 withdrew and 4 were lost to follow-up, resulting in 102 participants completing the trial (34 per group). Compared with the control group, both the LtaNS and BtaNS groups exhibited significantly greater improvements in the FMA-UE, FMA-LE, and WMFT scores at all post-intervention assessment time points. Moreover, the BtaNS group demonstrated superior motor recovery relative to the LtaNS group. In addition, BtaNS was associated with significantly greater improvements in BBS and MBI scores at 4 weeks post-intervention and at follow-up compared with both the LtaNS and control groups. Subgroup analyses indicated that patients with a shorter time since stroke onset and those diagnosed with hemorrhagic stroke exhibited more pronounced improvements. No serious adverse events occurred; only mild, transient skin irritation was observed. Conclusion BtaNS is a safe and well-tolerated intervention that demonstrates superior efficacy compared to LtaNS in enhancing motor recovery, balance, and independence in activities of daily living following stroke. The underlying mechanism may be associated with increased bilateral cortical engagement. Registration This study was registered at Chinese Clinical Trial Registry: ChiCTR2400093825.
A 67-year-old male with Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-Like Episodes (MELAS) who developed life-threatening Stevens-Johnson Syndrome (SJS) more than one month after initiating lamotrigine (LTG) for epilepsy management. Despite prompt LTG discontinuation and aggressive immunomodulatory therapy, the patient succumbed to severe infection and multiple organ failure. LTG-induced SJS is associated with multiple risk factors. The immune-activating microenvironment resulting from mitochondrial dysfunction may potentiate the risk of LTG-induced SJS. Lamotrigine should be used cautiously for epilepsy in high-risk patients, particularly those with mitochondrial encephalomyopathy (ME), and comprehensive evaluation is required to minimize severe hypersensitivity reactions.
Introduction:In the contemporary endovascular thrombectomy (EVT) era, treatment decisions are often made without routine perfusion imaging. However, perfusion remains central to intravenous thrombolysis (IVT) beyond 4.5 hours. Evidence across extended and very late windows remains uncertain. Objectives:To evaluate the efficacy and safety of perfusion-guided IVT beyond 4.5 hours after acute ischemic stroke and to assess the robustness of evidence across the 4.5-9 hour and 9-24 hour windows. Design:Time-stratified systematic review and meta-analysis of phase III randomized controlled trials. Data Sources and Methods:We systematically searched PubMed, Embase, and the Cochrane Library from inception to February 8, 2026. Phase III randomized controlled trials enrolling perfusion-selected AIS patients treated 4.5-24 hours from last known well were included; trials permitting stratification into 4.5-9 and 9-24 hours were prioritized. Outcomes included 90 days excellent outcome (mRS 0-1), favorable (mRS 0-2), good (mRS 0-3), mortality, and symptomatic intracerebral hemorrhage (sICH). Random-effects meta-analysis and trial sequential analysis (TSA) were performed. Results:Five randomized controlled trials (n=1,798) were included. IVT increased excellent outcome in both the 4.5-9 hour window (n=866; RR 1.30, 95% CI 1.08-1.56; I2=0%; absolute risk difference (ARD)=9.1%; NNT=11) and the 9-24 hour window (n=563; RR 1.41, 95% CI 1.10-1.79; I2=0%; ARD=11.1%; NNT=9). Across 4.5-24 hours, IVT improved favorable (RR 1.18, 95% CI 1.07-1.29; I2=0%) and good outcomes (RR 1.11, 95% CI 1.03-1.21; I2=0%), with no significant effect on mortality (RR 1.14, 95% CI 0.85-1.52; I2=0%). IVT increased sICH risk overall (RR 5.63, 95% CI 2.17-14.57; I2=0%; ARD=approximately 3.0%; NNH=33). TSA suggested that the cumulative evidence has not yet reached the required information size for firm conclusiveness. Conclusion:In the contemporary EVT era, perfusion-guided IVT may remain clinically relevant for selected patients treated beyond 4.5 hours, particularly those not eligible for thrombectomy or without immediate EVT access. Current phase III randomized evidence suggests improved functional outcomes but increased symptomatic intracerebral hemorrhage. However, TSA indicates that the evidence remains underpowered for definitive conclusions. Evidence for the 9-24 hour window is particularly limited and derived from China-based trials; therefore, these findings should be interpreted as hypothesis-supporting rather than conclusive.
Bilateral medial medullary infarction is a rare and clinically severe form of brainstem stroke. A patient presented with acute neurological deficits, and diffusion-weighted imaging revealed a distinctive pattern resembling a “fidget spinner.” CT angiography demonstrated marked asymmetry of the vertebral arteries, with hypoplasia of the right vertebral artery. A review of 97 previously reported cases confirmed the exceptional rarity of cardioembolic etiology in this condition. In this context, the present case represents an uncommon coexistence of a rare anatomical pattern and a rare vascular mechanism. These findings suggest that infarct morphology on diffusion-weighted imaging may reflect underlying vascular anatomy and the level of arterial involvement in bilateral medial medullary infarction.
Background Idiopathic normal pressure hydrocephalus (iNPH) is a reversible disorder characterized by cognitive, gait, and urinary dysfunction. While the cerebrospinal fluid (CSF) tap test can predict surgical response, screening-based cognitive assessment protocols remain undefined, limiting prognostic accuracy. Objectives To delineate temporal patterns of recovery for individual cognitive subdomains after the CSF tap test in patients with iNPH, and to establish high-sensitivity, time-stratified cognitive subdomains to improve preoperative prognostication and surgical decision-making. Design Single-centre retrospective observational study with rigorous inclusion/exclusion criteria. All patients underwent a full series of multidimensional cognitive assessments before and at 24, 48, and 72 hours after the CSF tap test. Cognitive functions were stratified into six standardized subdomains using validated weighted composite scores. All enrolled patients underwent ventriculoperitoneal (VP) shunt surgery and completed 3-month postoperative cognitive follow-up. Longitudinal changes were analysed using repeated-measures ANOVA, linear mixed models, and receiver operating characteristic curve analysis. Methods In this study, 53 patients with iNPH were included. Cognitive assessments were performed consistently across all time points using the Mini-Mental State Examination (MMSE), Animal Fluency Test (AFT), Trail Making Test (TMT and TMT-A), and Clock Drawing Test (CDT). Quantitative composite scores for each cognitive subdomain were computed and analysed longitudinally. Results Stratified analyses showed that language ability at 24 hours (P < 0.01), orientation ability at 48 hours (P < 0.01), and recall combined with attention and calculation at 72 hours (recall: P < 0.001; attention and calculation: P < 0.01) were the most sensitive and predictive for assessing the effects of the CSF tap test across time points. All enrolled patients underwent VP shunt surgery after multi-index assessment. These improvements correlated with 3-month postoperative cognitive benefits. Conclusions A time-stratified, subdomain-specific cognitive assessment protocol enhances tap test sensitivity, reduces misclassification, and supports personalized surgical decision-making for patients with iNPH.
Background: This study compares age at death in patients with myasthenia gravis (MG) and multiple sclerosis (MS) with the general U.S. population and examines age at death patterns during a period preceding modern high-efficacy therapies. Objective: To compare age at death among individuals with MG and MS with the general population and assess differences in age at death between MG and MS. Design: Retrospective population-based study using death certificate data from four U.S. states (Florida, Wisconsin, Texas, and New York) for 2000, 2005, 2010, and 2015. Methods: Individuals with MG or MS listed on death certificates were identified. Age at death was compared between MG and MS among four states and contemporaneously with U.S. population via Social Security life tables, adjusting for sex and geography. Because data were provided in different formats across states (individual-level, aggregated, and categorical), analyses were tailored to each dataset while addressing the same underlying question. During the study period, high-efficacy targeted therapies for both conditions were not yet available, allowing comparison of mortality patterns under standard-of-care treatment. Results: Age at death of MS patients was significantly lower than the general population (−12.4 years, p < 0.001). In contrast, MG patients showed a higher mean age at time of death compared with the general population (+4.8 years, p < 0.0001) and died significantly later than MS patients (+15.5 years, p < 0.001, adjusted for sex and year). These patterns were consistent across datasets. Despite a higher reported burden of age-related comorbidities in MG populations, MG patients demonstrated higher mean age at death than both MS patients and the general population. Conclusion: MG was associated with significantly older age at death compared with both MS and the general population under historical standard-of-care conditions. These findings suggest that survival patterns in MG differ from those in MS and raise questions about the factors driving this difference. Further studies are needed to clarify the roles of disease biology, comorbidity, age at diagnosis, and healthcare utilization in shaping long-term outcomes.
Background: Previous studies demonstrated that cannabinoids may reduce spasticity in patients with spinal cord injury (SCI); however, the effect of naturally extracted THC:CBD oil, the most commonly used naturally extracted cannabinoids, has yet to be elucidated. Objectives: To assess the effect of a 1:1 THC:CBD oil on reducing spasticity in chronic SCI patients Design: A single-center, placebo-controlled, double-blind crossover clinical trial. Methods: Sixteen chronic SCI patients with intractable spasticity were randomly assigned to either the intervention (1:1 THC:CBD oil) or control (placebo) phase for 1 month, then crossed over. The primary outcome (combined Ashworth Scale [AS] of all involved muscle groups) and the secondary outcomes, including patient-rated visual analog scale (VAS) of spasticity, were assessed before and after both phases and analyzed using a multilevel mixed-effects model. Results: All participants completed the study. The average (SD) dose of THC:CBD oil was 11.6 (1.3) mg. No significant difference in the total AS score for all involved muscle groups was found between the pre- and post-treatment phases, or between the experimental and control phases (all p > 0.05). A significant reduction was observed in the patient rating VAS (effect size = −13.9 [95% CI: −25.5 to −2.3; p = 0.010). Conclusion: In people with chronic SCI who had intractable spasticity, there was no statistically significant effect of 1:1 THC:CBD oil on spasticity-related outcomes, except for patient rating VAS reduction. Further studies are needed to evaluate the efficacy of higher doses of THC (>12 mg/day) and to use patient-reported spasticity scores as the primary outcome measure. Trial registration: The study was registered with the Thai Clinical Trials Registry (TCTR identification number: TCTR20220329001).
Background Sex-based differences in treatment response to neuroprotective strategies during endovascular treatment (EVT) for acute ischemic stroke remain poorly understood. Objectives This study aimed to evaluate sex-specific effects of methylprednisolone on outcomes after EVT for acute ischemic stroke due to large vessel occlusion. Design Secondary analysis of the MARVEL (Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke) randomized controlled trial. Methods We compared outcomes following methylprednisolone versus placebo, stratified by sex. We also compared outcomes between women and men receiving methylprednisolone. The primary outcome was defined as the 90-day modified Rankin Scale score (mRS) ordinal shift. Secondary outcomes included mRS score of 0-4, 0-3, 0-2, 0-1 at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 hours. Results This study included 1680 patients (49.9% methylprednisolone, 56.7% men). Stratified by sex, among men, the methylprednisolone group was more likely to have a primary outcome compared with placebo [adjusted OR (aOR) 1.26 (1.00-1.59), P = 0.047] and reduce mortality ( P < 0.01) and sICH ( P = 0.031); among women, the primary outcome was similar between two treatment arms ( P = 0.66), with similar findings for the safety outcomes. Additionally, stratified by different treatment arms, no significant difference was found in the primary outcome between men and women treated with methylprednisolone ( P = 0.31) and placebo ( P = 0.68). Conclusions In this exploratory analysis, methylprednisolone appeared to be associated with better clinical outcomes in men compared with placebo. Nevertheless, the interaction between treatment and sex was not statistically significant. Furthermore, among patients receiving methylprednisolone, clinical outcomes did not differ significantly between men and women. Registration ChiCTR.org.cn Identifier: ChiCTR2100051729.
Background: Cerebral small vessel disease (CSVD) is associated with poor outcomes after endovascular thrombectomy (EVT), but the underlying mechanism remains unclear. Impaired dynamic cerebral autoregulation (dCA), a fundamental function of cerebral microvasculature, has been proposed as a potential mediator but has not been systematically investigated. Objectives: To determine whether CSVD burden influences functional outcomes through alterations in dCA. Design: Observational-cohort-study. Methods: We included 107 patients with anterior circulation large-vessel occlusion and successful EVT (expanded Thrombolysis in Cerebral Infarction ⩾2b). CSVD burden was assessed using standardised neuroimaging markers and dichotomised as none-to-mild (score 0–1) versus moderate-to-severe (score 2–3). dCA was assessed at two time points: early phase (T1, around 24 h post-EVT) and early subacute phase (T2, around 4–5 days post-EVT). Mediation analysis was performed to assess whether dCA changes mediated the association between CSVD burden and functional independence (modified Rankin Scale (mRS) score 0–2) at 90 days. Results: Patients with moderate-to-severe CSVD ( n = 38) demonstrated distinct dCA recovery patterns compared with those with none-to-mild CSVD ( n = 69). While patients with none-to-mild CSVD exhibited improved very low frequency (VLF, 0.02–0.07 Hz) phase differences from T1 to T2 (+7.67° (−9.73, 35.53)), those with moderate-to-severe CSVD exhibited deterioration (−7.17° (−25.03, −0.74), p = 0.004), which remained significant after multivariable adjustment (β = −20.06, 95% confidence interval (CI): −37.78 to −0.90, p = 0.040). Functional independence was achieved in 73.9% of patients with none-to-mild CSVD versus 52.6% in those with moderate-to-severe CSVD (adjusted OR 0.25, 95% CI 0.09–0.74, p = 0.012). Mediation analysis revealed that VLF phase changes in the affected side mediated 24.48% of the association between CSVD burden and functional outcome (average causal mediation effect: −7%, p < 0.001; total effect: −29%, p = 0.020). Conclusion: Higher CSVD burden was associated with worse functional outcomes after EVT, partially explained by impaired dCA. Patients with moderate-to-severe CSVD exhibited deteriorating dCA, whereas those with none-to-mild CSVD showed progressive improvement. Larger powerful studies are warranted to validate these findings and elucidate underlying mechanisms. Trial registration: ClinicalTrials.gov, NCT06361017.
