Multiple Sclerosis Journal最新文献

Background: Ecological comparisons suggest that neuromyelitis optic spectrum disorder (NMOSD) is more common in African Caribbean and Asian compared to White people.

Objective: The aim is to rigorously assess susceptibility across multiple racial and ethnic groups from the same cohort.

Methods: We conducted a retrospective cohort study of > 39 million person-years of observation from members of Kaiser Permanente Southern California. The electronic health records of individuals with at least one International Classification of Diseases (ICD) code for NMOSD were reviewed to identify persons who met 2015 diagnostic criteria for NMOSD.

Results: We identified 153 NMOSD cases, 105 incident and 105 prevalent. The age- and sex-standardized incidence (2013-2022) and prevalence (2019) according to the 2020 US Census per 100,000 person-years was significantly higher in Black persons (incidence = 0.90, 95% confidence interval (CI) = 0.59-1.21; prevalence = 8.44, 95% CI = 5.52-11.36) compared to all other racial and ethnic groups. The incidence was similar among Asian/Pacific Islander (0.32, 95% CI = 0.16-0.48) compared to Hispanic people (0.19, 95% CI = 0.13-0.25) and lowest in White people (incidence = 0.13, 95% CI = 0.07-0.19).

Discussion: NMOSD susceptibility is highest in Black people, followed by Asian/Pacific Islands, then Hispanic people, and lowest in White people. Studies in diverse groups of minoritized people are needed to determine whether this increased susceptibility is due to shared genetic ancestry, the ill-health consequences of racism, or both.

Background: Siponimod, a sphingosine-1-phosphate (S1P) receptor modulator, reduces relapses and delays disability progression in patients with active progressive multiple sclerosis (MS).

Objective: EXCHANGE assessed the safety/tolerability of siponimod in patients with advancing relapsing MS (RMS) converting from other disease-modifying therapies (DMTs).

Methods: This 6-month, open-label, multicenter, single-arm, phase 3b study (NCT03623243) enrolled 185 patients with advancing RMS previously treated with other DMTs for ⩾3 months. Patients were converted to siponimod via a 6-day dose-titration regimen, or converted immediately, depending on prior DMT use.

Results: Treatment-related adverse events (AEs) were reported by 31.9% (59/185) of patients, with headache (8.1%, n = 15), dizziness (3.8%, n = 7), and nausea (3.2%, n = 6) most commonly reported. Overall, an increase in heart rate (HR) 6 hours following the first dose of siponimod was observed (+2.47 bpm [0.66; 4.29]; p = 0.008). Patients switching from fingolimod without dose titration experienced no change in HR. Serious AEs were reported by 4.9% (9/185) of patients, and 8.6% (16/185) of patients discontinued the study treatment due to AEs.

Conclusion: Conversion to siponimod from other DMTs was found to be generally well tolerated. Patients switching from other S1P-receptor modulators may be able to immediately transition to the siponimod maintenance dose without effects on HR.

Clinical trial registration: ClinicalTrials.gov: NCT03623243 (https://clinicaltrials.gov/study/NCT03623243).

Background: Seizures are associated with reduced cognition in the general population and worse outcomes in people with multiple sclerosis (pwMS). Yet, it remains unclear whether seizures are linked to cognitive dysfunction in pwMS.

Objectives: To evaluate the connection between seizure history and poorer cognition in pwMS.

Methods: A consecutive sample of 803 pwMS reported any prior seizures. Covariates included age, sex, Wechsler Test of Adult Reading scores, educational years, Expanded Disability Status Scale (EDSS) scores, disease duration, disease subtype, high-efficacy disease-modifying therapy use, Hospital Anxiety and Depression Scale scores for anxiety and depression and Modified Fatigue Impact Scale scores. Linear regression analyses, controlling for covariates, were undertaken to predict Minimal Assessment of Cognitive Function in MS scores from seizure history.

Results: Mean age was 44.01 years (SD = 11.58), 76.84% were female, and median EDSS was 2.0 (interquartile range (IQR) = 1.5-3.5). Accounting for covariates, people with seizures (n = 43, 5.35%) performed worse than those without (n = 760) on Judgement of Line Orientation (β = -0.09, p < 0.01), California Verbal Learning Test-II learning (β = -0.08, p < 0.01) and memory (β = -0.10, p < 0.01), Brief Visuospatial Memory Test-Revised learning (β = -0.08, p = 0.01) and memory (β = -0.07, p = 0.05), Symbol Digit Modalities Test (β = -0.06, p = 0.04), Paced Auditory Serial Addition Test (β = -0.10, p < 0.01) and Delis-Kaplan Executive Function System (β = -0.07, p = 0.02).

Conclusions: A seizure history independently predicts reduced cognition in pwMS.

Background: Smoking and vascular risk factors (VRFs) are reported to have adverse effects in multiple sclerosis but data are limited in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). This study aimed to measure their impact on disability.

Methods: Smoking status was defined as never, past or current smokers and VRF comprised of ⩾1: hypertension, dyslipidemia, high body mass index or diabetes. Logistic regression models were fitted to predict their influence on recovery from onset attack and first optic neuritis (ON) attack.

Results: A total of 442 patients were included. Current MOGAD smokers had a higher risk of disability from onset attack and first ON attack than never smokers (odds ratio (OR) 2.9, 95% confidence interval (CI) 1.3-6.9; OR 3.3, 95% CI 1.4-7.8). VRF in MOGAD was not predictive of disability. Current AQP4-NMOSD smokers and VRFs had a higher risk of residual disability from onset attacks (OR 7.5, 95% CI 2.1-27.7; OR 1.9, 95% CI 1.0-3.4). VRF was associated with higher risk of visual disability (OR 2.6, 95% CI 1.08-6.46) while smoking status was not.

Conclusions: Current smoking status detrimentally influenced onset attack recovery in AQP4-NMOSD and MOGAD patients, including visual recovery in MOGAD. Non-smoking VRFs influenced clinical and visual outcomes in AQP4-NMOSD.

Background: Cognitive decline in multiple sclerosis (MS) is commonly assessed using the Symbol Digit Modalities Test (SDMT). However, the written (wSDMT), oral (oSDMT), and electronic (eSDMT) versions may display differing psychometric properties, despite often being used interchangeably.

Objective: The objective of the study is to compare the wSDMT, oSDMT, and eSDMT, including inter-test reliability, and to assess demographic and motor disability influences on test performance.

Methods: In this within-subjects study, 85 participants with MS completed all three SDMT versions. Statistical analyses included assessment of intraclass correlation coefficients (ICCs) and sequential multiple regression modeling.

Results: The three SDMT versions demonstrated good inter-test reliability (ICC = 0.77) and similar mean scores (range: 53.5-56.2). Scores on all three test versions declined with age (p < 0.05), but the decline was significantly steeper in the eSDMT. Education correlated with eSDMT but not wSDMT or oSDMT scores. Paced Auditory Serial Addition Task (PASAT) scores predicted performance across all versions, while 9HPT times predicted only wSDMT and eSDMT scores (p < 0.01).

Conclusion: The wSDMT and eSDMT show signs of motor disability influence, while the eSDMT displays the greatest sensitivity to the influences of age and education. This differential construct validity necessitates SDMT version-specific normative data and motor-adjustments for accurate cognitive assessment in MS.