Multiple Sclerosis Journal最新文献

Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.

Objective: Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS).

Methods: In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCC_brain) was obtained. Impact of sex and menopause on UCC_brain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated.

Results: UCC_brain was smaller in pwMS (n = 118, 51.4 ± 5.3 mm²) than controls (n = 118, 54.2 ± 4.4 mm², p < 0.001) and inversely correlated with older age in pwMS (r = -0.24, p = 0.010) but not in controls (r = -0.025, p = 0.786). In 173 pwMS (413 brain MRIs), UCC_brain was smaller in men (49.5 ± 5.9 mm²) than women (51.6 ± 5.5 mm², p = 0.001), postmenopausal women (49.4 ± 5.6 mm²) than premenopausal women (52.9 ± 4.1 mm², p < 0.001), and progressive (47.5 ± 5.6 mm²) than relapsing MS (52.1 ± 5.2 mm², p < 0.001). UCC_brain also correlated with disease duration (r = -0.39, p < 0.001), 9-hole peg test (r = -0.26, p = 0.005), and severe ambulatory disability (Expanded Disability Status Scale ⩾6) (r = -0.27, p < 0.001).

Conclusion: UCC_brain, a biomarker of progressive MS, is inversely associated with age, disease duration, male sex, and menopause, highlighting the potential impact of sex and hormones on neurodegeneration in MS.

Background: Existing metrics of patient-reported cognitive difficulties in multiple sclerosis (MS) are lengthy, lack psychometric rigor, and/or fail to query prevalent expressive language deficits.

Objective: Develop a brief psychometrically robust metric of patient-reported cognitive deficits that includes language items; the Multiple Sclerosis Cognitive Scale (MSCS).

Method: Exploratory factor analysis (EFA) was conducted on 20 Perceived Deficits Questionnaire (PDQ) items plus five newly developed language questions in a large MS sample and matched respondents without neurologic disease. Independent confirmatory principal components analysis (PCA) assessed EFA factor structure. Reliability of the new scale and subscales, and relationships with objective cognitive impairment and cognitive change, were assessed.

Results: EFA in patients (n = 502) and controls (n = 350), item analyses, and confirmatory PCA in an independent sample (n = 361 patients; 150 controls) supported construction of an eight-item scale with four two-item subscales: Executive/Speed, Working Memory, Expressive Language, and Episodic Memory. Internal consistency and test-retest reliability were excellent for the total MSCS (α = 0.93, ICC = 0.95) and good for each subscale (α's:0.83-0.87; ICCs: 0.86-0.92). MSCS showed medium-size links to cross-sectional objective cognitive impairment (η² = .06) and cognitive change over time (η² = .07); the traditional PDQ did not (η²s = 0.01 and 0.02).

Conclusion: The brief MSCS is a psychometrically robust, reliable, and valid metric of patient-reported cognitive deficits in MS that holds promise for improving assessment of MS cognitive dysfunction.

Background: Retrospective studies did not show strong evidence of higher risk of adverse neonatal or pregnancy outcomes in women with multiple sclerosis (MS) compared to general population, but there are contradictory data on prematurity, cesarean section, and small birthweight for gestational age (SGA).

Methods: We compared pregnancy and birth outcomes in MS women included in RESPONSE, a French prospective cohort, with a recent survey (Enquête Nationale Périnatale (ENP)) describing leading indicators in perinatal epidemiology in France.

Results: On 7 April 2023, 476 pregnancies (461 MS women, 482 expected newborns) from RESPONSE were available. The ENP study reported 12,723 women and 12,939 expected newborns in March 2021. MS patients were older (mean age 32.6 ± 4.4 vs. 30.9 ± 5.3 years, p < 0.001), with similar rate of cesarean (23.8% vs. 21.4%, p = 0.115) and use of locoregional analgesia (86.6% vs. 85.1%, p = 0.51). Preterm birth was less frequent (4.0% vs. 7.0%, p = 0.001). Birthweight of children from MS mothers was similar to general population (3240 ± 477.2 vs. 3264.5 ± 552.9 g, p = 0.22), with slightly more children with SGA (13.4% vs. 9.8%, p = 0.04).

Conclusion: This prospective and contemporary comparison of pregnancy in MS women and the French population provides reassuring results. In the future, we need to assess the impact of disease-modifying treatment exposure during conception.

Background: In Europe, ofatumumab is approved for breastfeeding, but data on its transfer into breast milk and clinical experience are lacking.

Objective: To analyze (1) health, development, and adverse events after live vaccination of ofatumumab-exposed breastfed infants and (2) detectability of ofatumumab in breast milk, and to calculate the relative infant dose (RID) using two methods, the traditional method and a second method considering maternal exposure to multiple ofatumumab doses and extended collection period.

Methods: In this observational study, clinical data were collected by standardized telephone interviews up to 2 years postpartum. Breastmilk samples were analyzed by enzyme-linked immunosorbent assay.

Results: Twelve mothers started ofatumumab-exposed breastfeeding between 0.6 and 19.6 months postpartum. Infants showed neither abnormalities in infections, antibiotic use, or hospitalizations nor developmental delay. Five infants with available B cells had normal levels. Eight (66.7%) infants received live vaccines during/after exposed breastfeeding. None had complications. Ofatumumab concentration in breast milk varied widely between a median RID of average concentration 0.027% (range: 0.019%-0.115%) using method 1 and 2.912% (range: 1.301%-12.322%) using method 2.

Conclusion: Ofatumumab-exposed breastfeeding did not adversely affect infants' health or development. Despite higher RIDs using the more appropriate method 2, the risk of substantial antibody absorption by infants appears to be low.

Background: Many common symptoms in post-acute sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) overlap with those of multiple sclerosis (MS). We examined symptoms and performance of the PASC score, developed in the general population, in MS based on infection history.

Methods: We surveyed North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants regarding infections and categorized participants based on infection history. Symptoms experienced before, during, and after infection were used to identify persistent new symptoms. PASC was defined as a score ⩾ 12 based on the National Institutes of Health (NIH) study RECOVER.

Results: Of 4787 participants surveyed, 2927 were included: 294 (10%) having recent COVID-19; 853 (29.1%) recent non-COVID-19 infection; 246 (8.4%) recent COVID-19 and non-COVID-19 infection; 1534 (52.4%) uninfected, defined as never having COVID-19 nor any infection within the past 6 months. Compared to those uninfected, infection groups reported at least a two-fold increase in fever, cough, loss of smell/taste, and shortness of breath. Based on persistent new symptoms, PASC was identified in only 1.5% of participants with COVID-19.

Conclusion: Our study suggests lower than expected prevalence of PASC in MS and a complex association between infections and development of new persistent symptoms following infections. The similar proportions classified with PASC across infection groups shows that symptoms of PASC are common and complicate assessment of PASC in MS.

Background: Detection of subtle changes in cognition in multiple sclerosis (MS) may be enabled by ambulatory smartphone-based cognitive tests.

Objective: To examine the feasibility, reliability, and validity of ambulatory cognitive tests in people with MS.

Method: Adults with MS (N = 255) completed the NIH Toolbox Cognitive Battery, Symbol Digit Modalities Test, Paced Auditory Serial Addition Test-3, and 14 days of 4X/day ambulatory cognitive tests of working memory (dot memory) and processing speed (symbol search). Feasibility (response rates), measurement reliability (overall and by number of days of tests), and construct validity (convergent validity and known-groups analyses) were calculated.

Results: Participants completed 80.1% of available testing sessions. Reliability was 0.98 for dot memory and 0.99 for symbol search. Reliability attained ⩾0.90 within 3 days for dot memory and 1 day for symbol search. Symbol search scores correlated significantly with neuropsychological tests of processing speed (rs range = |0.53-0.69|) and differed significantly by disability level (t = -3.95, p < 0.001) and MS subtype (t = -2.81, p = 0.005). Dot memory scores correlated with neuropsychological tests of working memory (rs range = |0.45-0.58|); dot memory scores did not differ by disability level or MS subtype.

Conclusion: Smartphone-administered tests of working memory and processing speed demonstrate good feasibility, reliability, and construct validity in MS.