Multiple Sclerosis Journal最新文献

Background: The clinical course of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is variable. However, robust markers of poor outcome and/or relapse risk are still missing.

Objective: To evaluate the frequency of cerebrospinal fluid-restricted oligoclonal bands (CSF-OCB) in a national cohort of adult MOGAD patients and to assess their prognostic value for the risk of relapse and severity.

Methods: We included MOGAD adult patients fulfilling the MOGAD 2023 criteria who underwent CSF analysis at maximum 3 months from onset.

Results: Data from 190 patients were collected. We found the presence of CSF-OCB in 32 patients (16.8%). Positive and negative CSF-OCB patients were similar for median age at onset, sex, clinical presentation, severity at onset, and residual disability. Relapses were more frequent in the CSF-OCB+ group (p = 0.049), particularly within the first year of follow-up (p = 0.007). Although CSF-OCB+ was more frequently associated with imaging features suggestive of multiple sclerosis (MS) (p = 0.014), 78% of these patients fulfilled the 2023 supportive features and 65% experienced lesion vanishing at follow-up magnetic resonance imaging (MRI).

Conclusion: We found a higher risk of relapse in MOGAD with CSF-OCB particularly during the first year. Close attention is recommended regarding the risk of misdiagnosis with MS.

An 80-year-old man with aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder presented with a 2-week history of cough and hiccups, followed by progressive bilateral lower limb weakness, a bandlike burning sensation in the upper body, and urinary retention. Magnetic resonance imaging showed area postrema and thoracic central medullary lesions. Thorax computed tomography showed bilateral upper lung lobe consolidations. Lung biopsy confirmed organizing pneumonia. Immunohistochemistry of these lesions demonstrated aquaporin-4 loss, immunoglobulin G-binding, and complement deposits, akin to central nervous system lesions found in neuromyelitis optica spectrum disorder. Thus, aquaporin-4-antibodies may be involved in extra-central nervous system manifestations of neuromyelitis optica spectrum disorder.

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: Real-world studies are needed to expand our knowledge concerning populations underrepresented in clinical trials.

Objective: This study aimed to evaluate the safety and effectiveness of ocrelizumab in Hispanic/Latino people with multiple sclerosis (pwMS).

Methods: Prospective longitudinal observational study including pwMS who received at least one dose of ocrelizumab between June 2018 and October 2023.

Results: A total of 305 pwMS (223 relapsing-remitting MS (RRMS), 29 secondary progressive MS (SPMS), and 53 primary progressive MS (PPMS)), 67% female, mean age 38.7, mean disease duration 7 years, and median Expanded Disability Status Scale (EDSS) 2.0 (range 0-7). Median follow-up under ocrelizumab 29.5 (range 6-65) months. Only 1 patient had a relapse, 12-week-confirmed disability worsening was observed in 12.4% of the full cohort. Survival analysis showed higher risk of 12-week-confirmed disability worsening in SPMS compared with RRMS and PPMS (p = 0.0009). Magnetic resonance imaging (MRI) activity was significantly reduced from baseline across all disease phenotypes. Serious infections were observed in 4.6%, and two patients died during follow-up (one serious COVID-19 and one metastatic cancer). Notably, 22 pregnancies were reported, with 11 newborns and 6 pregnancies still on course.

Conclusion: This study supports the effectiveness of ocrelizumab in a real-world cohort of individuals from traditionally underrepresented groups, such as the Latin American population, with a consistent safety profile in patients receiving care at a specialized MS Unit.

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: A digital adaptation of the nine-hole peg test (9HPT) was developed with the potential to provide novel disability features for patients with multiple sclerosis (PwMS).

Objectives: The objectives were to evaluate the 9HPT features based on reliability, prognosis, and discrimination between treatment groups.

Methods: The MS partners Advancing Technology and Health Solutions (MS PATHS) cohort data were used to derive new features including completion time and speed. Association and reliability between features and clinical outcomes were tested by intraclass correlation coefficients (ICCs) with repeated measures. The added prognostic value of the features for a clinically meaningful decline was assessed by time-to-event analyses with likelihood ratio tests. The estimated effect size between treatment efficacy groups was acquired from linear mixed-effects models. Sample size was calculated for a hypothetical randomized clinical trial.

Results: For the 10,843 PwMS, speed and completion time were associated with MS disability. Compared with time, speed showed higher reliability (ICC = 0.78 vs 0.74), added benefits in predicting disability worsening (p < 0.001), better discrimination between high- and low-efficacy groups (effect size: 0.035 vs 0.015), and an 18% reduction in required sample size for a 1-year clinical trial.

Conclusion: Integrating horizontal hand distances traveled over the 9HPT pegboard can be a more reliable measure of hand function.

Despite the commonly observed association of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies with bilateral optic neuritis, their connection to uveitis is largely unexplored. The presented case involves a 41-year-old male with uveitis and bilateral optic neuritis, subsequently diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This case, characterized by bilateral optic neuritis associated to anti-MOG antibodies and the concurrent onset of unilateral anterior uveitis, provides further evidence concerning the features of intraocular inflammation in MOGAD. The patient's treatment response, including the use of rituximab due to contraindications to oral steroids, emphasizes the importance of personalized management strategies in MOGAD-associated ocular manifestations.

Background: Limited licensed medications are available for multiple sclerosis (MS) in pediatric patients.

Objective: To evaluate the efficacy, safety, and tolerability of alemtuzumab in pediatric patients with relapsing-remitting multiple sclerosis (RRMS) and disease activity on prior disease-modifying therapies (DMTs).

Methods: LemKids was a multicenter, multinational, single-arm, open-label, switch (from ongoing DMT to alemtuzumab treatment) study in pediatric RRMS patients (aged 10-<18 years), with disease activity on DMT. The primary endpoint was a comparison of the number of new/enlarging T2 lesions on the magnetic resonance imaging of the brain between the prior-DMT period and alemtuzumab treatment.

Results: This study was prematurely terminated due to low enrollment and an European Medicines Agency Article-20 pharmacovigilance review of alemtuzumab in adult RRMS. Of 46 screened patients, 16 were enrolled; 12 completed prior-DMT treatment period; 11 received alemtuzumab of whom 7 completed treatment. Patients on alemtuzumab developed fewer new/enlarging T2 lesions compared with prior-DMT (7 vs 178, relative risk (95% confidence interval): 0.04 (0.01-0.14)). No significant pharmacodynamic changes or safety concerns were noted in this limited dataset.

Conclusion: Alemtuzumab treatment was associated with a low number of new/enlarging T2 lesions in pediatric patients with RRMS and was safe and well tolerated in seven patients during infusion and the initial 4 months.

Background: The effect of cognitive reserve (CR) on cognition in people with relapsing-remitting multiple sclerosis (pwRRMS) has been partially investigated.

Objectives: We aimed to explore the long-term cognitive trajectories of pwRRMS based on their CR, measured using the Vocabulary Knowledge Test (VOC).

Methods: 78 pwRRMS underwent a neuropsychological evaluation at baseline and after a mean follow-up of 6.5 years. We carried out several mixed-design ANCOVA to test the effect of CR on longitudinal cognitive trajectories, controlling for the effects of disability and depression. Regression analyses were performed to assess the clinical predictors of longitudinal cognitive variation.

Results: At follow-up, we observed improvements in cognitive scores within pwRRMS with high CR and a decline within pwRRMS with low CR. VOC scores increased at follow-up evaluation in the whole sample, and this change was associated with the female sex. VOC emerged as the only predictor of cognitive changes over time.

Conclusions: CR, estimated by VOC, can increase over time by engaging in intellectually enriching activities, and may predict long-term cognitive outcomes in pwRRMS. The identification of pwRRMS with low CR, and therefore, most at risk of future cognitive decline, should prompt the implementation of CR enhancement interventions to delay the onset of cognitive impairment.