Multiple Sclerosis Journal - Experimental, Translational and Clinical最新文献

The deep cervical lymph nodes (dCLNs) are sites of immune presentation and B-cell maturation from the brain, and potentially involved in mechanisms of neuroinflammation. We hypothesized a reduction in dCLN volume following B-cell depletion therapy. In a retrospective cohort, we segmented bilateral dCLN from T2-FLAIR MRI at "prebaseline," "baseline," and "post-B-cell depletion" timepoints. Using a multivariable mixed-effect regression model, we find no changes in dCLN volumes between prebaseline and baseline timepoints (p > 0.05), but a significant decrease of 158 mm³ following ocrelizumab infusion (t = -3.3, p = 0.005). Baseline use of a disease-modifying therapy was also significantly associated with a smaller dCLN volume and attenuated the effects of B-cell depletion. These results are congruent with therapeutic mechanisms, although other alternative explanations for reductions in dCLN volumes cannot be ruled out based on this data. Deep CLN represent potential imaging biomarkers of pharmacological or clinical utility and warrant further investigation.

Background: Fingolimod was approved in 2010 for the treatment of relapsing-remitting multiple sclerosis, generally as second-line therapy. While its efficacy in reducing the relapse rate is well-recognized, the dermatologic complications of fingolimod remain unexplored. Herein, we aimed to report our experience with multiple sclerosis patients treated with fingolimod who underwent periodic dermatologic examinations.

Materials and methods: A prospective cohort of 323 patients with multiple sclerosis treated with fingolimod were assessed for dermatologic manifestations over 60 months. The neurologic and dermatologic examinations were done biannually to identify and categorize skin-related adverse events.

Results: Over a mean follow-up of 60 months, of the 323 patients, 32.19% (104 patients) developed skin abnormalities after a mean interval of 25.77 ± 24.36 months since fingolimod initiation. The majority of patients (91.34%) were female, with a mean age of 36.40 ± 7.45 years and a mean disease duration of 122 ± 58.56 months. The most common findings included melanocytic nevus (65.38%) and infectious lesions (11.53%). The severity of skin lesions varied, with most cases manageable with topical treatments. However, ten patients (9.61%) who developed refractory genital human papillomavirus (n = 2), melanocytic nevus (n = 3), dysplastic nevi (n = 3), fibrous papules (n = 1), and molluscum contagiosum (n = 1) had to discontinue their treatment.

Conclusion: Fingolimod treatment in patients with multiple sclerosis is associated with a range of dermatologic findings, predominantly mild to moderate in severity. This population warrants awareness of these potential adverse events and regular follow-up.

Background: Multiple sclerosis (MS), a chronic neurological disease, is typically managed with disease-modifying therapies (DMTs) to reduce relapse rates and slow disease progression. Some of these DMTs can cause infusion-related reactions (INRRs), which range from mild symptoms to severe allergic reactions. Corticosteroids are commonly used in premedication regimens to mitigate INRRs. However, long-term use of corticosteroids carries health risks. This study aims to compare the effectiveness of a standard corticosteroid regimen with an adjusted, low-dose regimen in reducing INRRs among people living with MS, receiving ocrelizumab (Xacrel), with the goal of optimizing safety while minimizing corticosteroid exposure.

Methods: In a single-blind, randomized, parallel-group clinical trial conducted at Sina Hospital, 200 adult patients with MS who had previously received ocrelizumab were recruited and randomly assigned to either a standard or adjusted premedication regimen groups. The standard regimen group (n = 101) received 100 mg intravenous (IV) methylprednisolone, along with cetirizine and acetaminophen tablets as premedication, while the adjusted regimen group (n = 99) received a reduced dose of 8 mg IV dexamethasone. The incidence of INRRs and their severity was monitored up to 1-hour post-infusion and 24-h post-infusion. Statistical analyses, including Chi-square tests and logistic regression, were used to evaluate the frequency of INRRs, characterize symptom profiles, and identify potential predictive factors for INRRs occurrence.

Results: Overall, the standard premedication demonstrated more efficacy in reducing the occurrence of INRRs, while the adjusted regimen group showed a significantly higher incidence of INRRs compared to the standard regimen group (78.8% vs. 40.6%, p-value <0.01). Specific INRRs symptoms, such as itching (29.3% in the adjusted group vs. 8.3% in the standard group, p-value <0.01) and throat irritation (65.7% vs. 31.7%, p-value <0.01), were notably more frequent in the adjusted regimen group. Most INRRs were mild to moderate in severity in both groups. There was no statistically significant difference in the occurrence of severe reactions between the two groups. Notably, a history of INRRs from previous infusions was identified as a strong predictor of INRRs in the current study, with an odds ratio of 6.27 (95% CI: 3.36-11.70), highlighting the importance of patients' history in managing INRRs risk.

Conclusions: The standard premedication regimen was more effective in reducing INRRs in people living with MS, receiving Xacrel compared to the reduced corticosteroid regimen. However, the findings suggest that a lower corticosteroid regimen may be beneficial for some patients, as there was no significant difference in the incidence of severe INRRs between the two groups.

Background: Early disease-modifying therapy (DMT) improves outcomes in patients with relapsing-remitting multiple sclerosis (pwRRMS), but reasons for delayed or absent initiation are unclear.

Objective: To investigate reasons and trends for delayed or absent DMT initiation among Finnish pwRRMS.

Methods: A nationwide retrospective study using the Finnish MS Registry identified 2363 pwRRMS diagnosed between 2010 and 2019 in the participating centers. Patients never receiving DMT or starting >2 years post-diagnosis were compared to those initiating DMT within a year of diagnosis.

Results: We identified 193 pwRRMS who never started DMT, 88 had delayed initiation over 2 years, and 1944 started within a year. The no/delayed DMT group was older at diagnosis (mean 38.7 vs 35.2 years, p < 0.001). Corticosteroid-treated relapses were more frequent among early initiators. Optic neuritis was more common in patients with delayed or no DMT. Treatment refusal was the primary reason for delayed/no DMT (35.6%), with 68% of refusers never starting. From 2010to 2019, delayed/no DMT initiation (p = 0.007) and treatment refusal (p = 0.004) decreased significantly.

Conclusion: Delayed or absent DMT initiation is linked to older age, optic neuritis, disease inactivity, and treatment refusal, which declined over time, likely due to expanded DMT options.

Background: Epilepsy is two to three times more common in patients with multiple sclerosis (pwMS) compared to the general population. Patients with MS and epilepsy without other identifiable causes (MS + E) show greater cortical damage than those without epilepsy (MS-E). However, it's unclear whether MS + E patients exhibit distinct cognitive and neuropsychological features requiring specific management.

Methods: In a cohort of pwMS from three MS centers, MS + E patients were identified and data on MS clinical features, epilepsy history, and treatments were collected. A matched group of MS-E patients was included. Assessments included cognitive and neuropsychiatric tests. Cognitive impairment (CI) was defined as scoring ≥1.5 standard deviations below normative values in ≥1 cognitive domain.

Results: CI was more prevalent in MS + E (n = 33) patients than in MS-E (n = 33). MS + E patients had lower processing speed (p < 0.01) and visuospatial memory (p = 0.03). MS + E was independently associated with CI (odds ratio 3.6, 95% confidence interval 1.21-12). Somatization, phobia, anxiety, and depression were the most affected neuropsychological domains in MS + E, with global psychological distress negatively correlating with processing speed (rho -0.36, p = 0.048).

Conclusions: MS + E is associated with higher CI, particularly in processing speed and visuospatial memory, alongside psychological distress, highlighting the need for targeted multidisciplinary care to improve outcomes and quality of life.

Background and objectives: Late-onset MS (LOMS, symptom onset after age 50) remains underrepresented in clinical trials, leading to a gap in knowledge about the efficacy of disease-modifying therapies (DMTs). This study aims to evaluate treatment outcomes in relapsing LOMS.

Methods: A retrospective electronic medical record study at Northwestern University analyzed patients with LOMS presenting between 2004 and 2021. Demographic, clinical, DMT, and MRI data were extracted. Statistical analyses evaluated progression based on DMT efficacy.

Results: Overall, 63 patients (63% female, 76% white, median onset 55 years) were followed for a median of 7.6 years. Most patients (73%) were started on low/moderate efficacy DMTs (LET/MET). Increasing baseline EDSS was associated with an increased risk of reaching EDSS 6 (P < .001), but increasing age at diagnosis/treatment was not associated with increasing disability attainment (P = .527). Patients on LET/MET had no difference in progression to EDSS 6.0 compared to no DMT (P = .354) or change in Age-Related Multiple Sclerosis Severity Score (ARMSS) from the start of treatment/diagnosis to last follow-up (P = .477).

Discussion: The effect of LET/MET DMTs is less pronounced in older adults and may not significantly impact long-term disability outcomes.

Background: Cognitive impairment is common in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) combined with adaptive cognitive training (aCT) may improve clinical outcomes.

Objective: To evaluate the effect of active vs. sham home-based tDCS + aCT on cognitive function.

Methods: Participants with MS and fatigue, without depression or severe cognitive impairment, were randomized to complete 30 remotely supervised 20-minute sessions of active (2.0 mA) or sham tDCS targeting the left anodal dorsolateral prefrontal cortex, paired with aCT. Randomization was stratified by high (H) vs. low (L) EDSS. The Brief International Cognitive Assessment in MS (BICAMS) was administered at baseline and intervention end, with scores converted to demographics-adjusted z-scores.

Results: Out of 117 participants, 106 completed BICAMS assessments. Compliance was high; 92% completed >25 sessions. Mean change in BICAMS z-score was significantly greater in the active (n = 55: 0.06 ± 0.56) versus sham (n = 51: -0.16 ± 0.50) group (p = 0.035). The interaction between treatment and EDSS for BICAMS z-score was not significant (p = .254), but benefits were greater in H EDSS (-0.00 ± 0.57 vs. -0.37 ± 0.39; p = .022) than L EDSS (0.11 ± 0.56 vs. -0.01 ± 0.53; p = .411).

Conclusions: Active vs. sham tDCS + aCT resulted in significantly better cognitive outcomes, with the greatest benefit in those with high neurologic disability.CLINICALTRIALS.GOV; https://clinicaltrials.gov/study/NCT03838770; IDENTIFIER: NCT03838770.

Background: Mood-behavioral symptoms, fatigue and pain are frequent among people with multiple sclerosis (pwMS). Music therapy (MT) is a non-pharmacological option for symptomatic treatment in neurological diseases.

Objectives: To assess effects of 6-week-outpatient MT on anxiety (primary outcome) as well as: depression, fatigue, pain and body perception (secondary outcomes) in pwMS.

Methods: We randomized pwMS 1:1 to music therapy group (MTG) and control group (CG). Both had one 45-min session per week, MTG with a monochord, CG without music. A blinded rater assessed endpoints at baseline and week 6 with standardized questionnaires (e.g. hospital anxiety and depression scale, HADS) and quantitative sensory testing (QST). Immediate session effects were also assessed. The analysis included linear mixed models, adjusted for pwMS's characteristics and baseline scores.

Results: Fifty-seven pwMS (age: 50.1 ± 12.4 years, 47 women, MTG: n = 30, CG: n = 27) were included. In MTG, anxiety levels (HADS) did not differ from CG at week 6 (p = 0.109). Among secondary outcomes, psychosocial fatigue was reduced (p = 0.029), QST heat pain thresholds were higher (p = 0.024) and immediate subjective effects stronger in MTG (e.g. feeling balanced: p < 0.001, relaxed: p < 0.001, less pain: p < 0.001).

Conclusion: Despite no difference in anxiety, we observed effects of receptive MT on fatigue, pain and body perception.

Background: People with relapsing forms of multiple sclerosis (PwRMS) treated with ofatumumab, a fully human anti-CD20 monoclonal antibody, can experience local/systemic injection-related reactions (IRRs). However, data on the occurrence and management of local/systemic IRRs in real-world clinical settings are limited.

Objective: This study aimed to better understand clinicians' perspectives regarding occurrence and management of local/systemic IRRs among PwRMS treated with ofatumumab in clinical practice.

Methods: A panel of US-based neurologists and advanced practice providers experienced with ofatumumab therapy in PwRMS participated in a three-round online modified Delphi study. In round 1, participants completed a demographics survey and Delphi questionnaire on IRR management. In round 2, they attended a live webinar to obtain feedback on round 1 results. In round 3, they reviewed round 1 and 2 feedback and provided their final responses.

Results: Forty participants (neurologists, n = 31; nurse practitioners, n = 5; and physician assistants, n = 4) completed all three rounds. Participants strongly agreed that local/systemic IRRs, regardless of severity, were unlikely with ofatumumab. Pre-/post-treatment of systemic IRRs was not uniformly required.

Conclusion: This study gives health care providers insight into the potential occurrence and management of IRRs with ofatumumab in the clinical practice setting.

Background: Comorbidities are a critical concern for clinicians in both the treatment and diagnosis of multiple sclerosis. Autoimmune diseases, including multiple sclerosis, often co-occur within individuals. However, most studies examining the incidence or prevalence of autoimmune diseases in persons with multiple sclerosis compared to healthy controls have used relatively small sample sets, with only a few being population-based.

Objectives: To analyze the co-occurrence of other autoimmune diseases in persons with multiple sclerosis and determine whether common genetic susceptibility factors contribute to the co-occurrence of autoimmune diseases.

Methods: We conducted a population-based study using administrative health records to include all residents of Piedmont, an Italian Region with about 4.3 million inhabitants, identifying individuals with multiple sclerosis and 14 other autoimmune diseases. For a subset of persons with multiple sclerosis with available genome-wide genotyping data, we investigated the influence of their genetic backgrounds using a polygenic risk score.

Results: The prevalence of all 14 tested autoimmune diseases was higher in persons with multiple sclerosis compared to those without multiple sclerosis. Furthermore, persons with multiple sclerosis with autoimmune disease comorbidities had a higher polygenic risk score compared to persons with multiple sclerosis without comorbidities.

Conclusion: Our findings confirm the co-occurrence of multiple sclerosis with several autoimmune diseases, and suggest that shared genetic susceptibility factors may influence this association.