Multiple Sclerosis Journal最新文献

Recognizing neuromyelitis optica spectrum disorder (NMOSD) and differentiating NMOSD from multiple sclerosis (MS) and other disorders can be challenging yet it is extremely important to prevent misdiagnosis, defined in this review as the incorrect diagnosis of patients who truly have NMOSD, particularly in aquaporin-4-IgG (AQP4-IgG)-seronegative cases. The heterogeneity of clinical presentations and wide range of differential diagnoses often lead to missed diagnoses of NMOSD. Misapplication of the 2015 NMOSD criteria and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis in clinical practice. Despite the presence of a specific biomarker for NMOSD (AQP4-IgG), misdiagnosis rates have been reported as high as 35%. Studies indicate that misdiagnosed patients often undergo unnecessary prolonged immunotherapy, leading to health risks and increased morbidity. Accurate definitive diagnosis is crucial as long-term outcomes and treatment approaches differ based on the correct diagnosis, and inappropriate immunotherapy can lead to disability in NMOSD patients. This review outlines factors linked to NMOSD misdiagnosis and briefly discusses strategies to reduce misdiagnosis.

Background: Teriflunomide has been associated with an increased risk of hypertension. Real-world studies including adequate control groups are lacking. We hypothesized that patients with multiple sclerosis (MS) treated with teriflunomide would be at higher risk of developing hypertension than those treated with dimethyl fumarate.

Methods: We conducted a cohort study linking the Danish Multiple Sclerosis Registry with national health registries during a 10-year period. Teriflunomide (N = 2656) and dimethyl fumarate (N = 2237) exposure was defined by the first treatment record lasting ⩾ 3 months, at which time follow-up started. We included 4893 adult patients without hypertension at baseline. Hypertension was defined as an International Classification of Diseases 10th Revision code for hypertension and by dispensed prescription drugs identified by the respective Anatomical Therapeutic Chemical codes. We used multivariable-adjusted Cox regression.

Results: We found 40.6 (teriflunomide) and 13.1 (dimethyl fumarate) hypertension events per 1000 person-years. Compared to dimethyl fumarate-treated patients, patients treated with teriflunomide had a higher risk of developing hypertension (adjusted hazard ratio = 2.80; 95% confidence interval = 2.19-3.56). The number needed to harm was 16 and 9 at 3 and 5 years of follow-up, respectively.

Conclusion: We found an increased risk of hypertension in adult patients with MS treated with teriflunomide.

Background: CLASSIC-MS explored long-term outcomes of patients treated with cladribine tablets.

Objective: Assess long-term efficacy in patients previously enrolled in ORACLE-MS, a Phase III parent trial.

Methods: ORACLE-MS included patients with a first clinical demyelinating event (FCDE or clinically isolated syndrome) who received ⩾1 course of cladribine tablets or placebo. With a median follow-up time of 9.5 years, CLASSIC-MS assessed conversion rates to clinically definite multiple sclerosis (CDMS), time-to-conversion, relapse rates, long-term mobility/disability status and subsequent disease-modifying therapy (DMT) use.

Results: Of 227 patients from the ORACLE-MS cohort of 616, 68.7% were exposed to cladribine tablets and 31.3% were never exposed. Of the exposed patients at risk, 51.5% converted to CDMS with a median conversion time of 8.4 (95% confidence interval (CI): 5.4-not estimable) years, versus 80.6%, median time 0.8 (95% CI: 0.3-2.4) years, for never exposed. Exposed patients were less likely to be using a wheelchair or ambulatory device or receive subsequent DMTs, and 53.2% were relapse-free versus 28.2% never exposed.

Conclusions: Proportionally, more FCDE patients exposed to cladribine tablets experienced delayed conversion to CDMS and fewer relapses and were less likely to use a wheelchair or ambulatory device than never-exposed patients, at 9.5 years (median).

Background: Studies have reported an association between socioeconomic status and disability progression in multiple sclerosis (MS), but findings using the pre-MS individual socioeconomic status are missing.

Objective: The objective was to investigate the association between education level and disability progression.

Methods: All Observatoire Français de la Sclérose en Plaques (OFSEP) patients with MS clinical onset over 1960-2014, and aged ⩾25 years at MS onset were included. Education level was classified into four categories from low (primary/secondary school) to very high (master/doctoral degree). Time from MS onset to EDSS 4.0 was studied using flexible parametric survival models adjusted for age, period, and center, and stratified by phenotype (relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS)) and sex.

Results: A total of 11,586 patients were included (women/men ratio = 2.5; age = 36.7 ± 8.6 years; follow-up duration 16.7 ± 9.3 years; 86.4% RMS). For women with RMS, the risk of reaching the outcome at 5 years was inversely associated with the education level (Hazard Ratio medium: 0.74 (0.63-0.87), high: 0.51 (0.43-0.62), very high: 0.39 (0.30-0.50) vs low). Results were similar for men. In PPMS, the risk was significantly different between the extreme groups (very high vs low) for women (0.45 (0.28-0.75)) and men (0.54 (0.32-0.91)), but no gradient was evident.

Conclusion: Our study showed a strong association between education level and disability progression, regardless of sex and phenotype.

Background: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS).

Objective: This study aimed to analyze the association between education level and DMT use in France.

Methods: All patients from OFSEP network with MS onset over 1996-2014 and aged ⩾ 25 years at onset were included. Three time-to-event outcomes were investigated using flexible parametric survival regression models: time from MS onset to first DMT (any) and to platform therapy, and time from platform therapy to switch to high-efficacy therapy.

Results: Overall, 7563 patients were included (mean follow-up 12.6 ± 5.9 years). The percentages of patients aged less than 40 years at MS onset and who initiated treatment before the age of 40 years were significantly higher in the groups with a higher education level. The time-to-event outcomes showed no major difference in DMT practices according to education level, except for women who had a significantly shorter time to DMT initiation in medium to very high education level groups versus low, at 5 years from MS clinical onset.

Conclusion: Our results suggest that the association between education level and MS disability progression does not solely reflect different therapeutic practices, particularly in men.

Background: Epstein-Barr virus (EBV) infection increases the risk of having multiple sclerosis (MS). Data on adults with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are lacking.

Objective: To compare EBV serological status in MOGAD versus MS.

Methods: We measured antibodies to Epstein-Barr nuclear antigen (EBNA-1) and viral capsid antigen (VCA) antigens in 129 patients (MS = 74, MOGAD = 55) by chemiluminescence immunoassays.

Results: VCA-IgG were detected in 97.3% of MS and 96.4% of MOGAD cases, while EBNA-1-IgG in 97.3% of MS and 80% of MOGAD (p = 0.001). EBNA-1 (p < 0.001) and VCA (p = 0.03) antibodies levels were higher in MS patients.

Conclusion: EBV antibodies are higher in MS versus MOGAD, suggesting a possible different role of EBV in the pathogenesis of the two conditions.

Background: Literature on the intricate relationship between self-reported and objectively assessed cognitive functioning suggests a discrepancy between self-reported cognitive complaints (SCC) and actual test performance.

Objectives: To investigate the interplay between patient-reported outcome measures (PROMs) and objective cognitive functioning using network analysis in people with multiple sclerosis (PwMS).

Methods: We collected PROMs on anxiety, depression, fatigue and SCC, and cognitive functioning across six domains (n = 703 PwMS; 71% female, mean age = 46.3 ± 11.2 years). We constructed cognitive symptom networks using Gaussian Graphical Models, in which the aforementioned variables were presented as nodes linked by regularized partial correlations. We compared global network strength between relevant subgroups.

Results: The networks primarily showed clustering of PROMs and cognitive domains into two separate modules, with weaker links connecting both modules. Global network strength was lower for PwMS with impaired information processing speed (IPS; indicating lower symptom interrelatedness) compared to those with preserved IPS (3.57 versus 4.51, p = 0.001), but not when comparing SCC subgroups (p = 0.140).

Conclusions: Cognitive symptom networks deepen our understanding of the discrepancy between self-reported and objectively assessed cognitive functioning. Lower symptom interrelatedness in PwMS with impaired IPS might suggest a nonlinear relation between PROMs and cognitive domains, which depends on the cognitive status.

Trigeminal neuralgia (TN) is commonly associated with multiple sclerosis (MS). Whether TN should be considered a clinical relapse or evidence of active disease lacks consensus. TN was diagnosed in 0.9%-1.9% (n = 171) of people with multiple sclerosis (pwMS) at three international sites. In 9.9%, TN was their first potential demyelinating symptom. In 86%, TN onset occurred a median of 13-16 years after MS diagnosis. A clinical relapse occurred within 6 months of TN onset in 20% of pwMS. These data suggest TN onset should be evaluated as active disease and incorporated in diagnostic and therapeutic decisions in MS.