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Background and Purpose: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation., Methods: Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence., Results: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate., Conclusions: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Several studies have shown that pregnancy reduces multiple sclerosis (MS) relapses, which increase in the early postpartum period. Postpartum relapse risk has been predicted by pre-pregnancy disease activity in some studies., Objective: To re-examine effect of pregnancy on relapses using the large international MSBase Registry, examining predictors of early postpartum relapse., Methods: An observational case-control study was performed including pregnancies post-MS onset. Annualised relapse rate (ARR) and median Expanded Disability Status Scale (EDSS) scores were compared for the 24 months pre-conception, pregnancy and 24 months postpartum periods. Clustered logistic regression was used to investigate predictors of early postpartum relapses., Results: The study included 893 pregnancies in 674 females with MS. ARR (standard error) pre-pregnancy was 0.32 (0.02), which fell to 0.13 (0.03) in the third trimester and rose to 0.61 (0.06) in the first three months postpartum. Median EDSS remained unchanged. Pre-conception ARR and disease-modifying treatment (DMT) predicted early postpartum relapse in a multivariable model., Conclusion: Results confirm a favourable effect on relapses as pregnancy proceeds, and an early postpartum peak. Pre-conception DMT exposure and low ARR were independently protective against postpartum relapse. This novel finding could provide clinicians with a strategy to minimise postpartum relapse risk in women with MS planning pregnancy.

Objective: To analyze time-trends in age at disability milestones among MS patients who were enrolled into the MSBase International Registry during 1996-2010 period., Methods: We used linear regression to describe the relationship between mean age at major EDSS benchmarks and calendar time. We then assessed time-trend in age at initial EDSS rating with a three level linear growth model specifying that patients were nested within each of 20 participating countries. The model estimated the average of time-trends in mean age at initial clinical assessment within each country while controlling for patients' EDSS and sex in each country. Analyses were repeated in subsamples of patients diagnosed according to Poser or McDonald criteria., Results: The MSBase Registry contained data on 11,108 MS patients enrolled between 1996 and 2010 who fulfilled our inclusion criteria. During the 1996-2010 period, enrollment age for patients with EDSS 4/4.5 increased by 7.9 years, from 43 to 51 years (p<0.001), and for EDSS 6/6.5 - by 4.9 years, from 48 to 53 year (p<0.001). These trends were consistent across 20 investigator countries and were observed in Poser-diagnosed as well as McDonald-diagnosed patient subsets., Conclusions: The more recent MSBase enrollees in each of the mild-to-moderate disability strata were significantly older than earlier enrollees. Possible explanations for this phenomenon are discussed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS., Methods: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months' double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses., Results: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04)., Conclusion: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation., Classification of Evidence: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.

An elderly female smoker presented with nausea and anorexia. Imaging and histopathology were consistent with a diagnosis of small cell lung cancer (SCLC). She subsequently developed a progressive sensorimotor neuropathy with high titres of anti-Hu antibodies. Development of the neuropathy was associated with marked regression in the lung neoplasm. Repeat investigation with radioimaging and bronchoscopy showed no evidence of neoplasia. Paraneoplastic sensorimotor neuropathies are commonly associated with SCLC particularly in the presence of anti-Hu antibodies. Regression of SCLC with anti-Hu antibodies has only been reported twice previously. The authors believe this case supports the theory that anti-Hu antibodies confer anti-tumour activity causing tumour regression.

Objective: To investigate the possibility that susceptibility loci in multiple sclerosis (MS) have a role in determining the disease outcome in Northern Ireland population., Background: The Genetic Analysis of Multiple Sclerosis in Europeans (GAMES) initiative and follow-up refined analysis identified 15 candidate susceptibility loci within the Northern Irish population for MS. We aimed to investigate the 12 most significant markers for their role in disease outcome., Methods: Cases with probable or definite MS (Poser criteria) were classified as benign onset (Kurtzke Expanded Disability Status Scale [EDSS]or=6.0 by 10 years), or primary progressive MS. All cases were Caucasian of Northern Irish origin. DNA was extracted from venous blood, microsatellite markers were amplified using polymerase chain reaction and typed using fluorescent fragment analysis. Allele frequencies were compared statistically using a chi-squared test with allowance for multiple comparisons (critical P<0.0042); significant markers were further analyzed by CLUMP (critical P<0.0014)., Results: Two microsatellite markers were significant: D3S1278 (Chr 3q13, P<0.001) and tumor necrosis factor (TNF)-alpha (Chr 6p21, P<0.001). A further three markers were significant in our preliminary analysis suggesting a trend toward impact on disease outcome; D4S432 (Chr 4p16, P=0.001), D2S347 (Chr 2q14, P=0.003), and D19S903 (Chr 19p13, P=0.003)., Conclusions: This is the first study to suggest a role for TNF-alpha in the disease outcome in MS. Larger replication studies need to be performed to assess the role of markers D4S432, D2S347, and D19S903.

Objective: To investigate the psychometric properties of the Multiple Sclerosis Impact Scale (MSIS-29) and to assess the relationship between the Kurtzke Expanded Disability Status Scale and the physical and psychological parts of this score., Methods: A population-based study identified cases with definite multiple sclerosis (MS) in the north-east region of Ireland. They were examined and completed the MSIS-29. Cases were classified as mild (Expanded Disability Status Score (EDSS) 0-3.0), moderate (EDSS 3.5-5.5), or severe (6.0-9.5) MS., Results: The 248 participants (82 male, 166 female) had a mean age of 49.1 years (SD 12.4). EDSS ranged from 0 to 9.5 (median 6.0). Data quality was excellent (0.02% missing data), physical and psychological scores spanned the entire range with low floor and ceiling effects. Internal consistency was high (Cronbach's alpha 0.97 - physical score, 0.93 - psychological score). The convergent validity of the physical impact score of the MSIS-29 with the Kurtzke EDSS was confirmed with a high Spearman's rank coefficient correlation of 0.63 (P = 0.01). Physical impact scores for mild, moderate, and severe disability as were statistically different at 25.9%, 48.0%, and 63.9%, respectively. Mean psychological score was non-significantly higher in the moderately disabled group at 47.4% compared with the severely disabled at 44.3% (P = 0.58)., Conclusions: The MSIS-29 is an acceptable, reliable, and valid method of recording quality of life. A significant relationship between higher physical impact scores of the MSIS-29 and higher Kurtzke EDSS values suggests that is may be of use in clinical trials to monitor progression.

Background: Northern Ireland is recognized as an area of high risk for multiple sclerosis. The original study of Allison and Millar in 1951 found a prevalence of 51/100,000 and mean annual incidence of 2.74/100,000/year. Subsequent studies in 1961, 1986, and 1996 suggested rising prevalence--80, 138, and 168.2/100,000, respectively., Methods: In 2004, we surveyed the North-East of Northern Ireland (population 160,446, area 2030 km(2)) using multiple sources of case ascertainment, all satisfying the Poser criteria for definite or probable multiple sclerosis (MS) or the McDonald criteria., Results: From a provisional list of 469 cases, 370 (123 males, 247 females) were identified. The prevalence was 230.6 per 100,000 (95% CI 207.0-255.4) with significantly higher prevalence in females (300.8/100,000) than males (157.0/100,000). Direct standardization to the 1961 Northern Ireland population reduced the overall prevalence rate to 200.5/100,000 (95% CI 193.2-208.0), in females to 270.2/100,000 (95% CI 258.8-282.4) and in males to 131.1/100,000 (95% CI 122.8-139.9). In 1996, incidence had risen to 9.3/100,000/year (14 cases in population of 151,000) with a higher incidence in females (10.3/100,000/year) than males (8.3/100,000/year)., Conclusions: Northern Ireland continues to have a rising prevalence of MS. The increase in incidence suggests a true increase in the disease.

Oral methotrexate is a potent immunosuppressant, which could have a beneficial effect on relapse rates and delay disease progression in multiple sclerosis (MS). We performed a systematic review of all randomized controlled trials of oral methotrexate for MS. Of the two randomized controlled trials identified, one was excluded due to its allocation concealment and definition of a relapse and time to sustained disease progression. The other trial studied 60 participants with progressive MS only. This trial reported a non-significant reduction in sustained Expanded Disability Status Scale (EDSS) progression and number of relapses in favour of methotrexate therapy. There were no data on relapse rate and no difference in time to first relapse. Minor side-effects were reported in both methotrexate (87.1%) and placebo groups (89.7%), but there were no major side-effects. Further trials are required in both relapsing-remitting and progressive groups to establish the role of oral methotrexate in MS.

Abstract Brainstem injuries are classically associated with a grave prognosis. We present a case of a male with primary isolated brainstem injury who had a right internuclear ophthalmoplegia who made a complete recovery. A review of literature suggests that the mortality from such injuries is about 6% and most make a good functional recovery.