Diffusely abnormal white matter in clinically isolated syndrome is associated with parenchymal loss and elevated neurofilament levels.

We characterized the frequency of diffusely abnormal white matter (DAWM) across a broad spectrum of multiple sclerosis (MS) participants. 35% of clinically isolated syndrome (CIS), 57% of relapsing remitting and 64% of secondary progressive MS participants demonstrated DAWM. CIS with DAWM had decreased cortical thickness, higher lesion load and a higher concentration of serum neurofilament light chain compared to CIS without DAWM. DAWM may be useful in identifying CIS patients with greater injury to their brains. Larger and longitudinal studies are warranted.

Cannabis-based product use in a multiple sclerosis cohort.

OBJECTIVE: The objective of this study was to characterize the use of cannabis-based products (CBPs) by multiple sclerosis (MS) patients who attend the University of British Columbia Hospital (UBCH) MS clinic. METHODS: All patients attending the UBCH MS clinic from January to March 2018 were invited to participate in an anonymous survey that included: patient demographics (sex, age and employment status), self-reported MS-specific data (subtype, disease duration, previous and current disease modifying therapies, symptomatic medications) and CBP use (formulation, frequency, perceived benefits/side-effects). A second cohort of retrospective patient data (CBP use, sex, age, disease subtype and Expanded Disability Status Scale) was extracted from the UBCH MS clinic electronic medical record (EMR). RESULTS: Of 600 surveys distributed, 188 were returned with completed CBP usage. CBP use was daily for 19% (n = 37), weekly for 6% (n = 11), monthly for 4% (n = 7), rarely for 21% (n = 39) and 50% (n = 94) never used. Of the CBP users (daily, weekly and monthly), CBP use included: oral (n = 43/55), smoked/vaporized (n = 42/55), topical (n = 14/55) and mucosal (n = 5/55). EMR data was available for 561 MS patients where cannabis use/non-use was documented. CBP users represented 19% (107/561). CONCLUSIONS: CBP use is common based on volunteer reporting, with approximately one out of four patients who attend the UBCH MS clinic using CBPs.

The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: most disease-modifying therapies (DMTs) for multiple sclerosis (MS) are self-injectable medications that must be taken on an ongoing basis to reduce disease activity. Thus, adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy. This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing-remitting MS. METHODS: this was an observational, multicenter, multinational, phase 4 study. Patients and physicians received paper questionnaires regarding adherence to DMTs approved at the time of the study, including intramuscular interferon beta-1a (IFNß-1a), subcutaneous IFNß-1a, IFNß-1b, and glatiramer acetate. Quality of life and cognition data also were collected. Multivariate analysis was conducted to identify factors associated with adherence to long-term DMTs. RESULTS: two thousand six hundred and forty-eight patients were studied, revealing an average treatment duration of 31 months. Seventy-five percent of patients (n = 1923) were adherent to therapy. The most common reasons for non-adherence were forgetting to administer the injection (50.2%) and other injection-related reasons (32.0%). Adherent patients reported better quality of life (P < 0.05) and fewer neuropsychological issues (P < 0.001) than non-adherent patients. Adherent patients had significantly shorter duration of disease (P < 0.001) and shorter duration of therapy (P = 0.005) than non-adherent patients. Women were more likely than men to adhere to treatment. CONCLUSION: identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy, thereby helping maximize the benefits of long-term DMTs.

Impact of multiple sclerosis relapses on progression diminishes with time.

OBJECTIVE: The relationship between relapses and long-term disability in multiple sclerosis (MS) remains to be fully elucidated. Current literature is conflicting and focused on early relapses. We investigated the effects of relapses at different stages on disability progression. METHODS: We conducted a retrospective review of 2,477 patients with definite relapsing-onset MS followed until July 2003 in British Columbia, Canada. Time-dependent Cox proportional hazards models examined the effect of relapses at different time periods (0-5; >5-10; >10 years postonset) on time to cane (Expanded Disability Status Scale [EDSS]) and secondary progressive MS (SPMS). Findings were derived from hazard ratios with 95% confidence intervals (CIs), adjusted for sex, onset age, and symptoms. RESULTS: Mean follow-up was 20.6 years; 11,722 postonset relapses were recorded. An early relapse (within 5 years postonset) was associated with an increased hazard in disease progression over the short term, by 48%; 95% CI 37%-60% for EDSS 6 and 29%; 95% CI 20%-38% for SPMS. However, this substantially lessened to 10%; 95% CI 4%-16% (EDSS 6) and 2%; 95% CI -2%-7% (SPMS) after 10 years postonset. The impact of later relapses (>5-10 years postonset) also lessened over time. Effects were modulated by age, impact being greatest in younger (<25 years at onset) and least in older (>or=35 years) patients where relapses beyond 5-years postonset typically failed to reach significance. Relapses during SPMS had no measurable impact on time to EDSS 6 from SPMS. CONCLUSION: Relapses within the first 5 years of disease impacted on disease progression over the short term. However, the long-term impact was minimal, either for early or later relapses. Long-term disease progression was least affected by relapses in patients with an extended disease duration (>10 years) or already in the secondary progressive phase.

Relapses in multiple sclerosis are age- and time-dependent.

OBJECTIVES: To examine the relative relapse-rate patterns over time in a relapsing multiple sclerosis (MS) cohort and to investigate potential predictors of relapse rates and periods of low-relapse activity. METHODS: This retrospective cohort study followed 2477 relapsing-remitting (RR) MS patients from onset to 1 July 2003. Annualised relapse rates were examined according to sex, age at onset, the patient's current age and disease duration. The relationship between relapse rates and baseline characteristics (sex, onset age and onset symptoms) were examined using Poisson regression. Time to the first 5 years relapse-free was examined using Kaplan-Meier survival analysis. RESULTS: The mean follow-up time (from onset of MS symptoms) was 20.6 years, during which time 11,722 post-onset relapses were recorded. The relapse rate decreased by 17% every 5 years (between years 5 to 30 post-onset), but this decline increased in magnitude with increasing onset age. Women and those with onset sensory symptoms exhibited a higher relapse rate (p< or =0.001). More than three-quarters of patients (1692/2189) experienced a 5-year relapse-free period during the RR phase. CONCLUSION: Relapse rates were age- and time-dependent. Our observations have clinical implications: 1) any drug able to modify relapse rates has the greatest potential for a population impact in patients <40 years old and within the first few demi-decades of disease; 2) continuation of drug beyond these times may be of limited value; 3) long-term follow-up studies must consider that relapse rates probably decline at different rates over time according to the patient's onset age; 4) a relapse-quiescent period in MS is not uncommon.

The immune system and hormones: review and relevance to pregnancy and contraception in women with MS.

Two-thirds of multiple sclerosis (MS) patients are women, and the average age of onset overlaps the childbearing years. Clinicians are frequently asked, therefore, about the most appropriate form of contraception and the risk of an MS relapse/exacerbation during pregnancy and the post-partum period. This paper reviews the literature on the immune system and the effects of pregnancy, oral contraceptives and hormone replacement therapy on MS.

Early onset multiple sclerosis: a longitudinal study.

OBJECTIVE: To evaluate the clinical course of MS in individuals with onset of MS before age 16. METHODS: Patients with onset of MS before age 16 (n = 116) with complete clinical information on the clinical course from the MS Clinic at The University of British Columbia (UBC) Site Hospital computerized database (MS-COSTAR) were included in this study. The data were compared to those from the Canadian natural history study for MS clinic attendees, regardless of age at onset. RESULTS: The mean duration of observation was 19.76 +/- 0.90 years; the mean age at MS onset was 12.73 +/- 0.25 years. Only three cases (2.6%) had a primary progressive (PP) MS course. To date, 60 (53.1%) of 113 subjects have developed secondary progressive (SP) MS. The 50% probability for SPMS was reached 23 years after onset. For patients with relapsing remitting (RR) or SPMS the mean disease duration from onset to the time of confirmed Expanded Disability Status Scale (EDSS) 3.0 was 16.03 +/- 1.17 years (at mean age 28.47 +/- 1.14); mean duration from onset to the time of EDSS 6.0 was 19.39 +/- 1.43 years (at mean age 32.32 +/- 1.44). Annual relapse rate was 0.54 +/- 0.05 per year. The correlation between the number of relapses during the first year of disease and the course of the disease was also significant. CONCLUSIONS: The prevalence of early onset MS (3.6%) in our study confirms the previous findings on early onset MS. A RR course was seen in the majority of cases of early onset MS. A high frequency of relapses, early age at permanent disability, and the presence of malignant cases raise the question of possible early use of disease-modifying therapy in patients with early onset MS.

Genetic susceptibility to MS: a second stage analysis in Canadian MS families.

Four published genome screens have identified a number of markers with increased sharing in multiple sclerosis (MS) families, although none has reached statistical significance. One hundred and five markers previously identified as showing increased sharing in Canadian, British, Finnish, and American genome screens were genotyped in 219 sibling pairs ascertained from the database of the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No markers examined met criteria for significant linkage. Markers located at 5p14 and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS was confirmed (P<0.0001). Significant transmission disequilibrium was also observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of searching for genes with only mild-to-moderate effects on susceptibility, although large effects of specific loci may still be present in individual families. Future progress in the genetics of this complex trait may be helped by (1) focussing on more ethnically homogeneous samples, (2) using an increased number of MS families, and (3) using transmission disequilibrium analysis in candidate regions rather than the affected relative pair linkage analysis.

Continuous intrathecal pump infusion of baclofen with antibiotic drugs for treatment of pump-associated meningitis. Case report.

Intrathecal baclofen administered by means of an implantable pump is being increasingly used for successful treatment of spasticity. Meningitis following intrathecally administered baclofen is a rare but serious complication that is difficult to treat without removal of the pump. Because success rates with intravenously administered antibiotic drugs for the treatment of meningitis have been low, intrathecal administration of antibiotic agents is often required to eradicate the pathogen. The authors report the case of a patient in whom Staphylococcus epidermidis meningitis developed after insertion of an intrathecal baclofen pump. The patient was successfully treated by intrathecal coadministration of vancomycin and baclofen.