Multiple Sclerosis Symptom Onset Research Articles

Shifting our attention earlier in the multiple sclerosis disease course.

Revisions of multiple sclerosis (MS) diagnostic criteria enable clinicians to diagnose patients earlier in the biologic disease course. Prompt initiation of therapy correlates with improved clinical outcomes. This has led to increased attention on the earliest stages of MS, including the MS prodrome and radiologically isolated syndrome (RIS). Here, we review current understanding and approach to patients with preclinical MS. MS disease biology often begins well before the onset of typical MS symptoms, and we are increasingly able to recognize preclinical and prodromal stages of MS. RIS represents the best characterized aspect of preclinical MS, and its diagnostic criteria were recently revised to better capture patients at highest risk of conversion to clinical MS. The first two randomized control trials evaluating disease modifying therapy use in RIS also found that treatment could delay or prevent onset of clinical disease. Despite progress in our understanding of the earliest stages of the MS disease course, additional research is needed to systematically identify patients with preclinical MS as well as capture those at risk for developing clinical disease. Recent data suggests that preventive immunomodulatory therapies may be beneficial for high-risk patients with RIS; though management remains controversial.

Disease-modifying therapies in managing disability worsening in paediatric-onset multiple sclerosis: a longitudinal analysis of global and national registries

High-efficacy disease-modifying therapies have been proven to slow disability accrual in adults with relapsing-remitting multiple sclerosis. However, their impact on disability worsening in paediatric-onset multiple sclerosis, particularly during the early phases, is not well understood. We evaluated how high-efficacy therapies influence transitions across five disability states, ranging from minimal disability to gait impairment and secondary progressive multiple sclerosis, in people with paediatric-onset multiple sclerosis. Longitudinal data were obtained from the international MSBase registry, containing data from people with multiple sclerosis from 151 centres across 41 countries, and the Italian Multiple Sclerosis and Related Disorders Register, containing data from people with multiple sclerosis from 178 Italian multiple sclerosis centres. People younger than 18 years at the onset of multiple sclerosis symptoms were included, provided they had a confirmed diagnosis of relapsing-remitting multiple sclerosis and at least four Expanded Disability Status Scale (EDSS) scores recorded within 12-month intervals. The primary outcome was the time to change in disability state: minimal disability (EDSS scores 0, 1·0, and 1·5), mild disability (EDSS scores 2·0 and 2·5), moderate disability (EDSS scores 3·0 and 3·5), gait impairment (EDSS scores ≥4·0), and clinician diagnosed secondary progressive multiple sclerosis. A multi-state model was constructed to simulate the natural course of multiple sclerosis, modelling the probabilities of both disability worsening and improvement simultaneously. The impact of high-efficacy disease-modifying therapies (alemtuzumab, cladribine, daclizumab, fingolimod, mitoxantrone, natalizumab, ocrelizumab, rituximab, or autologous haematopoietic stem cell transplantation) and low-efficacy disease-modifying therapies (dimethyl fumarate, glatiramer acetate, interferon beta, or teriflunomide), compared with no treatment, on the course of disability was assessed. Apart from recruitment, individuals with lived experience of multiple sclerosis were not involved in the design and conduct of this study. A total of 5224 people (3686 [70·6%] female and 1538 [29·4%] male) with mean age at onset of multiple sclerosis 15·24 years (SD 2·52) were included. High-efficacy therapies reduced the hazard of disability worsening across the disability states. The largest reduction (hazard ratio 0·41 [95% CI 0·31-0·53]) was observed in participants who were treated with high-efficacy therapies while in the minimal disability state, compared with those remained untreated. The benefit of high-efficacy therapies declined with increasing disability. Young people with minimal disability who received low-efficacy therapy also experienced a reduced hazard (hazard ratio 0·65 [95% CI 0·54-0·77]) of transitioning to mild disability, in contrast to those who remained untreated. Treatment of paediatric-onset relapsing-remitting multiple sclerosis with high-efficacy therapy substantially reduces the risk of reaching key disability milestones. This reduction in risk is most pronounced among young people with minimal or mild disability when treatment began. Children with relapsing-remitting multiple sclerosis should be treated early with high-efficacy therapy, before developing significant neurological impairments, to better preserve their neurological capacity. National Health and Medical Research Council, Australia; MSBase Foundation Fellowship; MS Australia Postdoctoral Fellowship.

Empowering Minds and Bodies: The Impact of Exercise on Multiple Sclerosis and Cognitive Health.

Multiple sclerosis (MS) is a global health concern affecting around 2.6 million people. It is characterised by neural inflammation, myelin breakdown and cognitive decline. Cognitive impairment, especially reduced cognitive processing speed (CPS), which affects up to 67% of MS patients and frequently manifests before mobility concerns, is one of the disease's most serious side effects. Effective adaptation and the application of cognitive rehabilitation treatments depend on the early diagnosis of cognitive impairment. Although pharmaceutical therapies have some drawbacks, endurance training has become a promising alternative. Intensity-controlled endurance exercise has the ability to delay the onset of MS symptoms and enhance cognitive function. Exercise has also been shown to have neuroprotective effects in a number of neurological disorders, including MS, Parkinson's disease and stroke. This includes both aerobic and resistance training. A mix of aerobic exercise and weight training has shown promise, especially for people with mild cognitive impairment, but according to recent studies any amount of physical activity is beneficial to cognitive performance. In conclusion, this in-depth analysis highlights the crucial part endurance exercise plays in treating MS-related cognitive impairment. It improves not only neurological health in general but also cognitive performance. Exercise can help control MS in a way that dramatically improves quality of life and well-being.

Gastrointestinal conditions in the multiple sclerosis prodrome.

To investigate gastrointestinal (GI)-related physician visits and drug dispensations in the 5 years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset. Using linked administrative and clinical data from British Columbia (1996-2013), Canada, we identified an administrative cohort via a validated algorithm (n = 6863), a clinical cohort diagnosed at a MS clinic (n = 966), and matched controls (administrative cohort: n = 31,865; clinical cohort: n = 4534). In each cohort, the 5 years before a first demyelinating event or MS symptom onset (i.e., index date) were examined. We compared rates of GI-related physician visits and risk of ≥1 GI-related dispensation between MS cases and controls using negative binomial and robust Poisson models. Sex differences were tested using interaction terms. The administrative cohort MS cases had higher rates of physician visits related to gastritis and duodenitis (adjusted rate/risk ratio (aRR):1.42, 95% CI: 1.10-1.83) and diseases of the esophagus (aRR: 1.46, 95% CI: 1.06-2.02) prior to the index date. MS cases also had greater risk of at least one dispensation for several drug classes, including constipation-related (aRR: 1.82, 95% CI: 1.50-2.22), antiemetics/antinauseants (aRR: 1.64, 95% CI: 1.43-1.89), and propulsives (promotility drugs; aRR: 1.62, 95% CI: 1.47-1.79). Men had a disproportionally higher relative risk for propulsives than women (aRR: men = 2.32, 95% CI: 1.79-3.00; women = 1.54, 95% CI: 1.36-1.72). Several findings were similar in the smaller clinical cohort though none reached statistical significance. GI-related physician visits and drug dispensations were more common in the 5 years before the first demyelinating event versus matched controls. GI symptoms are a measurable feature of the prodromal or early phase of MS, with a sex difference evident.

Immunoglobulin levels are higher at multiple sclerosis onset - a part of natural history?

Changes in immunoglobulin (Ig) levels may occur in association with various drugs targeting immunity, including disease-modifying drugs (DMD) and corticosteroids (CS) used to treat multiple sclerosis (MS). However, kinetics of Ig levels during the natural history of MS is poorly described. To describe the natural history of the Ig levels in MS. Monocentric retrospective study examining changes in Ig levels in relation with CS intake in a series of 304 consecutive MS patients (and 1204 samples) followed or hospitalized for 7 years in a single centre. Ig levels are routinely collected in MS patients followed in our centre. IgG levels were higher in samples taken at diagnosis than in those taken after the onset of MS symptoms. This effect was also observed in patients remaining free of DMD or CS since onset. On the other hand, overall Ig levels remained stable across fixed time points ranging from 1 to 20 years after onset CONCLUSION: An unanticipated finding of this study was the transient higher IgG levels in samples taken at onset, which suggests that strong inflammatory processes may occur early.

Comparative efficacy and safety of ozanimod and ponesimod for relapsing multiple sclerosis: A matching-adjusted indirect comparison.

Ozanimod and ponesimod are sphingosine 1-phosphate receptor modulators approved by the U.S. Food and Drug Administration for treatment of relapsing forms of multiple sclerosis (MS). Given that no head-to-head trials have assessed these two treatments, we performed a matching-adjusted indirect comparison (MAIC) to compare efficacy and safety outcomes between ozanimod and ponesimod for MS. A MAIC compared efficacy and safety of ozanimod and ponesimod at 2 years. Outcomes included annualized relapse rate (ARR) and percentage change from baseline in brain volume loss (BVL) as well as rates of any treatment-emergent adverse events (TEAEs), serious adverse events (AEs), AEs leading to discontinuation, and other safety outcomes. Individual patient-level data were obtained for ozanimod from the RADIANCE-B trial, while aggregate-level patient data were obtained for ponesimod from the OPTIMUM trial. The MAIC was not anchored owing to lack of a common comparator across the two trials. The following characteristics were matched between the trials' populations: age, sex, time since MS symptom onset, relapses in prior year, Expanded Disability Status Scale score, disease-modifying therapies received in the prior 2 years, absence of gadolinium-enhancing T1 lesions, and percentage of patients from Eastern Europe. After matching, key baseline characteristics were balanced between patients receiving ozanimod and ponesimod. Compared with ponesimod, ozanimod had a numerically lower ARR (rate ratio: 0.80 [95% CI: 0.57, 1.10]) and was associated with a significant reduction in BVL (% change difference: 0.20 [95% CI: 0.05, 0.36]). Additionally, ozanimod was associated with a significantly lower risk of TEAEs (risk difference: -11.9% [95% CI: -16.8%, -7.0%]), AEs leading to discontinuation (-6.1% [95% CI: -8.9%, -3.4%]), and lymphocyte count <0.2K/μL (-2.3% [95% CI: -4.2%, -0.5%]). There were no statistically significant differences in the other safety outcomes. The MAIC results suggest that, compared with ponesimod, ozanimod is more effective in preserving brain volume, is comparable in terms of reducing relapse rates, and has a favorable safety profile.

Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry

BackgroundEarly recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time.ObjectiveTo identify...

Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study.

The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS. This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration's Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS. The 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35' and 56°16') were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes <40°, more severe disease was associated with higher latitudes (β = 0.08, 95% CI 0.04-0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40° (β = -0.02, 95% CI -0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 years (β = - 0.5, 95% CI -0.6 to 0.4) and 18 years (β = - 0.6, 95% CI -0.7 to 0.4), as well as with lower lifetime UVB exposure at the time of disability assessment (β = -1.0, 95% CI -1.1 to 0.9). In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.

Perinatal Depression and Anxiety in Women With Multiple Sclerosis: A Population-Based Cohort Study.

ObjectiveTo assess the occurrence of perinatal depression and anxiety in women before and after diagnosis of multiple sclerosis (MS).MethodsA total of 114,629 pregnant women were included in the Norwegian Mother, Father and Child Cohort study (1999–2008). We assessed depression and anxiety by questionnaires during and after pregnancy. Women with MS were identified from national health registries and hospital records and grouped into (1) MS diagnosed before pregnancy (n = 140) or MS diagnosed after pregnancy with (2) symptom onset before pregnancy (n = 98) or (3) symptom onset after pregnancy (n = 308). Thirty-five women were diagnosed with MS in the postpartum period. The reference group (n = 111,627) consisted of women without MS.ResultsWomen with MS diagnosed before pregnancy had an adjusted odds ratio of 2.0 (95% confidence interval, 1.2–3.1) for depression in the third trimester. Risk factors were adverse socioeconomic factors and history of psychiatric disease and physical/sexual abuse. The risk of anxiety was not increased. Women diagnosed with MS in the postpartum period had especially high risk of postpartum depression. Women with MS symptom onset within 5 years after pregnancy had increased risk of both depression and anxiety during pregnancy, whereas women with more than 5 years until symptom onset did not.ConclusionWomen diagnosed with MS have increased risk of perinatal depression. Women with MS symptom onset within 5 years after pregnancy have increased risk of both depression and anxiety during pregnancy.

Disease Progression and Obstetric Outcomes of Women with Multiple Sclerosis at a Reference Center in Northeastern Brazil.

To describe the obstetric outcomes of patients with multiple sclerosis (MS) and the impact of pregnancy and the postpartum period on the progression of the disease. A case series study performed between December 2019 and February 2020, reporting pregnancies occurred between 1996 and 2019. The subjects included were women with MS undergoing follow-up at an MS referral center in Northeastern Brazil, and who had at least one pregnancy after the onset of MS symptoms, or who had their first relapse in the first year after delivery. In total, 26 women and 38 pregnancies were analyzed - 32 of them resulted in delivery, and the remaining 6, in miscarriages. There was a significant increase in the prevalence of relapse during the postpartum period when compared with the gestational period. In 16 (42.1%) of the pregnancies, there was exposure to disease-modifying therapies (DMTs) - 14 (36.8%), to interferon β, and 2 (5.3%), to fingolimod. Higher rates of abortion, prematurity and low birth weight were reported in the group was exposed to DMT when compared with the one who was not. In the sample of the present study, there was a significant increase in the rate of MS relapse during the postpartum period when compared with the gestational period. Additionally, it seems that exposure to DMTs during pregnancy may affect the obstetric outcomes of the patients.

Change and onset-type differences in the prevalence of comorbidities in people with multiple sclerosis.

Little is known about the change in prevalence of comorbidities during the disease course of people with multiple sclerosis (MS) and whether the prevalences vary by MS onset type. To calculate the change in prevalence of comorbidities between symptom onset and the time of study, to compare the prevalences of comorbidities with those in the Australian population at the time of study and to examine onset-type differences. Comorbidity data from 1518 participants of the Australian MS Longitudinal Study and Australian population comparator data (2014-2015 National Health Survey) were used. The change in prevalence between time points and prevalence ratios (PR) at the time of study (crude, age and sex adjusted, and stratified by onset type) was calculated. Comorbidities were common, and those with the largest increases in prevalence between MS symptom onset and the time of study were depression (+ 26.9%), anxiety (+ 23.1%), hypertension (+ 21.9%), elevated cholesterol (+ 16.3%), osteoarthritis (+ 17.1%), eye diseases (+ 11.6%), osteoporosis (+ 10.9%) and cancer (+ 10.3%). Compared to the general population and after age and sex adjustment, participants had a significantly higher prevalence for 14/19 comorbidities at the time of study. The associations were strongest for anaemia, cancer (both PR > 4.00), anxiety, depression, migraine (all PR > 3.00), psoriasis and epilepsy (both PR > 2.00). No significant differences were seen by onset type. Comorbidities are common at MS symptom onset and increase with MS duration. Having MS may thus contribute to accrual of comorbidities. This emphasises the importance of optimal screening for and management of comorbidities in early MS and throughout the disease course.

Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis

Serum neurofilament light chain (NfL) is emerging as an important biomarker in multiple sclerosis (MS). Our objective was to evaluate the prognostic value of serum NfL levels obtained close to the time of MS onset with long-term clinical outcomes. In this prospective cohort study, we identified patients with serum collected within 5 years of first MS symptom onset (baseline) with more than 15 years of routine clinical follow-up. Levels of serum NfL were quantified in patients and matched controls using digital immunoassay (SiMoA HD-1 Analyzer, Quanterix). Sixty-seven patients had a median follow-up of 18.9 years (range 15.0–27.0). The median serum NfL level in patient baseline samples was 10.1 pg/mL, 38.5% higher than median levels in 37 controls (7.26 pg/mL, p = 0.004). Baseline NfL level was most helpful as a sensitive predictive marker to rule out progression; patients with levels less 7.62 pg/mL were 4.3 times less likely to develop an EDSS score of ≥ 4 (p = 0.001) and 7.1 times less likely to develop progressive MS (p = 0.054). Patients with the highest NfL levels (3rd-tertile, > 13.2 pg/mL) progressed most rapidly with an EDSS annual rate of 0.16 (p = 0.004), remaining significant after adjustment for sex, age, and disease-modifying treatment (p = 0.022). This study demonstrates that baseline sNfL is associated with long term clinical disease progression. sNfL may be a sensitive marker of subsequent poor clinical outcomes.

Fatigue, sleep disorders, anaemia and pain in the multiple sclerosis prodrome

Background: There is increasing evidence of prodromal multiple sclerosis (MS). Objective: The aim of this study was to determine whether fatigue, sleep disorders, anaemia or pain form part of the MS prodrome. Methods: This population-based matched cohort study used linked administrative and clinical databases in British Columbia, Canada. The odds of fatigue, sleep disorders, anaemia and pain in the 5 years preceding the MS cases’ first demyelinating claim or MS symptom onset were compared with general population controls. The frequencies of physician visits for these conditions were also compared. Modifying effects of age and sex were evaluated. Results: MS cases/controls were assessed before the first demyelinating event (6863/31,865) or MS symptom onset (966/4534). Fatigue (adj.OR: 3.37; 95% CI: 2.76–4.10), sleep disorders (adj.OR: 2.61; 95% CI: 2.34–2.91), anaemia (adj.OR: 1.53; 95% CI: 1.32–1.78) and pain (adj.OR: 2.15; 95% CI: 2.03–2.27) during the 5 years preceding the first demyelinating event were more frequent among cases, and physician visits increased for cases relative to controls. The association between MS and anaemia was greater for men; that between MS and pain increased with age. Pre-MS symptom onset, sleep disorders (adj.OR: 1.72; 95% CI: 1.12–2.56) and pain (adj.OR: 1.53; 95% CI: 1.32–1.76) were more prevalent among cases. Conclusion: Fatigue, sleep disorders, anaemia and pain were elevated before the recognition of MS. The relative anaemia burden was higher in men and pain more evident among older adults.

Gender identity and sexual orientation affect health care satisfaction, but not utilization, in persons with Multiple Sclerosis

ObjectiveWe aimed to determine the association between gender identity and sexual orientation on health care utilization in persons with multiple sclerosis (MS), as well as satisfaction with their doctor and comfort discussing sexual health with their doctor. MethodsWe surveyed participants from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding their gender identity and sexual orientation in 2017. Participants also reported their sociodemographic characteristics, disability status, health behaviors and health care utilization, including whether any hospitalizations or emergency room (ER) visits occurred or any disease-modifying therapy (DMT) was used within the last six months. We compared the likelihood of hospitalizations, ER visits and DMT use between (i) cisgender and transgender participants; and (ii) heterosexual, homosexual, and “other sexual orientation” participants using multivariable logistic regression models adjusting for potential confounding factors. ResultsOf the 5,604 eligible responders, 1168 (20.8%) reported their sex at birth as male and 4436 reported their sex at birth as female (79.2%). Twenty-five (0.45%) participants identified as transgender and 260 (4.6%) as non-heterosexual individuals. As compared to participants who reported their sexual orientation as heterosexual, non-heterosexual participants were younger, with an earlier age at MS symptom onset, more likely to have a post-secondary education, and more likely to be single. The frequency of any ER visits, any hospital admissions, and DMT use did not differ according to gender identity did not differ according to gender identity or sexual orientation. As compared to cisgender participants, transgender participants reported less comfort (p < 0.042) discussing sexual health with their doctor; findings were similar for non-heterosexual participants as compared to heterosexual participants. Participants reporting other sexual orientation also reported lower satisfaction (p < 0.039) with their doctor than other participants. ConclusionGender identity and sexual orientation were not associated with differences in healthcare utilization in persons with MS. However, health care experiences and satisfaction with care may be altered by gender identity and sexual orientation.

Socioeconomic status and disability progression in multiple sclerosis: A multinational study.

To examine the association between socioeconomic status (SES) and disability outcomes and progression in multiple sclerosis (MS). Health administrative and MS clinical data were linked for 2 cohorts of patients with MS in British Columbia (Canada) and South East Wales (UK). SES was measured at MS symptom onset (±3 years) based on neighborhood-level average income. The association between SES at MS onset and sustained and confirmed Expanded Disability Status Scale (EDSS) 6.0 and 4.0 and onset of secondary progression of MS (SPMS) were assessed using Cox proportional hazards models. EDSS scores were also examined via linear regression, using generalized estimating equations (GEE) with an exchangeable working correlation. Models were adjusted for onset age, sex, initial disease course, and disease-modifying drug exposure. Random effect models (meta-analysis) were used to combine results from the 2 cohorts. A total of 3,113 patients with MS were included (2,069 from Canada; 1,044 from Wales). A higher SES was associated with a lower hazard of reaching EDSS 6.0 (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.89-0.91), EDSS 4.0 (aHR 0.93, 0.88-0.98), and SPMS (aHR 0.94, 0.88-0.99). The direction of findings was similar when all EDSS scores were included (GEE: β = -0.13, -0.18 to -0.08). Lower neighborhood-level SES was associated with a higher risk of disability progression. Reasons for this association are likely to be complex but could include factors amenable to modification, such as lifestyle or comorbidity. Our findings are relevant for planning and development of MS services.

How do patients enter the healthcare system after the first onset of multiple sclerosis symptoms? The influence of setting and physician specialty on speed of diagnosis

Background: Diagnosing multiple sclerosis (MS) early is crucial to avoid future disability. However, potentially preventable delays in the diagnostic cascade from contact with a physician to definite diagnosis still occur and their causes are still unclear. Objective: To identify the possible causes of delays in the diagnostic process. Methods: We analyzed the data of the Swiss MS Registry. With logistic regression, we modeled the time from the first contact to the first consultation (contact-to-evaluation time, ⩽1 month/>1 month) and the evaluation-to-diagnosis time (⩽6 months/>6 months). Potential factors were health system characteristics, sociodemographic variables, first symptoms, and MS type. Results: We included 522 participants. Mostly, general practitioners (67%) were contacted first, without delaying the diagnosis. In contrast, first symptoms and MS type were the major contributors to delays: gait problems were associated with longer contact-to-evaluation times, depression as a concomitant symptom with longer evaluation-to-diagnosis times, and having primary progressive MS prolonged both phases. In addition, living in mountainous areas was associated with longer contact-to-evaluation times, whereas diagnosis after 2000 was associated with faster diagnoses. Conclusion: For a quicker diagnosis, awareness of MS as a differential diagnosis of gait disorders and the co-occurrence of depression at onset should be raised, and these symptoms should be attentively followed.

Factors associated with perceived need for mental health care in multiple sclerosis

BackgroundWithin the multiple sclerosis (MS) population, depression and anxiety are highly prevalent comorbidities that are associated with adverse outcomes such as diminished quality of life and disability progression. In the general population, many people who do not meet formal diagnostic criteria for depression or anxiety disorders still identify a need for mental health care. Limited data are available regarding the perceived need for mental health care among persons with MS. ObjectiveWe aimed to determine factors associated with a perceived need for mental health care in the MS population. MethodsParticipants with MS completed the Hospital Anxiety and Depression Scale (HADS) to assess severity of depression and anxiety symptoms, and reported whether they perceived a need for mental health care, in the context of a larger study examining the burden of psychiatric disorders in immune-mediated inflammatory disease. Participants were also evaluated using the Structured Clinical Interview for DSM-IV-TR (SCID) to diagnose depression or anxiety disorders. Participants reported their sociodemographic characteristics, and underwent physical assessments to determine their disability status. Descriptive analyses and binary logistic regression models were used to determine sociodemographic and clinical factors associated with perceived need for mental health care. ResultsOf 255 participants enrolled, 251 were included in this analysis. Most participants were women, Caucasian, with post-secondary education, with a mean (SD) age at enrollment of 50.9 (12.9) years. They predominantly had a relapsing-remitting MS course. Nearly one-quarter of participants had a current SCID diagnosis of depression or anxiety (n = 57, 22.7%). Overall, 31.8% (n = 80) of participants reported a need for mental health care. These individuals were slightly younger at enrollment (p = 0.037), but otherwise did not differ with respect to sociodemographic characteristics, compared to participants not reporting this need. Those identifying need for mental health care also had an earlier age of MS symptom onset (p = 0.011). After adjusting for sociodemographic and clinical factors, elevated symptoms of depression (odds ratio [OR] 2.36; 95%CI: 1.06, 5.25) and anxiety (OR 6.08; 95%CI: 2.78, 13.3) were associated with an increased likelihood of reporting a need for mental health care. Any current SCID diagnosis of depression or anxiety was not associated with perceived need for mental health care after accounting for symptoms of depression and anxiety. ConclusionsOne-third of people with MS identified a need for mental health care. Symptoms of anxiety and depression, but not current diagnosed mental health disorders, were the predominant factors associated with a perceived need for care.

The use of satellite data to measure ultraviolet-B penetrance and its potential association with age of multiple sclerosis onset

BackgroundStudies have indicated an association between low Ultraviolet B (UVB) exposure and an increased risk of developing multiple sclerosis (MS). Few studies, however, have explored whether UVB exposure is associated with the age at MS symptom onset. ObjectiveWe investigated the potential association between cumulative early life ambient UVB exposure and age at MS onset, using satellite data to measure ambient UVB exposure. MethodsAdult onset MS patients were selected from the University of British Columbia's MS genetic database (1980–2005). Patients’ places of residence from birth to age 18 years were geocoded (latitude and longitude) and assigned UVB values using NASA's Total Ozone Mapping Spectrometer (TOMS) dataset. Linear regression was used to explore the relationship between cumulative UVB exposure (measured for age periods 0–6, 7–12, 13–18, 0–12, and 0–18) and age at MS onset. Results3226 patients were included in the analysis. Of these, 74% were female, with an overall mean symptom onset age of 33.3 years. At onset, a total of 2944 (91%) had a relapsing-remitting disease course, 254 (8%) had primary progressive and the disease course for 28 (1%) was unknown. No significant associations between cumulative early life ambient UVB exposure and age at MS onset were observed. Patient sex, MS phenotype, and immigration to Canada after age 18 were significantly associated with age of onset (p < 0.01). ConclusionsEarly life ambient UVB, as measured by satellite imagery, was not significantly associated with the age at MS onset.

Effects of physical comorbidities on disability progression in multiple sclerosis.

To examine the association between physical comorbidities and disability progression in multiple sclerosis (MS). We conducted a retrospective cohort study using linked health administrative and clinical databases in 2 Canadian provinces. Participants included adults with incident MS between 1990 and 2010 who entered the cohort at their MS symptom onset date. Comorbidity status was identified with validated algorithms for health administrative data and was measured during the 1 year before study entry and throughout the study period. The outcome was the Expanded Disability Status Scale (EDSS) score as recorded at each clinic visit. We used generalized estimating equations to examine the association between physical comorbidities and EDSS scores over time, adjusting for sex, age, cohort entry year, use of disease-modifying drugs, disease course, and socioeconomic status. Meta-analyses were used to estimate overall effects across the 2 provinces. We identified 3,166 individuals with incident MS. Physical comorbidity was associated with disability; with each additional comorbidity, there was a mean increase in the EDSS score of 0.18 (95% confidence interval [CI] 0.09-0.28). Among specific comorbidities, the presence of ischemic heart disease (IHD) or epilepsy was associated with higher EDSS scores (IHD 0.31, 95% CI 0.01-0.61; epilepsy 0.68, 95% CI 0.11-1.26). Physical comorbidities are associated with an apparent increase in MS disability progression. Appropriate management of comorbidities needs to be determined to optimize outcomes.

Physical activity and the incidence of multiple sclerosis.

To study whether physical activity during adulthood or early life is associated with multiple sclerosis (MS) incidence in 2 prospective cohorts of women. Women in the Nurses' Health Study (NHS) (n = 81,723; 1986-2004) and NHS II (n = 111,804; 1989-2009) reported recent physical activity at baseline and in selected follow-up questionnaires. Using this information, we calculated total metabolic equivalent hours of physical activity per week, a measure of energy expenditure. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. To estimate relative rates (RRs) and 95% confidence intervals (CIs), we used Cox proportional hazards models, adjusting for age, latitude of residence at age 15, ethnicity, smoking, supplemental vitamin D, and body mass index at age 18. Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS (RRpooled = 0.73, 95% CI 0.55-0.98; p-trend 0.08); this trend was not present in 6-year lagged analyses. Change in physical activity analyses suggested that women reduced activity before onset of MS symptoms. In NHS and NHS II, higher strenuous activity at ages 18-22 years was weakly associated with a decreased MS rate. However, in NHS II, total early-life activity at ages 12-22 was not associated with MS. Though higher physical activity at baseline was weakly associated with lower MS risk, this may have been due to women reducing physical activity in response to subclinical MS.