Onset Of Progressive Multiple Sclerosis Research Articles

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case–control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

Premorbid Sociodemographic Status and Multiple Sclerosis Outcomes in a Universal Health Care Context

Multiple sclerosis (MS) severity may be informed by premorbid sociodemographic factors. To determine whether premorbid education, income, and marital status are associated with future MS disability and symptom severity, independent of treatment, in a universal health care context. This nationwide observational cohort study examined data from the Swedish MS Registry linked to national population registries from 2000 to 2020. Participants included people with MS onset from 2005 to 2015 and of working age (aged 23 to 59 years) 1 year and 5 years preceding disease onset. Income quartile, educational attainment, and marital status measured at 1 and 5 years preceding disease onset. Repeated measures of Expanded Disability Status Scale (EDSS) scores and patient-reported Multiple Sclerosis Impact Scale (MSIS-29) scores. Models were adjusted for age, sex, relapses, disease duration, and treatment exposure. Secondary analyses further adjusted for comorbidity. All analyses were stratified by disease course (relapse onset and progressive onset). There were 4557 patients (mean [SD] age, 37.5 [9.3] years; 3136 [68.8%] female, 4195 [92.1%] relapse-onset MS) with sociodemographic data from 1-year preonset of MS. In relapse-onset MS, higher premorbid income and education correlated with lower disability (EDSS, -0.16 [95% CI, -0.12 to -0.20] points) per income quartile; EDSS, -0.47 [95% CI, -0.59 to -0.35] points if tertiary educated), physical symptoms (MSIS-29 physical subscore, -14% [95% CI, -11% to -18%] per income quartile; MSIS-29 physical subscore, -43% [95% CI, -35% to -50%] if tertiary educated), and psychological symptoms (MSIS-29 psychological subscore, -12% [95% CI, -9% to -16%] per income quartile; MSIS-29 psychological subscore, -25% [95% CI, -17% to -33%] if tertiary educated). Marital separation was associated with adverse outcomes (EDSS, 0.34 [95% CI, 0.18 to 0.51]; MSIS-29 physical subscore, 35% [95% CI, 12% to 62%]; MSIS-29 psychological subscore, 25% [95% CI, 8% to 46%]). In progressive-onset MS, higher income correlated with lower EDSS (-0.30 [95% CI, -0.48 to -0.11] points per income quartile) whereas education correlated with lower physical (-34% [95% CI, -53% to -7%]) and psychological symptoms (-33% [95% CI, -54% to -1%]). Estimates for 5-years preonset were comparable with 1-year preonset, as were the comorbidity-adjusted findings. In this cohort study of working-age adults with MS, premorbid income, education, and marital status correlated with disability and symptom severity in relapse-onset and progressive-onset MS, independent of treatment. These findings suggest that socioeconomic status may reflect both structural and individual determinants of health in MS.

Association of volumetric MRI measures and disability in MS patients of the same age: Descriptions from a birth year cohort.

Although MRI-based markers of neuroinflammation have proven crucial for the diagnosis of multiple sclerosis (MS), predicting clinical progression with inflammation remains difficult. Neurodegenerative markers such as brain volume loss show stronger clinical (predictive) correlations, but also harbor age-related variation that must be disentangled from disease duration. In this study we investigated how clinical disability is related to volumetric MRI measures in a cohort of MS patients and healthy controls (HC) of the same age: Project Y. This study included 234 MS patients born in 1966 and 112 HC born between 1965 and 1967 in the Netherlands. Disability was quantified using the expanded disability status scale (EDSS), nine hole peg test (9HPT), and timed 25 foot walking test (T25FWT). Volumes were quantified on 3T MRI as normalized whole brain (NBV) and regional gray matter (GM) volumes using the same scanner and MRI protocol: cortical (normalized cortical gray matter volume; NCGMV), deep (NDGMV), thalamic (NThalV), and cerebellar (NCbV) GM volumes. In addition, mean upper cervical cord area (MUCCA), white matter lesion volume (LV), and spinal cord lesions were assessed. These measures were compared between patients and HC, and related to disability measures using linear regression. Mean age of people with MS (PwMS) was 52.8 years (SD 0.9) and median disease duration 15.8 years (IQR 8.7-24.8). All global and regional brain measures were lower in MS patients compared to HC. Univariate regression models showed that NDGMV (β=-0.20) and MUCCA (β=-0.38) were most strongly related to the EDSS in all PwMS. After subtype stratification, MUCCA was most strongly related to the EDSS (β=-0.60) and 9HPT (β=-0.55) in secondary progressive PwMS. Multivariate regression models demonstrated that in all PwMS, the EDSS was best explained by lower MUCCA, longer disease durations and a progressive disease course (adjusted-R (Sastre-Garrigaetal., 2017)=0.26, p < 0.001). MUCCA was a consistent correlate in separate models of the EDSS for all PwMS, relapsing and progressive onset PwMS. The 9HPT (adjusted-R (Sastre-Garrigaetal., 2017)=0.20, p < 0.001) was best explained by lower MUCCA, higher LV and pack years, while lower limb disability (adjusted-R (Sastre-Garrigaetal., 2017)=0.11, p < 0.001) was best explained by lower MUCCA, progressive onset MS and female sex. Our results indicate that in a cohort unbiased by age differences, spinal cord and deep gray matter volumes best related to physical disability. Our results support the use of these measures in clinical practice and trials.

1234Smoking, infectious mononucleosis, early-life exposures and risk of progressive-onset Multiple Sclerosis: a case-control study

Abstract Background Risk factors in Multiple Sclerosis (MS) have been identified in samples that contain predominantly cases with relapse-onset MS (ROMS). It is unknown whether the risk factors differ in people with a progressive-onset MS (POMS). Methods The case-control study included 147 POMS cases, 264 ROMS cases and 558 community controls. Questionnaires were used to collect information on smoking, infections, breastfeeding and vitamin use in early life. Logistic regression was used to examine associations. Odds ratios (ORs) were adjusted for age, sex and latitude band. Results Compared with controls, POMS cases were more likely to have smoked ≥20 pack-years (AOR 2.83, 1.53-5.24) and ROMS cases were more likely to have ever been a smoker (AOR 1.48, 1.09-2.01). POMS cases (AOR 1.75, 1.05-2.93) and ROMS cases (AOR 1.74, 1.21-2.49) were both more likely to have had infectious mononucleosis. In childhood, POMS cases were less likely to use vitamin supplements (AOR 0.52, 0.30-0.91) or being breastfed (AOR 0.49, 0.31-0.79). Conclusions Smoking and infectious mononucleosis are associated with increased risk of both POMS and ROMS. Vitamin supplements in early life and being breastfed are associated with reduced risk of POMS, but there is no association in ROMS. Key messages POMS and ROMS share some commonly known risk factors. Some protective factors were identified in POMS that were not observed in ROMS.

Does health-related quality of life differ between people with relapse onset and progressive onset Multiple Sclerosis?

BackgroundMultiple Sclerosis (MS) can be categorised as relapse onset MS (ROMS) and progressive onset MS (PROMS). We aimed to examine if health-related quality of life (in terms of health state utilities [HSUs] and dimensional scores) differed by onset type, in which health dimensions the differences were most pronounced, and whether these differences remained when stratified by disability severity. MethodsWe estimated HSUs and the unique composite ‘super-dimension’ and ‘individual dimension’ scores (crude, age, sex, disease duration and disease modifying therapies use adjusted; and stratified by onset type and disability severity) for a sample of 1577 participants in the Australian MS Longitudinal Study, using the Assessment of Quality of Life (AQoL)-8D. ResultsAdjusted mean overall HSU of PROMS was 0.55, 0.07 lower than ROMS. Adjusted mean physical and psychosocial super-dimension scores for PROMS were 0.51 and 0.28, 0.07 and 0.06 lower than for ROMS, respectively. For the individual health dimensions, the largest difference was seen in independent living (–0.12), followed by relationships (–0.07), and self-worth (–0.07). Whilst HSUs and dimensional scores were negatively associated with increasing disability severity in both onset types, estimates by disability severity did not differ between the two cohorts. ConclusionsOur study provides a comprehensive assessment of the effects of MS onset type on the overall and disability-severity specific HRQoL scores using a detailed preferentially sensitive AQoL-8D instrument. While overall HRQoL was substantially lower in PROMS than in ROMS, the mean HRQoL values for each disability level did not differ by onset type, indicating that future health economic models can use the same HSU inputs for both onset types.

Factors affecting the risk of relapsing-onset and progressive-onset multiple sclerosis

ObjectiveIt has been debated whether the different clinical disease courses in multiple sclerosis (MS) are the consequence of different pathogenic mechanisms, with distinct risk factors, or if all MS clinical...

Multiple Sclerosis Phenotypes as a Continuum: The Role of Neurologic Reserve.

Purpose of ReviewThis review presents the hypothesis that loss of neurologic reserve explains onset of progressive multiple sclerosis (PrMS).Recent FindingsEvidence supporting the separate classification of PrMS and relapsing multiple sclerosis (RMS) is limited and does not explain PrMS or the response of these patients to therapy.SummaryWe argue that multiple sclerosis (MS) progresses along a continuum from RMS to PrMS, with differing levels of neurologic reserve accounting for phenotypic differences. In early MS, inflammation causes brain atrophy with symptoms buffered by neurologic reserve. As brain loss from normal aging and MS continues, reserve is depleted and effects of subclinical MS disease activity and aging are unmasked, manifesting as PrMS. Most therapies show limited benefit in PrMS; patients are older, have fewer inflammatory events, and the effects of aging cause continued loss of neurologic function, even if inflammation is terminated. Loss of neurologic reserve means patients with PrMS cannot recover function, unlike patients with RMS.

Physical activity, sitting time and exercise types, and associations with symptoms in Australian people with multiple sclerosis

Purpose Multiple sclerosis (MS) often leads to reduced physical activity and exercise participation. Sedentary behaviour is associated with poor health, whereas exercise is effective in managing MS symptoms. This study assessed physical activity, exercise and sedentary sitting time, and identified associations with symptoms. Material and methods Participants of the Australian MS Longitudinal Study completed surveys in 2016. We measured physical activity and sitting time via the International Physical Activity Questionnaire (short-form), and assessed participation in exercise (type and duration). Multivariable regression models assessed associations between physical activity, sitting time and exercise; and demographic characteristics and MS-related symptoms. Results Of the 1216 participants, 53.0% reported moderate-high physical activity levels (71.5% among those with no/mild disability). Median sitting time was 7 h/day. Most (78.4%) participated in aerobic exercise, while only 16.4% participated in strength training. Having a progressive MS onset, more severe symptoms (i.e., cognitive impairment, depression, fatigue, mobility impairment) and being male was indicative of lower physical activity levels and higher sitting time. Conclusions Health promotion efforts should encourage physical activity and exercise, in particular strength training, among people with MS. People with more severe symptoms and progressive disease may require focused exercise promotion from healthcare professionals. Implications for Rehabilitation Comprehensive MS management should include strategies to increase physical activity and exercise participation, with particular focus upon people with higher MS-symptom burden (i.e., depression, fatigue and mobility and cognitive impairment), men, and those with progressive onset MS. Efforts to promote physical activity guidelines for people with MS and address barriers to physical activity must be implemented in standard MS care, with a particular focus on adhering to strength training guidelines. Exercise type and duration varies among people with MS, and it would behove healthcare professionals and researchers to consider promoting activities which align with individuals preferences and abilities when promoting exercise.

PMU23 Measurement of Health-Related Quality of Life in Australians with Progressive Onset Multiple Sclerosis

PMU23 Measurement of Health-Related Quality of Life in Australians with Progressive Onset Multiple Sclerosis

Reproductive history and progressive multiple sclerosis risk in women

Being a woman is one of the strongest risk factors for multiple sclerosis. The natural reproductive period from menarche to natural menopause corresponds to the active inflammatory disease period in multiple sclerosis. The fifth decade marks both the peri-menopausal transition in the reproductive aging and a transition from the relapsing-remitting to the progressive phase in multiple sclerosis. A short reproductive period with premature/early menopause and/or low number of pregnancies may be associated with an earlier onset of the progressive multiple sclerosis phase. A cross-sectional study of survey-based reproductive history in a multiple sclerosis clinical series enriched for patients with progressive disease, and a case–control study of multiple sclerosis and age/sex matched controls from a population-based cohort were conducted. Menarche age, number of complete/incomplete pregnancies, menopause type and menopause age were compared between 137 cases and 396 control females. Onset of relapsing-remitting phase of multiple sclerosis, progressive disease onset and reaching severe disability (expanded disability status scale 6) were studied as multiple sclerosis-related outcomes (n = 233). Menarche age was similar between multiple sclerosis and control females (P = 0.306). Females with multiple sclerosis had fewer full-term pregnancies than the controls (P < 0.001). Non-natural menopause was more common in multiple sclerosis (40.7%) than in controls (30.1%) (P = 0.030). Age at natural menopause was similar between multiple sclerosis (median, interquartile range: 50 years, 48–52) and controls (median, interquartile range: 51 years, 49–53) (P = 0.476). Nulliparous females had earlier age at progressive multiple sclerosis onset (mean ± standard deviation: 41.9 ± 12.5 years) than females with ≥1 full-term pregnancies (mean ± standard deviation: 47.1 ± 9.7 years) (P = 0.069) with a pregnancy-dose effect [para 0 (mean ± standard deviation: 41.9 ± 12.5 years), para 1–3 (mean ± standard deviation: 46.4 ± 9.2 years), para ≥4 (mean ± standard deviation: 52.6 ± 12.9 years) (P = 0.005)]. Menopause age was associated with progressive multiple sclerosis onset age (R2 = 0.359, P < 0.001). Duration from onset of relapses to onset of progressive multiple sclerosis was shorter for females with premature/early menopause (n = 26; mean ± standard deviation: 12.9 ± 9.0 years) than for females with normal menopause age (n = 39; mean ± standard deviation: 17.8 ± 10.3 years) but was longer than for males (mean ±standard deviation: 10.0 ± 9.4 years) (P = 0.005). There was a pregnancy-dose effect of age at expanded disability status scale 6 (para 0: 43.0 ± 13.2 years, para 1–3: 51.7 ± 11.3 years, para ≥4: 53.5 ± 4.9 years) (P = 0.013). Age at menopause was associated with age at expanded disability status scale 6 (R2 = 0.229, P < 0.003). Premature/early menopause or nulliparity was associated with earlier onset of progressive multiple sclerosis with a ‘dose effect’ of pregnancies on delaying progressive multiple sclerosis and severe disability. Although causality remains uncertain, our results suggest a beneficial impact of oestrogen in delaying progressive multiple sclerosis. If confirmed in prospective studies, our findings have implications for counselling women with multiple sclerosis about pregnancy, surgical menopause and menopausal hormone therapy.

Determinants of Disability in Progressive Onset Multiple Sclerosis.

To describe the clinical and socio-demographic profiles of the patients with the progressive onset Multiple Sclerosis (MS) and to explore the determinants of disability. This is a retrospective study, which was conducted in a university hospital. Patients with a progressive clinical course at onset were included in the study. In the first analysis, the clinical and demographic properties of the cohort were defined. In the second analysis the effects of age, sex, clinical activity during course, initial clinical symptoms and cerebrospinal fluid analyses on the course were evaluated. Clinical activity during the course, older age, male gender, medulla spinalis involvement at onset and detection of paraparesis at initial neurological examination was found as a poor prognostic factor. This research confirms previous findings of the studies conducted in populations of Europe and America. Further studies are needed to confirm and validate these findings and to provide greater insight into the effects of ethnic or geographical differences on the course.

Predictors of Change in Employment Status and Associations with Quality of Life: A Prospective International Study of People with Multiple Sclerosis

Purpose This prospective international study aimed to assess the changes in employment, and predictors thereof, and associated change in mental health quality of life in people with multiple sclerosis (MS). Methods People with MS were recruited online through social media, forums and newsletters to complete an online English-language survey in 2012 and again in 2015, to assess changes in employment and clinical characteristics. Results 1276 people with MS of working age were included of whom 35.9% were employed full time, 25.6% part-time, 3.1% were unemployed and seeking employment, 19.7% were retired due to disability and 15.7% were not in the labour force. Part/full time employment decreased from 61.4 to 57.1% of the sample 2.5 years later, and 25.5% experienced some change in employment status. Lower level of education and higher level of disability at baseline predicted loss of employment at follow-up. 62.0% of the sample indicated that MS impacted on employment over their lifetime, associated with a lower level of education and progressive MS at time of diagnosis. Retiring due to disability was predictive of a decreased mental health related QOL score. Conclusion Employment status was negatively impacted by MS for most participants. We showed for the first time that employment loss was prospectively associated with poorer mental health related quality of life. Employment support including vocational services, reasonable flexibility in the workplace, and legal protection against discrimination should be widely available to assist people with MS, especially for those with progressive onset MS, higher disability and lower levels of education who are at higher risk of employment loss.

Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades

Clinicians' experience and findings from recent natural history studies suggest that multiple sclerosis (MS) may now be running a more slowly progressing course than before. To investigate whether the risk of reaching MS disability milestones has changed over the last decade in Sweden. A nationwide population-based retrospective cohort study. By April 2017, 12 512 patients with available information on demographics, MS phenotype, and date of MS onset and diagnosis were registered in the Swedish MS Registry of which 7331 patients with at least 2 recorded Expanded Disability Status Scale scores (EDSS) and diagnosed between January 1995 and December 2010 were included. No further exclusion criteria were applied. Patients were followed up until December 2016 with a median duration follow-up of 8.5 (interquartile range, 4.7-13.8) years. Statistical analysis began in April 2017. Patients were followed up from MS onset date to the date of sustained EDSS 3.0, 4.0, and 6.0. To handle interval-censored observations, a Weibull model was fit, and the change in the risk of EDSS 3.0, 4.0, and 6.0 over calendar years was estimated and hazard ratios (HRs) with corresponding CIs were calculated. Of 7331 patients, 5196 (70.9%) were women, and the mean (SD) age at diagnosis was 38.3 (11.7) years. Adjusting for sex, number of clinic visits, diagnostic delay, and onset age, a 3% decrease per calendar year of diagnosis for the risk of sustained EDSS 3.0 (HR, 0.97; 95% CI, 0.96-0.97), a 6% decrease for the risk of EDSS 4.0 (HR, 0.94; 95% CI, 0.93-0.95), and a 7% decrease for the risk of EDSS 6.0 (HR, 0.93; 95% CI, 0.91-0.94) among patients with relapsing-onset MS was found. The trends were not significant for patients with progressive-onset MS (EDSS 3.0: HR, 1.01; 95% CI, 0.98-1.03; EDSS 4.0: HR, 1.00; 95% CI, 0.98-1.02; EDSS 6.0: HR, 1.00; 95% CI, 0.98-1.02). Risk of reaching major disability milestones has significantly decreased over the last decade in patients with relapsing-onset MS in Sweden. Several factors could potentially be responsible for this observation. However, given that no change was seen in disability accrual of patients with progressive-onset MS and the absence of efficacious treatment option in this group, increased use of more efficacious disease-modifying treatments could be a possible driver of this change.

Patient-reported outcomes are worse for progressive-onset multiple sclerosis than relapse-onset multiple sclerosis, particularly early in the disease process.

Treatments for progressive-onset multiple sclerosis (MS) are lacking. To improve the disease management for progressive-onset MS, the differences between relapse-onset MS and progressive-onset MS in patient-reported disability, progression and symptoms were examined. A total of 1985 participants of the Australian Multiple Sclerosis Longitudinal Study were included. Associations between onset type and outcomes were assessed with negative binomial regression. The severity of 17 of the 19 outcomes was significantly higher for progressive-onset MS patients than relapse-onset MS patients, including perspectives from disability, progression over the last year, fatigue, sensory, walking difficulties, pain, balance, spasticity, sexual dysfunction, bladder, bowel, anxiety, depression and the European quality of life (EQ-5D) (P<0.05; adjusted mean ratio ranged from 1.11 to 1.52). The differences between the two onset types were most pronounced early in the disease process and reduced with increasing MS duration, and the interaction was significant for disability, progression over the last year, walking difficulties, bladder problems, bowel problems and spasticity. Participants with progressive-onset MS were significantly worse off on nearly all patient-reported outcomes than relapse-onset MS participants, and the differences were most pronounced early in the disease course, highlighting the importance of early intervention for those with progressive-onset MS.

Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis

The role of inflammatory disease activity as a determinant of disability in progressive-onset multiple sclerosis (MS) remains contested. To examine the association of superimposed relapses in progressive-onset MS on disease outcomes. Observational cohort study from MSBase, a prospectively collected, international database. Data were collected between January 1995 and February 2017. Analyses began in February 2017. From 44 449 patients at time of extraction, 1419 eligible patients (31.9%) were identified for analysis. Inclusion criteria consisted of primary progressive MS (PPMS) or progressive-relapsing MS (PRMS), adult-onset disease, and minimum data set (including ≥3 visits with disability recorded, ≥3 months between second and last visit). Data were analyzed using multivariable regression models (Andersen-Gill) with mixed effects. Two sensitivity analyses to exclude both relapse-related disability progression and bout-onset progressive MS were performed. Grouped according to presence or absence of relapse, defined as an acute episode of clinical worsening. Quantifiable disability change or correlation on imaging was not required to confirm relapse. Cumulative hazard of disability progression. Patients with PRMS were younger than those with PPMS (mean [SD] age, 46 [15] vs 51 [10] years, Cohen d = 0.40) and demonstrated a mean lower Expanded Disability Status Scale score (mean [SD] score, 4.0 [3] vs 4.5 [2.5], Cohen d = 0.28) at inclusion. The ratio of men to women was similar in the PRMS and PPMS groups (252:301 vs 394:472). The overall mean (SD) age was 48 (11) years for men and 50 (10) years for women. Likelihood of confirmed disability progression was lower in patients with superimposed relapses (hazard ratio [HR], 0.83; 95% CI, 0.74-0.94; P = .003). Proportion of follow-up time spent on disease-modifying therapy significantly reduced the hazard of confirmed disability progression in the cohort with relapse (HR, 0.96; 95% CI, 0.94-0.99; P = .01) but not in those without relapse (HR, 1.02; 95% CI, 0.99-1.05; P = .26). When accounting for relapse-related progression, the association of disease-modifying therapy in the cohort with superimposed relapse was no longer observed (HR, 1.10; 95% CI, 0.96-1.24; P = .16). In progressive-onset MS, superimposed relapses are associated with a lower risk of confirmed disability progression. This is most likely attributed to the association of disease-modifying therapy with the prevention of relapse-related disability accrual in patients with superimposed relapse. These findings suggest that inflammatory relapses are an important and modifiable determinant of disability accrual in progressive-onset disease.

Progressive Onset Multiple Sclerosis: Demographic, Clinical and Laboratory Characteristics of Patients With and Without Relapses in the Course

Progressive Onset Multiple Sclerosis: Demographic, Clinical and Laboratory Characteristics of Patients With and Without Relapses in the Course

Progressive Onset Multiple Sclerosis: Demographic, Clinical and Laboratory Characteristics of Patients With and Without Relapses in the Course.

Primer progresif multipl skleroz (PPMS) ve progresif relapsing multipl skleroz (PRMS) başlangıçtan beri olan progresyon ile karakterize MS tipleridir. Nadir görülmelerinden dolayı, literatürde diğer MS formlarına göre daha az bilgi bulunmaktadır. Bu çalışmanın amacı progresif başlangıçlı MS (PBMS) hastalarında klinik ve laboratuvar özelliklerini ortaya koymaktır. PBMS hastaları 2010-2014 yılları arasında değerlendirilip demografik, klinik özellikleri ve beyin omurilik sıvısı (BOS) bulguları belirlendi. Otuz iki PBMS hastası ile ilgili veriler değerlendirildi. Hastalık seyri 24 hastada relaps olmadan (PPMS), sekiz hastada ise relapslı progresifti (PRMS). Kadın/erkek oranı tüm grupta 1'di. Ortalama başlangıç yaşı tüm grup için 40 (23-55) yaştı. Gruplar arasında hastalık başlangıç yaşı ortancası anlamlı farklı bulunmadı (p=0,053). En sık prezantasyon belirtisi motor bozukluklardı. Relapslar tüm hastalarda hastalığın ilk 10 yılında görüldü. BOS analizinde oligoklonal bant pozitifliği ve artmış IgG indeksi açısından gruplar arasında fark saptanmadı (p=0,938, p=0,058). Hastalık süresi her iki grupta da benzer olduğu halde, PPMS grubunda değerlendirme sırasında ortanca EDSS skoru daha yüksek bulundu (p=0,020). Çalışmamız Türk PBMS hastalarının klinik seyir ve laboratuvar bulgularına odaklanmış ilk çalışmadır. İki grubun klinik ve laboratuvar bulgularının karşılaştırılması benzer sonuçlar göstermiştir. Gruplar arasında hastalık başlangıç yaşı ve artmış IgG indeksi açısından farklılık olup olmadığını netleştirmek için gelecekte daha geniş örneklemli çalışmalar yapılması gerekmektedir.

Self-reported levels of education and disability progression in multiple sclerosis.

The purpose of our study is to investigate whether socioeconomic indicators such as education, financial concerns, employment, and living status are associated with disease progression in relapsing-onset and progressive-onset Multiple Sclerosis (MS). We performed a cross-sectional survey among individuals with MS, registered by the Flemish MS society and included socioeconomic indicators. A Cox proportional hazard regression was performed with the time from MS onset and from birth to reach an ambulatory disability milestone corresponding to Expanded Disability Status Scale (EDSS) 6 (requiring a cane) as outcome measure, adjusted for gender, age at MS onset, and immunomodulatory treatment. Among the participants with relapsing-onset MS, subjects reporting education for more than 12 years had a reduced risk of reaching EDSS 6 compared to subjects reporting education for less than 12 years [HR from onset 0.68 (95% CI 0.49-0.95); HR from birth 0.71 (95% CI 0.51-0.99)]. In progressive-onset MS, longer education was associated with an increased hazard to reach EDSS 6 [HR from onset 1.25 (95% CI 0.91-1.70); HR from birth 1.39 (95% CI 1.02-1.90)]. Our study shows an association of self-reported levels of education with disability progression in MS, with the highest level being protective in relapsing-onset MS.

Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis.

To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS). We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test). In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse. Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.

Inverse correlation of genetic risk score with age at onset in bout-onset and progressive-onset multiple sclerosis

We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) (n=544). We observed an opposite relationship in the two disease courses: a higher weighted genetic risk score was associated with an earlier age at onset in BOMS (rho= −0.1; p=5 × 10−3) and a later age at onset in PrMS cases (rho=0.07; p=0.15) (p of difference of regression=1.4 × 10−2). These findings suggest that established MS risk variants anticipate the onset of the inflammatory phase, while they have no impact on, or even delay, the onset of the progressive phase.