Five years before multiple sclerosis onset: Phenotyping the prodrome

Wijnands, José M.A.; Zhu, Feng; Kingwell, Elaine; Zhao, Yinshan; Ekuma, Okechukwu; Lu, Xinya; Evans, Charity; Fisk, John D.; Marrie, Ruth Ann; Tremlett, Helen

doi:10.1177/1352458518783662

Cited by 74 publications

(98 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They enable the identification of risk factors many years prior to MS diagnosis . They have also been used to demonstrate an “MS prodrome” in the years preceding a clinical diagnosis of MS . Previous studies have not been able to study ethnicity across prospectively collected risk factors …”

mentioning

confidence: 99%

Ethnic and Socioeconomic Associations with Multiple Sclerosis Risk

Dobson

Jitlal

Marshall

et al. 2020

Annals of Neurology

View full text Add to dashboard Cite

Objective Epidemiological research in multiple sclerosis (MS) has mainly been performed in socioeconomically and ethnically limited populations; influences on MS risk have not been studied in prospectively collected non‐White populations. We set out to study the influence of previously described MS risk factors in an ethnically diverse population. Methods A nested case–control study was created using primary care records of >1 million individuals, >50% of whom identify as Black, Asian, and Minority Ethnic (BAME). MS cases were compared to an age‐ and sex‐matched control cohort (1:4), and to a large unmatched cohort. Odds ratios (ORs) of disease were determined according to exposure of interest, and a multivariate model including all exposures was created. Potential pairwise interactions were considered where both indicated a significant effect. Results A total of 1,344 confirmed MS cases were included. MS OR in blacks aged <40 years was 1.15 (95% confidence interval [CI] = 0.81–1.62) compared to whites. MS odds in BAME current (OR = 1.71, 95% CI = 1.24–2.31) and ex‐smokers (OR = 2.83, 95% CI = 2.14–3.72) were considerably higher than in Whites (OR = 1.09, 95% CI = 0.88–1.34; OR = 1.44, 95% CI = 1.19–1.74, respectively). Prior infectious mononucleosis was associated with increased odds of MS in Blacks (OR = 4.94, 95% CI = 1.23–17.89). An increase in MS odds was seen in the least‐deprived quintile (OR = 2.46, 95% CI = 1.40–4.24), but no effect across deprived quintiles was seen. Interpretation This cohort provides novel data on factors potentially driving MS susceptibility in a diverse population, one‐third of whom live in poverty. Environmental exposures have differential risk across ethnicity. ANN NEUROL 2020;87:599–608

show abstract

mentioning

confidence: 99%

Ethnic and Socioeconomic Associations with Multiple Sclerosis Risk

Dobson

Jitlal

Marshall

et al. 2020

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…Therefore, pre-clinical symptoms of MS could contribute to development or diagnosis of another chronic disease as pwMS have been shown to have increased health-care utilization 5 years prior to MS onset. 27 Awareness of CMD is especially important for pwMS, they may interpret symptoms as part of their MS, leading to synergistic negative effects of multiple conditions having an impact on disability, 28 quality of life, 29 and risk of hospital admission. 11 Implications of CMD and MS MS treatment typically takes a multi-disciplinary approach to manage the wide breadth of symptoms.…”

Section: Discussionmentioning

confidence: 99%

Comorbid disease burden among MS patients 1968–2012: A Swedish register–based cohort study

et al. 2020

View full text Add to dashboard Cite

Background: People with multiple sclerosis (pwMS) have increased comorbid disease (CMD) risk. Most previous studies have not considered overall CMD burden. Objective: To describe lifetime CMD burden among pwMS. Methods: PwMS identified using Swedish registers between 1968 and 2012 ( n = 25,476) were matched by sex, age, and county of residence with general-population comparators ( n = 251,170). Prevalence, prevalence ratios (PRs), survival functions, and hazard ratios by MS status, age, and time period compared seven CMD: autoimmune, cardiovascular, depression, diabetes, respiratory, renal, and seizures. Results: The magnitude of the PRs for each CMD and age group decreased across time, with higher PRs in earlier time periods. Before 1990, younger age groups had higher PRs, and after 1990, older age groups had higher PRs. Male pwMS had higher burden compared with females. Overall, renal, respiratory, and seizures had the highest PRs. Before 2001, 50% of pwMS received a first/additional CMD diagnosis 20 years prior to people without MS, which reduced to 4 years after 2001. PwMS had four times higher rates of first/additional diagnoses in earlier time periods, which reduced to less than two times higher in recent time periods compared to people without MS. Conclusion: Swedish pwMS have increased CMD burden compared with the general population, but this has reduced over time.

show abstract

“…13,14,22 Moreover, a recent study characterized specific categories of symptoms that may precede a CIS, with digestive symptoms being one of these categories. 17 Our study further characterizes the extent and prevalence of specific bowel symptoms patients may experience during this phase, in addition to delineating a time course for the onset of these symptoms in relation to the CIS.…”

Section: In This Retrospective Analysis Of Ms Patients With Bowel Symmentioning

confidence: 95%

“…15 Additionally, recent studies have demonstrated an increase in healthcare utilization up to 5 years prior to the first demyelinating event in MS patients with digestive symptoms, among others, present during this phase. 16,17 Despite the known relationship between bowel dysfunction and MS, there is little objective evidence that bowel symptoms can precede more classic neurological symptoms. We therefore sought to determine the relationship between antecedent bowel symptoms and the subsequent development of MS in a large cohort of patients evaluated for MS at two large tertiary treatment centers.…”

mentioning

confidence: 99%

Bowel symptoms predate the diagnosis among many patients with multiple sclerosis: A 14‐year cohort study

Almeida

Silvernale

Kuo

et al. 2019

Neurogastroenterology Motil

View full text Add to dashboard Cite

Background Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease frequently complicated by bowel symptoms. Multiple sclerosis typically first manifests with a demyelination event, also known as a clinically isolated syndrome (CIS). We sought to examine the prevalence of prodromal bowel symptoms predating a CIS in patients with MS as part of a recently characterized prodromal phase of disease. Methods We constructed a retrospective cohort of MS patients with bowel symptoms and an identifiable CIS at two tertiary care centers over 14 years using administrative and billing data. We determined the date of onset of reported bowel symptoms in comparison with the date of first CIS and determined the overall prevalence of prediagnosis bowel symptoms within 1, 2, 3, and >3 years from a CIS. We used multivariable modeling to determine demographic and clinical risk factors for prediagnosis bowel symptoms. Key Results Among 385 MS patients with reported bowel symptoms, 122 (31.6%) reported bowel symptoms prior to CIS. The most common first bowel symptom was constipation (50.0%), followed by diarrhea (29.5%). The average lead time between a first bowel symptom and a CIS event was 3.7 ± 3.4 years. Pre‐CIS fatigue (OR 4.48, 95% CI: 2.68‐7.51, P < 0.001) and pre‐CIS sensory disturbances (OR 1.88, 95% CI: 1.15‐3.08, P < 0.05) were all associated with bowel symptoms prior to a CIS event. Conclusions and Inferences Nearly a third of MS patients with bowel symptoms reported bowel symptoms prior to a demyelinating event/CIS. Characterization of a prodromal phase of disease may provide important insights into understanding disease progression.

show abstract

Five years before multiple sclerosis onset: Phenotyping the prodrome

Abstract: Phenotyping the prodrome 5 years before clinical recognition of MS is feasible.

Cited by 74 publications

References 27 publications

Ethnic and Socioeconomic Associations with Multiple Sclerosis Risk

Ethnic and Socioeconomic Associations with Multiple Sclerosis Risk

Comorbid disease burden among MS patients 1968–2012: A Swedish register–based cohort study

Bowel symptoms predate the diagnosis among many patients with multiple sclerosis: A 14‐year cohort study

Contact Info

Product

Resources

About