Prodromal symptoms of multiple sclerosis in primary care

Disanto, Giulio; Zecca, Chiara; MacLachlan, Sharon; Sacco, Rosaria; Handunnetthi, Lahiru; Meier, Ute‐Christiane; Simpson, Alex; McDonald, Laura; Rossi, Andrea; Benkert, Pascal; Kuhle, Jens; Ramagopalan, Sreeram; Gobbi, Claudio

doi:10.1002/ana.25247

Cited by 123 publications

(130 citation statements)

References 31 publications

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“…For example, neurologist or ophthalmologist/otolaryngologist encounters were similarly higher relative to controls, but did not differ when the two MS phenotypes were compared directly. Previous studies have reported the presence of a MS prodrome [2][3][4][5][6][7][8]. However, only one other study reported results by phenotype; Norwegian men aged 18-19 years entering military service exhibited cognitive deficits in the 2 years pre-onset of both RMS and PPMS, but possibly up to 20 years before PPMS onset [2].…”

Section: Discussionmentioning

confidence: 97%

“…This period can include nonspecific symptoms before the 'classic' onset of disease. Previous studies have reported the presence of a MS prodrome [2][3][4][5][6][7][8] but have seldom considered the MS phenotypes. However, the phenotypes differ clinically [1,9]; recognition and diagnosis of PPMS are particularly challenging and subsequent therapeutic options are limited.…”

Section: Introductionmentioning

confidence: 99%

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Prodrome in relapsing‐remitting and primary progressive multiple sclerosis

Wijnands

Zhu

Kingwell

et al. 2019

Euro J of Neurology

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Background and purpose The multiple sclerosis prodrome remains poorly understood. We aimed to examine the prodrome in people with relapsing remitting multiple sclerosis at onset (RMS) and primary progressive multiple sclerosis (PPMS). Methods We conducted a matched cohort study using clinical and linked health administrative data in two Canadian provinces. We identified people with RMS, PPMS and age‐ sex‐ and geographically‐matched population controls, and compared the number of physician encounters (total number, per International Classification of Diseases chapter, and per physician speciality) in the five years before symptom onset. Negative binomial regression models were sex, age, socioeconomic status and calendar year adjusted. Results We identified 1887 RMS, 171 PPMS cases, and 9837 matched population controls. No difference existed in the total number of encounters in the five years before index between RMS and PPMS, or between the phenotypes and their respective controls. Compared to RMS cases, PPMS cases had more nervous system‐related encounters (adjusted rate ratio, 3.00; 95% confidence interval, 1.06–8.49) and fewer encounters with dermatologists (adjusted rate ratio 0.53; 95% confidence interval, 0.30–0.96). Conclusion Findings suggest that people with RMS and PPMS may both experience a prodrome, although aspects may differ.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Prodrome in relapsing‐remitting and primary progressive multiple sclerosis

Wijnands

Zhu

Kingwell

et al. 2019

Euro J of Neurology

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“…These results are of particular interest because a recent study has observed pwMS had significantly higher risk of presenting up to 10 years prior to a first demyelinating event with gastric, intestinal, urinary and anorectal disturbances, anxiety, depression, insomnia, fatigue, headache and various types of pain. (26) These autonomic symptoms that precede MS for up to 10 years are called MS prodrome and the more symptoms are present so is the risk of MS greater. If we put the results of the former study into the context with the autonomic MS prodrome, we may speculate that ANS is an important predictor of disease activity, even before the first demyelinating event.…”

Section: What Happens With Ad With the Progression Of Ms?mentioning

confidence: 99%

Immune and autonomic nervous system interactions in multiple sclerosis: clinical implications

Habek

2019

Clin Auton Res

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Multiple sclerosis is characterized by a wide spectrum of clinical manifestations, among which dysfunction of the autonomic nervous system represents an important cause of multiple sclerosis related disability. The aim of this review is to give an overview of autonomic dysfunction in people with multiple sclerosis, to discuss the interactions between immune and autonomic nervous systems and consequences of these interactions on various aspects of multiple sclerosis. Autonomic dysfunction in people with multiple sclerosis can be demonstrated clinically and on molecular level. Clinically it can be demonstrated by measuring autonomic symptoms with Composite Autonomic Symptom Score (COMPASS-31) and neurophysiologically, with different autonomic nervous system tests. Both symptomatic and objectively determined autonomic dysfunction can be related to increased risk of multiple sclerosis disease activity. Further supporting these clinical observations are molecular changes on immune cells. Changes in the sympathetic autonomic system, like different expression of dopaminergic and adrenergic receptor on immune cells, or modulation of the cholinergic anti-inflammatory pathway over different subunits of the nicotinic acetylcholine receptor in peripheral immune system, may mediate different effects on multiple sclerosis disease activity.

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“…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

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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

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Prodromal symptoms of multiple sclerosis in primary care

Abstract: Various clinical disturbances precede MS diagnosis by several years, supporting a prodromal phase to the disease and improving our clinical knowledge of early MS. Integrating these symptoms in the diagnostic procedure may help earlier disease identification. Ann Neurol 2018.

Cited by 123 publications

References 31 publications

Prodrome in relapsing‐remitting and primary progressive multiple sclerosis

Prodrome in relapsing‐remitting and primary progressive multiple sclerosis

Immune and autonomic nervous system interactions in multiple sclerosis: clinical implications

Ethnic and Socioeconomic Associations with Multiple Sclerosis Risk

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