A systematic review of morbidities suggestive of the multiple sclerosis prodrome

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Abstract
Introduction: The identification of a prodromal phase in multiple sclerosis (MS) could have major implications for earlier recognition and management of MS. The authors conducted a systematic review assessing studies of morbidities before, or at, MS onset or diagnosis. Areas covered: Two independent reviewers searched Medline, Embase, Psycinfo and CINAHL from inception to February 8th, 2019. To be eligible, studies had to be published in English and report the relative occurrence of at least one morbidity or symptom before, or at, MS onset or diagnosis among MS cases in comparison to a control group not known to have MS. Findings were narratively synthesized. Study quality was assessed using the Newcastle–Ottawa scale (NOS, maximum score 9). Expert opinion: Twenty-nine studies were included, which comprised 83,590 MS cases and 396,343 controls. Most were case-control studies (25/29), 8/29 were of high quality (NOS≥8) and 19/29 examined the period before MS symptom onset. Most studies assessing anxiety, depression, migraine and lower cognitive performance found these conditions to be more prevalent before MS onset or diagnosis relative to controls. There was limited evidence to implicate other conditions. Thus, there is evidence that anxiety, depression, migraine and lower cognitive performance form part of the MS prodrome.

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