background  Manic-depressive illness (MDI) or bipolar disorder seems more prevalent in patients suffering from multiple sclerosis (MS), than in the general population.
aim  To examine (1) the epidemiological relationship between MDI and MS; (2) which explanatory models have been described that relate to this connection; and (3) the consequences for treatment. method  A systematic literature review has been conducted, with the help of the databases Medline and embase using as key words multiple sclerosis, manic-depressive illness, mania en bipolar disorder. Relevant articles were found in the period from 1887 till 2002.
results  Thirty-one studies were found (92 MS-patients with MDI). They mainly concerned case reports. MDI was reported in 2-13% of the MS-patients. Neuropathological, psychoneuroimmunological, psychoneuroendocrine, genetic, circadian, psychological and MS medication-related hypotheses are formulated in order to explain this relationship.
conclusions  An epidemiological relationship between MS and MDI seems evident. The nature of this association is still not clear. The main reason for this is that pathophysiological mechanisms underlying both illnesses are not yet fully understood. Other reasons are difficulty of defining MDI, selection bias, and low prevalence of ms-patients with MDI. Affective episodes in MS-patients respond as well to standard pharmacotherapy, as do such episodes in 'primary' MDI.