In most cases, the diagnosis of multiple sclerosis (MS) presents few difficulties. Clinical evidence of lesions disseminated in time and space, backed up by magnetic resonance imaging (MRI) and/or spinal fluid changes, commonly leave neither room nor reason for doubt. Occasionally, however, a rogue erythrocyte sedimentation rate (ESR), an atypical (or normal) MRI scan, or an unexpected symptom or sign—fever, rash, headache, fits, etc (table 1)—give rise to doubt.

The absence of diagnostic tests means that uncertainty can be extremely difficult to resolve. MRI, spinal fluid examination, and evoked potential recordings are sensitive tests for MS but do not have comparable specificity. The range of disorders thatcan mimic MS is vast; as the prototypical inflammatory demyelinating disorder, it may be confused with both unrelated demyelinating diseases (metabolic or inherited) and unrelated inflammatory disease; additionally, diseases which are directly related to MS must also be considered. To offer a systematic account of all would be unrealistic, and not a little unreadable. Therefore, only a few comments relating to salient clinical features or discriminating investigations will be mentioned.