The curious incident of disability in multiple sclerosis trials.

Inspector Gregory: " Is there any point to which you would wish to draw my attention? " Holmes: " To the curious incident of the dog in the night-time. " Inspector: " The dog did nothing in the night-time. " Holmes: " That was the curious incident. " Conan Doyle's The Silver Blaze There was a time when a neurologist could choose, rightly or wrongly, to downplay the signifi cance of the fi rst symptoms of demyelination: the " clinically isolated syndrome ". No longer. Within minutes of an internet search, the person aff ected by, say, optic neuritis is faced with the possibility they might experience attacks of diverse symptoms, some indeterminate time away, and so develop " multiple sclerosis ". And with that prospect come the spectres of disability, marginalisation, and frustrated ambitions. Sooner or later, come the questions: what does the future hold? Am I going to end up in a wheelchair? Handling this situation is a severe test of a neurologist's technical and pastoral skills. MRI brain scans can be useful; abnormalities consistent with plaques at presentation increase the risk of subsequent conversion to multiple sclerosis. For instance, 14 years later, nearly 90% of those who had an abnormal MRI scan will have developed multiple sclerosis, compared with less than 20% of those who had a normal MRI scan. 1 Those people with a clinically isolated syndrome and an abnormal MRI brain scan ask: what can I do now to prevent further attacks and future disability? The answer is, embarrassingly, unclear. And the BENEFIT (Betaferon in newly emerging multiple sclerosis for initial treatment) trial 2 , reported recently in Neurology, helps not one jot or tittle. It is the latest of a trilogy of placebo-controlled trials, testing the effi cacy of interferon beta to reduce the rate of conversion to multiple sclerosis in people with clinically isolated syndromes and abnormal MRI brain scans. Of the few drugs licensed to modify the course of multiple sclerosis, the innocuous safety profi le of the interferons makes them the most appropriate to test on these mainly young, well people. CHAMPS (controlled high-risk subjects Avonex multiple sclerosis prevention study; n=383) of once-weekly intramuscular 30 μg interferon beta-1a (Avonex) was designed as a 3 year study, but was stopped early because of an interim analysis in favour of interferon so that only 262 patients (68%) generated the 2 year data. 3 …