Early relapse risk after a first CNS inflammatory demyelination episode: examining international consensus definitions

Abstract

The International Pediatric Multiple Sclerosis Study Group (IPMS) has recently proposed consensus definitions for paediatric multiple sclerosis (MS) and related disorders. The term 'acute disseminated encephalomyelitis' (ADEM) has been used previously to describe any monophasic episode of disseminated demyelination. The study group now propose that ADEM must be multifocal, polysymptomatic, and include encephalopathy (as an essential requirement). An alternative diagnosis for a first acute inflammatory event is 'clinically isolated syndrome' (CIS). A CIS event may be either monofocal (such as isolated optic neuritis) or multifocal, but cannot include encephalopathy. As with adults, children with two or more discrete demyelinating events separated in time and space meet criteria for MS. In children with MS, the demyelination events must not meet ADEM criteria. To test the usefulness of these new criteria, a new cohort of 40 patients (18 males, 22 females; mean age 8 y [SD 4 y 4 mo]) with central nervous system (CNS) demyelination were studied. Using IPMS definitions, the presenting diagnosis was ADEM in 12 patients and CIS in 28 patients. At presentation, patients with CIS were more likely to have intrathecal synthesis of oligoclonal bands and fulfil KIDMUS MS magnetic resonance imaging criteria, compared with patients with ADEM (p<0.025). Patients were followed-up for a mean of 2 years 2 months. Only one of 12 patients with ADEM went on to develop MS during the study period, whereas 13 of 28 patients with CIS relapsed and fulfilled a diagnosis of MS (p<0.025). The new diagnostic criteria for ADEM may be criticized for being overly restrictive (particularly with encephalopathy being an essential criterion), and it is suspected that many practising physicians will be of the opinion that these new criteria will underdiagnose ADEM, and overdiagnose MS at the expense of multiphasic ADEM. However, it is hoped that these new criteria may improve prognostic specificity and provide uniformity to future paediatric CNS demyelination research.