A single lesion—And yet MS?

Abstract

Barts and The London School of Medicine & Dentistry 2 Newark Street, London E1 2AT, United KingdomThe cornerstone for a clinical diagnosis of multiple sclerosis(MS) is the demonstration of dissemination in space (DIS)and time (DIT) of lesions in the central nervous systemsuggestive of demyelination in the absence of a differentialdiagnosis that would better explain a patient’s symptoms(Polman et al., 2011).In a paper published in Neurology, Schmalstieg et al.(2012) reported seven cases of progressive myelopathy thatneither fulfilled standard criteria for MS nor for any of itsmany differential diagnoses (Miller et al., 2008). Rather,symptoms and signs were attributable to a solitary lesionsuggestive of demyelination in the brainstem or spinal cord.None of the reported cases developed any further lesion,neither clinically nor – where available – on MRI.The case series reported by Schmalstieg et al. consists ofquite a heterogeneous group of patients. Three had aninsidious onset, another three had relapses and remissionsreferable to the same site and one had a sub-acute coursewith partial resolution and subsequent progression after6 months. Only three of their cases had follow-up MRIconfirming short lesions in the brainstem or spinal cord,and for one patient no MRI was available at all. Of the sixcases where cerebro-spinal fluid was tested, four hadunmatched oligoclonal bands. The three cases tested forNMO immunoglobulin G had negative results. The medianfollow-up was 3 years. What unified these cases was thereported solitary lesion causing symptoms.Excluding one outlier who had been symptomatic for 27years, the average disease duration of the cohort was5.5 years, making it difficult to predict whether some of theirpatients will still develop classic DIS, thereby fulfilling currentdiagnostic criteria for MS ( Polman et al., 2011). In a recentstudy, based on the natural history cohort from LondonOntario, over 20% of patients with relapse onset MS had afirst inter-attack interval of 6 years or more (Scalfari et al.,2010). Further, we can only assume patients’ ethnicity in thestudy by Schmalstieg et al. (white Caucasian?), and that theytested negative for antibodies against HTLV-1.However, despite the incomplete nature of their auditdata, and the limited time of follow-up, Schmalstieg et al.highlight a challenge any neurologist with an interest in MSoccasionally faces: the patient with a single lesion ofpresumed demyelinaton who develops a chronic progressivesyndrome clinically undistinguishable from primary progres-sive MS – whilst never fulfilling the criterion for DIS.To some extent, the study by Schmalstieg et al. remindsus of the limited toolbox currently available to clinicians,which does not regularly include techniques such as quanti-tative and high-field MRI or optical coherence tomography,both highly sensitive tools to detect tissue damage as itcharacteristically occurs in MS. For example, whilst corticalMS lesions are well described histologically, only non-standard MRI techniques such a double inversion recovery(DIR; Boulby et al., 2004) are able to detect (a proportionof) such lesions. It would be interesting to investigate thecohort reported by Schmalstieg et al. using DIR or othernovel techniques such as phase sensitive inversion recovery(Sethi et al., 2012) to explore whether the detection ofcortical lesions could help to establish DIS, keeping in mindthat lesions in the cortex have yet to be formally incorpo-rated in a diagnostic algorithm for MS (Geurts et al., 2011).Schmalstieg et al. speculate about potential mechanismsunderlying axonal degeneration in their small cohort, but inthe absence of further data on, for example, brain atrophythe basis for this discussion remains limited. Diagnostically,however, we share their impression that of the small numberof patients in which application of standard diagnostictools does not underpin the disseminated nature of an