Clinical Study The utility of multimodal evoked potentials in multiple sclerosis prognostication Sudarshini Ramanathan a,b , Kerry Lenton c , Therese Burke c , Lavier Gomes b,d , Karen Storchenegger a , Con Yiannikas e , Steve Vucic a,b,⇑ a Department of Neurology, Westmead Hospital, Corner Hawkesbury and Darcy Roads, Westmead, Sydney, NSW 2145, Australia b Westmead Clinical School, University of Sydney, Sydney, NSW, Australia c Institute for Immunology and Allergy Research, Westmead Millennium Institute, Sydney, NSW, Australia d Department of Radiology, Westmead Hospital, Sydney, NSW, Australia e Department of Neurology, Concord Hospital, Sydney, NSW, Australia article info Article history: Received 18 April 2012 Accepted 15 January 2013 Keywords: Evoked potentials Multiple sclerosis Relapsing–remitting Secondary progressive abstract The ability to predict disability development in multiple sclerosis (MS) is limited. While abnormalities of evoked potentials (EP) have been associated with disability, the prognosticating utility of EP in MS remains to be fully elucidated. The present study assessed the utility of multimodal EP as a prognostic biomarker of disability in a cohort of clinically heterogeneous MS patients. Median and tibial nerve somatosensory, visual, and brainstem auditory EP were performed at initial assessment on 63 MS patients (53 relapsing–remitting and 10 secondary progressive) who were followed for an average of 2 years. A combined EP score (CEPS) was calculated consisting of the total number of abnormal EP tests, and was correlated with the Expanded Disability Status Scale (EDSS) at baseline and follow-up. There was a significant correlation between multimodal EP and baseline and follow-up EDSS. Specifically, tibial nerve P37 latencies correlated with EDSS (R BASELINE = 0.49, p < 0.01; R FOLLOW-UP = 0.47, p < 0.01), as did the median nerve N13 (R BASELINE = 0.40, p < 0.01; R FOLLOW-UP = 0.35, p < 0.05) and N20 latencies (R BASE- LINE = 0.43, p < 0.01; R FOLLOW-UP = 0.47, p < 0.01), and P100 full-field (R BASELINE = 0.50, p < 0.001; R FOLLOW- UP = 0.45, p < 0.001) and central field latencies (R BASELINE = 0.60, p < 0.001; R FOLLOW-UP = 0.50, p < 0.001). In addition, there was a significant correlation between the CEPS with baseline (R = 0.65, p < 0.001) and follow-up (R = 0.57, p < 0.01) EDSS. In contrast, white matter disease burden, as measured by T2 lesion load, exhibited a weaker correlation with EDSS (R BASELINE = 0.28, p < 0.05). In conclusion, these find- ings suggest that abnormalities of EP, as quantified by the novel CEPS, may be a useful biomarker for prognosticating clinical disability in MS, and may aid in the quantification of MS disease severity and in guiding therapeutic decisions. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Multiple sclerosis (MS) is an autoimmune disorder of the cen- tral nervous system. Up to 80% of MS patients develop permanent disability. 1 The pathophysiological mechanisms underlying dis- ability in MS remain to be fully elucidated, and reliable biomarkers of disability development are yet to be defined. Conventional MRI studies assessing white matter disease burden, such as T2 lesion load (T2LL), only modestly correlate with functional impairment, resulting in the so-called ‘‘clinico–radiological paradox’’. 2–6 Cortical or grey matter dysfunction has been suggested as being a biomarker of disability in MS. 5,7–11 Specifically, pathological evi- dence of demyelination, apoptosis, and microglial activation within the cortex of MS patients has been associated with disability. 7,8 Radiological studies utilising sophisticated MRI techniques estab- lished that grey matter atrophy was a robust predictor of disabil- ity. 5,9,12 Paired-pulse transcranial magnetic stimulation techniques have also established a link between cortical dysfunction and dis- ability in MS. 10,11 These specialised techniques, however, may not be readily available in all centres, thereby potentially limiting their prognosticating utility in a clinical or trial setting. The function of visual and somatosensory pathways and their respective cortices can be readily assessed using multimodal evoked potentials (EP). 13 While the diagnostic utility of EP in MS is established, recent reports have suggested a re-emergence of EP in MS prognostication, although these outcomes have been var- ied. 6,14–20 Some studies have reported that abnormalities of multi- modal EP at initial assessment were a predictor of long-term disability in MS 6,16–20 , while others failed to demonstrate this. 15 0967-5868/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2013.01.020 ⇑ Corresponding author. Tel.: +61 2 9845 6097. E-mail address: s.vucic@neura.edu.au (S. Vucic). Journal of Clinical Neuroscience 20 (2013) 1576–1581 Contents lists available at SciVerse ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn