The utility of multimodal evoked potentials in multiple sclerosis prognostication.

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(BASELINE)=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 findings 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.

Differentiating patterns of oligoclonal banding in the cerebrospinal fluid improves diagnostic utility for multiple sclerosis.

BACKGROUND: Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is an important adjunct to the diagnosis of multiple sclerosis (MS) and clinically isolated syndromes (CIS). OCBs are considered present if two or more extra IgG bands are present in CSF in comparison to a simultaneously collected serum sample. However, using isoelectric focusing and immunofixation with anti-IgG, we observed two distinct banding patterns, one in which the bands were numerous and prominent (which we termed 'delta') and a much more subtle pattern, with fewer, more indistinct bands ('theta'). AIM: To perform a prospective study to determine the diagnostic implications of the two OCB patterns for multiple sclerosis. METHODS: Over a 2-year period, 56 consecutive CSF samples with OCBs were identified. Clinical information and radiological data were collected and correlated with the two banding patterns. RESULTS: : Of the 56 positive CSF samples, 46 (82%) demonstrated a delta pattern, and 10 (18%), a theta pattern. The delta pattern was associated with MS/CIS in 34 of 46 (74%) samples, compared with zero of the 10 theta samples (0%, p < 0.001). Exclusion of the theta pattern samples increased the positive predictive value of OCB testing from 61% to 74% for MS/CIS. CONCLUSION: The diagnostic significance of oligoclonal bands in CSF for MS/CIS can be improved by restricting interpretation to the delta banding pattern alone.

Cortical dysfunction underlies disability in multiple sclerosis.

BACKGROUND: Gray matter atrophy has been implicated in the development of secondary progressive multiple sclerosis (SPMS). Cortical function may be assessed by transcranial magnetic stimulation (TMS). Determining whether cortical dysfunction was a feature of SPMS could be of pathophysiological significance. OBJECTIVES: Consequently, novel paired-pulse threshold tracking TMS techniques were used to assess whether cortical dysfunction was a feature of SPMS. METHODS: Cortical excitability studies were undertaken in 15 SPMS, 25 relapsing-remitting MS patients (RRMS) and 66 controls. RESULTS: Short interval intracortical inhibition (SPMS 3.0 ± 2.1%; RRMS 12.8 ± 1.7%, p < 0.01; controls 10.5 ± 0.7%, p < 0.01) and motor evoked potential (MEP) amplitude (SPMS 11.5 ± 2.2%; RRMS 26.3 ± 3.6%, p <0.05; controls 24.7 ± 1.8%, p < 0.01) were reduced in SPMS, while intracortical facilitation (SPMS -5.2 ± 1.9%; RRMS -2.0 ± 1.4, p < 0.05; controls -0.9 ± 0.7, p < 0.01) and resting motor threshold were increased (SPMS 67.5 ± 4.5%; RRMS 56.0 ± 1.5%, p < 0.01; controls 59.0 ± 1.1%, p < 0.001). Further, central motor conduction time was prolonged in SPMS (9.1 ± 1.2 ms, p < 0.001) and RRMS (7.0 ± 0.9 ms, p < 0.05) patients compared with controls (5.5 ± 0.2 ms). The observed changes in cortical function correlated with the Expanded Disability Status Scale. CONCLUSION: Together, these findings suggest that cortical dysfunction is associated with disability in MS, and documentation of such cortical dysfunction may serve to quantify disease severity in MS.