British Society for Clinical Neurophysiology

...to promote and encourage for the public benefit the science and practice of clinical neurophysiology and related sciences

Abstract Details

The Growing Potential of Long Tract Neurophysiology in Primary Progressive Multiple Sclerosis – A Prospective Investigation over 3 years

OBJECTIVE To evaluate the longitudinal relationship of multimodal evoked potential abnormality burdens with progression of clinical disability and assess their candidacy as surrogate biomarkers of disability for translational research in Primary Progressive Multiple Sclerosis (PPMS). BACKGROUND Evoked Potentials sensitively reflect the functional integrity of pathways which centrally determine physical disability in Multiple Sclerosis. It is hoped they may offer a surrogate outcome able to meaningfully associate with disability and through deterministic association accurately predict findings in large trials using FDA and EMA accepted clinical outcomes. METHOD 28 patients with PPMS were recruited and underwent clinical disability rating by EDSS and MSFC at baseline and 6, 12, 24 and 36 months subsequently. Contemporaneous Multi-modal Evoked Potential recordings were also made at each time point and abnormalities quantified by the established semi-quantitative Multimodal EP Score system (MEPS). The EP battery comprised bilateral visual, brainstem auditory, 4 limb somatosensory and 4 limb TMS-evoked Motor evoked potentials. The relationship between composite MEP score and time to confirmed disability progression was explored. RESULTS Combined sensory and motor potentials of all 4 limbs (MEP-4) demonstrated consistent cross-sectional relationship with disability over time (Spearman’s Rs=.325 to .747 p<.005). Individuals with a higher baseline MEP-4 manifested greater and more accelerated progression by both EDSS and the newer EDSS-Plus criteria (Log Rank p<.05 and Area under the ROC of .71). There was fair agreement between MEP-4 change and pattern of disability change over the first 12 months (Cohen’s k=.34) and subsequent year (Cohen’s k=.35). The average rate of MEP-4 worsening was approximately steady for the whole cohort and separate high/low MEP-4 cohorts over time, increasing by an average of 1 point per year. CONCLUSIONS Focussed neurophysiological interrogation of the spinal afferent and efferent long tracts offers meaningful quantitative information about the key determinants of disability detected by the accepted clinical trial outcome measures. Higher MEP-4 burden conferred a worse prognosis, with subjects displaying shorter times to progression and ultimately worse levels of clinical disability. The average rate of neurophysiological decline is also congruent with the observed natural history of the PMS phenotype. Evoked Potentials offer a means to prognosticate, enrich trial cohorts for those most likely to manifest clinical outcomes and track changes (including improvement) over desirable intervals.

TitleForenamesSurnameInstitutionLead AuthorPresenter
DrLuke J W CanhamThe Grey Walter Neurophysiology Deparment, Southmead Hospital, North Bristol NHS Trust, Bristol
DrNick MKaneGrey Walter Dept of Clinical Neurophysiology
MrPeterWalshThe Grey Walter Neurophysiology Deparment, Southmead Hospital, North Bristol NHS Trust, Bristol
DrAgyepongOwareThe Grey Walter Neurophysiology Deparment, Southmead Hospital, North Bristol NHS Trust, Bristol
DrDavidCottrellThe Grey Walter Neurophysiology Deparment, Southmead Hospital, North Bristol NHS Trust, Bristol
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