Multimodal neurophysiological evaluation of primary progressive multiple sclerosis – An increasingly valid biomarker, with limits

Canham, Luke; Kane, Nick; Oware, Agyepong; Walsh, Peter; Blake, Kelly; Inglis, Kirsty; Homewood, Jenny; Witherick, Jonathan; Faulkner, Howard J.; White, Paul; Lewis, A. C.; Furse-Roberts, C.; Cottrell, David A.

doi:10.1016/j.msard.2015.07.009

Cited by 18 publications

(23 citation statements)

References 40 publications

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“…For the first time, a significant correlation was uncovered between multimodal EP score and the upper limbs motor function. In contrast to a recent study [22], the weaker correlation between EP score and T25FW could be attributed to the lower disability of our patient population (median EDSS 3) as well to the MS phenotype (PP in Canham's population, mainly RR in the present study), suggesting that some neuronal plasticity or functional adaptation persisted in our patients. Due to their sensitivity to sub-clinical abnormalities, EP can anticipate future walking deterioration.…”

Section: Discussioncontrasting

confidence: 99%

Do evoked potentials contribute to the functional follow-up and clinical prognosis of multiple sclerosis?

et al. 2016

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The clinical variability and complexity of multiple sclerosis (MS) challenges the individual clinical course prognostication. This study aimed to find out whether multimodal evoked potentials (EP) correlate with the motor components of multiple sclerosis functional composite (MSFCm) and predict clinically relevant motor functional deterioration. One hundred MS patients were assessed at baseline (T ) and about 7.5 years later (T), with visual, somatosensory and motor EP and rated on the Expanded Disability Status Scale (EDSS) and the MSFCm, including the 9 Hole Peg Test and the Timed 25 Foot Walk (T25FW). The Spearman correlation coefficient (r ) was used to evaluate the cross-sectional and longitudinal relationship between EP Z scores and clinical findings. The predictive value of baseline electrophysiological data for clinical worsening (EDSS, 9-HPT, T25FW, MSFCm) during follow-up was assessed by logistic regression analysis. Unlike longitudinal correlations, cross-sectional correlations between EP Z scores and clinical outcomes were all significant and ranged between 0.22 and 0.67 (p< 0.05). The global EP Z score was systematically predictive of EDSS and MSFCm worsening over time (all p < 0.05). EP latency was a better predictor than amplitude, although weaker than latency and amplitude aggregation in the global EP Z score. The study demonstrates that EP numerical scores can be used for motor function monitoring and outcome prediction in patients with MS.

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Section: Discussioncontrasting

confidence: 99%

Do evoked potentials contribute to the functional follow-up and clinical prognosis of multiple sclerosis?

et al. 2016

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“…103 Interestingly enough, EPs may reveal dysfunctions even in the absence of evident MRI lesions affecting the tested pathway. 104 Combined multimodal EPs have been reported to correlate with global measures of disability in mixed cohorts of RRMS and progressive MS, 103,105 as well as in PPMS in cross-sectional 106,107 and longitudinal evaluations. 107 Unfortunately, studies specifically addressing progressive patients are scarce and involve small samples and in mixed cohorts, with the relapsing-remitting form typically over-represented (for a review, see Hardmeier et al).…”

Section: Electrophysiological Outcomesmentioning

confidence: 98%

Fluid biomarker and electrophysiological outcome measures for progressive MS trials

et al. 2017

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Progressive multiple sclerosis (MS) is characterized by insidious clinical worsening that is difficult to accurately quantify and predict. Biofluid markers and electrophysiological measures are potential candidate outcome measures in clinical trials, allowing the quantification of nervous damage occurring in the disease. Neurofilaments are highly specific neuronal proteins. They may have come closest to such applications by their higher concentrations repeatedly demonstrated in cerebrospinal fluid (CSF) in all stages of MS, during relapses, their responsiveness to disease-modifying treatments in relapsing and progressive MS and their associations with measures of inflammatory and degenerative magnetic resonance imaging (MRI) outcomes. Digital single-molecule array (Simoa) technology improves accuracy of bioassays in the quantification of neurofilament light chain (NfL) in serum and plasma. NfL seems to mark a common final path of neuroaxonal injury independent of specific causal pathways. CSF and blood levels of NfL are highly correlated across various diseases including MS, suggesting that blood measurements may be useful in assessing response to treatment and predicting future disease activity. Other biomarkers like matrix metalloproteinases, chemokines, or neurotrophic factors have not been studied to a similar extent. Such measures, especially in blood, need further validation to enter the trial arena or clinical practice. The broadening armamentarium of highly sensitive assay technologies in the future may shed even more light on patient heterogeneity and mechanisms leading to disability in MS. Evoked potentials (EPs) are used in clinical practice to measure central conduction of central sensorimotor pathways. They correlate with and predict the severity of clinical involvement of their corresponding function. Their validation for use in multicenter studies is still lacking, with the exception of visual EPs. If further validated, EPs and fluid biomarkers would represent useful outcome measures for clinical trials, being related to specific mechanisms of the ongoing pathologic changes.

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“…Different EPs (VEP, BAEP, SSEP and MEP) associated with the EP score have shown moderate and useful correlation with clinical status in patients with primary progressive MS -PPMS (25). The numerical score based on VEP, SSEP and MEP results correlates well with disability in PPMS and allows some prediction of the disease course over three years (26).…”

Section: Evoked Potentials In Multiple Sclerosismentioning

confidence: 99%

Clinical Neurophysiology of Multiple Sclerosis

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Adamec

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et al. 2017

Multiple Sclerosis: Bench to Bedside

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Different neurophysiological methods such as evoked potentials (EP), testing of the autonomic nervous system (ANS) or polysomnography have the potential to detect clinically silent lesions or to confirm the existence of an association between a clinical symptom and multiple sclerosis (MS); previously undetected by MRI. Therefore, in the most recent MRI criteria for the diagnosis of MS (MAGNIMS consensus guidelines), neurophysiological confirmation of optic nerve dysfunction (slowed conduction on visual EP), support dissemination in space and, in patients without concurrent visual symptoms, dissemination in time. In this chapter we will review the existing evidence regarding the role of different neurophysiological tests (specifically the role of EPs, autonomic nervous system testing and sleep testing in MS) in the diagnosis and management of MS.

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Multimodal neurophysiological evaluation of primary progressive multiple sclerosis – An increasingly valid biomarker, with limits

Cited by 18 publications

References 40 publications

Do evoked potentials contribute to the functional follow-up and clinical prognosis of multiple sclerosis?

Do evoked potentials contribute to the functional follow-up and clinical prognosis of multiple sclerosis?

Fluid biomarker and electrophysiological outcome measures for progressive MS trials

Clinical Neurophysiology of Multiple Sclerosis

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