Motor Unit Number Index (MUNIX) of hand muscles is a disease biomarker for adult spinal muscular atrophy

Günther, René; Neuwirth, Christoph; Koch, Jan Christoph; Lingor, Paul; Braun, Nathalie; Untucht, Robert; Petzold, Daniel; Weber, Markus; Hermann, Andreas

doi:10.1016/j.clinph.2018.11.009

Cited by 51 publications

(59 citation statements)

References 14 publications

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“…An adapted system, combining incremental stimulus and multiple point analysis is increasingly used to improve estimate accuracy. Novel, computerized methods of MUNE are coming to the fore including the MScan fit and MUNIX methods, to improve analysis accuracy and time, and circumvent biases incurred by operator input, which are intrinsic weaknesses noted in traditional methods (94, 95). Their clinical role is yet to be elucidated in terms of sensitivity, specificity, and reproducibility in healthy controls and for individuals with SMA.…”

Section: Electrophysiological Biomarkersmentioning

confidence: 99%

Biomarkers and the Development of a Personalized Medicine Approach in Spinal Muscular Atrophy

et al. 2019

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Recent unprecedented advances in treatment for spinal muscular atrophy (SMA) enabled patients to access the first approved disease modifying therapy for the condition. There are however many uncertainties, regarding timing of treatment initiation, response to intervention, treatment effects and long-term outcomes, which are complicated by the evolving phenotypes seen in the post-treatment era for patients with SMA. Biomarkers of disease, with diagnostic, prognostic, predictive, and pharmacodynamic value are thus urgently required, to facilitate a wider understanding in this dynamic landscape. A spectrum of these candidate biomarkers, will be evaluated in this review, including genetic, epigenetic, proteomic, electrophysiological, and imaging measures. Of these, SMN2 appears to be the most significant modifier of phenotype to date, and its use in prognostication shows considerable clinical utility. Longitudinal studies in patients with SMA highlight an emerging role of circulatory markers such as neurofilament, in tracking disease progression and response to treatment. Furthermore, neurophysiological biomarkers such as CMAP and MUNE values show considerable promise in the real word setting, in following the dynamic response and output of the motor unit to therapeutic intervention. The specific value for these possible biomarkers across diagnosis, prognosis, prediction of treatment response, efficacy, and safety will be central to guide future patient-targeted treatments, the design of clinical trials, and understanding of the pathophysiological mechanisms of disease and intervention.

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Section: Electrophysiological Biomarkersmentioning

confidence: 99%

Biomarkers and the Development of a Personalized Medicine Approach in Spinal Muscular Atrophy

et al. 2019

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“…Keeping in mind the current costs for this treatment, 4 the semi-invasive administration by lumbar puncture, 5,6 as well as lacking data regarding drug efficacy in adolescents and adults, objective markers indicating an early effective treatment response are urgently needed. 7…”

Section: Introductionmentioning

confidence: 99%

Neurochemical markers in CSF of adolescent and adult SMA patients undergoing nusinersen treatment

Wurster

Günther

Steinacker

et al. 2019

Ther Adv Neurol Disord

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Background: There is limited information on neurochemical markers being used to support and monitor the affection of motoneurons in patients with spinal muscular atrophy (SMA). The objective of this study was to examine neurochemical markers in cerebrospinal fluid (CSF) under treatment with the antisense-oligonucleotide (ASO), nusinersen. Methods: We measured markers of axonal degeneration [neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)] along with basic CSF parameters in 25 adolescent and adult SMA type 2 and 3 patients at baseline and after four intrathecal injections of nusinersen. Neurochemical markers were compared with controls. In addition, neurochemical markers in SMA patients were related to the Hammersmith Functional Rating Scale Expanded (HFMSE). Results: No significant difference in neurofilament (Nf) values was observed between SMA and control group, neither at baseline nor after four injections of nusinersen. NfL, protein and quotients of albumin (Qalb) increased slightly in SMA patients after the fourth injection. The slight increase of NfL could be related to the development of mild CSF flow change. No relations were observed between changes in Nf and HFMSE. Conclusion: We assume that Nf levels in CSF in these patients may result from slow disease progression in this stage of disease, pre-existing loss of motoneurons due to long disease duration besides affection of the LMN only. Therefore, we conclude that Nf levels in CSF do not seem useful as diagnostic and monitoring markers in adolescent and adult SMA type 2 and 3 patients.

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“…The ADM is often used as a target muscle in the clinical application of MUNE and MUNIX . The significance of the results of these studies should be reconsidered.…”

Section: Clinical Implications and Future Perspectivementioning

confidence: 99%

Far‐field potentials in the compound muscle action potential

Sonoo

2019

Muscle and Nerve

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It has long been believed that the compound muscle action potential (CMAP) in motor‐nerve conduction studies (MCSs) records the action potential beneath the active electrode over the muscle belly. However, recent studies have revealed the contribution of the reference electrode to the CMAP, most prominent in the tibial nerve, followed by the ulnar nerve. This “reference electrode potential” is recorded when the conventional reference electrode distal to the muscle belly is connected to a proximal reference. It must be a far‐field potential (FFP) considering its distribution, although the precise mechanism of its generation has not been clarified. The conventional theory of termination of the action potential at the muscle‐tendon junction is insufficient. Regarding the ulnar CMAP, interosseous muscles mostly contribute to the FFPs. New understanding of CMAP based on the FFP theory may provide new insights into the interpretation of MCSs and related techniques, including motor unit number estimation.

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Motor Unit Number Index (MUNIX) of hand muscles is a disease biomarker for adult spinal muscular atrophy

Cited by 51 publications

References 14 publications

Biomarkers and the Development of a Personalized Medicine Approach in Spinal Muscular Atrophy

Biomarkers and the Development of a Personalized Medicine Approach in Spinal Muscular Atrophy

Neurochemical markers in CSF of adolescent and adult SMA patients undergoing nusinersen treatment

Far‐field potentials in the compound muscle action potential

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