Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS
Abstract The neurophysiological technique motor unit number index (MUNIX) is increasingly used in clinical trials to measure loss of motor units. However, the heterogeneous disease course in amyotrophic lateral sclerosis (ALS) obfuscates robust correlations between clinical status and electrophysiol...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-19911-0 |
| _version_ | 1797998297831440384 |
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| author | Theresa Ebersbach Annekathrin Roediger Robert Steinbach Martin Appelfeller Anke Tuemmler Beatrice Stubendorff Simon Schuster Meret Herdick Hubertus Axer Otto W. Witte Julian Grosskreutz |
| author_facet | Theresa Ebersbach Annekathrin Roediger Robert Steinbach Martin Appelfeller Anke Tuemmler Beatrice Stubendorff Simon Schuster Meret Herdick Hubertus Axer Otto W. Witte Julian Grosskreutz |
| author_sort | Theresa Ebersbach |
| collection | DOAJ |
| description | Abstract The neurophysiological technique motor unit number index (MUNIX) is increasingly used in clinical trials to measure loss of motor units. However, the heterogeneous disease course in amyotrophic lateral sclerosis (ALS) obfuscates robust correlations between clinical status and electrophysiological assessments. To address this heterogeneity, MUNIX was applied in the D50 disease progression model by analyzing disease aggressiveness (D50) and accumulation (rD50 phase) in ALS separately. 237 ALS patients, 45 controls and 22 ALS-Mimics received MUNIX of abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. MUNIX significantly differed between controls and ALS patients and between ALS-Mimics and controls. Within the ALS cohort, significant differences between Phase I and II revealed in MUNIX, compound muscle action potential (CMAP) and motor unit size index (MUSIX) of APB as well as in MUNIX and CMAP of TA. For the ADM, significant differences occurred later in CMAP and MUNIX between Phase II and III/IV. In contrast, there was no significant association between disease aggressiveness and MUNIX. In application of the D50 disease progression model, MUNIX can demonstrate disease accumulation already in early Phase I and evaluate effects of therapeutic interventions in future therapeutic trials independent of individual disease aggressiveness. |
| first_indexed | 2024-04-11T10:46:28Z |
| format | Article |
| id | doaj.art-3241867be43544948eaded26894198f6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T10:46:28Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3241867be43544948eaded26894198f62022-12-22T04:29:01ZengNature PortfolioScientific Reports2045-23222022-09-0112111010.1038/s41598-022-19911-0Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALSTheresa Ebersbach0Annekathrin Roediger1Robert Steinbach2Martin Appelfeller3Anke Tuemmler4Beatrice Stubendorff5Simon Schuster6Meret Herdick7Hubertus Axer8Otto W. Witte9Julian Grosskreutz10Department of Neurology, Jena University HospitalDepartment of Neurology, Jena University HospitalDepartment of Neurology, Jena University HospitalDepartment of Neurology, Jena University HospitalDepartment of Neurology, Jena University HospitalDepartment of Neurology, Jena University HospitalPrecision Neurology, University of LübeckPrecision Neurology, University of LübeckDepartment of Neurology, Jena University HospitalDepartment of Neurology, Jena University HospitalPrecision Neurology, University of LübeckAbstract The neurophysiological technique motor unit number index (MUNIX) is increasingly used in clinical trials to measure loss of motor units. However, the heterogeneous disease course in amyotrophic lateral sclerosis (ALS) obfuscates robust correlations between clinical status and electrophysiological assessments. To address this heterogeneity, MUNIX was applied in the D50 disease progression model by analyzing disease aggressiveness (D50) and accumulation (rD50 phase) in ALS separately. 237 ALS patients, 45 controls and 22 ALS-Mimics received MUNIX of abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. MUNIX significantly differed between controls and ALS patients and between ALS-Mimics and controls. Within the ALS cohort, significant differences between Phase I and II revealed in MUNIX, compound muscle action potential (CMAP) and motor unit size index (MUSIX) of APB as well as in MUNIX and CMAP of TA. For the ADM, significant differences occurred later in CMAP and MUNIX between Phase II and III/IV. In contrast, there was no significant association between disease aggressiveness and MUNIX. In application of the D50 disease progression model, MUNIX can demonstrate disease accumulation already in early Phase I and evaluate effects of therapeutic interventions in future therapeutic trials independent of individual disease aggressiveness.https://doi.org/10.1038/s41598-022-19911-0 |
| spellingShingle | Theresa Ebersbach Annekathrin Roediger Robert Steinbach Martin Appelfeller Anke Tuemmler Beatrice Stubendorff Simon Schuster Meret Herdick Hubertus Axer Otto W. Witte Julian Grosskreutz Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS Scientific Reports |
| title | Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS |
| title_full | Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS |
| title_fullStr | Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS |
| title_full_unstemmed | Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS |
| title_short | Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS |
| title_sort | motor unit number index munix in the d50 disease progression model reflects disease accumulation independently of disease aggressiveness in als |
| url | https://doi.org/10.1038/s41598-022-19911-0 |
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