Motor Unit Number Index Research Articles

Effects of Type II Diabetes on upper extremity muscle characteristics in older adults.

With one in every four older adults living with T2D and one in every two older adults meeting the criteria for prediabetes, neuromuscular changes due to T2D are likely to impact functional activities in this population. Limited work in evaluating motor unit number and size across muscles in the upper extremity in persons with Type II Diabetes (T2D) exists, mostly due to the traditional belief bias that the upper extremity is relatively spared in T2D as compared to the lower extremities. The purpose of the current study was to evaluate motor unit number and size (using electrophysiological motor unit number index (MUNIX) and motor unit size index (MUSIX)) across the upper extremity in older adults with T2D (n = 13) as compared to healthy age- and sex-matched controls (n = 12). Persons with T2D presented with more motor units and larger motor unit sizes (p < 0.05) as compared to age- and sex-matched control participants. These changes were not dependent upon muscle location within a limb, indicating systemic neuromuscular changes associated with T2D. These group effects were clarified when health state covariates (e.g., blood pressure) were accounted for. Findings are consistent with emerging data that show altered neuromuscular characteristics with health state considerations in persons with T2D.

199P The use of the Motor Unit Number Index (MUNIX) as a biomarker for disease progression in late-onset 5q-spinal muscular atrophy treated with nusinersen

199P The use of the Motor Unit Number Index (MUNIX) as a biomarker for disease progression in late-onset 5q-spinal muscular atrophy treated with nusinersen

Motor unit number index in Bell's palsy: A potential electrophysiological biomarker for early evaluation.

Reliable, noninvasive early diagnostics of neuromuscular function in Bell's palsy, which causes facial paralysis and reduced quality of life, remain to be established. Here, we aimed to evaluate the utility of the motor unit number index (MUNIX) for the quantitative electrophysiological assessment of early-stage Bell's palsy, its correlation with clinical assessments, changes following treatment, and association with clinical prognosis. MUNIX measures were recorded from the bilateral zygomaticus, orbicularis oculi, and orbicularis oris muscles of 10 healthy individuals and 64 patients with Bell's palsy. The patients were assessed by two specialist neurologists using the House-Brackmann and Sunnybrook Facial Grading Systems. Repeat assessments were performed on 20 patients with Bell's palsy who received treatment. Additionally, the 64 patients were reassessed using clinical scales after a 1-month interval. The MUNIX values of the main affected muscles on the affected side were lower than those on the healthy side in patients with Bell's palsy (p<.05). The MUNIX measurements significantly correlated with the clinical facial nerve palsy scale scores (p<.05). Significant improvements were observed in the MUNIX values on repeat testing following treatment (p<.05). The baseline motor unit size index (the compound muscle action potential amplitude divided by MUNIX) was positively associated with improved clinical presentation after 1 month (p<.05). MUNIX can be used as an electrophysiological biomarker for the quantitative assessment of facial nerve palsy and treatment response, and as a prognostic biomarker, in patients with early Bell's palsy, and is recommended as a complement to conventional neurophysiological examinations.

Effect of surface electrode recording area on compound muscle action potential scan processing for motor unit number estimation.

MScanFit is a model-based algorithm for motor unit number estimation (MUNE) from compound muscle action potential (CMAP) scan data. It is a clinically applicable tool because of its quick and automatic implementation. Electrodes with different recording areas were employed to record CMAP scan data in existing studies. However, the effect of electrode recording area on MScanFit MUNE and other CMAP scan parameters has not been studied. CMAP scan was performed on the abductor pollicis brevis muscle of both hands on 14 healthy subjects using three different electrodes with recording areas of 10 mm × 10 mm, 11 mm × 14 mm, and 22 mm × 26 mm, respectively. Motor unit number was estimated using MScanFit for each CMAP scan. Two motor unit number index parameters, i.e., D50 and step index (STEPIX), were also derived from the CMAP scan data. No significant difference in D50, STEPIX, and MScanFit MUNE was observed across three different electrode recording areas, although the amplitude of CMAP decreased significantly when a larger electrode was used. Intraclass correlation coefficients of 0.792 and 0.782 were obtained for MScanFit MUNE and STEPIX, respectively. Compared with CMAP amplitude, D50, STEPIX, and MScanFit MUNE are less sensitive to variation in electrode recording area. However, the repeatability of MScanFit MUNE could be compromised by the inconsistency in the electrode recording area.

Could the motor unit number index be an early prognostic biomarker for amyotrophic lateral sclerosis?

ObjectiveTo evaluate the associations between motor unit number index (MUNIX) and disease progression and prognosis in amyotrophic lateral sclerosis (ALS) in a large-scale longitudinal study. MethodsMUNIX was performed at the patient's first visit, at 3, 6, and 12 months in 4 muscles. MUNIX data from the patients were compared with those from 38 age-matched healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), the forced vital capacity (FVC), and the survival of the patients. ResultsEighty-two patients were included at baseline, 62 were evaluated at three months, 48 at six months, and 33 at twelve months. MUNIX score was lower in ALS patients compared to controls. At baseline, MUNIX was correlated with ALSFRS-R and FVC. Motor unit size index (MUSIX) was correlated with patient survival. Longitudinal analyses showed that MUNIX decline was greater than ALSFRS-R decline at each evaluation. A baseline MUNIX score greater than 378 predicted survival over the 12-month period with a sensitivity of 82% and a specificity of 56%. ConclusionsThis longitudinal study suggests that MUNIX could be an early quantitative marker of disease progression and prognosis in ALS. SignificanceMUNIX might be considered as potential indicator for monitoring disease progression.

Utility of single fibre electromyography (SFEMG)and motor unit number estimation technique (MUNE) in the diagnosis and differentiation of polyneuropathies of different aetiology.

To determine whether single fibre electromyography and motor unit number index can distinguish between axonal and myelin lesions in polyneuropathies. This case-control study was conducted at the Department of Medical Physiology, School of Medicine, University of Duhok, Iraq, and the Neurophysiology Department, Hawler Teaching Hospital, Erbil, Iraq, from January 2021 to March 2022. Group A had patients diagnosed with polyneuropathy regardless of the aetiology, while group B had age-matched healthy controls. Both groups were subjected to single fibre electromyography and motor unit number index as well as conventional nerve conduction study and concentric needle electromyography. Data was analysed using SPSS 26. Of the 140 subjects, 60(43%) were patients in group A; 40(67%) males and 20(33%) females with mean age 55.3±7.2 years. There were 80(57%) controls in group B; 43(54%) females and 37(46%) males with mean age 53.81±7.15. Group A had significantly higher single fibre electromyography jitter, and mean consecutive difference (MCD) values than group B (p<0.05). Group A patients with axonal polyneuropathy had a higher mean jitter (MCD) value (36.476.7ms) than those with demyelinating polyneuropathy (23.262.31 ms) (P <0.05). Patients in group A had a motor unit number index value with a significantly lower mean value (p<0.05) when compared to the controls. Axonal polyneuropathy patients had a lower MUNIX value (99.612.8) than demyelinating polyneuropathy patients (149.845.7) (P< 0.05). Single fibre electromyography and motor unit number index could help differentiate between the pathophysiology of axonal and demyelinating polyneuropathy.

Utility of split hand index with different motor unit number estimation techniques in ALS

ObjectiveUtility of the split hand index (SI) in amyotrophic lateral sclerosis (ALS) has been reported when using the compound muscle action potential (CMAP) amplitude method (SICMAP amp). A motor unit number index (MUNIX) based SI method (SIMUNIX) was purported to exhibit higher sensitivity. The present study assessed the clinical utility of SI, derived by CMAP amplitude, MUNIX and MScan-MUNE (SIMScanFit-MUNE) methods, in ALS. MethodsSixty-two consecutive patients with neuromuscular symptoms (36 ALS and 26 ALS-mimics) were prospectively recruited. The SI was derived by dividing the product of the CMAP amplitude, MUNIX and MScan-MUNE values recorded over first dorsal interosseous and abductor pollicis brevis by values recorded over abductor digit minimi. ResultsSICMAP amp, SIMUNIX and SIMScanFit-MUNE were significantly reduced in ALS, with SICMAP amp (area under curve (AUC) = 0.801) and SIMScanFit-MUNE (AUC = 0.805) exhibiting greater diagnostic utility than SIMUNIX (AUC = 0.713). SICMAP amp and SIMScanFit-MUNE exhibited significant correlations with clinical measures of functional disability and weakness of intrinsic hand muscles. ConclusionsSI differentiated ALS from mimic disorders, with SICMAP amp and SIMScanFit-MUNE exhibiting greater utility. SignificanceThe split hand index represents could serve as a potential diagnostic biomarker in ALS.

Prognostic Usefulness of Motor Unit Number Index (MUNIX) in Patients Newly Diagnosed with Amyotrophic Lateral Sclerosis.

24 ALS patients with short disease duration (<24 months from symptoms' onset) were enrolled and divided according to their baseline DPR into two groups (normal [DPR-N] and fast [DPR-F] progressors). MUNIX values were obtained from five muscles (TA, APB, ADM, FDI, Trapezius) and averaged for each subject. MUNIX was found to predict DPR at follow up in a multivariable linear regression model; namely, patients with lower MUNIX values were at risk of showing greater DPR scores at follow up. The result was replicated in a simple logistic regression analysis, with the dichotomic category "MUNIX-Low" as the independent variable and the outcome "DPR-F" as the dependent variable. our results pave the way for the use of the MUNIX method as a prognostic tool in early ALS, enabling patients' stratification according to their rates of future decline.

Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): a phase 2, randomised, double-blind, placebo-controlled trial and open label extension.

CNM-Au8® is a catalytically-active gold nanocrystal neuroprotective agent that enhances intracellular energy metabolism and reduces oxidative stress. The phase 2, randomised, double-blind, placebo-controlled trial and open label extension RESCUE-ALS trial evaluated the efficacy and safety of CNM-Au8 for treatment of amyotrophic lateral sclerosis (ALS). RESCUE-ALS and its long-term open label extension (OLE) were conducted at two multidisciplinary ALS clinics located in Sydney, Australia: (i) the Brain and Mind Centre and (ii) Westmead Hospital. The double-blind portion of RESCUE-ALS was conducted from January 16, 2020 (baseline visit, first-patient first-visit (FPFV)) through July 13, 2021 (double-blind period, last-patient last-visit (LPLV)). Participants (N=45) were randomised 1:1 to receive 30mg of CNM-Au8 or matching placebo daily over 36 weeks in addition to background standard of care, riluzole. The primary outcome was mean percent change in summed motor unit number index (MUNIX), a sensitive neurophysiological biomarker of lower motor neuron function. Change in total (or summated) MUNIX score and change in forced vital capacity (FVC) were secondary outcome measures. ALS disease progression events, ALS Functional Rating Scale (ALSFRS-R) change, change in quality of life (ALSSQOL-SF) were assessed as exploratory outcome measures. Long-term survival evaluated vital status of original active versus placebo randomisation for all participants through at least 12 months following last-patient last-visit (LPLV) of the double-blind period. RESCUE-ALS and the open label study are registered in clinicaltrials.gov with registration numbers NCT04098406 and NCT05299658, respectively. In the intention-to-treat (ITT) population, there was no significant difference in the summated MUNIX score percent change (LS mean difference: 7.7%, 95% CI:-11.9 to 27.3%, p=0.43), total MUNIX score change (18.8, 95% CI:-56.4 to 94.0), or FVC change (LS mean difference: 3.6, 95% CI:-12.4 to 19.7) between the active and placebo treated groups at week 36. In contrast, survival analyses through 12-month LPLV demonstrated a 60% reduction in all-cause mortality with CNM-Au8 treatment [hazard ratio=0.408 (95% Wald CI: 0.166 to 1.001, log-rank p=0.0429). 36 participants entered the open label extension (OLE), and those initially randomised to CNM-Au8 exhibited a slower rate of disease progression, as measured by time to the occurrence of death, tracheostomy, initiation of non-invasive ventilatory support, or gastrostomy tube placement. CNM-Au8 was well-tolerated, and no safety signals were observed. CNM-Au8, in combination with riluzole, was well-tolerated in ALS with no identified safety signals. While the primary and secondary outcomes of this trial were not significant, the clinically meaningful exploratory results support further investigation of CNM-Au8 in ALS. The RESCUE-ALS was substantially funded by a grant from FightMND. Additional funding was provided by Clene Australia Pty Ltd.

D.2 Cross-sectional axonal excitability and motor unit number index profile in early stages of weakness in ALS

Background: What is the number and size of motor units, and axonal excitability profile in the early stages of muscle weakness in ALS compared to controls? Methods: We enrolled ALS patients with APB manual strength testing rated four or four-minus (ALS:4-arm) and four-plus (ALS:4+ arm) and control participants &gt;35 years-old from the University of Toronto, University of Alberta and Universidade Federal de Sao Paulo. Mean±SD, one-way ANOVA and ANCOVA of ALSFRS-R, PUMN Score, MUNIX, MUSIX, and nerve-excitability testing using QTRAC TROND protocol were reported. Results: Twenty-five ALS patients and 63 controls were included. Mean MUNIX was significantly lower (p&lt;0.0001) and MUSIX was significantly higher (p&lt;0.001) in both ALS groups compared to controls. Mean strength-duration time constant in the ALS:4- arm (0.50ms±0.11; p&lt;0.05) and superexcitability in both ALS groups (ALS:4- -29.05%±9.24, ALS:4+ -27.67%±8.03; p&lt;0.05) were relatively increased, supporting axonal hyperexcitability. Conclusions: Significant motor unit loss measured by MUNIX is already present at the earliest detection of muscle weakness in ALS. Increased MUSIX and altered axonal physiology are associated with axonal sprouting and geometry change(1), along with ion channel dysfunction(2). Future trials targeting muscle weakness in ALS should consider the altered neuronal physiology during early disease stages and utilize neurophysiological biomarkers only in normal-to-mildly weak muscles.

N°166 – Cross-sectional axonal excitability and motor unit number index profile in early stages of weakness in ALS

N°166 – Cross-sectional axonal excitability and motor unit number index profile in early stages of weakness in ALS

Cervical Spinal Cord Gray Matter Area is Associated with Motor Unit Number Index in Spinal Muscular Atrophy (S33.008)

<h3>Objective:</h3> To evaluate the association between spinal cord (SC) gray matter (GM) atrophy and Motor Unit Number Index (MUNIX) in patients with 5q-Spinal Muscular Atrophy (SMA). <h3>Background:</h3> There is an unmet need for valid imaging markers to monitor the disease course and therapeutic outcome in SMA. The novel rAMIRA (radially sampled Averaged Magnetization Inversion Recovery Acquisitions) method enables high in-plane resolution MR-imaging with improved contrast of SC GM in clinically feasible acquisition times. MUNIX is an established quantitative neurophysiological measure that provides an index of the number of functioning lower motor neurons that supply a muscle. The association between SC GM area and MUNIX has not been investigated in SMA yet. <h3>Design/Methods:</h3> Using axial 2D rAMIRA imaging, we prospectively investigated 21 patients with 5q-SMA, types 2 and 3 (mean age/SD 41.3/11.6y, 9 women) and 21 age- and sex-matched healthy controls (HC) (mean age/SD 41.7/11.4y, 9 women) at the intervertebral disc level C5/C6 perpendicular to the spinal cord. SC GM areas were determined using a semi-automated approach. MUNIX of the biceps brachii (BB) was measured following the ENCALS protocol. The association between SC GM area and MUNIX was assessed using multivariable regression analysis covarying for age and sex. <h3>Results:</h3> SC GM area at C5/6 was significantly reduced in patients compared to HC (mean GM area in mm² (SD): SMA 17.5 (2.2); HC 21.1 (2.3); relative reduction: 17.1% (p&lt;0.0001)). In multivariable regression analysis SC GM area at C5/6 explained 53% of MUNIX variance of the BB in SMA patients. <h3>Conclusions:</h3> In patients with SMA, SC GM area is strongly associated with motor neuron function quantitated by MUNIX in the corresponding myotome, indicating the functional relevance of this structural marker. Further longitudinal studies are necessary to evaluate the potential of this novel imaging marker for monitoring the disease course and therapeutic outcome. <b>Disclosure:</b> Dr. Wendebourg has nothing to disclose. Dr. Kesenheimer has nothing to disclose. An immediate family member of Dr. Weidensteiner has received personal compensation for serving as an employee of Siemens Healthineers. Dr. Sander has nothing to disclose. The institution of Matthias Weigel, PhD has received research support from Biogen. Matthias Weigel, PhD has received intellectual property interests from a discovery or technology relating to health care. Tanja Haas has nothing to disclose. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann La Roche AG. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann La Roche AG. Christoph Neuwirth has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen USA. Christoph Neuwirth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Switzerland. Nathalie Braun has nothing to disclose. Dr. Weber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Weber has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Granziera has nothing to disclose. Prof. Sinnreich has nothing to disclose. The institution of Oliver Bieri has received research support from Swiss National Science Foundation. The institution of Oliver Bieri has received research support from MIAC Foundation. The institution of Oliver Bieri has received research support from Biogen. Oliver Bieri has received intellectual property interests from a discovery or technology relating to health care. Regina Schlaeger has nothing to disclose.

Facial nerve vulnerability in spinal muscular atrophy and motor unit number index of the orbicularis oculi muscle.

Measures for assessing cranial nerve vulnerability in spinal muscular atrophy (SMA) have not yet been determined. Motor unit number index (MUNIX) studies have shown correlations with disease severity but have been used only in limb muscles. In the present study, we explore facial nerve response, MUNIX, and motor unit size index (MUSIX) of the orbicularis oculi muscle in a cohort of patients with SMA. Facial nerve response (measured as compound muscle action potential, CMAP), MUNIX, and MUSIX of the orbicularis oculi muscle were cross-sectionally recorded in patients with SMA and compared to healthy control subjects (HCs). Active maximum mouth opening (aMMO) was also measured at baseline in our SMA cohort. Thirty-seven patients with SMA (21 SMA II; 16 SMA III) and 27 HCs were recruited. CMAP of the facial nerve and MUNIX of orbicularis oculi proved to be feasible and well tolerated techniques. CMAP amplitude and MUNIX scores were significantly lower in patients with SMA compared to HCs (p < .0001). Both MUNIX and CMAP amplitude were significantly higher in patients with SMA III compared to SMA II. No significant difference emerged comparing CMAP amplitude, MUNIX and MUSIX scores between those with different functional status or nusinersen treatment. Our results provide neurophysiological evidence of facial nerve and muscle involvement in patients with SMA. CMAP of the facial nerve and MUNIX of orbicularis oculi showed high accuracy in discriminating between the various subtypes of SMA and in quantifying the motor unit loss of the facial nerve.

Motor unit number index (MUNIX) loss of 50% occurs in half the time of 50% functional loss according to the D50 disease progression model of ALS

Capturing disease progression in amyotrophic lateral sclerosis (ALS) is challenging and refinement of progression markers is urgently needed. This study introduces new motor unit number index (MUNIX), motor unit size index (MUSIX) and compound muscle action potential (CMAP) parameters called M50, MUSIX200 and CMAP50. M50 and CMAP50 indicate the time in months from symptom onset an ALS patient needs to lose 50% of MUNIX or CMAP in relation to the mean values of controls. MUSIX200 represents the time in months until doubling of the mean MUSIX of controls. We used MUNIX parameters of Musculi abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) of 222 ALS patients. Embedded in the D50 disease progression model, disease aggressiveness and accumulation were analyzed separately. M50, CMAP50 and MUSIX200 significantly differed among disease aggressiveness subgroups (p < 0.001) regardless of disease accumulation. ALS patients with a low M50 had a significantly shorter survival compared to high M50 (median 32 versus 74 months). M50 preceded the loss of global function (median of about 14 months). M50, CMAP50 and MUSIX200 characterize the disease course in ALS in a new way and may be applied as early measures of disease progression.

MUNIX repeatability evaluation method based on FastICA demixing.

To enhance the reproducibility of motor unit number index (MUNIX) for evaluating neurological disease progression, this paper proposes a negative entropy-based fast independent component analysis (FastICA) demixing method to assess MUNIX reproducibility in the presence of inter-channel mixing of electromyography (EMG) signals acquired by high-density electrodes. First, composite surface EMG (sEMG) signals were obtained using high-density surface electrodes. Second, the FastICA algorithm based on negative entropy was employed to determine the orthogonal projection matrix that minimizes the negative entropy of the projected signal and effectively separates mixed sEMG signals. Finally, the proposed experimental approach was validated by introducing an interrelationship criterion to quantify independence between adjacent channel EMG signals, measuring MUNIX repeatability using coefficient of variation (CV), and determining motor unit number and size through MUNIX. Results analysis shows that the inclusion of the full (128) channel sEMG information leads to a reduction in CV value by $1.5 \pm 0.1$ and a linear decline in CV value with an increase in the number of channels. The correlation between adjacent channels in participants decreases by $0.12 \pm 0.05$ as the number of channels gradually increases. The results demonstrate a significant reduction in the number of interrelationships between sEMG signals following negative entropy-based FastICA processing, compared to the mixed sEMG signals. Moreover, this decrease in interrelationships becomes more pronounced with an increasing number of channels. Additionally, the CV of MUNIX gradually decreases with an increase in the number of channels, thereby optimizing the issue of abnormal MUNIX repeatability patterns and further enhancing the reproducibility of MUNIX based on high-density surface EMG signals.

Motor unit properties do not correlate between MUNIX and needle EMG in remote polio in the biceps brachii muscle

ObjectiveTo compare the utility of MUNIX (motor unit number index) with needle EMG in characterizing motor unit (MU) properties in the biceps brachii (BB) muscle in subjects with remote polio. MethodsThirty subjects suffering from remote polio were investigated with MUNIX and needle EMG, all with Macro EMG and 16 of these subjects with concentric needle EMG. ResultsBoth MUNIX and the needle EMG methods showed abnormal results. Fiber density (FD) was the most sensitive parameter for showing signs of reinnervation. At a group level, the methods showed neurogenic findings, but there was no correlation between the results of the MUNIX and needle EMG investigations. ConclusionsBoth MUNIX and needle EMG are valuable methods for measuring neurogenic involvement in the BB muscle. However, there was a lack of correlation between the MUNIX and needle EMG findings. The cause for this missing correlation may be multifactorial as there are several differences between the methods. SignificanceThe reason for the lack of correlation between the MUNIX and needle EMG results is discussed. By combining the needle and surface recorded methods one can obtain more information on the denervation and reinnervation process compared to using just one of the methods alone.

Motor unit number index (MUNIX) in the D50 disease progression model reflects disease accumulation independently of disease aggressiveness in ALS.

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.

P 76 MUNIX in combination with D50 disease progression model reflects disease accumulation independently of disease aggressiveness in Amyotrophic Lateral Sclerosis

Introduction: Motor Unit Number Index (MUNIX) is a reliable and non-invasive neurophysiological technique to reflect functional loss of motor units in amyotrophic lateral sclerosis (ALS). MUNIX is even able to show loss of motor units in pre-symptomatic, non-wasted muscles [1,2]. So, it has been recognized as a promising biomarker in ALS. ALS, as a multisystemic neurodegenerative disease, shows a high heterogeneity in clinical presentation, including disease phenotypes, progression and survival. We urgently need reliable surrogate markers to describe the individual disease course, reduce diagnostic delay and monitor efficacy of therapeutic strategies in ALS [3]. Additionally to MUNIX, we use the D50 disease progression model to analyze disease aggressiveness and disease accumulation. Patients and Methods: 237 ALS patients, 45 healthy controls and 22 ALS-Mimics received MUNIX of abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) in clinical routine by trained and certified electrophysiologists using a standardized protocol [4]. MUNIX was further analyzed by disease aggressiveness (D50) and disease accumulation (rD50 phase) in ALS using the D50 progression model. Results: MUNIX and CMAP were significantly lower in ALS patients and ALS-mimics compared to healthy controls (p < 0,05) in all investigated muscles. In ALS subgroup analysis, MUNIX in APB and TA showed significant decrease between rD50 Phase I and II (p < 0,001/p < 0,01), while significant differences in ADM just occurred in advanced disease stage between Phase II and III/IV (p < 0,05). Throughout the subgroups of aggressiveness, there were no significant differences. Conclusion: MUNIX in combination with D50 progression model demonstrates disease accumulation in ALS, especially in APB in early disease compared to ADM. This supports the clinical split-hand-phenomenon. Also, MUNIX seems to be independent of disease aggressiveness. Therefore, we apply MUNIX in combination with the D50 disease progression model to reflect the individual disease course in ALS, which might be useful in clinical trials to evaluate therapeutic strategies and agents in ALS independently of disease aggressiveness.

The landscape of neurophysiological outcome measures in ALS interventional trials: A systematic review

ObjectiveWe collated all interventional clinical trials in amyotrophic lateral sclerosis (ALS), which utilised at least one neurophysiological technique as a primary or secondary outcome measure. By identifying the strengths and limitations of these studies, we aim to guide study design in future trials. MethodsWe conducted and reported this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight databases were searched from inception. In total, 703 studies were retrieved for screening and eligibility assessment. ResultsDating back to 1986, 32 eligible interventional clinical trials were identified, recruiting a median of 30 patients per completed trial. The most widely employed neurophysiological techniques were electromyography, motor unit number estimation (including motor unit number index), neurophysiological index and transcranial magnetic stimulation (including resting motor threshold and short-interval intracortical inhibition). Almost 40% of trials reported a positive outcome with respect to at least one neurophysiological measure. The interventions targeted either ion channels, immune mechanisms or neuronal metabolic pathways. ConclusionsNeurophysiology offers many promising biomarkers that can be utilised as outcome measures in interventional clinical trials in ALS. When selecting the most appropriate technique, key considerations include methodological standardisation, target engagement and logistical burden. SignificanceFuture trial design in ALS would benefit from a standardised, updated and easily accessible repository of neurophysiological outcome measures.

The value of MUNIX as an objective electrophysiological biomarker of disease progression in chronic inflammatory demyelinating polyneuropathy.

Objective outcome measures to monitor treatment response and guide treatment are lacking in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we aimed to evaluate the motor unit number index (MUNIX) as an outcome measurement in patients with CIDP and determine the correlation of MUNIX with functional and standard electrodiagnostic tests in a single follow-up study. We evaluated MUNIX of the abductor pollicis brevis, abductor digiti minimi, and tibialis anterior (TA) muscles bilaterally. Muscle force was assessed by Medical Research Council Sum Score (MRCSS). Functional measures used were the Overall Neuropathy Limitation Score (ONLS) and the Rasch-built Overall Disability Scale (R-ODS) score at baseline and after 6 months of treatment. Standard electrophysiology was evaluated by the Nerve Conduction Study Score (NCSS). Twenty patients were included at baseline, and 16 completed the follow-up study. Significant correlations were found between the MUNIX sum score and both MRCSS and NCSS at baseline, between both the pinch strength and grip and upper limb MUNIX at baseline and follow-up, and between MUNIX of TA and both lower limb MRCSSs with lower limb ONLS at baseline and follow-up. Significant correlations also were found between MUNIX sum score change and MRCSS change, R-ODS change, and ONLS change. MUNIX changes correlated with strength and electrophysiological improvements in CIDP patients. This suggests that MUNIX may represent a useful objective biomarker for patient follow-up.