Quantitative assessment of motor impairment and surgical outcome in Hirayama disease with proximal involvement using motor unit number index

ObjectiveTo assess the feasibility of motor unit number index (MUNIX) in quantitatively evaluating Hirayama disease (HD) with proximal involvement and to identify the effectiveness of anterior cervical fusion (ACF) in treating atypical HD with proximal involvement.MethodsThis study included 28 atypical HD patients with proximal involvement (proximal-distal vs. distal-proximal groups: 5 vs. 23) and 41 healthy controls. All patients underwent pre- and postoperative 1-year MUNIX tests on abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB) and deltoid (Del). The disabilities of arm, shoulder and hand (DASH) and Medical Research Council (MRC) scales were also performed in these patients before and one year after operation.ResultsPreoperatively, the patients in the distal-proximal group showed reduced compound muscle action potential (CMAP), decreased MUNIX and increased motor unit size index (MUSIX) in bilateral distal muscles and symptomatic-side proximal muscles (P < 0.05), and similar abnormalities were also observed in ADM, BB and Del on the symptomatic side in the proximal-distal groups (P < 0.05). Postoperative follow-up analysis identified increased MUNIX in the symptomatic-side proximal muscles with improved motor function in the proximal-distal groups (P < 0.05), and distal-proximal group patients showed an increase in both CMAP and MUSIX in the symptomatic-side proximal muscles (P < 0.05).ConclusionsMUNIX may serve as an available supplementary test to quantitatively evaluate the motor dysfunction and treatment outcome in HD with proximal involvement. ACF procedures can effectively treat these atypical HD patients, especially for those whose symptoms started in proximal muscles.     

Motor unit number index correlates with disability in Charcot-Marie-Tooth disease

Objective

The aim of this study was to assess the usefulness of motor unit number index (MUNIX) technique in Charcot-Marie-Tooth disease and test the correlation between MUNIX and clinical impairment.

The motor unit number index (MUNIX) profile of patients with adult spinal muscular atrophy

Objective

Objective of this study is the comprehensive characterisation of motor unit (MU) loss in type III and IV Spinal Muscular Atrophy (SMA) using motor unit number index (MUNIX), and evaluation of compensatory mechanisms based on MU size indices (MUSIX).

Motor unit number index as an individual biomarker: Reference limits of intra-individual variability over time in healthy subjects

ObjectiveMotor unit number index (MUNIX) is proposed to monitor neuromuscular disorders. Our objective is to determine the intra-individual variability over time of the MUNIX.MethodsIn 11 different hospital centres, MUNIX was assessed twice, at least 3 months apart (range 90–360 days), in tibialis anterior (TA), abductor pollicis brevis (APB), abductor digiti minimi (ADM) and deltoid muscles in 118 healthy subjects. MUNIX sum score 2, 3 and 4 were respectively the sum of the MUNIX of the TA and ADM, of the TA, APB and ADM and of the TA, APB, ADM and deltoid muscles.ResultsThe repeatability of the MUNIX was better for sum scores than for single muscle recordings. The variability of the MUNIX was independent of sex, age, interval between measurements and was lower for experienced than non-experienced operators. The 95th percentile of the coefficient of variability of the MUNIX sum score 2, 3 and 4 were respectively 22%, 18% and 15% for experienced operators.ConclusionsThe MUNIX technique must be performed by experienced operators on several muscles to reduce its variability and improve its reliability.SignificanceA variation of the MUNIX sum score ≥20% can be interpreted as a significant change of muscle innervation.     

Motor unit number index (MUNIX) in children and adults with 5q-spinal muscular atrophy: Variability and clinical correlations

Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness and motor disability. The motor unit number index (MUNIX) is a biomarker used to assess loss of motor units in later-onset SMA patients. Twenty SMA patients (SMA types 3 and 4), aged between 7 and 41 years, were clinically evaluated through the Hammersmith Motor Functional Scale Expanded and the Spinal Muscular Atrophy-Functional Rating Scale. The patients underwent compound motor action potential (CMAP) and MUNIX studies of the right abductor pollicis brevis, abductor digiti minimi and tibialis anterior (TA) muscles. Age-matched healthy controls (n = 20) were enrolled to obtain normative CMAP and MUNIX values from the same muscles. Compared to healthy controls, SMA patients showed significant reductions in MUNIX values among all muscles studied, whereas CMAP showed reductions only in the weaker muscles (abductor digiti minimi and TA). MUNIX variability was significantly higher in the SMA group than in the control group. MUNIX variability in TA correlated with CMAP variability. Motor functional scores correlated with TA MUNIX. The MUNIX study is feasible in later-onset SMA patients, and TA MUNIX values correlate with disease severity in patients with mild motor impairment.     

Motor unit number index (MUNIX) versus motor unit number estimation (MUNE): a direct comparison in a longitudinal study of ALS patients

ObjectiveTo evaluate how the motor unit number index (MUNIX) is related to high-density motor unit number estimation (HD-MUNE) in healthy controls and patients with amyotrophic lateral sclerosis (ALS).MethodsBoth MUNIX and HD-MUNE were performed on the thenar muscles in 18 ALS patients and 24 healthy controls. Patients were measured at baseline, within 2 weeks, and after 4 and 8 months. Clinical evaluation included Medical Research Council (MRC) scale and the ALS functional rating scale (ALSFRS).ResultsThere was a significant positive correlation between MUNE and MUNIX values in ALS patients (r = 0.49 at baseline; r = 0.56 at 4 months; r = 0.56 at 8 months, all p < 0.05), but not in healthy controls. After 8 months, both MUNE and MUNIX values of the ALS patients decreased significantly more compared to MRC scale, ALS functional rating scale (ALSFRS) and compound muscle action potential (CMAP) (p < 0.05). There was no significant difference in relative decline of MUNIX and HD-MUNE values.ConclusionsIn ALS patients, MUNIX and HD-MUNE are significantly correlated. MUNIX has an almost equivalent potential in detecting motor neuron loss compared to HD-MUNE.SignificanceMUNIX could serve as a reliable and sensitive marker for monitoring disease progression in ALS.     

The Dorsal Root Ganglion as a Novel Neuromodulatory Target to Evoke Strong and Reproducible Motor Responses in Chronic Motor Complete Spinal Cord Injury: A Case Series of Five Patients

ObjectivesCurrent strategies for motor recovery after spinal cord injury (SCI) aim to facilitate motor performance through modulation of afferent input to the spinal cord using epidural electrical stimulation (EES). The dorsal root ganglion (DRG) itself, the first relay station of these afferent inputs, has not yet been targeted for this purpose. The current study aimed to determine whether DRG stimulation can facilitate clinically relevant motor response in motor complete SCI.Materials and MethodsFive patients with chronic motor complete SCI were implanted with DRG leads placed bilaterally on level L4 during five days. Based on personalized stimulation protocols, we aimed to evoke dynamic (phase 1) and isotonic (phase 2) motor responses in the bilateral quadriceps muscles. On days 1 and 5, EMG-measurements (root mean square [RMS] values) and clinical muscle force measurements (MRC scoring) were used to measure motor responses and their reproducibility.ResultsIn all patients, DRG-stimulation evoked significant phase 1 and phase 2 motor responses with an MRC ≥4 for all upper leg muscles (rectus femoris, vastus lateralis, vastus medialis, and biceps femoris) (p < 0.05 and p < 0.01, respectively), leading to a knee extension movement strong enough to facilitate assisted weight bearing. No significant differences in RMS values were observed between days 1 and 5 of the study, indicating that motor responses were reproducible.ConclusionThe current paper provides first evidence that bilateral L4 DRG stimulation can evoke reproducible motor responses in the upper leg, sufficient for assisted weight bearing in patients with chronic motor complete SCI. As such, a new target for SCI treatment has surfaced, using existing stimulation devices, making the technique directly clinically accessible.     

Motor unit number index (MUNIX) in chronic inflammatory demyelinating polyneuropathy: A potential role in monitoring response to intravenous immunoglobulins

ObjectiveTo compare motor unit number index (MUNIX) values in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and healthy controls, to assess correlations between MUNIX and clinical assessments used in CIDP and to assess short-term changes in MUNIX in CIDP following intravenous immunoglobulins (IVIg).MethodsMUNIX sum scores were calculated from three muscles in patients and healthy controls. CIDP patients also underwent a series of clinical assessments and completed the Overall Neuropathy Limitations Scale (ONLS) and the Rasch-built Overall-Disability Scale (R-ODS). Repeat assessments were performed in CIDP patients receiving IVIg and CIDP patients not on active treatment.ResultsMUNIX sum scores were significantly lower in CIDP patients than healthy controls (mean values 214.0 vs 516.9, respectively; p < 0.001). MUNIX sum scores correlated with clinical assessment of motor and sensory function and ONLS and R-ODS scores in CIDP patients. Significant short-term improvements were seen in MUNIX values on repeat testing following IVIg (188.3–226.4, p = 0.001), but not in CIDP patients not receiving IVIg.ConclusionsMUNIX values show stronger correlation with commonly-used clinical assessments and disability scores than other routinely used electrophysiological parameters. Rapid improvements in MUNIX sum scores are seen following IVIg.SignificanceMUNIX sum score may provide an objective marker of response to IVIg.     

Monitoring the short-term effect of intravenous immunoglobulins in multifocal motor neuropathy using motor unit number index

Objective

To determine whether motor unit number index (MUNIX) is pertinent to monitor the effect of intravenous immunoglobulins (IVIg) in multifocal motor neuropathy (MMN).

Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in Amyotrophic Lateral Sclerosis

Objective

Motor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with Amyotrophic Lateral Sclerosis (ALS). However, it is unclear whether MUNIX also detects motor unit loss in strong, non-wasted muscles.

Motor unit number index (MUNIX) in patients with anti-MAG neuropathy

Objective

To investigate the relationship between Motor Unit Number Index (MUNIX) and functional scales in patients with anti-Myelin Associated Glycoprotein (MAG) neuropathy and to know if MUNIX is modify after rituximab (RTX) therapy.

MUNIX and incremental stimulation MUNE in ALS patients and control subjects

ObjectiveThis study compares the new Motor Unit Number Estimation (MUNE) technique, MUNIX, with the more common incremental stimulation MUNE (IS-MUNE) with respect to reproducibility in healthy subjects and as potential biomarker of disease progression in patients with ALS.MethodsThirteen ALS patients and 48 control subjects were prospectively investigated – both groups were studied with MUNIX and IS-MUNE applied on the abductor digiti minimi (ADM) muscle. Additional retest was performed on 14 control subjects. Follow-up tests were carried out on 6 patients. The analysis included measures of reproducibility (Intraclass Correlation Coefficient (ICC)) and diagnostic performance (Receiver Operating Characteristic (ROC) analysis).ResultsTest–retest reproducibility was low to moderate for MUNIX and IS-MUNE (ICC = 0.38 and 0.56, respectively). Repeated MUNIX and IS-MUNE measurements on the same subject had a mean percentage difference (MPD) of 20% and 46%, respectively (p = 0.039). In the control group, the coefficient of variation was markedly lower for MUNIX than for IS-MUNE (26% and 44%, respectively, p < 0.0005). In ALS patients MUNIX had a notably better responsiveness in follow-up than IS-MUNE (percent change per month, 9.4 versus 5.6, p = 0.046). ROC analysis suggested similar diagnostic accuracy of both tests.ConclusionsMUNIX is a useful MUNE indicator when assessing progression of lower motor neuron affection in ALS. Furthermore, MUNIX displayed lower intrasubject variability, but no evident better diagnostic yield compared with IS-MUNE.SignificanceThis study has established comparative assessment of MUNIX and IS-MUNE performance in test–retest setting and as diagnostic tests on a distal muscle in ALS patients.     

Altered motor axonal excitability in patients with cervical spondylotic amyotrophy

Objective

To investigate the changes in motor axonal excitability properties in cervical spondylotic amyotrophy (CSA).

Assessment of the reliability of the motor unit size index (MUSIX) in single subject “round-robin” and multi-centre settings

ObjectiveThe motor unit size index (MUSIX) is incorporated into the motor unit number index (MUNIX). Our objective was to assess the intra-/inter-rater reliability of MUSIX in healthy volunteers across single subject “round robin” and multi-centre settings.MethodsData were obtained from (i) a round-robin assessment in which 12 raters (6 with prior experience and 6 without) assessed six muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis and abductor hallucis) and (ii) a multi-centre study with 6 centres studying the same muscles in 66 healthy volunteers. Intra/inter-rater data were provided by 5 centres, 1 centre provided only intra-rater data.Intra/inter-rater variability was assessed using the coefficient of variation (COV), Bland-Altman plots, bias and 95% limits of agreement.ResultsIn the round-robin assessment intra-rater COVs for MUSIX ranged from 7.8% to 28.4%. Inter-rater variability was between 7.8% and 16.2%. Prior experience did not impact on MUSIX values. In the multi-centre study MUSIX was more consistent than the MUNIX. Abductor hallucis was the least reliable muscle.ConclusionsThe MUSIX is a reliable neurophysiological biomarker of reinnervation.SignificanceMUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation.     

Motor unit number estimation in the quantitative assessment of severity and progression of motor unit loss in Hirayama disease

Objective

To investigate motor unit number estimation (MUNE) as a method to quantitatively evaluate severity and progression of motor unit loss in Hirayama disease (HD).

ALS pathophysiology: Insights from the split-hand phenomenon

ObjectiveThe aim of the present study was to assess whether peripheral mechanisms, mediated through axonal dysfunction, may contribute to development of the split-hand in amyotrophic lateral sclerosis (ALS).MethodsMedian and ulnar nerve motor axonal excitability studies were undertaken on 21 ALS patients with motor responses recorded over the abductor pollicis brevis (APB), abductor digit minimi (ADM) and first dorsal interosseous (FDI) muscles, and results compared to 24 controls.ResultsThe split-hand index (SI), an objective biomarker of preferential atrophy of APB and FDI muscles, was significantly reduced in ALS (SI_ALS 7.8 ± 1.7, SI_CONTROLS 13.1 ± 1.1, P < 0.0001). Axonal excitability studies identified significant prolongation of strength-duration time constant in ALS patients when recording over the APB (P < 0.05) and ADM axons (P < 0.05) but not FDI axons (P = 0.22). Greater changes in depolarising threshold electrotonus were also evident across the range of intrinsic hand muscles and were accompanied by increases of superexcitability in APB (P < 0.01) and FDI (P < 0.05) axons.ConclusionThe present study reinforces the significance of the split-hand phenomenon in ALS and argues against a significant peripheral contribution in the underlying development.SignificanceAxonal dysfunction may appear as a downstream process that develops secondary to the intrinsic pathophysiological origins of ALS.     

Motor unit number index examination in dominant and non-dominant hand muscles

This study investigated the effect of handedness on motor unit number index (MUNIX). Maximal hand strength, compound muscle action potential (CMAP) and voluntary surface electromyography (EMG) signals were measured bilaterally for the first dorsal interosseous (FDI) and thenar muscles in 24 right-handed and 2 left-handed healthy subjects. Mean (±standard error) grip and pinch forces in the dominant hand were 43.99 ± 2.36 kg and 9.36 ± 0.52 kg respectively, significantly larger than those in the non-dominant hand (grip: 41.37 ± 2.29 kg, p < .001; pinch: 8.79 ± 0.46 kg, p < .01). Examination of myoelectric parameters did not show a significant difference among the CMAP area, the MUNIX or motor unit size index (MUSIX) between the two sides in the FDI and thenar muscles. In addition, there was a lack of correlation between the strength and myoelectric parameters in regression analysis. However, strong correlations were observed between dominant and non-dominant hand muscles in both strength and myoelectric measures. Our results indicate that the population of motor units or spinal motor neurons as estimated from MUNIX may not be associated with handedness. Such findings help understand and interpret the MUNIX during its application for clinical or laboratory investigations.     

Split‐hand phenomenon in amyotrophic lateral sclerosis: A motor unit number index study

Introduction: The split‐hand phenomenon refers to preferential wasting of the thenar muscles with relative sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS). Methods: We compared the split‐hand index (SI) calculated from the compound muscle action potential (CMAP; SI_CMAP) with that calculated from the motor unit number index (MUNIX; SI_MUNIX). We performed MUNIX on the abductor policis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles of 39 ALS patients and 40 age‐matched, healthy controls. SI is derived by multiplying the CMAP (or MUNIX) recorded over the APB and FDI and dividing by the CMAP (or MUNIX) recorded over the ADM. Results: Receiver‐operating characteristic curve analysis revealed good diagnostic accuracy for both indices, but better performance of SI_MUNIX than SI_CMAP. Conclusion: SI_MUNIX and SI_CMAP were useful in differentiating ALS patients from healthy controls. SI_MUNIX appears to be a better electrophysiological marker than SI_CMAP for the split‐hand sign of ALS. Muscle Nerve 53 : 885–888, 2016     

Motor unit number index and compound muscle action potential amplitude

ObjectivesMUNIX (motor unit number index), derived from the compound muscle action potential (CMAP) and surface EMG interference pattern (SIP) has become popular as a substitute for motor unit number estimation (MUNE). This study was undertaken to determine why, in recent recordings from amyotrophic lateral sclerosis (ALS) patients and healthy controls, we found that MUNIX values resembled CMAP amplitudes more closely than MUNE values.MethodsThe relationship between MUNIX and CMAP and SIP amplitudes was investigated by a theoretical analysis and by reanalysing the data from the previous study.ResultsTheory indicates that when motor unit potentials overlap extensively, information about motor unit size and number is lost, and MUNIX depends only on CMAP area and power. Accordingly, MUNIX values were found to be sensitive to changes in CMAP amplitude but insensitive to changes in SIP amplitude. The reproducibility of MUNIX measurements in healthy controls was found to depend almost entirely on correlation with CMAP properties.ConclusionsMUNIX gives misleading information about motor unit numbers in healthy controls, and provides little information about loss of motor units in ALS patients beyond that given by simple CMAP amplitude measurements.SignificanceMUNIX should not be interpreted as a MUNE method.     

Length dependent loss of motor axons and altered motor unit properties in human diabetic polyneuropathy

ObjectiveTo assess the number and properties of motor units in an upper and lower limb muscle (tibialis anterior [TA] and first dorsal interosseous [FDI]) in human diabetic polyneuropathy (DPN) using decomposition-based quantitative electromyography (DQEMG).MethodsDQEMG protocols were performed in the TA and FDI of 12 patients with confirmed diabetes mellitus and associated DPN, as well as 12 age-matched control participants. Maximal dorsiflexion strength was also assessed using a dynamometer.ResultsIn both muscles, patients with DPN had significantly reduced motor unit number estimates (MUNEs) (ΔTA ∼45%; ΔFDI ∼30%), compound muscle action potentials (CMAPs) (ΔTA ∼30%; ΔFDI ∼20%), and mean firing rates were reduced (ΔTA ∼15%; ΔFDI ∼15%) compared to controls (p < 0.05). For the TA, patients with DPN had larger mean surface motor unit potentials (SMUPs) (ΔTA ∼40%; p < 0.05), whereas in the FDI no differences were found (p > 0.05).ConclusionsDPN may result in motor unit loss, remodeling, and altered firing rate patterns. The magnitude of changes in the neuromuscular properties of DPN patients are muscle dependent and reflect a length-dependent disease progression.SignificanceDQEMG may be a clinically useful technique in identifying the presence and severity of neuromuscular pathophysiology and tracking disease progression in DPN.