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     

Hand weakness in Charcot-Marie-Tooth disease 1X

There have been suggestions from previous studies that patients with Charcot-Marie-Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker dominant hand; none had a stronger dominant hand. Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X.     

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.     

Reproducibility of MUNIX in patients with amyotrophic lateral sclerosis

Introduction: In this study we investigated the reproducibility of motor unit number index (MUNIX) in patients with amyotrophic lateral sclerosis (ALS). Methods: MUNIX was recorded in patients with ALS. Studies were performed in 18 thenar and 18 hypothenar muscles by two operators. The reproducibility was assessed using mean MUNIX values, linear regression, correlation coefficient, and coefficient of variation (COV) in individual studies. Results: The mean values showed no significant difference. The linear regression showed a strong correlation. Most patients had low COV. A high COV was seen when MUNIX was very low. The COV was higher in thenar than in hypothenar muscles. Conclusions: MUNIX has very good reproducibility in ALS patients. COV may exaggerate interoperator variation when MUNIX is very low. The higher variability in the thenar muscle is also due to variability in compound muscle action potential amplitude. Although both muscles show good reproducibility, the hypothenar is better suited for serial studies in individual patients Muscle Nerve, 2011     

Modulation of motor cortex excitability induced by pinch grip repetition

Summary. We examined the influence of right handed pinch grips and the effect of a motor training on motor cortex excitability of the left first dorsal interosseus muscle (FDI). TMS single and paired pulses were applied over the right human motor cortex (M1) during and after right handed pinch grips with low force. In another experiment, these stimulations were performed before and after a 30-minute right handed pinch grip training. Results: MEP amplitudes in left FDI were reduced when TMS single pulses were applied during the pinch grip. Simultaneously, motor cortex excitability was enhanced but returned to baseline after the training period. Conclusion: Phasic pinch grips of the right hand exert an inhibiting effect on the corticospinal excitability of the ipsilateral motor cortex and lead to an increase of intracortical excitability. These changes are distinct and independent of each other. Motor training has an interhemispheric effect on intracortical excitability.     

Further observations on forearm flexor weakness in inclusion body myositis

In order to further characterize and provide a possible mechanism for the asymmetrical involvement of forearm muscles in inclusion body myositis (IBM), we measured isometric hand and pinch grip strength, and forearm muscle girth on 15 IBM patients. Forearm muscle strength and girth were significantly greater on the dominant versus nondominant side: mean grip strength, 173.9 vs. 98.8 N; mean pinch strength, 47.6 vs. 29.7 N; and mean forearm girth, 22.5 vs. 19.9 cm. This observation may suggest a role for exercise in delaying the disease progression in IBM. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:659–661, 1998.     

The effect of handedness on grip strength in older adults with intellectual disabilities

Grip strength is an important predictor of several health outcomes in the general older population. Grip strength assessment is feasible and reliable in older adults with intellectual disabilities (ID), which makes it a valuable measurement for application in this population. The purpose of this study was to investigate the effect of handedness on grip strength in the older population with ID. Handedness and grip strength were assessed in a sample of 1050 older adults (≥50 years) with borderline to profound ID. Results showed that 26.2% of the study sample was left-handed. In right-handed participants the dominant hand (right) was on average 8.7% stronger than the non-dominant hand (p < 0.001). For lefthanded participants there was no significant difference between the dominant hand (left) and nondominant hand. However, more detailed analyses revealed that 34.5% of the participants were stronger with their non-dominant hand, (on average 16.6% stronger for right-handed and 16.3% stronger for left-handed participants). Because of the large strength ratios, distributed in favor of both the dominant as the non-dominant hand, it is recommended to assess both hands to get a valid result of grip strength in older adults with ID.     

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 (MUNIX): principle, method, and findings in healthy subjects and in patients with motor neuron disease

The motor unit number index (MUNIX) is a method for assessment of number and size (MUSIX) of motor units (MUs) using the compound muscle action potential (CMAP) and surface electromyographic interference pattern (SIP). This method was used to study the hypothenar muscle in 34 healthy subjects to define normal range, and to study reproducibility. Four healthy subjects and 13 patients with amyotrophic lateral sclerosis (ALS) were studied serially over a 1-year period. In healthy subjects, MUNIX showed good reproducibility. In serial studies, healthy subjects showed no change in the CMAP amplitude and MUNIX. ALS patients with minimal change in CMAP amplitude had a significant drop in MUNIX and increase in MUSIX, indicating MU loss compensated by reinnervation. When the CMAP changed significantly (>30%) in 1 year, the CMAP and MUNIX decreased in parallel. MUNIX would be useful to study MU loss in degenerative diseases of motor neurons. Muscle Nerve 42: 798-807, 2010.     

Hemispheric asymmetry of surround inhibition in the human motor system

ObjectiveSurround inhibition (SI) in the motor system is an essential mechanism for the selective execution of desired movements. To investigate the relationship between the efficiency of SI operation in the motor system and handedness, we performed a transcranial magnetic stimulation (TMS) study in 10 healthy, right-handed volunteers.MethodsTMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the adductor digiti minimi (ADM) and the flexor digitorum superficialis (FDS) muscles were compared between the dominant and non-dominant hands.ResultsDuring index finger flexion, MEP amplitudes of the ADM in the dominant hand were suppressed but not in the non-dominant hand, while MEP amplitudes of the FDS were comparably enhanced in both hands. F-wave amplitudes of ADM were comparably enhanced during index finger flexion in both hands.ConclusionThese results suggest that the functional operation of SI in the motor system is more efficient in the dominant hand than the non-dominant hand. More efficient SI in the dominant hand could lead to greater dexterity in the dominant hand.SignificanceHemispheric asymmetry of SI might be able to serve as a neurophysiological proxy for handedness.     

The split hand syndrome in amyotrophic lateral sclerosis

In amyotrophic lateral sclerosis (ALS), hand muscle wasting preferentially affects the 'thenar (lateral) hand', including the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles, with relative sparing of the hypothenar muscles (the abductor digiti minimi (ADM)). This peculiar pattern of dissociated atrophy of the intrinsic hand muscles is termed the 'split hand' and is rarely seen in diseases other than ALS. The muscles involved in the split hand are innervated through the same spinal segments (C8 and T1), and FDI and ADM, which are differentially affected, are both ulnar nerve innervated. The physiological mechanisms underlying the split hand in ALS are incompletely understood but both cortical and spinal/peripheral mechanisms are probably involved. Motor potentials evoked by magnetic stimulation are significantly smaller when recorded from the thenar complex, compared with the hypothenar muscles, supporting a cortical mechanism. But peripheral axonal excitability studies have suggested that APB/FDI motor axons have more prominent persistent sodium currents than ADM axons, leading to higher axonal excitability and thereby more ready degeneration. Pincer or precision grip is vital to human hand function, and frequent use of thenar complex muscles may lead to greater oxidative stress and metabolic demands at both upper and lower motoneurons innervating the APB and FDI. The split hand is a useful diagnostic sign in early ALS, and recent objective studies indicate that the sign has a high degree of specificity.     

The role of cutaneous inputs during magnetic transcranial stimulation

Latency and amplitude characteristics of motor evoked potentials (MEPs) from abductor digiti minimi (ADM) and first dorsal interosseus (FDI) muscles were evaluated in 7 healthy volunteers via magnetic transcranial stimulation of the hemiscalp overlying contralateral motor areas. MEPs in complete relaxation and during contraction were recorded in two different experimental conditions: before and following anesthesia of median (sensory + motor) and radial (sensory) nerve fibers at wrist. This procedure induced a complete loss of skin sensation from dorsal and palmar aspects of the hand area “enveloping” the FDI muscle. On the other hand, the skin overlying the ADM muscle, as well as the strength of ulnar nerve-supplied muscles were spared. This selective sensory deprivation lead to the following short-term changes: the physiological latency “jump” toward shorter values in contracted MEPs vs. relaxation was partially lost in the FDI (3.0 ± 1.4 ms in basal condition, 1.8 ± 1.1 ms after anesthesia, P = 0.028), while it was still clearly evident in the ADM (3.7 ± 0.9 ms and 3.3 ± 1.0 ms, respectively). Moreover, minor amplitude changes of MEPs during active contraction in the two muscles were detected: MEPs recorded from the FDI muscle were less potentiated during voluntary contraction than those recorded from the ADM muscle. The role of the cutaneous input in governing latency/amplitude characteristics of MEPs is discussed. © 1996 John Wiley & Sons, Inc.     

Age‐related changes in motor unit number estimates in adult patients with Charcot–Marie–Tooth type 1A

Background: Charcot–Marie–Tooth disease type 1A (CMT1A) is known as a demyelinating hereditary neuropathy. Secondary axonal dysfunction is the most important determinant of disease severity. In adult patients, clinical progression may be because of further axonal deterioration as was shown with compound muscle action potential (CMAP) amplitude reductions over time. The motor unit number estimation (MUNE) technique may be more accurate to determine the number of axons as it is not disturbed by the effect of reinnervation. The purpose of this study was to investigate the number and size of motor units in relation to age in patients and controls. Methods: In a cross‐sectional design, we assessed arm and hand strength and performed electrophysiological examinations, including CMAP amplitudes and MUNE of the thenar muscles using high‐density surface EMG in 69 adult patients with CMT1A and 55 age‐matched healthy controls. Results: In patients, lower CMAP amplitudes and MUNE values were related to hand weakness. The CMAP amplitude and MUNE value of the thenar muscles were significantly lower in patients than in controls. CMAP amplitudes declined with age in controls, but not in patients. MUNE values declined with age in both patients and controls. Conclusions: The age‐dependent decrease in the number of motor units was not significantly different between patients with CMT1A and controls, indicating that loss of motor units in adult patients is limited.     

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.

Transcranial direct current stimulation enhances mu rhythm desynchronization during motor imagery that depends on handedness

Transcranial direct current stimulation (tDCS) can modulate the amplitude of event-related desynchronization (ERD) that appears on the electroencephalogram (EEG) during motor imagery. To study the effect of handedness on the modulating effect of tDCS, we compared the difference in tDCS-boosted ERD during dominant and non-dominant hand motor imagery. EEGs were recorded over the left sensorimotor cortex of seven healthy right-handed volunteers, and we measured ERD induced either by dominant or non-dominant hand motor imagery. Ten minutes of anodal tDCS was then used to increase the cortical excitability of the contralateral primary motor cortex (M1), and ERD was measured again. With anodal tDCS, we observed only a small increase in ERD during non-dominant hand motor imagery, whereas the same stimulation induced a prominent increase in ERD during dominant hand motor imagery. This trend was most obvious in the participants who used their dominant hand more frequently. Although our study is preliminary because of a small sample size, these results suggest that the increase in ERD by applying anodal tDCS was stronger on the dominant side than on the non-dominant side. The background excitability of M1 may determine the strength of the effect of anodal tDCS on ERD by hand motor imagery.     

Motor unit number index: Guidelines for recording signals and their analysis

Introduction: This study proposes guidelines for motor unit number index (MUNIX) recording and analysis. Methods: MUNIX was measured in control participants and in patients with amyotrophic lateral sclerosis. Changes in MUNIX values due to E1 electrode position, number of surface electromyography interference pattern (SIP) epochs, SIP epoch duration, force of contraction, and outlier data points were investigated. Results: MUNIX depends on optimized compound muscle action potential (CMAP) amplitude. Individual muscles showed variations when the number of epochs was low or when the SIP duration was short. Longer SIP duration allowed better recognition of artifacts. MUNIX results were affected by SIP values at all force levels but was more affected when SIP area was low. Discussion: We recommend changing the E1 electrode position to maximize CMAP amplitude. Twenty or more SIP signals of 500‐ms duration should be recorded by using force levels ranging from slight to maximum. Traces should be reviewed to identify and exclude signals with tremor or solitary spikes. Muscle Nerve 58 : 374–380, 2018     

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.     

Change of facilitation during voluntary bilateral hand activation after stroke

BACKGROUND AND PURPOSE: The relearning of daily activities after stroke also involves performance of bimanual tasks. This raises the possibility that concurrent activation of the healthy hemisphere interferes with reorganization processes in the affected hemisphere due to inhibitory pathways between homologous motor cortex representations. This study investigated the effect of voluntary, simultaneous activation of both hands upon the non-dominant (healthy subjects) or affected (stroke patients) hemisphere. METHODS: Eleven healthy subjects and 16 stroke patients were investigated using transcranial stimulation (TMS). TMS was applied over the non-dominant/affected hemisphere during performance of an isometric pinch grip at different force levels (10% or 50% of maximal voluntary contraction) with the contralateral hand. The ipsilateral hand had to perform the pinch grip at various force levels (10%, 50%, or 100% of maximal voluntary contraction) simultaneously. Peak-to-peak amplitudes of motor evoked potentials (MEPs) were compared to assess differences in motor cortex excitability. RESULTS: Unilateral activity of either hand alone exerted a facilitatory effect upon the non-dominant or affected hemisphere. In healthy subjects, the activation of the ipsilateral hand simultaneously with the contralateral hand did not produce any significant change of the MEP amplitudes compared to unilateral activation of the contralateral hand. In patients, however, the additional activation of the ipsilateral hand caused an additional increase of the peak-to-peak amplitudes. CONCLUSION: In healthy subjects voluntary activation of the ipsilateral hand does not change the excitability of the motor cortex of the non-dominant hemisphere, when the contralateral hand is simultaneously activated. The facilitation of the contralateral hand seems to gate further facilitation by the ipsilateral hand. However, in stroke patients simultaneous activation of both hands causes an additional facilitation compared to activation of the affected hand alone.     

Hemispheric asymmetries of cortico-cortical connections in human hand motor areas.

OBJECTIVE: To evaluate possible functional asymmetries of the motor cortex on the hand-dominant versus the non-dominant hemisphere. METHODS: We assessed the handedness of 15 consenting volunteers using the Edinburgh Inventory. They were divided in two groups: 9 right-handers and 6 left-handers. We used single- and paired-transcranial magnetic stimulation (TMS) to measure the relaxed and active motor threshold and the ipsilateral cortico-cortical inhibition and facilitation curve for both hand motor areas. We looked for hemispheric asymmetries of variables related to the side of stimulation (dominant versus non-dominant) and to handedness.RESULTS: We found no significant intra- or intergroup hemispheric asymmetry for the relaxed and active thresholds. Among the right-handers, the cortico-cortical inhibition and facilitation curve showed an increased amount of facilitation in the dominant as compared with the non-dominant hand area. No such changes were seen among the left-handers. Both the dominant and the non-dominant hand areas of the right-handers showed more inhibition and less facilitation on the cortico-cortical inhibition and facilitation curve than the corresponding areas of left-handers. CONCLUSION: In the right-handers, paired TMS studies showed a functional asymmetry of the motor cortex between the dominant and the non-dominant hand. The left-handers did not show this lateralization. Under TMS investigation their motor cortex function appeared different from that of right-handers.     

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).