Upper motor neuron assessment in amyotrophic lateral sclerosis using the patellar tendon reflex and motor-evoked potentials to the lower limbs.

Amyotrophic lateral sclerosis (ALS) diagnosis relies on signs of progressive damage to both lower motoneuron (LMN), given by clinical examination and electromyography (EMG), and upper motoneuron (UMN), given by clinical examination only. Recognition of UMN involvement, however, is still difficult, so that diagnostic delay often remains too long. Shortening the time to clinical and genetic diagnosis is essential in order to provide accurate information to patients and families, avoid time-consuming investigations and for appropriate care management. This study investigates whether combined patellar tendon reflex recording with motor-evoked potentials to the lower limbs (T-MEP-LL) is relevant to assess corticospinal function in ALS, so that it might serve as a tool improving diagnosis. T-MEP-LL were recorded in 135 patients with suspected motor neuron disease (MND) from February 2010 to March 2021. The sensitivity, specificity, and ability to improve diagnosis when added to Awaji and Gold Coast criteria were determined. The main finding of the study is that T-MEP-LL can detect UMN dysfunction with a 70% sensitivity and 63% specificity when UMN clinical signs are lacking. The sensitivity reaches 82% when considering all MND patients. Moreover, at first evaluation, using T-MEP-LL to quantify reflex briskness and to measure central conduction time, can improve the diagnostic accuracy. T-MEP-LL is easy to perform and does not need any electrical stimulation, making the test rapid, and painless. By the simultaneous quantification of both UMN and LMN system, it could also help to identify different phenotype with more accuracy than clinical examination in this broad-spectrum pathology. The question whether T-MEP-LL could further be a real biomarker need further prospective studies.

How many motor units is enough? An assessment of the influence of the number of motor units on firing rate calculations.

The number of motor units included in calculations of mean firing rates varies widely in the literature. It is unknown how the number of decomposed motor units included in the calculation of firing rate per participant compares to the total number of active motor units in the muscle, and if this is different for males and females. Bootstrapped distributions and confidence intervals (CI) of mean motor unit firing rates decomposed from the tibialis anterior were used to represent the total number of active motor units for individual participants in trials from 20 to 100 % of maximal voluntary contraction. Bootstrapped distributions of mean firing rates were constructed using different numbers of motor units, from one to the maximum number for each participant, and compared to the CIs. A probability measure for each number of motor units involved in firing rate was calculated and then averaged across all individuals. Motor unit numbers required for similar levels of probability increased as contraction intensity increased (p < 0.001). Increased levels of probability also required higher numbers of motor units (p < 0.001). There was no effect of sex (p ≥ 0.97) for any comparison. This methodology should be repeated in other muscles, and aged populations.

Changes in neuromuscular function in elders: Novel techniques for assessment of motor unit loss and motor unit remodeling with aging.

Functional muscle fiber denervation is a major contributor to the decline in physical function observed with aging and is now a recognized cause of sarcopenia, a muscle disorder characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength. There is an interrelationship between muscle strength, motor unit (MU) number, and aging, which suggests that a portion of muscle weakness in seniors may be attributable to the loss of functional MUs. During normal aging, there is a time-related progression of MU loss, an adaptive sprouting followed by a maladaptive sprouting, and continuing recession of terminal Schwann cells leading to a reduced capacity for compensatory reinnervation in elders. In amyotrophic lateral sclerosis, increasing age at onset predicts worse survival ALS and it is possible that age-related depletion of the motor neuron pool may worsen motor neuron disease. MUNE methods are used to estimate the number of functional MU, data from MUNIX arguing for motor neuron loss with aging will be reviewed. Recently, a new MRI technique MU-MRI could be used to assess the MU recruitment or explore the activity of a single MU. This review presents published studies on the changes of neuromuscular function with aging, then focusing on these two novel techniques for assessment of MU loss and MU remodeling.

Endurance-exercise training adaptations in spinal motoneurones: potential functional relevance to locomotor output and assessment in humans.

It is clear from non-human animal work that spinal motoneurones undergo endurance training (chronic) and locomotor (acute) related changes in their electrical properties and thus their ability to fire action potentials in response to synaptic input. The functional implications of these changes, however, are speculative. In humans, data suggests that similar chronic and acute changes in motoneurone excitability may occur, though the work is limited due to technical constraints. To examine the potential influence of chronic changes in human motoneurone excitability on the acute changes that occur during locomotor output, we must develop more sophisticated recording techniques or adapt our current methods. In this review, we briefly discuss chronic and acute changes in motoneurone excitability arising from non-human and human work. We then discuss the potential interaction effects of chronic and acute changes in motoneurone excitability and the potential impact on locomotor output. Finally, we discuss the use of high-density surface electromyogram recordings to examine human motor unit firing patterns and thus, indirectly, motoneurone excitability. The assessment of single motor units from high-density recording is mainly limited to tonic motor outputs and minimally dynamic motor output such as postural sway. Adapting this technology for use during locomotor outputs would allow us to gain a better understanding of the potential functional implications of endurance training-induced changes in human motoneurone excitability on motor output.

A multidimensional facial surface EMG analysis for objective assessment of bulbar involvement in amyotrophic lateral sclerosis.

OBJECTIVE: To develop a multidimensional facial surface electromyographic (EMG) analysis for assessing bulbar involvement in amyotrophic lateral sclerosis (ALS). METHODS: Fifty-four linear and nonlinear features were extracted from the surface EMG recordings for masseter, temporalis, and anterior belly of digastric in 13 patients with ALS and 10 healthy controls, each performed a speech task three times. The features were factor analyzed and then evaluated in terms of internal consistency, relation to functional speech outcomes, and efficacy for patient-control classification. RESULTS: Five internally consistent, interpretable factors were derived, representing the functioning of masseter, temporalis, digastric, antagonists, and agonists, respectively. These factors explained 40-43% of the variance in the functional speech outcomes and were ≥90% accurate in patient-control classification. The jaw muscle performance of individuals with ALS was characterized by (1) reduced complexity and coherence of antagonist muscle activities, and (2) increased complexity and irregularity of temporalis activity. CONCLUSIONS: Two important bulbar muscular changes were identified in ALS, related to both upper and lower motor neuron pathologies. These changes reflected (1) decreased motor unit recruitment and synchronization for jaw antagonists, and (2) a potential neuromuscular adaptation for temporalis. SIGNIFICANCE: The surface EMG-based framework shows promise as an objective bulbar assessment tool.

iMAX: A new tool for assessment of motor axon excitability. A multicenter prospective study.

OBJECTIVE: This study was undertaken to establish by a multicentric approach the reliability of a new technique evaluating motor axon excitability. METHODS: The minimal threshold, the lowest stimulus intensity allowing a maximal response by 1 mA increments (iUP) and then by 0.1 mA adjustments (iMAX) were prospectively derived from three nerves (median, ulnar, fibular) in four university centers (Liège, Marseille, Fraiture, Nice). iMAX procedure was applied in 28 healthy volunteers (twice) and 32 patients with Charcot-Marie-Tooth (CMT1a), chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré syndrome (SGB) or axonal neuropathy. RESULTS: Healthy volunteers results were not significantly different between centers. Correlation coefficients between test and retest were moderate (> 0.5). Upper limits of normal were established using the 95th percentile. Comparison of volunteers and patient groups indicated significant increases in iMAX parameters especially for the CMT1a and CIDP groups. In CMT1a, iMAX abnormalities were homogeneous at the three stimulation sites, which was not the case for CIDP. CONCLUSIONS: The iMAX procedure is reliable and allows the monitoring of motor axon excitability disorders. SIGNIFICANCE: The iMAX technique should prove useful to monitor motor axonal excitability in routine clinical practice as it is a fast, non-invasive procedure, easily applicable without specific software or devices.

Estimates of persistent inward currents in tibialis anterior motor units during standing ramped contraction tasks in humans.

Persistent inward currents (PICs) play an essential role in setting motor neuron gain and shaping motor unit firing patterns. Estimates of PICs in humans can be made using the paired motor unit analysis technique, which quantifies the difference in discharge rate of a lower threshold motor unit at the recruitment onset and offset of a higher threshold motor unit (ΔF). Because PICs are highly dependent on the level of neuromodulatory drive, ΔF represents an estimate of level of neuromodulation at the level of the spinal cord. Most of the estimates of ΔF are performed under constrained, isometric, seated conditions. In the present study, we used high-density surface EMG arrays to discriminate motor unit firing patterns during isometric seated conditions with torque or EMG visual feedback and during unconstrained standing anterior-to-posterior movements with root mean square EMG visual feedback. We were able to apply the paired motor unit analysis technique to the decomposed motor units in each of the three conditions. We hypothesized that ΔF would be higher during unconstrained standing anterior-to-posterior movements compared with the seated conditions, reflecting an increase in the synaptic input to motoneurons drive while standing. In agreement with previous work, we found that there was no evidence of a difference in ΔF between the seated and standing postures, although slight differences in the initial and peak discharge rates were observed. Taken together, our results suggest that both the standing and seated postures are likely not sufficiently different, both being "upright" postures, to result in large changes in neuromodulatory drive.NEW & NOTEWORTHY In the present study, we show that the discharge rate of a lower threshold motor unit at the recruitment onset and offset of a higher threshold motor unit (ΔF) is similar between standing and seated conditions in human tibialis anterior motor units, suggesting that at least for these two upright postures neuromodulatory drive is similar. We also highlight a proposed technological development in using high-density EMG arrays for real-time muscle activity feedback to accomplish standing ramped contraction tasks and demonstrate the validity of the paired motor unit analysis technique during these conditions.

Rigorous performance assessment of the algorithms for resolving motor unit action potential superpositions.

It is necessary to decompose the intra-muscular EMG signal to extract motor unit action potential (MUAP) waveforms and firing times. Some algorithms were proposed in the literature to resolve superimposed MUAPs, including Peel-Off (PO), branch and bound (BB), genetic algorithm (GA), and particle swarm optimization (PSO). This study aimed to compare these algorithms in terms of overall accuracy and running time. Two sets of two-to-five MUAP templates (set1: a wide range of energies, and set2: a high degree of similarity) were used. Such templates were time-shifted, and white Gaussian noise was added. A total of 1000 superpositions were simulated for each template and were resolved using PO (also, POI: interpolated PO), BB, GA, and PSO algorithms. The generalized estimating equation was used to identify which method significantly outperformed, while the overall rank product was used for overall ranking. The rankings were PSO, BB, GA, PO, and POI in the first, and BB, PSO, GA, PO, POI in the second set. The overall ranking was BB, PSO, GA, PO, and POI in the entire dataset. Although the BB algorithm is generally fast, there are cases where the BB algorithm is too slow and it is thus not suitable for real-time applications.

Assessment of age-related differences in decomposition-based quantitative EMG in the intrinsic hand muscles: A multivariate approach.

OBJECTIVE: Decomposition-based quantitative electromyography (DQEMG) is one method of measuring neuromuscular physiology in human muscles. The objective of the current study is to compare the neuromuscular physiology of a typical aging population in the intrinsic hand muscles. METHODS: Measurements of DQEMG were detected with a standard concentric needle and surface EMG from the intrinsic hand muscles. DQEMG was obtained from the first dorsal interosseous (FDI), the abductor digiti minimi (ADM) and fourth dorsal interosseous (4DI). Multivariate analysis of variance (MANOVA) were performed for the surface and intramuscular EMG measures to identify age differences in motor unit properties. RESULTS: Large differences were observed between the age groups for the canonical intramuscular and surface EMG variables. Older adults demonstrated a large decrease in motor unit number estimation in the ADM and FDI. Likewise, medium to large decreases in motor unit stability were observed in the FDI, ADM and 4DI. CONCLUSIONS: With aging, there are decreases in motor unit number estimation and stability in the intrinsic hand muscles. Using a multivariate approach allows for age-related differences and the relationship between the variables to be further elucidated. SIGNIFICANCE: Multivariate analysis of DQEMG may be useful for identifying patterns of change in neuromuscular physiology with age-related changes to hand musculature. This may potentially lead to future prognostic biomarkers of age-related changes to hand muscles.

Assessment of Neuroplasticity With Strength Training.

Including a brief overview of current investigative approaches, the present Perspectives for Progress article offers an overview of potential future experiments in the field of exercise-related neuroplasticity to strength training. It is proposed that the combination of specific experimental approaches and recently developed techniques holds the potential for unraveling spinal and supraspinal mechanisms involved in the adaptation to strength training.

Assessment of vestibulocortical interactions during standing in healthy subjects.

The vestibular system is essential to produce adequate postural responses enabling voluntary movement. However, how the vestibular system influences corticospinal output during postural tasks is still unknown. Here, we examined the modulation exerted by the vestibular system on corticospinal output during standing. Healthy subjects (n = 25) maintained quiet standing, head facing forward with eyes closed. Galvanic vestibular stimulation (GVS) was applied bipolarly and binaurally at different delays prior to transcranial magnetic stimulation (TMS) which triggered motor evoked potentials (MEPs). With the cathode right/anode left configuration, MEPs in right Soleus (SOL) muscle were significantly suppressed when GVS was applied at ISI = 40 and 130ms before TMS. With the anode right/cathode left configuration, no significant changes were observed. Changes in the MEP amplitude were then compared to changes in the ongoing EMG when GVS was applied alone. Only the decrease in MEP amplitude at ISI = 40ms occurred without change in the ongoing EMG, suggesting that modulation occurred at a premotoneuronal level. We further investigated whether vestibular modulation could occur at the motor cortex level by assessing changes in the direct corticospinal pathways using the short-latency facilitation of the SOL Hoffmann reflex (H-reflex) by TMS. None of the observed modulation occurred at the level of motor cortex. Finally, using the long-latency facilitation of the SOL H-reflex, we were able to confirm that the suppression of MEP at ISI = 40ms occurred at a premotoneuronal level. The data indicate that vestibular signals modulate corticospinal output to SOL at both premotoneuronal and motoneuronal levels during standing.

Assessment of motor unit loss in patients with spinal muscular atrophy.

OBJECTIVE: To assess motor unit (MU) changes in patients with spinal muscular atrophy (SMA) using compound muscle action potential (CMAP) scans. METHODS: We performed CMAP scan recordings in median nerves of 24 treatment-naïve patients (median age 39; range 12-75 years) with SMA types 2-4. From each scan, we determined maximum CMAP amplitude (CMAPmax), a motor unit number estimate (MUNE), and D50 which quantifies the largest discontinuities within CMAP scans. RESULTS: Median CMAPmax was 8.1 mV (range 0.9-14.6 mV), MUNE was 29 (range 6-131), and D50 was 25 (range 2-57). We found a reduced D50 (<25) in patients with normal CMAPmax (n = 12), indicating MU loss and enlarged MUs due to reinnervation. Lower D50 values were associated with decreased MUNE (P < 0.001, r = 0.68, n = 43). CMAPmax, MUNE and D50 values differed between SMA types (P < 0.001). Lower motor function scores were related to patients with lower CMAPmax, MUNE and D50 values (P < 0.001). CONCLUSIONS: The CMAP scan is an easily applicable technique that is superior to routine assessment of CMAPmax in SMA. SIGNIFICANCE: The detection of pathological MU changes across the spectrum of SMA may provide important biomarkers for evaluating disease course and monitoring treatment efficacy.

Motor unit number index (MUNIX) in the quantitative assessment of severity and surgical outcome in cervical spondylotic amyotrophy.

OBJECTIVE: To assess the feasibility of motor unit number index (MUNIX) in the quantitative assessment of the cervical spondylotic amyotrophy (CSA). METHODS: MUNIX was recorded bilaterally on the abductor pollicis brevis, abductor digiti minimi, biceps brachii and middle deltoid in 41 normal controls and 47 patients with CSA (distal-type to proximal-type ratio: 25 to 22). Additionally, patients were assessed on handgrip strength (HGS), the disabilities of arm, shoulder and hand (DASH) and Medical Research Council (MRC) scales. These examinations were re-evaluated approximately 18 months after surgery in 37 of these CSA patients. RESULTS: MUNIX values were noticeably lower in the mainly affected muscles of CSA patients than those in controls (P < 0.05), and 49.0% (51/104) of the tested muscles with abnormal MUNIX measurements showed normal muscle strength. Significant correlations between MUNIX measurements and both DASH and MRC scores were observed in both CSA patient groups (P < 0.05). Postoperative longitudinal follow-up analysis identified significant increase in motor unit number in both CSA patient groups within approximately 18 months (P < 0.05), with or without improved measures of motor function. CONCLUSIONS: A significant reduction in MUNIX values related to motor impairment was observed in CSA patients, even in the subclinical stage. Compared to measures of motor function, the MUNIX measurements in the patients with CSA improved more noticeably after surgical intervention. SIGNIFICANCE: MUNIX may serve as an available supplementary test to quantitatively evaluate the motor dysfunction in CSA and to track its progression, that is complementary to conventional electromyography.

Improved Assessment of Muscle Excitation From Surface Electromyograms in Isometric Muscle Contractions.

We introduce two novel methods for the estimation of muscle excitation from surface electromyograms (EMGs), the so called cumulative motor unit activity index (CAI) and robust CAI (rCAI). Both methods aim to remove the detected motor unit action potential (MUAP) contributions from EMG but do not assess the individual motor unit spike trains. Instead, they directly estimate the cumulative motor unit spike train (CST). We compared the methods with the spatially averaged root-mean-square (RMS) envelope of the EMG signals and with the CST, estimated by the previously introduced convolution kernel compensation (CKC) method. The tests on synthetic EMG with known muscle excitation profiles demonstrated superior accuracy of newly introduced methods. In the case of 64 EMG channels and 20-dB noise, the RMS, CAI, rCAI, and CKC estimators, calculated on 0.125-s-long signal epochs, yielded the normalized RMS error (NRMSE) of 14.5% ± 2.8%, 4.4% ± 3.2%, 4.1% ± 1.8%, and 6.3% ± 4.6%, respectively. In the experimental signals from wrist extensors and flexors, the RMS, CAI, rCAI, and CKC estimations were compared to exerted muscle force. When calculated on 0.125-s-long signal epochs, they yielded the NRMSE of 11.2% ± 3.5%, 8% ± 5.6%, 10.7% ± 6.8%, and 9.0% ± 4.9%, respectively. Therefore, the newly introduced methods exhibit accuracy that is comparable to at least 200-times slower CKC method.

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

OBJECTIVE: The 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. METHODS: Data 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. RESULTS: In 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. CONCLUSIONS: The MUSIX is a reliable neurophysiological biomarker of reinnervation. SIGNIFICANCE: MUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation.

Simultaneous Assessment of Homonymous and Heteronymous Monosynaptic Reflex Excitability in the Adult Rat.

In order to successfully perform motor tasks such as locomotion, the central nervous system must coordinate contractions of antagonistic and synergistic muscles across multiple joints. This coordination is largely dependent upon the function of proprioceptive afferents (PAs), which make monosynaptic connections with homonymous motoneurons. Homonymous pathways have been well studied in both health and disease but their collateral fibers projecting to heteronymous, synergistic muscles receive relatively less attention. This is surprising given that PA collaterals have significant effects on the excitability of heteronymous motoneurons, and that their synaptic terminal density is activity dependent. It is likely that the relative lack of literature is due to the lack of a preparation which allows synergistic heteronymous pathways to be assessed in vivo. Here, we describe a method to simultaneously evoke homonymous and heteronymous (synergistic) monosynaptic reflexes (MSRs) and study their modulation by descending pathways in adult rats. Through stimulation of the medial plantar nerve, we were able to produce an H reflex in the intrinsic foot (IF) muscles of the hind paw with a latency of 10.52 ± 3.8 ms. Increasing the stimulus intensity evoked a robust signal with a monosynaptic latency (11.32 ± 0.35 ms), recorded in the ipsilateral gastrocnemius (Gs). Our subsequent analyses suggest that Gs motoneurons were activated via heteronymous afferent collaterals from the medial plantar nerve. These reflexes could be evoked bilaterally and were modulated by conditioning stimuli to the cortex (Cx) and reticular formation. Interestingly, cortical stimulation was equally efficient at modulating both ipsilateral and contralateral reflexes, indicating that cortical modulation of lumbar sensory afferents lacks the laterality demonstrated by studies of cortical muscle activation. This technique represents a novel, relatively simple way to assess heteronymous afferent pathways in normal motor control as well as in models of motor disorders where adaptive and maladaptive plasticity of PAs and descending systems affects functional outcomes.

Advanced Assessment of the Upper Limb in Tetraplegia: A Three-Tiered Approach to Characterizing Paralysis.

Background: More than half of all individuals who sustain a spinal cord injury (SCI) experience some degree of impairment in the upper limb. Functional use of the arm and hand is of paramount importance to these individuals. Fortunately, the number of clinical trials and advanced interventions targeting upper limb function are increasing, generating optimism for improved recovery and restoration after SCI. New interventions for restoring function and improving recovery require more detailed examination of the motor capacities of the upper limb. Objectives: The purpose of this article is to introduce a three-tiered approach to evaluating motor function, with specific attention to the characteristics of weak and fully paralyzed muscles during acute rehabilitation. The three tiers include (1) evaluation of voluntary strength via manual muscle testing, (2) evaluation of lower motor neuron integrity in upper motor neuron-paralyzed muscles using surface electrical stimulation, and (3) evaluation of latent motor responses in paralyzed muscles that exhibit a strong response to electrical stimulation, using surface electromyographic recording electrodes. These characteristics contribute important information that can be utilized to mitigate potential secondary conditions such as contractures and identify effective interventions such as activity-based interventions or reconstructive procedures. Our goal is to encourage frontline clinicians - occupational and physical therapists who are experts in muscle assessment - to consider a more in-depth analysis of paralysis after SCI. Conclusion: Given the rapid advancements in SCI research and clinical interventions, it is critical that methods of evaluation and classification evolve. The success or failure of these interventions may depend on the specific characteristics identified in our three-tiered assessment. Without this assessment, the physiological starting point for each individual is unknown, adding significant variability in the outcomes of these interventions.

H-reflex and M-wave recordings: effect of pressure application to the stimulation electrode on the assessment of evoked potentials and subject's discomfort.

This study aimed to compare the effect of different types of pressure applied to the stimulation electrode on assessing the efficiency of Ia-α-motoneuron transmission of the soleus muscle and the associated discomfort using electrical nerve stimulation. Twelve healthy young adults participated in three experimental sessions (one for each knee angle). The amplitudes of the maximal Hoffmann reflex (Hmax ) and motor potential (Mmax ) were recorded from the soleus muscle at 0°, 30° and 90° knee angles (0° full extension) through three pressure applications to the stimulation electrode: no pressure, pressure with manual application and pressure using adhesive tape. The soleus Hmax /Mmax were calculated to assess the efficiency of Ia-α-motoneuron transmission during varied knee angles and pressure application to the stimulation electrode. At the stimulation intensity evoking soleus Hmax and Mmax , subjects were asked to orally provide a value between 'no discomfort' (0) and 'worst possible discomfort' (10). The application of pressure on the stimulation electrode, particularly using adhesive tape, decreased both the stimulation intensity needed to evoke an electrophysiological response and the associated self-reported discomfort (P<0·05), while the Hmax /Mmax remained constant. At the stimulation intensity evoking Mmax , the electrical stimulation appeared to be more painful at 0° knee angle compared with 30° and 90° angles (P<0·01). To conclude, this study showed that a knee flexion and a pressure application to the stimulation electrode, especially using tape pressure, are recommended in the objective to reduce the patient/subjects' discomfort when eliciting evoked potentials on soleus muscle.

Why averaging multiple MUNIX measures in the longitudinal assessment of patients with ALS?

OBJECTIVE: To assess the impact of averaging multiple MUNIX trials on the follow-up of patients with amyotrophic lateral sclerosis (ALS). METHODS: We determined the percent relative change (%RC) of MUNIX, in healthy subjects and patients with ALS, by subtracting the MUNIX value in the second visit from the first. Both the mean of a set of three MUNIX (mean-MUNIX) and the first MUNIX sample (single-MUNIX) were evaluated. Then, we studied the sensitivity to detect relative changes over time and the statistical dispersion of the %RC from these two parameters. RESULTS: We found that the mean-MUNIX %RC has lower mean coefficient of variation than the single-MUNIX %RC in all muscles. The mean-MUNIX also resulted in more ALS patients with significant %RC, i.e., outside reference limits. CONCLUSION: The mean-MUNIX resulted in less dispersed values of %RC in patients with ALS and thus, increased the precision of the technique. The mean-MUNIX resulted also in an increase in the sensitivity to track changes over time in these patients. SIGNIFICANCE: The mean-MUNIX should be considered in any ALS follow-up study as a more reliable approach and as a way of potentially reducing the sample size needed for the study.