Strength-duration time constant and rheobase measurements: Comparison of the threshold tracking method and a manual procedure.

OBJECTIVE: To compare the strength-duration time constant (SDTC) and rheobase measurements obtained by the threshold tracking method (TT) and by a non-automated method (MM). METHODS: The MM procedure involved measuring, using a routine electrodiagnostic device, the intensity required to evoke a motor response whose amplitude corresponds to 40% of the maximum amplitude for four stimulus duration (1.0, 0.7, 0.5, 0.2 ms), and studying the linear relationship between stimulus charge and stimulus duration (slope = rheobase, intercept on the x-axis = SDTC). Using TT and MM, 30 successive healthy subjects (mean age = 38 years old) underwent a prospective evaluation of SDTC and rheobase of the median nerve motor axons at the wrist. Nerve stimulation and bipolar recording of evoked motor responses were performed with disposable self-adhesive surface electrodes. RESULTS: The Spearman correlations between the two methods were 0.78 (p < 0.0001) for SDTC and 0.96 (p < 0.0001) for the rheobase. The Bland-Altman analysis did not reveal any systematic bias of MM compared to TT. CONCLUSIONS: The MM procedure was reliable for strength-duration relationship analysis. SIGNIFICANCE: We encourage neurophysiologists, who do not have dedicated threshold tracking equipment, not to hesitate to use these simple tools to assess peripheral nerve excitability.

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.

Assessing the upper motor neuron in amyotrophic lateral sclerosis using the triple stimulation technique: A multicenter prospective study.

OBJECTIVE: To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. METHODS: Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. RESULTS: TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. CONCLUSIONS: TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. SIGNIFICANCE: This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

Normalizing gastrocnemius muscle EMG signal: An optimal set of maximum voluntary isometric contraction tests for young adults considering reproducibility.

BACKGROUND: Even though most studies normalize the surface EMG signal of the gastrocnemius muscle using a single position of maximum voluntary isometric contraction (MVIC), several studies tend to indicate that several positions are in fact needed to obtain a maximal voluntary activation (MVA) for most of the subjects. However, no combination of positions has already been described. RESEARCH QUESTION: A combination of MVIC positions to normalize the EMG signal of the gastrocnemius muscle is investigated. the influence of using several positions on the reproducibility of the normalization process is evaluated. METHODS: Twenty healthy volunteers (45 % female - 55 % male, 25.4 years (SD 4.3), 72.6 kg (SD 13.9), 1.78 m (SD 0.12)) were recruited. Six positions for MVIC were compared and the effect of several normalization combinations on a functional task (gait) was evaluated. RESULTS: Several positions are needed to obtain at least 90 % of the MVA for 90 % of the volunteers even though the use of a single well-chosen position (unipodal standing position with knee fully extended and ankle fully plantar-flexed) will lead to no statistically significant differences of the gait evaluation during stance phase. For each position, five repetitions of the MVIC are recommended to obtain a valid MVA. SIGNIFICANCE: This study confirms that using several MVIC positions is recommended when possible to normalize the gastrocnemius muscle EMG signal. However, in the situation of a patient where limited MVIC attempts are possible, using a single well-chosen position should not significantly influence the amplitude and the reproducibility of the measures.

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

OBJECTIVE: Motor unit number index (MUNIX) is proposed to monitor neuromuscular disorders. Our objective is to determine the intra-individual variability over time of the MUNIX. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: The MUNIX technique must be performed by experienced operators on several muscles to reduce its variability and improve its reliability. SIGNIFICANCE: A variation of the MUNIX sum score ≥20% can be interpreted as a significant change of muscle innervation.

Cosmetic Injection of Botulinum Toxin Unmasking Subclinical Myasthenia Gravis: A Case Report and Literature Review.

Cosmetic or therapeutic use of botulinum toxin type A (BoNT-A) is usually safe but can rarely cause iatrogenic botulism. Iatrogenic botulism and myasthenia gravis (MG) share similar clinical features, because both BoNT-A and anti-acetylcholine receptorantibodies impair neuromuscular transmission. We report a patient who underwent cosmetic BoNT-A injection and later developed serious local and systemic adverse reactions. The peculiarity of this case is that a latent seropositive MG was eventually discovered, suggesting that both iatrogenic botulism and MG contributed to the clinical picture. This patient is one of the less than 10 reported cases worldwide in whom MG was unmasked by BoNT-A injection. He is the first to be assessed in detail by single-fiber electromyography. This case emphasizes the risk associated with BoNT-A injection in patients with subclinical impairment of neuromuscular transmission and prompts the search for MG in case of exaggerated response.

Is the triple stimulation technique a better quantification tool of motor dysfunction than motor evoked potentials in multiple sclerosis?

The triple stimulation technique (TST) was rarely used in multiple sclerosis (MS). This study aimed to compare TST and motor evoked potentials (MEP) for the quantification of motor dysfunction. Central motor conduction based on MEP (four limbs) and TST (upper limbs) was assessed in 28 MS patients with a median Expanded Disability Status Scale (EDSS) of 4. EDSS, timed 25-foot walk (T25FW), grasping strength and motor components of the MS functional composite were evaluated. Regression analysis was used to assess the relationship between MEP, TST and clinical findings. TST was negatively correlated with EDSS (r = - 0.74, p < 0.0001) and to a lesser extent with T25FW (r = - 0.47, p < 0.05), and grasping strength (r = - 0.43, p < 0.05). A multiple regression analysis underlined the better correlation between clinical data and TST (R2 = 0.56, p < 0.0005) than with MEP (0.03 < R2 < 0.22, p > 0.05). This study evidenced the value of TST as a quantification tool of motor dysfunction. TST appeared to reflect a global disability since it was correlated not only to hand function but also to walking capacity.

Correlations between MUNIX and adapted multiple point stimulation MUNE methods.

OBJECTIVE: The aim of this study was to evaluate how the motor unit number index (MUNIX) is related to the adapted multiple point stimulation (AMPS) technique. METHODS: MUNIX and AMPS technique were prospectively performed on thenar muscles in 20 consecutive patients referred to our neurophysiological laboratory with the clinical diagnosis of a possible motoneurone disorder (MND). The clinical and paraclinical assessment confirmed the diagnosis of MND in 13 out of 20 patients, amyotrophic lateral sclerosis (ALS) in 9 (with MND group). In the other 7 patients, there were neither evidence of MND, nor of any peripheral nervous system disease (without MND group). RESULTS: AMPS and MUNIX data were significantly (p < 0.001) lower in patients with MND than in patients without MND. There was a strong significant positive linear correlation between AMPS and MUNIX values (n = 20; R = 0.83; p < 0.01). CONCLUSION: Both MUNIX and AMPS methods could serve as a reliable marker to document the motor unit loss. SIGNIFICANCE: The present paper constitutes one more clue of MUNIX reliability.

Normalizing shoulder EMG: An optimal set of maximum isometric voluntary contraction tests considering reproducibility.

Normalization of the electromyography (EMG) signal is often performed relatively to maximal voluntary activations (MVA) obtained during maximum isometric voluntary contraction (MVIC). The first aim was to provide an inter-session reproducible protocol to normalize the signal of eight shoulder muscles. The protocol should also lead to a level of activation >90% of MVA for >90% of the volunteers. The second aim was to evaluate the influence of the method used to extract the MVA from the EMG envelope on the normalized EMG signal. Thirteen volunteers performed 12 MVICs twice (one week interval). Several time constants (100ms to 2s) were compared when extracting the MVA from the EMG envelope. The EMG activity was also acquired during an arm elevation. Our results show that a combination of nine MVIC tests was required to meet our requirements including reproducibility. Both the number of MVIC tests and the size of the time constant influence the normalized EMG signal during the dynamic activity (variations up to 15%). A time constant of 1s was a good compromise to extract the MVA. These findings are valuable to improve the reproducibility of EMG signal normalization.

MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43).

OBJECTIVE: To identify the causative gene mutation in a 5-generation Belgian family with dominantly inherited spinocerebellar ataxia and polyneuropathy, in which known genetic etiologies had been excluded. METHODS: We collected DNA samples of 28 family members, including 7 living affected individuals, whose clinical records were reviewed by a neurologist experienced in ataxia. We combined linkage data of 21 family members with whole exome sequencing in 2 affected individuals to identify shared heterozygous variants mapping to potentially linked regions. Variants were screened for rarity and for predicted damaging effect. A candidate mutation was confirmed by Sanger sequencing and tested for cosegregation with the disease. RESULTS: Affected individuals presented with late-onset sensorimotor axonal polyneuropathy; all but one also had cerebellar ataxia. We identified a variant in the MME gene, p.C143Y, that was absent from control databases, cosegregated with the phenotype, and was predicted to have a strong damaging effect on the encoded protein by all algorithms we used. CONCLUSIONS: MME encodes neprilysin (NEP), a zinc-dependent metalloprotease expressed in most tissues, including the central and peripheral nervous systems. The mutated cysteine 143 forms a disulfide bridge, which is 100% conserved in NEP and in similar enzymes. The recent identification of recessive MME mutations in 10 unrelated individuals from Japan with axonal polyneuropathy further supports the causality of the mutation, despite the dominant mode of inheritance and the presence of cerebellar involvement in our study family. Functional studies are needed to identify the mechanisms underlying these differences.

Human muscle proteome modifications after acute or repeated eccentric exercises.

INTRODUCTION: Delayed-onset muscle soreness (DOMS), a condition triggered by eccentric exercise, affects muscle cells at a biochemical level in a poorly understood fashion. The objective of the present study was to examine human muscle proteome modifications induced by strenuous eccentric exercises after a specific training aimed to prevent DOMS. METHODS: Biopsy samples of the rectus femoris were obtained from healthy human volunteers in three successive conditions: 1) at rest, 2) 24 h after an injuring exercise protocol consisting of three series of 30 maximal contractions of the quadriceps on an isokinetic dynamometer, and 3) 24 h after a similar exercise bout preceded either by five eccentric training sessions or by no training. RESULTS: Muscle damage was assessed before and 1 d after each maximal eccentric test by comparing three indirect markers: plasma activity of creatine kinase, muscle stiffness, and subjective pain intensity. Compared with the first eccentric test, those markers were reduced after the second test and further reduced if this second test followed the eccentric training, thus confirming the protective effect of such training. Muscle protein extracts were subjected to a two-dimensional difference gel electrophoresis proteomic analysis coupled with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry protein identification. Surprisingly, we observed that myosin heavy chains decreased after the first eccentric test and were reduced further with other contractile proteins after the second test. Furthermore, the expression of several glycolytic enzymes decreased only after the second test, which was preceded by a specific training. CONCLUSIONS: These findings suggest that the eccentric training resulted in a switch to oxidative metabolism, which may be associated with protection from DOMS.

[Dorsal and lumbar paraspinal electromyographic study. Multi-MUP analysis and drawing up normal values in a reference population]. / Etude électromyographique paravertébrale dorso-lombaire. Analyse en mode multi-MUP et établissement de normes au sein d'une population de référence.

OBJECTIVE: The aim of this study was to contribute to draw up reference values relating to electromyographic (EMG) parameters in dorsal and lumbar paraspinal muscles. MATERIALS AND METHODS: 75 healthy subjects without back pain underwent electromyography of multifidus bundles, which are innervated uni-segmentally by the dorsal ram of the spinal nerve. T8, L3, L4, L5 and S1 myotomes were systematically explored. Output variables were spontaneous denervation activity and quantitative EMG data obtained by multi-MUP (Motor Unit action Potential) analysis. RESULTS: No abnormal insertional or spontaneous activity (such as fibrillation, positive sharp waves or fasciculation) was recorded at rest. Neither sex nor age influenced motor unit action potential features in our series. Reference values were drawn up for T8 and L5 segmental levels using the mean values of 20 motor unit potentials in each patient studied, the reference interval being defined by the lower and the upper outlier limits on individual values. CONCLUSION: This study offers reference data to electromyographers to help better identifying possible myogenic or neurogenic pathological changes, especially in lumbosacral radiculopathies.

Single motor axon conduction velocities of human upper and lower limb motor units. A study with transcranial electrical stimulation.

OBJECTIVES: To calculate conduction velocities (CV) of single motor axons innervating hand, forearm and leg muscles, weak anodal electrical transcranial stimuli were used and single motor unit potentials were recorded in 17 normal subjects. METHODS: The central motor conduction time and neuromuscular transmission delay were subtracted from the latency of unit response to cortical stimulation and single motor axon CV were calculated. RESULTS: In extensor indicis proprius (EIP) units, CV ranged from 30.3 to 76.1m/s (mean: 51.3 +/- 7.1m/s, 139 units). In first dorsal interosseous (FDI), they ranged from 45.1 to 66.2m/s (mean: 54.6 +/- 2.6m/s, 88 units). In tibialis anterior (TA), velocities ranged from 27.8 to 55.9m/s (mean: 41.3 +/- 7.5m/s, 123 units). In FDI units, velocities were compared with those obtained with the F-wave method (range: 50.3-64.5m/s, mean: 58.1 +/- 2.0m/s). CONCLUSIONS: Compared with previously published values, the present method gives better access to slow-conducting units, first recruited by transcranial stimulation and voluntary effort. The spectrum of individual CV was much broader for EIP and TA than for FDI. A linear decline of maximal CV with age was observed, while minimal CV were not affected, suggesting that aging causes a selective loss of the fastest-conducting units.