Maximal Compound Muscle Action Potential Research Articles

Sex-related differences in corticospinal excitability outcomemeasures of the biceps brachii during a submaximal elbow flexor contraction.

The purpose of this study was to investigate the effects of sex, muscle thickness, and subcutaneous fat thickness (SFT) on corticospinal excitability outcome measures of the biceps brachii. Eighteen participants (10 males and 8 females) completed this study. Ultrasound was used to assess biceps brachii muscle thickness and the overlying SFT. Transcranial magnetic stimulation (TMS) was used to determine corticospinal excitability by inducing motor-evoked potentials (MEPs) at eight different TMS intensities from 90% to 160% of active motor threshold (AMT) from the biceps brachii during an isometric contraction of the elbow flexors at 10% of maximum voluntary contraction (MVC). Biceps brachii maximal compound muscle action potential (Mmax) was also recorded prior to and after TMS. Males had higher (p < 0.001) biceps brachii muscle thickness and lower SFT, produced higher levels of MVC force and had, on average, higher (p < 0.001) MEP amplitudes at lower (p < 0.05) percentages of maximal stimulator output than females during the 10% elbow flexion MVC. Multiple linear regression modeling revealed that sex was not associated with any of the neurophysiological parameters examined, while SFT showed a positive association with the stimulation intensity required at AMT (p = 0.035) and a negative association with biceps brachii pre-stimulus electromyography (EMG) activity (p = 0.021). Additionally, there was a small positive association between muscle thickness and biceps brachii pre-stimulus EMG activity (p = 0.049). Overall, this study suggests that some measures of corticospinal excitability may be different between the sexes and influenced by SFT and muscle thickness.

Estimation of the number of motor units in the human extensor digitorum brevis using MScanFit.

Our aim was to determine the number and size parameters of EDB motor units in healthy young adults using MScanFit, a novel approach to motor unit number estimation (MUNE). Since variability in MUNE is related to compound muscle action potential (CMAP) size, we employed a procedure to document the optimal EDB electromyographic (EMG) electrode position prior to recording MUNE, a neglected practice in MUNE. Subjects were 21 adults 21-44 y. Maximum CMAPs were recorded from 9 sites in a 4 cm2 region centered over the EDB and the site with the largest amplitude was used in the MUNE experiment. For MUNE, the peroneal nerve was stimulated at the fibular head to produce a detailed EDB stimulus-response curve or "MScan". Motor unit number and size parameters underlying the MScan were simulated using the MScanFit mathematical model. In 19 persons, the optimal recording site was superior, superior and proximal, or superior and distal to the EDB mid-belly, whereas in 3 persons it was proximal to the mid-belly. Ranges of key MScanFit parameters were as follows: maximum CMAP amplitude (3.1-8.5 mV), mean SMUP amplitude (34.4-106.7 μV), mean normalized SMUP amplitude (%CMAP max, 0.95-2.3%), largest SMUP amplitude (82.7-348 μV), and MUNE (43-103). MUNE was not related to maximum CMAP amplitude (R2 = 0.09), but was related to mean SMUP amplitude (R2 = -0.19, P = 0.05). The EDB CMAP was highly sensitive to electrode position, and the optimal position differed between subjects. Individual differences in EDB MUNE were not related to CMAP amplitude. Inter-subject variability of EDB MUNE (coefficient of variation) was much less than previously reported, possibly explained by better optimization of the EMG electrode and the unique approach of MScanFit MUNE.

Determining intracortical, corticospinal and alpha motoneurone excitability in athletes with patellar tendinopathy compared to asymptomatic controls.

Lower capacity to generate knee extension maximal voluntary force (MVF) has been observed in individuals affected with patellar tendinopathy (PT) compared to asymptomatic controls. This MVF deficit is hypothesized to emanate from alterations in corticospinal excitability (CSE). The modulation of CSE is intricately linked to the excitability levels at multiple sites, encompassing neurones within the corticospinal tract (CST), intracortical neurones within the primary motor cortex (M1), and the alpha motoneurone. The aim of this investigation was to examine the excitability of intracortical neurones, CST neurones, and the alpha motoneurone, and compare these between volleyball and basketball athletes with PT and matched asymptomatic controls. Nineteen athletes with PT and 18 asymptomatic controls participated in this cross-sectional study. Transcranial magnetic stimulation was utilized to assess CST excitability, corticospinal inhibition (silent period, and short-interval cortical inhibition). Peripheral nerve stimulation was used to evaluate lumbar spine and alpha motoneurone excitability, including the evocation of lumbar-evoked potentials and maximal compound muscle action potential (MMAX ), and CSE with central activation ratio (CAR). Knee extension MVF was also assessed. Athletes with PT exhibited longer silent period duration and greater electrical stimulator output for MMAX , as well as lower MVF, compared to asymptomatic controls (p < 0.05). These findings indicate volleyball and basketball athletes with PT exhibit reduced excitability of the alpha motoneurone or the neuromuscular junction, which may be linked to lower MVF. Subtle alterations at specific sites may represent compensatory changes to excitability aiming to maintain efferent drive to the knee extensors.

Simulating progressive motor neuron degeneration and collateral reinnervation in motor neuron diseases using a dynamic muscle model based on human single motor unit recordings

Objective. To simulate progressive motor neuron loss and collateral reinnervation in motor neuron diseases (MNDs) by developing a dynamic muscle model based on human single motor unit (MU) surface-electromyography (EMG) recordings. Approach. Single MU potentials recorded with high-density surface-EMG from thenar muscles formed the basic building blocks of the model. From the baseline MU pool innervating a muscle, progressive MU loss was simulated by removal of MUs, one-by-one. These removed MUs underwent collateral reinnervation with scenarios varying from 0% to 100%. These scenarios were based on a geometric variable, reflecting the overlap in MU territories using the spatiotemporal profiles of single MUs and a variable reflecting the efficacy of the reinnervation process. For validation, we tailored the model to generate compound muscle action potential (CMAP) scans, which is a promising surface-EMG method for monitoring MND patients. Selected scenarios for reinnervation that matched observed MU enlargements were used to validate the model by comparing markers (including the maximum CMAP and a motor unit number estimate (MUNE)) derived from simulated and recorded CMAP scans in a cohort of 49 MND patients and 22 age-matched healthy controls. Main results. The maximum CMAP at baseline was 8.3 mV (5th–95th percentile: 4.6 mV–11.8 mV). Phase cancellation caused an amplitude drop of 38.9% (5th–95th percentile, 33.0%–45.7%). To match observations, the geometric variable had to be set at 40% and the efficacy variable at 60%–70%. The Δ maximum CMAP between recorded and simulated CMAP scans as a function of fitted MUNE was −0.4 mV (5th–95th percentile = −4.0 – +2.4 mV). Significance. The dynamic muscle model could be used as a platform to train personnel in applying surface-EMG methods prior to their use in clinical care and trials. Moreover, the model may pave the way to compare biomarkers more efficiently, without directly posing unnecessary burden on patients.

52. Varying Muscle Graft to Nerve Fiber Size and its Impact on Regenerative Peripheral Nerve Interface (RPNI) Reinnervation

PURPOSE: Currently there are more than 1.6 million people who suffer from limb loss. Regenerative Peripheral Nerve Interfaces (RPNI) currently exist as a method of capturing peripheral nerve signals for prosthetic control and preventing neuroma formation. While it is typically recommended that RPNIs are constructed to be 3 x 1 x 1.5 cm for human patients and approximately 150 mg in rat models, there is currently no recommendations or data to guide selection of muscle graft size for different nerve sizes. This consideration is especially important for RPNI construction as these factors may influence maximal optimal reinnervation for motor signal capture and neuroma prevention. The purpose of this study was to assess the ideal ratio of nerve size to muscle graft size for maximal RPNI compound muscle action potential (CMAP) signaling. METHODS: A total of 46 rats were assigned to 6 experimental groups that varied the size of nerve and muscle graft for RPNI creation. Extensor digitorum longus (EDL) was harvested, and different combinations of its four muscle heads were removed to create different size muscle grafts: 20% EDL, 60% EDL, and 100%EDL. To adjust nerve size, the tibial nerve was either left untouched or divided longitudinally along the nerve for approximately 15 cm. Depending on the experimental group, either 33% or 100% of the tibial nerve was implanted into the final muscle graft. All rats underwent a 3-month maturation period before undergoing electrophysiologic testing for obtaining CMAPs. An ANOVA test with post hoc analysis was performed to test for significant differences among the groups. RESULTS: For 33% nerve groups, maximum average CMAPs occurred at 2.2 mV with the 60% EDL RPNI. However, this average was not statistically different from that of the 20% (0.47 mV) or 100% (1.85 mV) EDL RPNI. With the 100% nerve group, maximum CMAP of the 100% EDL RPNI (4.5 mV) was significantly greater than that of the 20% (1.7 mV) or 60% (2.3 mV) EDL RPNIs. Furthermore, the maximum average CMAPs of the 100% nerve was significantly higher from that of the 33% nerve. CONCLUSIONS: This study’s findings suggest RPNI regeneration by large nerves requires the full EDL donor muscle for maximal reinnervation in the rat model, and that full reinnervation leads to significantly larger motor signals compared to smaller nerves. Thus, muscle graft size optimization to nerve size may be necessary in the clinical setting.

Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres

ObjectiveTo assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. MethodsFifteen groups in 9 countries recorded CMAP scans twice, 1–2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. ResultsComplete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. ConclusionsIt is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SignificanceMScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Intraoperative electrical stimulation promotes the short-term recovery of patients with cubital tunnel syndrome after surgery

BackgroundThis study was designed to investigate whether intraoperative electrical nerve stimulation has effects on the short-term recovery of cubital tunnel syndrome patients after ulnar nerve release.MethodsPatients diagnosed as cubital tunnel syndrome were selected. At the same time, they received conventional surgery treatment. The patients were divided by a randomized digits table into two groups. The control group underwent conventional surgery, and the electrical stimulation (ES) group underwent intraoperative electrical stimulation. All the patients were tested for sensory and motor functions, grip strength, key pinch strength, motor conductivity velocity (MCV), and maximum compound muscle action potential (CMAP) before operation and 1 month and 6 months after operation.ResultsIn patients treated with intraoperative ES, the sensory and motor functions and the strength of muscle were significantly improved after 1-month and 6-month follow-up than the control group. After the follow-up, the patients in the ES group had significantly higher grip strength and key pinch strength than the control group. After the follow-up, the patients in the ES group had significantly higher MCV and CMAP than the control group.ConclusionIntraoperative electrical stimulation of nerve muscle can significantly promote the short-term recovery of nerve and muscle functions after the surgery in cubital tunnel syndrome patients.

A Novel Analysis of CMAP Scans From Perspective of Information Theory: CMAP Distribution Index (CDIX).

The compound muscle action potential (CMAP) scan is a useful technique for examination of neuromuscular disorders. The objective of this study is to develop a novel analysis of CMAP scans from the perspective of information theory. A novel index parameter called CMAP distribution index (CDIX) was developed to characterize CMAP scan based on calculation of the information entropy. The performance of CDIX was evaluated using CMAP scan data from healthy control and spinal cord injury (SCI) subjects, and compared with D50 and MScanFit motor unit number estimation (MUNE). CDIX was significantly lower for the SCI subjects compared with the healthy control subjects (p < 0.001). A significant correlation ( R2 = 0.58, p < 0.001) was found between CDIX and MScanFit MUNE. Among all tested parameters (maximum CMAP, D50, MScanFit MUNE and CDIX), CDIX achieved the smallest relative width of the overlapping zone (WOZ%) between SCI and healthy control subjects. CDIX can be inferred as a useful index reflecting motor unit loss and muscle fiber reinnervation changes.

UBC-Nepal Expedition: Motor Unit Characteristics in Lowlanders Acclimatized to High Altitude and Sherpa.

With acclimatization to high altitude (HA), adaptations occur throughout the nervous system and at the level of the muscle, which may affect motor unit (MU) characteristics. However, despite the importance of MUs as the final common pathway for the control of voluntary movement, little is known about their adaptations with acclimatization. Ten lowlanders and Sherpa participated in this study 7 to 14 d after arrival at HA (5050 m), with seven lowlanders repeating the experiment at sea level (SL), 6 months after the expedition. The maximal compound muscle action potential (M max ) was recorded from relaxed biceps brachii. During isometric elbow flexions at 10% of maximal torque, a needle electrode recorded the MU discharge rate (MUDR) and MU potential (MUP) characteristics of single biceps brachii MUs. Compared with SL, acclimatized lowlanders had ~10% greater MUDR, ~11% longer MUP duration, as well as ~18% lower amplitude and ~6% greater duration of the first phase of the M max (all P < 0.05). No differences were noted between SL and HA for variables related to MUP shape (e.g., jitter, jiggle; P > 0.08). Apart from lower near-fiber MUP area for Sherpa than acclimatized lowlanders ( P < 0.05), no M max or MU data were different between groups ( P > 0.10). Like other components of the body, MUs in lowlanders adapt with acclimatization to HA. The absence of differences between acclimatized lowlanders and Sherpa suggests that evolutionary adaptations to HA are smaller for MUs than components of the cardiovascular or respiratory systems.

OC07: Monitoring disease progression with electrophysiological markers derived from compound muscle action potential scans in amyotrophic lateral sclerosis

To determine which electrophysiological markers derived from the compound muscle action potential (CMAP) scan are most sensitive to monitor disease progression in patients with amyotrophic lateral sclerosis (ALS), and whether they hold value for clinical trials. Methods: A multicenter collaboration was initiated between MND centers in Denmark, Turkey, Australia and the Netherlands to retrospectively assess longitudinal electrophysiological and ALS functional rating scale (ALSFRS-R) patterns. For each patient we determined the change over time in maximum CMAP (CMAPmax), D50 (number of largest discontinuities within CMAP scans), returners (number of increased CMAPs with decreasing stimulus currents), a motor unit number estimate (MUNE) and MU size properties (e.g. mean, largest unit). Linear mixed models were used to estimate variance components and population averages. Results were translated to required sample sizes for trials. Results: In total, 225 thenar CMAP scans from 65 patients were obtained. The ALSFRS-R decreased on average by 0.9 points/month (95% CI -1.2 to -0.7). MUNE, D50 and CMAPmax showed the largest decrease over time with -0.09, -0.09, and -0.05 standard deviations per month, respectively. In terms of sample size, the ALSFRS-R required 388 patients for a 6-month trial with visits every two months, whereas MUNE required 314 patients (-19.1%) to detect a 30% reduction in progression rate. Conclusion: The electrophysiological markers show considerable variability in their ability to monitor disease progression. MUNE showed to be the most suitable derivate. Further developments and standardization of the CMAP scan could refine its utility for ALS clinical trials.

HP51 : Motor unit integrity in multifocal motor neuropathy: A systematic evaluation with CMAP scans

To systematically study the yield of CMAP scan recordings in a large sample of MMN patients. Introduction: We identified motor unit (MU) integrity in a large cohort of patients with multifocal motor neuropathy (MMN). Methods: We performed compound muscle action potential (CMAP) scans in 40 MMN patients and 24 age-matched healthy controls. We derived the maximum CMAP amplitude (CMAPmax), a MU number estimate (MUNE) and the largest MU amplitude using MScanFit, stimulus current required to elicit 5% (S5), 50% (S50) and 95% (S95) of CMAPmax and relative ranges ([S95-S5]x100/S50). These MU characteristics were compared with clinical, laboratory and nerve conduction study (NCS) results. Results: CMAPmax and MUNE were reduced in MMN patients (both p<0.001). Largest MU amplitude as a percentage of CMAPmax was increased in MMN patients (p<0.001). Neither treatment duration nor presence of anti-GM1 antibodies were associated with MUNE. Relative range was larger in patients with confirmed presence of anti-GM1 antibodies than those without anti-GM1 antibodies (p=0.016) and controls (p<0.001). Largest MU amplitudes were larger in patients without anti-GM1 antibodies than patients with presence of anti-GM1 antibodies (p=0.037) and controls (p=0.044). Conclusion: We found that MU loss is common in MMN and accompanied by enlarged MUs. The presence of anti-GM1 antibodies is associated with an increase in relative range of MU thresholds and a reduction of largest MU amplitude, but not to MU loss. Our findings indicate that CMAP scan complements routine NCS, and may have potential for practical monitoring of treatment efficacy and disease progression.

Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan

ObjectiveTo determine which compound muscle action potential (CMAP) scan-derived electrophysiological markers are most sensitive for monitoring disease progression in amyotrophic lateral sclerosis (ALS), and whether they hold value for clinical trials. MethodsWe used four independent patient cohorts to assess longitudinal patterns of a comprehensive set of electrophysiological markers including their association with the ALS functional rating scale (ALSFRS-R). Results were translated to trial sample size requirements. ResultsIn 65 patients, 225 thenar CMAP scan recordings were obtained. Electrophysiological markers showed extensive variation in their longitudinal trajectories. Expressed as standard deviations per month, motor unit number estimation (MUNE) values declined by 0.09 (CI 0.07–0.12), D50, a measure that quantifies CMAP scan discontinuities, declined by 0.09 (CI 0.06–0.13) and maximum CMAP by 0.05 (CI 0.03–0.08). ALSFRS-R declined fastest (0.12, CI 0.08 – 0.15), however the between-patient variability was larger compared to electrophysiological markers, resulting in larger sample sizes. MUNE reduced the sample size by 19.1% (n = 388 vs n = 314) for a 6-month study compared to the ALSFRS-R. ConclusionsCMAP scan-derived markers show promise in monitoring disease progression in ALS patients, where MUNE may be its most suitable derivate. SignificanceMUNE may increase clinical trial efficiency compared to clinical endpoints.

The Short-Term to Midterm Follow-Up of Patients with Hirayama Disease After Anterior Cervical Discectomy and Fusion

Surgical treatment is widely used to treat patients with Hirayama disease (HD). However, postoperative follow-up with abundant samples is still scarce. This study investigated short-term to midterm clinical outcomes after anterior cervical discectomy and fusion (ACDF) among patients with HD. We enrolled 115 patients with HD who had undergone ACDF. Radiographic parameters included cervical lordosis (CL), sagittal vertical axis, segment lordosis (SL), T1 slope (T1S), T1S minus CL, range of motion (ROM), upper/lower adjacent segment ROM, and upper adjacent SL. Electrophysiologic parameters included the maximal compound muscle action potentials (CMAPs) of abductor digit minimi and abductor pollicis brevis, the latency of the ulnar nerve F reaction, and abnormal spontaneous action potentials. Clinical assessment included the selected brief-Michigan Hand Questionnaire and Odom scale. The average age was 19.5 ± 4.5 years. The mean follow-up time was 16.35 ± 9.21 months. CL, SL, and T1S increased, whereas sagittal vertical axis and ROM decreased at the final follow-up (P < 0.001). Upper adjacent SL, upper adjacent ROM, and lower adjacent ROM were stable after ACDF (P > 0.05). The maximal CMAPs of abductor digit minimi and the latency of the ulnar nerve F reaction improved bilaterally (P < 0.05), whereas there was no significance in the maximal CMAPs of abductor pollicis brevis (P > 0.05). Abnormal spontaneous action potentials reduced remarkably. The selected brief-Michigan Hand Questionnaire score increased after surgery (P < 0.001). The Odom scale showed a ratio of 79.1% (excellent and good ratio). This study showed favorable radiologic, electrophysiologic, and clinical outcomes after ACDF among patients with HD.

A study on the immediate effects of neuromuscular electrical stimulation on the corticospinal tract excitability of the infraspinatus muscle

Rotator cuff muscles are structurally and functionally different from other upper-limb muscles because they are responsible for glenohumeral joint stability. Neuromuscular electrical stimulation (NMES) induces excitability changes (increase or decrease) of the corticospinal tract (CST) in the peripheral muscles, such as those of the finger. However, it remains unclear whether similar results are obtained when targeting the infraspinatus muscle, which has properties that differ from other muscles, in healthy subjects. We investigated the immediate effects of NMES on the corticospinal excitability of the infraspinatus muscle, a rotator cuff muscle, in healthy subjects. Thirteen healthy right-handed men (mean age: 26.77 ± 2.08 years) participated in this study. The motor evoked potentials (MEPs) and the maximum compound muscle action potential (Mmax) were recorded before NMES to the right infraspinatus and within 15 minutes after the end of the NMES. NMES on the infraspinatus muscle significantly increased its MEP amplitude (Pre: 0.45 mV [0.33-0.48]; Post: 0.54mV [0.46-0.60] (median [lower quartile to higher quartile]); p= 0.005) but had no effect on Mmax (Pre: 2.95 mV [2.59-4.71]; Post: 3.35 mV [2.76-4.72]; p= 0.753). NMES application to the infraspinatus muscle increases CST excitability without producing immediate changes in the neuromuscular junction or muscle hypertrophy.

Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom

More than half of patients who recover from COVID-19 experience fatigue. We studied fatigue using neuropsychological and neurophysiological investigations in post-COVID-19 patients and healthy subjects. Neuropsychological assessment included: Fatigue Severity Scale (FSS), Fatigue Rating Scale, Beck Depression Inventory, Apathy Evaluation Scale, cognitive tests, and computerized tasks. Neurophysiological examination was assessed before (PRE) and 2 min after (POST) a 1-min fatiguing isometric pinching task and included: maximum compound muscle action potential (CMAP) amplitude in first dorsal interosseous muscle (FDI) following ulnar nerve stimulation, resting motor threshold, motor evoked potential (MEP) amplitude and silent period (SP) duration in right FDI following transcranial magnetic stimulation of the left motor cortex. Maximum pinch strength was measured. Perceived exertion was assessed with the Borg-Category-Ratio scale.Patients manifested fatigue, apathy, executive deficits, impaired cognitive control, and reduction in global cognition. Perceived exertion was higher in patients. CMAP and MEP were smaller in patients both PRE and POST. CMAP did not change in either group from PRE to POST, while MEP amplitudes declined in controls POST. SP duration did not differ between groups PRE, increased in controls but decreased in patients POST. Patients' change of SP duration from PRE to POST was negatively correlated to FSS.Abnormal SP shortening and lack of MEP depression concur with a reduction in post-exhaustion corticomotor inhibition, suggesting a possible GABAB-ergic dysfunction. This impairment might be related to the neuropsychological alterations.COVID-19-associated inflammation might lead to GABAergic impairment, possibly representing the basis of fatigue and explaining apathy and executive deficits.

Impact of stimulus duration on motor unit thresholds and alternation in compound muscle action potential scans

ObjectiveTo investigate the impact of stimulus duration on motor unit (MU) thresholds and alternation within compound muscle action potential (CMAP) scans. MethodsThe stimulus duration (0.1, 0.2, 0.6, and 1.0 ms) in thenar CMAP scans and individual MUs of 14 healthy subjects was systematically varied. We quantified variability of individual MU’s thresholds by relative spread (RS), MU thresholds by stimulus currents required to elicit target CMAPs of 5% (S5), 50% (S50) and 95% (S95) of the maximum CMAP, and relative range (RR) by 100*[S95-S5]/S50. We further assessed the strength-duration time constant (SDTC). Experimental observations were subsequently simulated to quantify alternation. ResultsRS, unaffected by stimulus duration, was 1.65% averaged over all recordings. RR increased for longer stimulus duration (11.4% per ms, p < 0.001). SDTC shortened with higher target CMAPs (0.007 ms per 10% CMAP, p < 0.001). Experiments and simulations supported that this may underlie the increased RR. A short compared to long stimulus duration recruited relative more MUs at S50 (more alternation) than at the tails (less alternation). ConclusionsThe stimulus duration significantly affects MU threshold distribution and alternation within CMAP scans. SignificanceStimulation settings can be further optimized and their standardization is preferred when using CMAP scans for monitoring neuromuscular diseases.

Assessment of motor unit loss in patients with spinal muscular atrophy

ObjectiveTo assess motor unit (MU) changes in patients with spinal muscular atrophy (SMA) using compound muscle action potential (CMAP) scans. MethodsWe 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. ResultsMedian 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). ConclusionsThe CMAP scan is an easily applicable technique that is superior to routine assessment of CMAPmax in SMA. SignificanceThe detection of pathological MU changes across the spectrum of SMA may provide important biomarkers for evaluating disease course and monitoring treatment efficacy.

Factors Associated With Minimum Effective Volume of Lidocaine 1.5% for Sciatic Nerve Blocks.

The objectives of this study were to investigate the correlations between the minimum effective volume (MEV) of lidocaine 1.5% for an ultrasound-guided popliteal sciatic nerve block and individual factors including the cross-sectional nerve area, sex, age, body mass index, and the depth of the sciatic nerve and to evaluate the safety of combined femoral and sciatic nerve blocks by monitoring the plasma concentration of local anesthetics. Forty patients received combined single-shot femoral and continuous sciatic nerve blocks. The femoral nerve block was performed with an in-plane technique and 15 mL of lidocaine 1.5%. A continuous peripheral nerve block annular tube was positioned between the tibial and peroneal nerves inside the paraneural sheath. Thirty minutes after the femoral nerve block, a loading dose of 5 mL of lidocaine 1.5% was given to block the sciatic nerve after obtaining the maximum compound muscle action potential (CMAP) amplitude using nerve conduction studies. Additional lidocaine 1.5% was pumped at a rate of 30 mL/h through the indwelling annular tube if, after 8 minutes, the CMAP amplitude was still present. The CMAP amplitude monitored by the nerve conduction studies and pinprick tests were recorded every 2 minutes after the administration of lidocaine 1.5%. When the CMAP amplitude decreased to nearly 0 mV, this MEV was recorded. The influences of the cross-sectional area of the sciatic nerve, sex, age, body mass index, and the depth of the sciatic nerve on the MEV were analyzed using stepwise multiple linear regression. Blood samples were collected from 10 patients to evaluate the safety of combined femoral and sciatic nerve blocks by ultra-performance liquid chromatography-tandem mass spectrometry. Blood was drawn at 0 minutes before femoral nerve injection; 0 minutes before sciatic nerve injection; 8 minutes after sciatic nerve injection; and 0, 10, 20, 30, 45, 60, 75, 90, and 120 minutes after the pumping of lidocaine 1.5% stopped. A significant correlation was found between the MEV of lidocaine 1.5% and the cross-sectional area of the sciatic nerve (r=0.459), with a regression equation of the MEV (mL)=5.969+0.095×(the cross-sectional area of the sciatic nerve). The coefficient of determination was 0.211 (P<0.05). The MEV of lidocaine 1.5% for complete sciatic nerve blocks ranged from 7 to 15 mL. The maximum concentrations of lidocaine, monoethylglycinexylidide, and glycinexylidide were 1672.9 (227.6), 265.7 (32.7), and 42.2 (22.4) ng/mL, respectively. There is a positive correlation between the cross-sectional area of the sciatic nerve and the MEV. The regression equation can help to predict the MEV of lidocaine 1.5% for popliteal sciatic nerve blocks. The maximum concentrations of lidocaine and its metabolites did not approach toxic threshold limits in this study.

Neuromuscular maturation in the neonate: Combined electroneurographic and ultrasonographic study

BackgroundThe combined electroneurography and muscle ultrasound examination (ENG-USM) in adult patients showed a correlation between the compound motor action potential (CMAP) and muscular thicknesses (MT). No similar studies exist regarding the neonatal period. AimTo evaluate the correlations between the maximum compound muscle action potential (CMAP) and maximum muscle thickness (MT) in term and premature newborns versus a group of young adults, as measured by combined electroneurography-ultrasonography (ENG-USM) to assess the stages. Study designObservational cohort study. SubjectsWe studied 36 subjects (14 premature and 11 term infants, and 11 young adults), who underwent ENG-USM of the tibialis anterioris (TA) muscle. Outcome measuresWe measured: 1) Onset-Peak (O-P) and Peak-to-Peak (P-P) maximum CMAP; 2) maximum MT; and 3) MT at the detected maximum CMAP. ResultsThe maximum CMAP in term newborns studied was about 1/3 of the mean value measured in the adults; the differences between O-P and P-P values of the term versus premature infants were not significant. We did not find a good correlation between maximum MT and maximum CMAP in the term (r = 0.63) newborns, contrary to what was found in preterms (r = 0.95) and in young adults (r = 0.98). ConclusionOur ENG-USM study shows that in newborns, the site of innervation of the neuromuscular plaque does not correspond to MT since muscle growth is related to the period of development, and depends on the progression of the nerve terminal branches that go to innervate the same muscle.

Safety and pharmacodynamics of a novel recombinant botulinum toxin E (rBoNT-E): Results of a phase 1 study in healthy male subjects compared with abobotulinumtoxinA (Dysport®)

Naturally occurring botulinum toxin (BoNT) serotypes have different pharmacological features of therapeutic and aesthetic interest. This phase 1, double-blind, placebo-controlled study (EudraCT: 2016–002609-20) assessed safety, tolerability and pharmacodynamics (PD) of the first recombinant BoNT serotype E (rBoNT-E) versus abobotulinumtoxinA (Dysport®), administered to extensor digitorum brevis (EDB) of healthy males. Subjects were randomised 3:1 (n = 28) to single ascending rBoNT-E (0.04–3.6 ng) doses or placebo. A further 24 subjects received abobotulinumtoxinA (20, 40, or 70 U) or placebo. PD were assessed using compound muscle action potential (CMAP) amplitude. Demographics were similar between groups. All rBoNT-E doses were well tolerated (no severe treatment-emergent adverse events [TEAEs], serious adverse events, or treatment-related toxicities). Most TEAEs were mild/moderate and treatment-unrelated. rBoNT-E had a faster onset of action (days 1–2 post-injection), greater peak effect (>90% CMAP inhibition), and shorter duration of effect at highest tested doses versus abobotulinumtoxinA (onset of action ≤7 days post-injection; 70% maximal CMAP inhibition). rBoNT-E duration of effect was 2–7 weeks versus >26 weeks for abobotulinumtoxinA. Dose-dependent effects were observed for magnitude and duration of EDB CMAP inhibition, plateauing at 0.9 and 3.6 ng. rBoNT-E demonstrated a good safety profile and a PD profile that may address unmet therapeutic and aesthetic patient needs.