Size Of Compound Muscle Action Potential Research Articles

Safety, Tolerability, and Effect of Nusinersen in Non-ambulatory Adults With Spinal Muscular Atrophy.

Objective: Investigation of the safety, tolerability, and treatment effect of nusinersen treatment in non-ambulatory adults with spinal muscular atrophy (SMA).Methods: Non-ambulatory individuals, aged 18 years or older with genetically confirmed 5q SMA were enrolled. In participants with spinal fusion, fluoroscopy guided cervical C1–C2 lateral approach was used. Outcomes at 2, 6, 10, and 14 months post-treatment were compared with baseline assessment. Forced vital capacity (FVC) was the primary outcome, and RULM, HFMSE, the modified SMA-FRS, and ulnar nerve electrophysiology [compound muscle action potential (CMAP), single motor unit size, and motor unit number] were secondary. Adverse and serious adverse events and clinically significant vital sign or lab abnormalities were recorded.Results: Results from 12 women and 7 men (mean age: 39.7 ± 13.9, range: 21–64 years) were analyzed. No clinically significant changes of vital signs or laboratory parameters were observed. Five participants were hospitalized for pneumonia. Other adverse events included headache, back pain, cervical injection site pain, and upper respiratory and urinary tract infections. High baseline protein/creatinine ratio without significant change on treatment noted in 4 participants. FVC was feasible in all participants. HFMSE and RULM were not feasible in the majority of participants. FVC and functional outcomes were stable without improvement. CMAP and single motor unit potential sizes showed enlargement while motor unit numbers were stable.Conclusions: Nusinersen, including C1/C2 delivery, was safe overall and well-tolerated. Several outcome measures were limited by floor effect. Overall, treatment resulted in stability of motor outcomes, but motor unit and CMAP size were increased.

Relationship of Anabolic Hormones With Motor Unit Characteristics in Quadriceps Muscle in Healthy and Frail Aging Men.

Anabolic hormones are important factors in maintaining muscle mass for aging men, but their role in overall motor unit structure and function is unclear. The objective of this work is to determine associations of anabolic and reproductive hormone levels with motor unit characteristics in quadriceps muscle in older healthy and frail men. This work is an observational cohort study of community-dwelling men. Participants included healthy and frail men younger than 65 years. No intervention was performed. Quantitative assessments of electromyography-derived motor unit potential size (MUP) and compound muscle action potential size (CMAP) of the vastus lateralis muscle. We studied 98 men (mean ± SD: age 73 ± 6 years; body mass index [BMI] 25.7 ± 4.0 kg/m2; diabetes 11%) of whom 45% were prefrail and 18% frail. After adjusting for age, BMI, and prevalent diabetes, higher total and free testosterone levels were significantly related to larger CMAP (total testosterone: β [95% CI]: 0.3 [0.08-0.53]; free testosterone: 0.34 [0.13-0.56]). Exploratory analysis showed the relationship between free testosterone and CMAP was stronger in frail rather than robust men. In univariate analyses, estradiol was associated with CMAP size (0.37 [0.16-0.57]); and vitamin D was associated with MUP size (0.22 [0.01-0.43]) but these relationships were no longer significant after adjusting for potential confounders. Our data highlight the associations between androgen levels and the electrophysiological characteristics of older men, particularly in the frail. Clinical trials involving administration of androgens will help to elucidate the potential benefits of intervention on neuromuscular function and/or frailty status.

Activity-dependent changes in intrinsic excitability of human spinal motoneurones produced by natural activity

The current study was designed to evaluate activity-dependent changes intrinsic to the spinal motoneurones (MNs) associated with sustained contractions. The excitability of spinal MNs (reflected by the antidromically evoked F-wave) innervating the abductor digiti minimi muscle (ADM) was measured in 12 healthy subjects following maximum voluntary contractions (MVCs) of ADM lasting 5 s, 15 s, 30 s, and 60 s. Upon cessation of the contractions, F-waves showed a depression, which increased in depth and duration with increasing duration of contraction. Following a 5-s contraction, there was a 20% decrease, which waned in 2 min, whereas a 60-s contraction produced a 40% decrease and waned in over 15 min. The changes in excitability of peripheral motor axons produced by the MVCs were measured by recording an ADM compound muscle action potential (CMAP) of ~50% of maximum to a constant ulnar nerve electrical stimulation. On cessation of the contractions, there was a prominent decrease in size of the CMAP: following a 5-s MVC, it produced a 10% decrease in the size of the test CMAP, which recovered in 2 min, whereas following a 60-s MVC, it produced a 30% decrease, which recovered in over 15 min. Statistical analysis (correntropy) showed a high-order mutual dependence between F-wave and CMAP, and both were significantly dependent on MVC duration. Because of the parallel excitability changes in peripheral axons and spinal MNs, our interpretation is that intrinsic excitability of the axon initial segment (i.e., where the action potential is generated) and peripheral axon segments changed in a similar, activity-dependent manner.

Concurrent Chronic Motor Axonal Polyneuropathy and Synaptic Impairment of Neuromuscular Junction

Polyneuropathies may exhibits clinical, electrophysiologic signs of neuromuscular junction impairment. Distal motor nerve terminals and neuromuscular junction contain pre or postsynaptically specific targets for circulating autoantibodies, if present in neuropathies. Motor nerve terminal blockade either reversible or permanent is a putative factor of muscle weakness. A 59-year-old patient exhibited oropharyngeal, facial, extremity weakness, fluctuating fatigability, and areflexia. Elecectrophysiologic studies showed purely motor axonal polyneuropathy. Thenar, facial slow rate repetitive stimulation revealed up to 47% decrement of compound muscle action potential size. Single fiber electromyography on voluntary activation confirmed increased jitter and impulse blocking in all muscles examined in one third of the fibers. Repeated testings for antibodies to gangliosides, acetylcholine, muscle tyrosine kinase receptors, voltage-gated calcium channels were negative. Oral pyridostigmine bromide improved bulbar symptoms. Pulse intravenous immunoglobulin, oral steroids, and azathioprine had steady benefit. Impairment of neuromuscular transmission if occurring in chronic axonal neuropathies highlights mechanisms and significance of neuromuscular chronic "synaptopathies."

Supramaximal responses can be elicited in hand muscles by magnetic stimulation of the cervical motor roots

The amplitude of compound muscle action potentials (CMAPs) evoked in response to magnetic cervical motor root stimulation (MRS) has rarely been used as a diagnostic parameter because of the difficulty in obtaining supramaximal CMAPs. To clarify whether supramaximal CMAPs could be elicited by MRS, and if so, whether their amplitude and area could be used to evaluate the conduction of proximal motor roots. With the use of a custom-made high-power magnetic stimulator, the CMAPs evoked in response to MRS of the first dorsal interosseous, abductor digiti minimi, and abductor pollicis brevis (APB) muscles were compared with those evoked by electrical stimulation at the wrist, brachial plexus, and cervical motor roots. The collision technique was also used to exclude volume conduction. The correlation between MRS-induced CMAP latency and body height was evaluated. In 32 of 36 normal subjects, supramaximal CMAPs were obtained in response to MRS. The size of CMAPs occurring in response to MRS was the same as the size of those occurring in response to high-voltage electrical cervical motor root stimulation. The collision technique revealed that the APB muscle was highly contaminated by volume conduction from adjacent muscles. CMAP latency correlated significantly with body height. Supramaximal CMAPs can be obtained in most normal subjects. In subjects exhibiting confirmed supramaximal CMAPs in response to MRS, not only the latency of these CMAPs but also their amplitude and area can be clinically useful, excluding CMAPs in the APB muscle.

Motor unit number estimation in facial paralysis

The value of motor unit number estimation (MUNE) in determining the prognosis of acute peripheral facial paralysis (PFP) was evaluated in 89 patients with PFP on days 6, 8, 11, 14, 20, and 30 of PFP and repeated once per month until complete recovery or the end of the first year. The symptomatic/asymptomatic side ratios of the compound muscle action potential (CMAP) amplitudes recorded from nasalis muscles and MUNEs studied using the incremental method by recording from the same muscle were assessed with regard to three outcome groups (Group I, complete recovery; Group II, mild dysfunction; Group III, moderate-moderately severe dysfunction). CMAP and MUNE ratios were parallel to each other in all patient groups throughout the observation period with lower values in the more severe groups. However, CMAP amplitude loss was significantly greater than the MUNE loss in the first 3 weeks of PFP. The MUNE method is not superior to CMAP size in determining prognosis in PFP. However, the significant disparity between the CMAP and MUNE ratios in the early period may have some physiological relevance with regard to the pathophysiology of the Wallerian degeneration process and deserves further research into its potential sources.

Decrement pattern in Lambert–Eaton myasthenic syndrome is different from myasthenia gravis

The decrement pattern at low rates of repetitive nerve stimulation in myasthenia gravis (MG) is characterized by a decrease of compound muscle action potential size within the first 4–5 responses. With subsequent stimuli, compound muscle action potential size either increases or does not change. Following an observation that the pattern of decrement might be different in patients with Lambert–Eaton myasthenic syndrome (LEMS), we retrospectively studied traces from eight LEMS patients and 14 patients with seropositive generalized MG, calculating decrement percent from first to fourth and from first to ninth compound muscle action potential. In the LEMS patients, compound muscle action potential amplitude decreased progressively from first to ninth stimulus at 2, 3 or 5 Hz in all traces but one. In contrast, MG patients demonstrated the expected improvement after the initial decrement in all traces except one. In the evaluation of patients suspected of having myasthenia gravis, the finding of progressive decrement pattern at low rates of repetitive nerve stimulation may alert the electromyographer to the possibility of Lambert–Eaton syndrome and prompt the performance of further electrodiagnostic tests.

No clinical or neurophysiological evidence of botulinum toxin diffusion to non-injected muscles in patients with hemifacial spasm

Botulinum toxin injected into a muscle may diffuse to nearby muscles thus producing unwanted effects. In patients with hemifacial spasm, we evaluated clinically and neurophysiologically, whether botulinum toxin type A (BoNT-A) diffuses from the injection site (orbicularis oculi) to untreated muscles (orbicularis oris from the affected side and orbicularis oculi and oris from the unaffected side). We studied 38 patients with idiopathic hemifacial spasm. Botulinum toxin was injected into the affected orbicularis oculi muscle alone (at 3 standardized sites) at a clinically effective dose. Patients were studied before (T0) and 3-4 weeks after treatment (T1). We evaluated the clinical effects of botulinum toxin and muscle strength in the affected and unaffected muscles. We also assessed the peak-to-peak amplitude compound muscle action potential (CMAP) recorded from the orbicularis oculi and orbicularis oris muscles on both sides after supramaximal electrical stimulation of the facial nerve at the stylomastoid foramen. In all patients, botulinum toxin treatment reduced muscle spasms in the injected orbicularis oculi muscle and induced no muscle weakness in the other facial muscles. The CMAP amplitude significantly decreased in the injected orbicularis oculi muscle, but remained unchanged in the other facial muscles (orbicularis oris muscle on the affected side and contra-lateral unaffected muscles). In conclusion, in patients with hemifacial spasm, botulinum toxin, at a clinically effective dose, induces no clinical signs of diffusion and does not reduce the CMAP size in the nearby untreated orbicularis oris or contralateral facial muscles.

The stimulus–response curve and motor unit variability in normal subjects and subjects with amyotrophic lateral sclerosis

The behavior and stability of motor units (MUs) in response to electrical stimulation of different intensities can be assessed with the stimulus-response curve, which is a graphical representation of the size of the compound muscle action potential (CMAP) in relation to stimulus intensity. To examine MU characteristics across the whole stimulus range, the variability of CMAP responses to electrical stimulation, and the differences that occur between normal and disease states, the curve was studied in 11 normal subjects and 16 subjects with amyotrophic lateral sclerosis (ALS). In normal subjects, the curve showed a gradual increase in CMAP size with increasing stimulus intensity, although one or two discrete steps were sometimes observed in the upper half of the curve, indicating the activation of large MUs at higher intensities. In ALS subjects, large discrete steps, due to loss of MUs and collateral sprouting, were frequently present. Variability of the CMAP responses was greater than baseline variability, indicating variability of MU responses, and at certain levels this variability was up to 100 microVms. The stimulus-response curve shows differences between normal and ALS subjects and provides information on MU activation and variability throughout the curve.

Cortical and spinal mechanisms of facilitation to brain stimulation.

Compound muscle action potentials (CMAPs) evoked by magnetic brain stimuli are larger if the subject provides a steady background voluntary contraction of the target muscle. This facilitation could be due either to cortical or spinal mechanisms, or both. Both magnetic and electrical stimuli given immediately after the onset of a ballistic contraction also evoke markedly facilitated CMAPs. By contrast, responses some 200 ms after the onset of such a contraction are facilitated if stimuli are magnetic but not if they are electrical. This second phase of facilitation is largely cortical in origin. By comparing the size of CMAPs evoked by magnetic stimuli at two different delays after electromyogram onset, the total facilitation could be dissected into its spinal and cortical components. The relationship between CMAP area in the first dorsal interosseous and stimulus intensity was different in the two phases of facilitation, suggesting a constant background level of spinal facilitation upon which an increasing descending volley operated. In experiments in which ballistic contractions at increasing force levels were performed it was found that at low force levels, spinal facilitation predominated, but at forces greater than 10% maximum there were roughly equal contributions from increased spinal cord and cortex excitability.

A new method to measure the distribution of motor conducgtion velocity in man

A new method of measuring the distribution of conduction velocities in human motor fibers is described. In this method, a modification of Kimura's collision technique is combined with Hopf's technique. This enabled us to determine the collision end-point in Hopf's technique, from which the minimum velocity is derived. The size of the distorted compound muscle action potential (CMAP) measured with Hopf's technique is corrected using the CMAP size with the modified Kimura technique. This revolves the problem of CMAP distortion due to transient change in muscle conduction in Hopf's technique. In addition, a new equation to correct for the refractory period was developed. This can be applied even if there is stimulus spread. Using our method, one can clearly determine the maximum and minimum velocities. The former corresponds to the motor conduction velocity as measured by the conventional method.