The Promising Application of a New Ulnar Nerve Compound Muscle Action Potential Measurement Montage in Amyotrophic Lateral Sclerosis

Objective Detecting peripheral nerve damage by electrophysiology examination accurately and sensitively is important for the follow-up evaluation of amyotrophic lateral sclerosis(ALS). In this study, we applied a new proximal E2 electrode in the ulnar motor nerve conduction study with E1 on abductor digiti minimi(ADM), and investigated its effect on the compound muscle action potential(CMAP) of the ulnar nerve. Methods We included 64 ALS patients and 64 age- and sex- matched controls. Patients characteristics were collected for phenotype, symptom duration and site of onset. The revised ALS Functional Rating Scale(ALSFRS-R) was evaluated at the time of administration to assess the severity of ALS. The ulnar nerve CMAP was recorded using an E1 electrode on the muscle belly and an E2 electrode on distal tendon(traditional montage, CMAP-dE2) and proximal tendon(new montage, CMAP-pE2) respectively. Results The waveform of CMAP-pE2 was steadier presenting a uniform unilobed pattern. In the controls, there were no significant differences between the amplitudes of CMAP-dE2 and CMAP-pE2(p=0.96). In ALS patients, the amplitude of CMAP-pE2 was significantly lower than that of CMAP-dE2(p<0.01), especially for patients with ADM spontaneous activity and muscular atrophy. Using the new method, the damaged axons were more likely to be stratified into more severe decreased levels. Furthermore, the decline of CMAP-pE2 was significantly correlated with ALSFRS-R(p<0.01). Conclusions The new electrode configuration in the ulnar nerve conduction test could reflect the degree of axonal injury much more sensitively after the presence of ulnar nerve degeneration and was more suitable for the evaluation of disease progression.

Large-gap Peripheral Nerve Repair Using Xenogeneic Transplants in Primates

Early surgical intervention is required to successfully treat severe, large-gap peripheral nerve injuries. However, all existing treatments have shortcomings, and for large-gap injuries (≥4 cm), there is no reported alternative to autologous nerve. We report preclinical repair of large (4 cm), complete transectional radial nerve damage in Rhesus macaques using viable, whole sciatic nerve from genetically engineered, designated pathogen free porcine donors. Porcine nerves are physiologically similar to human nerves, contain neurotrophic growth factors and a matrix-rich scaffold, and offer greater clinical availability. We demonstrate regeneration of the transected nerve, distal muscle reinnervation, and recovery of conduction velocity and compound muscle action potential across xenogeneic transplants resulting in functional recovery comparable to autologous controls. We also show the lack of systemic porcine cell migration and the elimination of detectable transplanted porcine tissue. Our findings support the safety and efficacy of neural porcine therapeutics and the broader clinical potential of xenotransplantation.

A novel mutation of the COLQ gene causes congenital myasthenic syndromes: A case report

Congenital myasthenic syndromes (CMS) are a group of heterogeneous disorders of the neuromuscular junctions, characterised by fluctuating and fatigable weakness with an early onset. Endplate acetylcholinesterase deficiency (EAD) due to mutations in COLQ is a subtype of CMS whose key clue for diagnosis is repetitive compound muscle action potential (R-CMAP) under nerve conduction studies. In light of the significant overlap of clinical symptoms, misdiagnosis is common for CMS, causing delayed or incorrect treatments. Here, we report a case of CMS due to a novel mutation in COLQ with a typical R-CMAP and discuss the significance of R-CMAP for diagnosis.

Correlations between Electrophysiological Parameters, Lymphocyte Distribution and Cytokine Levels in Patients with Chronic Demyelinating Inflammatory Polyneuropathy

The goal of this study was to analyse, in relation to electrophysiological results, the distribution of lymphocyte subpopulations and the level of cytokines in patients with the typical form of chronic demyelinating inflammatory polyneuropathy (CIDP) before immunoglobulin treatment. The study group consisted of 60 patients (52 men, eight women), with a mean age 64.8 ± 11.2, who fulfilled the diagnostic criteria for the typical variant of CIDP, with (23 patients) and without (37 patients) diabetes mellitus. We analysed the results of the neurophysiological tests, and correlated them with the leukocyte subpopulations, and cytokine levels. In CIDP patients, IL-6, IL-2, IL-4 and TNF-α levels were significantly increased compared to the control group. Fifty patients had decreased levels of T CD8+ lymphocytes, and 51 patients had increased levels of CD4+ lymphocytes. An increased CD4+/CD8+ ratio was also found. Negative correlations were observed mainly between compound muscle action potential (CMAP) amplitudes and cytokine levels. The study enabled the conclusion that electrophysiological parameters in CIDP patients are closely related to the autoimmune process, but without any clear differences between patients with and without diabetes mellitus. Correlations found in the study indicated that axonal degeneration might be independent of the demyelinating process and might be caused by direct inflammatory infiltration.

Duration and temporal dispersion measurements in CIDP subjects from the Polyneuropathy And Treatment with Hizentra (PATH) study

Introduction: Distal compound muscle action potential (dCMAP) duration and temporal dispersion (TD) are electrophysiological hallmarks of demyelination and important for the diagnosis of CIDP. While the impact of CIDP treatment on other nerve conduction parameters has been examined, the effects on dCMAP and TD remain unexplored. The aim of the study was to examine the impact of withdrawal of immunoglobulin treatment on dCMAP duration and TD, and also the influence of the measurement technique on dCMAP duration and TD. Methods: Nerve conduction studies were analyzed from the PATH (Polyneuropathy And Treatment with Hizentra) study which randomized patients with CIDP to two doses of IgPro 20 and placebo. Distal CMAP duration and TD were obtained by two methods of measurements (D1 and D2, TD1 and TD2) from the median and peroneal nerves. Results: The dCMAP and TD were obtained from 389 tracings. While the two methods of measurement showed differences in D1 and D2 with D2 longer than D1 in all the three groups, there was no difference between the TD1 and TD2. There was no difference at baseline in dCMAP duration or TD among the three groups. At the end of treatment, patients in the placebo arm had no worsening of dCMAP and TD compared to baseline or the treated groups. Conclusion: dCMAP duration and TD did not show a difference between treated and placebo groups, and may be less sensitive measures than other nerve conduction parameters when evaluating changes in treatment. The method of dCMAP duration measurement does not affect TD as long as a consistent method is followed.

Characterization of LRP4/Agrin Antibodies From a Patient with Myasthenia Gravis

Objective:To determine whether human anti-LRP4/agrin antibodies are pathogenic in mice and to investigate underpinning pathogenic mechanisms.Methods:Immunoglobulin (Ig) was purified from a MG patient with anti-LRP4/agrin antibodies and transferred to mice. Mice were characterized for body weight, muscle strength, twitch and tetanic force, NMJ functions including CMAP (compound muscle action potential) and endplate potentials, and NMJ structure. Effects of the antibodies on agrin-elicited MuSK activation and AChR clustering were studied and the epitopes of these antibodies were identified.Results:Patient Ig-injected mice suffered MG symptoms, including weight lost and muscle weakness. Decreased CMAPs, reduced twitch and tetanus force, compromised neuromuscular transmission, and NMJ fragmentation and distortion were detected in Patient Ig-injected mice. Patient Ig inhibited agrin-elicited MuSK activation and AChR clustering. The patient Ig recognized the β3 domain of LRP4 and the C-terminus of agrin and reduced agrin-enhanced LRP4-MuSK interaction.Conclusions:Anti-LRP4/agrin antibodies in the MG patient is pathogenic. It impairs the NMJ by interrupting agrin-dependent LRP4-MuSK interaction.

Enhanced Effect of Botulinum Toxin A Injections into the Extensor Digitorum Brevis Muscle after Local Mechanical Leg Vibration: A Case Report

Background: The aim of this study was to demonstrate an increase in muscle action potentials and an enhancement of the efficacy of botulinum toxin (BoNT) after mechanical leg vibration. Methods: A 53-year-old healthy male volunteer underwent vibration ergometry training (VET) every morning and every evening for 10 min for 14 days. Compound muscle action potential (CMAP) of the right (R) and left (L) extensor digitorum brevis (EDB) muscle was analyzed by supramaximal peroneal nerve stimulation before and after VET 12 times during the 14 days. Thereafter, VET was stopped and 20 U incobotulinumtoxin (incoBoNT/A) were injected into the right EDB. During the following 10 days, CMAP of both EDBs was tested 12 times. Results: Under VET, the CMAP of both EDBs significantly increased (L: p < 0.01; R: p < 0.01). During the first 14 days, CMAP of the left EDB before VET was significantly (<0.008) lower than 20 min later after VET. This was not the case for the better trained right EDB. After day 14, CMAP of the untreated left EDB further increased for 6 days and then decreased again. In the right EDB, BoNT-treated EDB CMAP rapidly and highly significantly (p < 0.0001) decreased during the first 48 h by about 90%, from a level of about 14 mV down to a plateau of around 1.5 mV. Conclusion: Local mechanical leg vibration has a short- and long-term training effect. Compared to other studies analyzing the reduction in EDB CMAPs after BoNT injections, the reduction of EDB CMAPs in the present study observed after combined application of BoNT and VET was much faster and more pronounced.