Decrement Of Compound Muscle Action Potential Research Articles

The diagnostic and prognostic utility of repetitive nerve stimulation in patients with myasthenia gravis

Repetitive nerve stimulation (RNS) is a standard test for the diagnosis of myasthenia gravis (MG), where decrement of compound muscle action potentials (CMAP) corresponds to clinical muscle fatigability. Our aim was to ascertain the diagnostic and prognostic utility of RNS in MG patients. This study included MG patients treated between 01/2000 and 12/2016, with an observational period of at least one year and a minimum of two neurological examinations. Clinical and electrophysiological data were retrospectively gathered from patient records, and CMAP decrement was correlated with autoantibody titers and clinical disease severity at different time points. Ninety-four patients were included, with 88.3% of the cohort testing positive for acetylcholine receptor autoantibodies (AChR-Abs). RNS sensitivity was higher in patients with generalized disease (71.6%) than in purely ocular MG (38.5%). CMAP decrement did not significantly correlate with AChR-Ab titers, nor with clinical symptom severity at the time of testing or last follow up. However, there was a significant correlation between CMAP decrement and the worst recorded clinical status on a group level. RNS testing is more sensitive in generalized disease and AChR-Ab positive patients, but our data do not support RNS as a tool for long-term outcome prediction. Future studies with a prospective study design could help to overcome a number of limiting factors discussed in our study.

Alterations in fast-twitch muscle membrane conductance regulation do not explain decreased muscle function of SOD1G93A rats.

Both neuromuscular junction (NMJ) dysfunction and altered electrophysiological properties of muscle fibers have been reported in amyotrophic lateral sclerosis (ALS) patients. ALS-related preclinical studies typically use rodent SOD1G93A overexpression models, but translation to the human disease has been challenged. The present work explored NMJ function and cellular electrophysiological properties of muscles fibers in SOD1G93A overexpression rats. Longitudinal studies of compound muscle action potentials (CMAPs) were performed in SOD1G93A rats. Cellular studies were performed to evaluate electrophysiological properties of muscle fibers, including the resting membrane conductance (Gm ) and its regulation during prolonged action potential (AP) firing. SOD1G93A rats showed a substantial loss of gastrocnemius CMAP amplitude (35.8 mV, P< .001) and a minor increase in CMAP decrement (8.5%, P= .002) at 25 weeks. In addition, SOD1G93A EDL muscle fibers showed a lower baseline Gm (wild-type, 1325 μS/cm2 ; SOD1G93A , 1137 μS/cm2 ; P< .001) and minor alterations in Gm regulation during repeated firing of APs as compared with wild-type rats. The current data suggest that loss of CMAP amplitude is largely explained by defects in either lower motor neuron or skeletal muscle with only minor indications of a role for neuromuscular transmission defects in SOD1G93A rats. Electrophysiological properties of muscle fibers were not markedly affected, and an elevated Gm , as has been reported in motor neuron disease (MND) patients, was not replicated in SOD1G93A muscles. Collectively, the neuromuscular pathology of SOD1G93A rats appears to differ from that of ALS/MND patients with respect to neuromuscular transmission defects and electrophysiological properties of muscle fibers.

CMAP decrement by low-frequency repetitive nerve stimulation in different hand muscles of ALS patients.

To study compound muscle action potential (CMAP) decrement by low-frequency repetitive nerve stimulation (RNS) in different hand muscles of amyotrophic lateral sclerosis (ALS) patients and the relationship with split hand phenomenon and clinical manifestation. Clinical and decrement data of 51 ALS patients who had done RNS in different hand muscles were retrospectively reviewed from November 2016 to July 2017. Decrement data of 24 myasthenia gravis (MG) and 20Lambert Eaton myasthenia syndrome (LEMS) patients was also reviewed to compare decrement pattern with hand muscles of ALS patients. There was statistical significance between the decrement ratio of abductor digiti minimi (ADM) and abductor pollicis brevis (APB) as well as ADM and first dorsal interosseous (FDI). The decrements of the APB, ADM, and FDI were negatively correlated with their amplitude of CMAPs respectively. The difference between the decrement ratio of the APB and ADM was negatively correlated with the division ratio (CMAPAPB/CMAPADM). The decrement ratio of APB and FDI was negatively correlated with their muscle strength. There was a mild correlation between decrement ratio of APB and disease course. There was no statistical significance in the decrement pattern of the three-hand muscles of ALS patients. There was statistical significance in decrement pattern between APB of ALS and LEMS patients. Dysfunction of neuromuscular transmission was found in hand muscles of ALS patients, APB was involved most significantly. The dysfunction of neuromuscular transmission might be involved in the formation of the split hand phenomenon.

Compound Muscle Action Potential Decrement to Repetitive Nerve Stimulation Between Hirayama Disease and Amyotrophic Lateral Sclerosis

To compare repetitive nerve stimulation (RNS) between Hirayama disease (HD) and amyotrophic lateral sclerosis (ALS). The 3-Hz RNS test was performed on bilateral abductor pollicis brevis, abductor digiti minimi, middle deltoid, and upper trapezius muscles in 33 HD patients and 37 ALS patients. In HD patients, none of tested muscles showed any abnormal decrements (≥10%). Significant decrements were observed in 73% of the ALS patients, and decrements were more frequently observed in proximal muscles (deltoid: 70.3%; trapezius: 48.6%). Illness duration did not correlate with decrement percentage in either patient group, and there was no relationship between decrement incidence and ALS diagnostic category (P > 0.05). The significantly different RNS results between ALS and HD patients support the application of RNS, especially performing RNS in proximal muscles, as a supplementary test in distinguishing these two diseases, even in the early stages. These results may also imply a difference in underlying pathophysiology between ALS and HD.

Correlations between slow-rate repetitive nerve stimulation and characteristics associated with amyotrophic lateral sclerosis in Chinese patients.

[Purpose] To clarify the features associated with decrements in compound muscle action potentials (CMAP) during slow-rate repetitive nerve stimulation (RNS) of muscles involved in amyotrophic lateral sclerosis (ALS) in mainland China. [Subjects and Methods] A retrospective study of decremental responses to slow-rate RNS was performed to compare patients with ALS to those with myasthenia gravis (MG). [Results] A significant decrement (>5%) was observed in at least one muscle in 54% of ALS patients. The trapezius muscle was the most commonly affected (67%). In the ALS group, the CMAP amplitude evoked by the first stimulus was negatively correlated with the CMAP decrement in ulnar but not accessory nerves. Additionally, a positive decrement was associated with disease progression but not gender, age at onset, disease duration, region of onset, ALSFRS-R scores, or ALS diagnostic subgroup in ALS. Furthermore, the incidence of positive decrements and the decremental percentages were significantly higher in myasthenia gravis (MG) than in ALS. [Conclusions] The lower CMAP amplitude by the first RNS stimulus was more likely to induce a positive decrement in the ulnar nerve in ALS patients. The positive decremental responses to RNS observed in ALS indicate the faster progress of the disease, which is helpful for evaluating prognoses.

Myasthenia Gravis Associated with Diabetes about an Observation in Dakar, Senegal (West Africa) and Review of the Literature

Myasthenia gravis is a rare disease with very few confirmed cases described in the African setting. We report the case of a 41-year-old woman with a history of type 2 diabetes, high blood pressure (well monitored), and migraine with aura. She was received at the outpatient neurology consultation for a left ptosis, diplopia, chewing and walking difficulties. She reported abnormal and fluctuating muscle fatigability at effort, responsible for several falls. These symptoms were marked at evening, and were evolving since four years before her consultation in our center. She also reported a history of palpitations, exertional dyspnea, dysphonia, dysphagia and 20 kg weight loss. Neurological examination found a horizontal diplopia, a left ptosis and abnormal weakness at dynamic eyes and limb muscles testing. Otherwise the remaining neurological examination was unremarkable. Repetitive nerve stimulation found a significant compound muscle action potentials decrement. The immunological tests showed a very high level of antibodies to acetylcholine receptors (anti-AChR) at 1220.00 nmol/l (normal value <0.40 nmol/l). Thyroid tests and the remaining biological tests were normal. Thorax CT-scan was normal, with no thymoma. Considering these results, the diagnosis of anti-AchR myasthenia gravis was established. She was started on pyridostigmine 60 mg four times daily associated to her previous hypertension and diabetes therapy. Outcome after five months of treatment was marked by a complete recovery of muscle weakness and weight. Myasthenia gravis is a rare disease, frequently leading to a misdiagnosis. His association with diabetes is well established. It is worth to think about it when dealing with patients presenting fatigue with a history of diabetes.

CMAP decrement as a potential diagnostic marker for ALS.

We previously reported that decrement of compound muscle action potential (CMAP) by repetitive nerve stimulation (RNS) was greater in the median nerves than in the ulnar nerves of patients with amyotrophic lateral sclerosis (ALS). The aim of this study was to evaluate whether CMAP decrement by RNS is a feasible marker for the differentiation of ALS from other diseases. We performed RNS in the median and ulnar nerves of 51 patients with ALS and 40 patients with other diseases. The CMAP decrement was significantly greater in the median nerves of patients with ALS, compared to the disease control patients. In the median nerves of patients with ALS, CMAP decrement was significantly greater in the cervical region-onset group than in the other region-onset group. The finding of CMAP decrement in the median nerves can be useful for differentiating ALS patients with cervical region onset from other controls with active neuropathic diseases.

Fast-channel congenital myasthenic syndrome with a novel acetylcholine receptor mutation at the α–ε subunit interface

Congenital myasthenic syndromes (CMS) result from the failure to achieve muscle depolarisation due to disorders in the structure and/or function of the neuromuscular synapse. Mutations of the nicotinic acetylcholine receptor (nAChR) form a major subset of CMS. We describe a patient who presented with recurrent apnoeic crises in the neonatal period requiring ventilator support. Electromyography revealed compound muscle action potential decrement upon repetitive stimulation. Sequencing of nAChR subunit genes revealed two missense mutations. One previously reported null mutation p.εTyr15His, and a second novel missense mutation, p.εThr38Lys, that is well expressed in mammalian cell culture and thus likely to exert its effect via alteration of ion channel kinetics. Functional analysis revealed abbreviated ion channel bursts characteristic of a fast channel CMS. The mutation p.εThr38Lys occurs at the interface between the α and ε subunits of the nAChR pentamer and leads to instability of the open channel. The effects of this mutation on channel function were investigated in relation to other fast channel mutants at an analogous subunit interface within the nAChR pentamer. Fast channel syndromes are frequently characterised by severe myasthenic weakness with apnoeic crises; knowledge of the underlying mutation and its functional consequences can be vital for appropriate therapy and patient management.

P.15.9 An X-linked dominant mutation in LAMP2 causing Danon disease associated with myotonia expanding the spectrum

We describe a family with strong family history of cardiomyopathy. The mother has dilated cardiomyopathy with symptoms onset around 40 years old requiring treatment for both heart failure and atrial fibrillation. She does not have muscle weakness and her creatine kinase level was normal. The elder son has hypertrophic cardiomyopathy with symptoms onset at 20 years old, a mildly elevated creatine kinase of 1000 U/L but no muscle weakness. The younger brother with limited intelligence was asymptomatic all along. At the age of 15 with an incidental finding of raised serum transaminase levels he was referred for further investigations. Initial consultation confirmed mild proximal weakness, calves hypertrophy, creatine kinase up to 3500 U/L and echocardiogram confirmed hypertrophic cardiomyopathy. Needle electromyography showed myotonia after ice application. Nerve conduction study with short exercise test showed compound muscle action potentials decrement confirming myotonia. Metabolic workup, DMD gene and CTG repeat mutation study were all negative. The muscle biopsy of the elder brother showed vacuolar myopathy. Subsequent LAMP2 mutation study on exome sequencing confirmed Danon Disease. Mother has subsequently undergone heart transplantation, and vacuolar myocytes are noted in the cardiac muscles. This report describe a family with Danon disease, a rare X-linked dominant condition, but an important differential diagnosis for patient with cardiomyopathy, myopathy and learning difficulty, having a strong family history of cardiomyopathy. While skeletal muscles biopsy showed vacuolar myopathy, these abnormal vacuolar changes also extended to the cardiac muscles. Diagnostic confirmation is important when counseling the long term prognosis for this family. While symptomatic treatment is available for the heart failure, with a progressive course of cardiomyopathy the ultimate cure is heart transplantation.

Significant CMAP decrement by repetitive nerve stimulation is more frequent in median than ulnar nerves of patients with amyotrophic lateral sclerosis

Several studies have shown a significant amplitude decrement in compound muscle action potentials (CMAPs) on repetitive nerve stimulation (RNS) of muscles involved in amyotrophic lateral sclerosis (ALS). In ALS, muscle wasting preferentially affects the thenar muscles (APB) rather than the hypothenar muscles (ADM). We performed RNS studies in the APB and ADM muscles of 32 ALS patients to determine whether the effect of RNS differs between the median and ulnar nerves. The decremental responses to RNS were greater in the APB than in the ADM. Reduced CMAP amplitude was negatively correlated with CMAP decrement in median but not in ulnar nerves. The greater CMAP decrement in median nerve is attributable to preferential involvement of the APB in the pathophysiology of ALS or some underlying difference in the biology of the two muscles/nerves. Further investigations will better our understanding of the pathophysiology of ALS.

Comparative efficacy of repetitive nerve stimulation, exercise, and cold in differentiating myotonic disorders

The decremental response of the compound muscle action potential (CMAP) to provocative tests is not characterized in genetically verified myotonic disorders. We therefore studied the relationship between decremental responses and mutation type in 10 patients with recessive myotonia congenita (rMC), two with paramyotonia congenita (PMC), nine with myotonic dystrophy type 1 (DM1), four with DM2, and 14 healthy people. CMAPs were measured at rest, just after a short exercise test (SET), and during short, 5- and 10-HZ, repetitive nerve stimulation (RNS) trains at 32 degrees C and at 20 degrees C. The degree of decrement was not related to the severity of clinical myotonia. Controls and PMC patients had similar responses when warm, but with cooling PMC patients had a persistent decrement of CMAPs. In the rMC patients the decremental responses were related to the type of mutation of the CLCN1 gene, as a decrement was encountered in the T268M, R894X, IVS17+1 G>T, K248X, and 2149 del G, but not with the IVS1+3 A>T, F167L, or dominant A313T mutations. In DM1 patients there was no relationship between decrement and CTG repeats. The degree of partial inexcitability in myotonic muscle membrane therefore depends on the mutation type rather than degree of clinical myotonia. RNS at 10 HZ is more sensitive than SET for demonstrating abnormalities in rMC patients when warm; differences are less marked when cold, which is useful to diagnose PMC. Provocative tests are therefore useful in myotonias to demonstrate muscle inexcitability, which depends on the chloride or sodium channelopathy.

Estudo neurofisiológico na síndrome miastênica congênita do canal lento: relato de caso

The slow-channel syndrome is one of the congenital myasthenic syndromes attributed to inherited kinetic disorders of the ion channel of the acetylcholine receptor of the neuromuscular junction. This is a case report of 25-years-old man with progressive ptosis and limitation of ocular movements since infancy, presented a 6-years history of worse of the external ophthalmoparesis and muscular weakness in the shoulders and hands. The motor nerve conduction studies after a supramaximal single stimulus disclosed a double compound muscle action potential (CMAP) that disappeared after a voluntary contraction of 30 seconds. Repetitive stimulation of facial and spinal accessory nerves showed a CMAP decrement greater than 10% with disappeared of the second potential. The patient received fluoxetine with mild improvement of muscular weakness, but persisted with: ptosis, limitation of ocular movements and repetitive CMAP in the motor nerve conduction study. The characteristic of disease are discussed.

Muscle force and fatigue in patients with sepsis and multiorgan failure

Neuromuscular abnormalities are found frequently in sepsis and multiorgan failure (MOF). Surprisingly, however, there are no data on maximum skeletal muscle force and fatigue in these patients. To test the research hypotheses that adductor pollicis (AP) force would be lower in patients with sepsis, whereas fatigue would not differ between patients and immobilized but not infected volunteers. Prospective study; university intensive care unit and laboratory. Patients with sepsis and MOF (sequential organ failure assessment (SOFA) score >10) and healthy volunteers. Fatigue was evoked during 20[Symbol: see text]min of intermittent tetanic ulnar nerve stimulation achieving 50% of maximum AP muscle force. We measured evoked AP muscle force and fatigue, and compound muscle action potential (CMAP), and performed standard electrophysiological tests in 13 patients, and in 7 volunteers before and after immobilization. Maximum force (20+/-16 vs 65+/-19N; p<0.01) and CMAP (3.6+/-2.5 vs 10+/-2.5 mV; p<0.05) were markedly decreased in patients; however, fatigue and ulnar nerve conduction velocity did not differ from volunteers, and a decrement of CMAP was not observed with nerve stimulation frequencies up to 40 Hz. All patients with critical illness polyneuropathy, and an additional 50% of those without, had significant muscle weakness. Peripheral muscle force is markedly decreased in sepsis, without evidence for an increased fatigability. Muscle weakness was most likely due to a sepsis-induced myopathy and/or axonal neuropathy, and was not the result of an immobilization atrophy.

Decrement in surface-recorded motor unit potentials in amyotrophic lateral sclerosis

A decrement to repetitive stimulation sometimes occurs in ALS. The ability to isolate individual surface-recorded motor unit potentials (SMUPs) indirectly allows the analysis of the decrement by comparing the effect of different rates of stimulation on the size of the isolated SMUP. The median or ulnar nerve or both were studied in 11 patients with reduced compound muscle action potential (CMAP) amplitude. Isolated SMUPs were identified and studied using standard electrophysiologic techniques. One- and 3-Hz stimulation frequencies were compared in isolated SMUP by collecting > or =100 responses to a nonvarying stimulus. Changes in individual SMUP size and activation with change in stimulus frequency were compared with the size of the SMUP and with the CMAP decrement to a train-of-four stimulus. Fifteen studies were obtained from the 11 subjects. Eight studies showed a decrement of the total CMAP to a train-of-four stimulus. Twenty-nine well-defined, isolated SMUPs were studied. SMUP size reductions of 1 to 16% occurred with an increase in the stimulus frequency. No conduction block of individual SMUP occurred with the SMUP size reduction. No consistent change in variance was found. The SMUP size reduction was related to the size of the CMAP and the CMAP train-of-four decrement and less so to the size of the SMUP. The decrement of the total compound muscle action potential to repetitive stimulation appears to arise from individual surface-recorded motor unit potentials and does not result from loss of activation of the main motor axon. The probable mechanism lies at the nerve terminal and neuromuscular junction. No consistent change in variance occurs with different rates of stimulation.

Congenital Myasthenic Syndrome: Presentation, Electrodiagnosis, and Muscle Biopsy

We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2-10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies (n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.

Congenital Myasthenic Syndrome: Presentation, Electrodiagnosis, and Muscle Biopsy

We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2–10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies ( n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.

Decrement of compound muscle action potential is related to mutation type in myotonia congenita.

Decrement of the compound muscle action potential (CMAP) during 10-HZ repetitive nerve stimulation is thought to be an unusual finding in dominant myotonia congenita, and has not previously been reported in patients with the genetically verified disorder. It was the purpose of the present study to elucidate the relation between decrement and CLCN1 mutation type in myotonia congenita. Decrement and genotypes were studied in eight Danish families with myotonia congenita. Six patients with the known dominant mutation P480L had decrements of 30-84%. Patients heterozygous for the R894X mutation had decrements of 20-47%. Three novel CLCN1 mutations (two dominant and one recessive) were found segregating with the Thomsen/Becker phenotypes. In families with the novel dominant mutations M128V and E193K, decrement was absent in all family members tested. In conclusion, CMAP decrement may be pronounced in dominant myotonia congenita, and the presence of decrement is related to mutation type.

Transient weakness and compound muscle action potential decrement in myotonia congenita.

Twenty-five Turkish patients with recessive myotonia congenita (RMC), 16 of whom had genetic confirmation, were studied. Nineteen had transient weakness. In the upper extremities, onset age of transient weakness was usually in the early teens. All untreated RMC patients had a compound muscle action potential decrement of > or =25%, usually above 50%, with repetitive nerve stimulation at 10/s for 5 s. Patients with other nondystrophic diseases with myotonia, except 1 patient with dominant myotonia congenita, had no transient weakness and a CMAP decrement below 25%.