Stimulated Single-fiber Electromyography Research Articles

Stimulated Single Fiber Electromyography (SFEMG) for Assessing Neuromuscular Junction Transmission in Rodent Models

Stimulated Single Fiber Electromyography (SFEMG) for Assessing Neuromuscular Junction Transmission in Rodent Models

Eaton lambert syndrome (LEMS) is a diagnostic challenge and stimulated single fiber electromyography (SSFEMG) is offering a great role in its early diagnosis

LEMS is a presynaptic neuromuscular disorder, its early recognition is particularly important because of its strong association with small cell lung cancer (SCLC) and up to 50% are misdiagnosed. LEMS is often suspected according to symptoms. Electrodiagnostic approach includes Routine motor nerve conduction stimulation typically elicits a small amplitude compound muscle action potential (CMAP), with its increase >100% increment after After isometric contraction for 10 s, or high rate repetitive supramaximal stimulation, but what if it increases but not reaching 100%?

Combined Muscle Biopsy and Comprehensive Electrophysiology in General Anesthesia is Valuable in Diagnosis of Neuromuscular Disease in Children.

The diagnostic workup in patients with delayed motor milestones suspected of having either myopathy or a congenital myasthenic syndrome is complex. Our hypothesis was that performance of a muscle biopsy and neurophysiology including stimulated single-fiber electromyography during an anesthetic procedure, combined with genetic testing has a high diagnostic quality. Clinical and paraclinical data were retrospectively collected from 24 patients aged from 1 month to 10 years (median: 5.2 years). Neurophysiology examination was performed in all patients and was abnormal in 11 of 24. No patients had findings suggestive of a myasthenic syndrome. Muscle biopsy was performed in 21 of 24 and was normal in 16. Diagnostic findings included nemaline rods, inclusion bodies, fiber size variability, and type-II fiber atrophy. Genetic testing with either a gene panel or exome sequencing was performed in 18 of 24 patients, with pathogenic variants detected in ACTA1, NEB, SELENON, GRIN2B, SCN8A, and COMP genes. Results supporting a neuromuscular abnormality were found in 15 of 24. In six patients (25%), we confirmed a genetic diagnosis and 12 had a clinical neuromuscular diagnosis. The study suggests that combined use of neurophysiology and muscle biopsy in cases where genetic testing does not provide a diagnosis can be useful in children with delayed motor milestones and clinical evidence of a neuromuscular disease.

Sensitivity and specificity of single-fibre EMG in the diagnosis of ocular myasthenia varies accordingly to clinical presentation.

Single-fibre electromyography (SF-EMG) is considered as the most sensitive test for the diagnosis of MG. However, previous studies had limitations, such as a retrospective design, non-consecutive sampling, incorporation bias or were performed in small or mixed populations. Our aims were to determine the diagnostic sensitivity and specificity of SF-EMG of the orbicularis oculi in OMG and the utility of this test in relation to patients' clinical presentation. We studied 232 consecutive patients referred to the SF-EMG laboratory for a suspected OMG. Stimulated SF-EMG was performed on the orbicularis oculi muscle. OMG was diagnosed in 165 cases and other disorders (OD) in 67. SF-EMG showed a sensitivity of 0.79 (95% CI 0.73-0.85) and a specificity of 0.80 (95% CI 0.71-0.90). False negative results were associated with mild symptoms and with isolated diplopia. Comparison of the diagnostic yield among patients with different clinical presentations showed a similar diagnostic accuracy of SF-EMG in patients with ptosis and in patients with ptosis and diplopia, significantly higher than in patients with isolated diplopia (P < 0.0001). Twenty-two patients with OMG presenting with isolated ptosis or diplopia, who initially tested negative, were re-tested in relation to a worsening of their symptoms showing a positivisation in 91% of cases. SF-EMG on the orbicularis oculi muscle is very sensitive in patients with ptosis. In contrast, in patients with isolated diplopia SF-EMG does not exclude OMG. Therefore, the interpretation of the results of the test should take into account the patients' clinical presentation.

61. Stimulated single-fiber electromyography of the frontal muscle: Normative data using concentric needle

To obtain normative values we performed in healthy volunteers (HV) stimulated single-fiber electromyography (SFEMG) of the Frontal muscle using concentric needle electrode (CNE). Frontal muscles SFEMG, after stimulation with needle electrodes of the temporal branch of facial nerve, was conducted in 16 HV (6 males, mean age 43.1, range 20–60 years). Filter settings were 1000 Hz to 10 kHz.The mean consecutive difference (MCD) of the individual fiber and the mean MCD per study were determined. Using the 95% percentile the upper normal limit for the individual fibers of jitter and the mean MCD per study in the HV was 37 μs and 27 μs respectively. Having defined these limits, we evaluated 7 patients affected by seronegative Ocular Myasthenia gravis. All these patients showed mean MCD >27 μs and >2 individual fiber Jitter >37 μs. The 95% prediction limit might be optimal cut-off value, depending on the clinical question. The obtained reference values were narrow than those reported previously using concentric needles. Stimulation jitter recordings with CNE could be used in practice but borderline findings should be carefully assessed in a prospective study in which consecutive patients with clinical suspicion of Myasthenia Gravis will be enrolled.

Stimulated single-fibre electromyography (SFEMG) in ocular and generalized myasthenia

Patients presenting to eye clinics with variable diplopia, ptosis and generalized muscular weakness are often suspected to have myasthenia gravis(MG). Single-fibre electromyography (SFEMG) which measures NMJ blockade is widely considered to be a more sensitive investigation compared to serology for antibody detection. Our study aimed to characterise clinical findings most predictive for MG, as confirmed by SFEMG and subsequent treatment response.

54. Early neurophysiological signs of disease in SOD1G93A mouse model: A stimulated single-fiber electromyography study

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration of the corticospinal tract motor neurons. Growing evidence, especially derived from studies in murine models, could suggest that ALS is a distal axonopathy in which axonal degeneration occurs early during the disease, preceding the degeneration of motoneuron soma in the ventral horn of the spinal cord and the onset of symptoms (Fischer et al., 2004; Dadon-Nachum et al., 2011). A combination of molecular and subcellular events, such as protein misfolding, oxidative damage, mitochondrial alterations, impairment of glutamate transmission leading to excitotoxicity, and axonal transport impairment has been implicated in motoneuron vulnerability in ALS (Ferraiuolo et al., 2011). These observations led to consider the neuromuscular junction (NMJ) as a major player in the initiation and progression of ALS. Aim of this study was to investigate the functionality of the NMJ through all the course of the disease in the hSOD1G93A ALS mouse model, by means of single-fiber electromyography (SFEMG) technique. A comprehensive neurophysiological investigation (including sciatic nerve conduction, MEPs by transcranial electrical stimulation and sSFEMG) was carried out on 5 WT and 5 hSOD1G93A mice, at different time-points (50-70-90-110 ± 3 PND). In the early pre-symptomatic phase (50 PND), hSOD1G93A mice presented a significant jitter elongation [MCD (mean ± SE): 18.36 ± 3.21 in hSOD1G93A, 8.23 ± 0.84 in WT; p 0.021] together with increased fiber density [FD (mean ± SE): 1.62 ± 0.17 in hSOD1G93A, 1.27 ± 0.10 in WT; p 0.117] when compared with controls, suggestive of recent reinnervation process. No difference were found in peripheral conduction and MEPs parameters at the same time-point. Our results show that the neuromuscular transmission of hSOD1G93A mice is altered since the early presymptomatic phase of the disease. This probably derive from an early denervation-reinnervation process resulting in immature collateral nerve terminals and instability of neuromuscular transmission. SFEMG seems to be more sensitive in detecting the early signs of the disease compared to the other neurophysiological techniques, and could be a valuable tool for monitoring the effectiveness of new experimental therapeutic approach.

Determining jitter values in the very young by use of the e-norms methodology.

The diagnosis of myasthenia gravis in very young infants is a challenging one. In young infants, stimulated single-fiber electromyography (StimSFEMG) is the most appropriate technique, but it has serious limitations due to the absence of reference values in this subpopulation. Here we present our efforts to derive a reference range of jitter in a patient cohort of infants <3 years of age using the extrapolated norms, or e-norms, technique. The e-norms method was used to calculate jitter mean consecutive difference (MCD) descriptive statistics for children <3 years of age. The e-norms derived jitter upper MCD limit was 45 μs in children <1 year, 33 μs in those <2 years, and 26 in those <3 years of age. In the absence of jitter reference values for the very young, the e-norms method can be used as an alternative to derive these values from laboratory cohorts. Muscle Nerve 55: 51-54, 2017.

Miller Fisher syndrome with presynaptic neuromuscular transmission disorder

Miller Fisher syndrome is defined by a triad of symptoms, namely areflexia, ataxia, and ophthalmoparesis. The ophthalmoparesis is mostly severe, undulating weakness of eye movements with ptosis and increased fatigability resembling a neuromuscular transmission disorder. We present a 52-year-old man with severe Miller Fisher syndrome with a high level of anti-GQ1b antibodies and a presynaptic type of neuromuscular transmission disorder. The diagnosis was confirmed by stimulated single-fiber electromyography with the use of a concentric needle electrode and various stimulation rates.

P337: Stimulated single fibre electromyography using concentric needle electrode in organophosphate insecticide poisoning in Sri Lanka

P337: Stimulated single fibre electromyography using concentric needle electrode in organophosphate insecticide poisoning in Sri Lanka

Functional Changes in Motor Endplates of the Target Muscle after Amputation of the C7 Nerve Root

There are limited data on structural and functional changes in motor endplates and muscle fibers in the target muscle following amputation of the 7th cervical nerve root, a transplantation-related procedure in surgical treatment in the case of avulsions of the brachial plexus roots. We examined functional changes in these structures using stimulated single-fiber electromyography (sSF-EMG) in an animal model. Unilateral amputation of the 7th cervical nerve root was performed in 36 male rats, and the m. triceps brachii muscle was tested by sSF-EMG at different time points. We observed significant differences in the jitter (mean consecutive difference, MCD, of the latencies between adjacent muscle fibers) at post-amputation weeks 1, 2, 4, and 6. The post-operation fiber density (FD) values within the zone of effective stimulation also gradually increased. At post-amputation weeks 8 and 12, the jitter values returned to normal levels, whereas FD values continued to rise. Our results indicate that the post-amputation compensatory processes in the target muscles of the 7th cervical nerve root are mostly completed at 9-12 weeks after amputation.

DOK7 congenital myasthenic syndrome in childhood: Early diagnostic clues in 23 children

Mutations in DOK7 are a common cause of congenital myasthenia. Treatment with ephedrine or salbutamol is effective, but diagnosis is often delayed. The aim of our study was to find early clues to the diagnosis of DOK7 congenital myasthenic syndrome. We included 23 children of 20 families. Onset of symptoms ranged from birth to age 3years. 13 presented at birth with feeding difficulties, 11 with stridor (documented vocal cord palsy in 7), 3/11 with hypotonia/poor head control. Weakness was more pronounced proximally in all, axial in early presenting infants. Muscle biopsy showed non-specific features in 15/16, type 1 fibre predominance in 14/16, areas devoid of oxidative enzyme activity in 7/16. Muscle imaging was normal in 8/10, 2/10 showed mild non-specific changes. A diagnostic clue suggesting CMS rather than myopathy was the discrepancy between muscle imaging or histology findings compared with the degree of weakness. Repetitive nerve stimulation and stimulation single fibre electromyography were pathological in 9/17 and 13/14, respectively. In conclusion, stridor and feeding difficulties at birth or progressive weakness despite normal milestones in infancy point to the diagnosis and should lead to neurophysiological and genetic investigation. Fatigability can be absent or easily missed in the first years of life.

119. Stimulated single fiber electromyography using a concentric needle electrode among normal filipino subjects

119. Stimulated single fiber electromyography using a concentric needle electrode among normal filipino subjects

Activity-dependent changes in impulse conduction of single human motor axons: A stimulated single fiber electromyography study

Objective The aim of this study is to develop a novel method to assess activity-dependent hyperpolarization in human single motor axons at a constant stimulus frequency by using intra-muscular axonal stimulating single fiber electromyography (s-SFEMG). Methods We performed s-SFEMG in the extensor digitorum communis (EDC) muscle of 10 normal subjects, and measured changes in latencies for single muscle fiber action potentials (MAPs) during 500 stimuli delivered at 5, 10 and 20 Hz. The data were analyzed with a repeated measurement analysis, and multiple comparisons were performed. Results A total of 585 MAPs were examined at 5 Hz ( n = 190), 10 Hz ( n = 210), and 20 Hz ( n = 185) steady stimulation. There was a progressive linear prolongation of latencies, as the stimulus rate increased ( F = 95.6, p < 0.001); the least square means (SEM) of latency change were 100.7 (0.28)% at 5 Hz, 102.3 (0.27)% at 10 Hz and 105.3 (0.28)% at 20 Hz. There were statistically significant differences between frequencies by Tukey–Kramer’s method. Despite the significant latency prolongation, no activity-dependent conduction block developed. A 20 Hz electric stimulation to intramuscular axons was well-tolerated in all the subjects. Conclusions Tetanic stimulation at a constant rate results in significant latency increase in single human motor axons, the extent of which depends on the stimulus frequency. The findings imply that physiological discharge rates will activate the Na +/K + pump and thereby produce axonal hyperpolarization in single motor axons. Significance This technique may detect activity-dependent conduction block if the safety margin of impulse transmission is significantly reduced by demyelination or increased branching due to collateral sprouting in a variety of neuromuscular disorders.

Electrophysiologic Evidence of Spinal Accessory Neuropathy in Patients With Cervical Myofascial Pain Syndrome

Chang C-W, Chang K-Y, Chen Y-R, Kuo P-L. Electrophysiologic evidence of spinal accessory neuropathy in patients with cervical myofascial pain syndrome. Objective To evaluate whether or not spinal accessory neuropathy exists in patients with cervical myofascial pain syndrome (MFPS). Design Prospective study. Setting A neurophysiologic laboratory in a university hospital. Participants Patients with cervical MFPS (n=25) and healthy controls (n=20). Interventions Not applicable. Main Outcome Measures We performed nerve conduction studies (NCSs) in bilateral spinal accessory nerves, and electromyography and stimulated single-fiber electromyography in the trapezius muscles of all patients and controls. Parameters including nerve conduction velocities (NCVs), amplitudes and areas of compound muscle action potentials (CMAPs), and mean consecutive differences (MCDs) in single-fiber electromyography were measured, analyzed, and compared with the disease durations of the patients. Results Spinal accessory NCSs showed normative NCVs but with prominently reduced CMAP amplitude in the patients with cervical MFPS, which is recognized as an axonal neuropathy of the spinal accessory nerves. Electromyography showed prominent evidence of denervation and reinnervation patterns in 48% of the MFPS patients. The abnormal MCDs in single-fiber electromyography indicated a synaptic delay of motor endplates in the motor units, and may signify evolving instability of neuromuscular transmission in the spinal accessory nerves innervating trapezius muscles of the patients. Conclusions This study demonstrates electrophysiologic evidence of neuroaxonal degeneration and neuromuscular transmission disorder in a significant proportion of patients with cervical MFPS. We suggest that spinal accessory neuropathy may be associated with cervical MFPS.

Electrophysiological Dysfunction in the Peripheral Nervous System Following Spinal Cord Injury

To evaluate peripheral nervous system function after chronic spinal cord injury (SCI). Case series. Academic medical center. Sixteen subjects (13 men, 3 women) with complete thoracic or cervical level SCI of 3-32 years' duration since injury. Clinical electrophysiology of the lower extremities. Compound motor action potentials (CMAP), sensory nerve action potentials, repetitive nerve stimulation, concentric needle electromyography (EMG), stimulated single-fiber EMG. Subject ages ranged from 20 to 71 years with a mean (SD) of 42 ± 15 years. The average time since injury was 11 ± 8 years (range, 3-32 years). Sural sensory nerve action potentials were elicited in only 4 of 16 subjects (25%), and peroneal CMAPs were elicited in 7 of 16 subjects (44%). All of the subjects had spontaneous activity (fibrillation and/or sharp potentials) in at least 1 of 4 tested muscles. Eighty-one percent of subjects demonstrated spontaneous activity in 3 of the 4 tested muscles. Peroneal motor repetitive nerve stimulation was within normal limits for 7 subjects but could not be performed in the other 9 subjects because of the absence of CMAPs. Stimulated single-fiber EMG was elicited in the tibialis anterior, extensor digitorum brevis, vastus lateralis, or vastus medialis muscles of 8 of 16 subjects. The high prevalence of spontaneous activity demonstrates that denervation of the skeletal muscles served by motor neurons below the level of the lesion occurs in individuals with chronic complete SCI. The electrophysiological testing revealed the striking absence of sensory and motor nerve conduction and aberrant neuromuscular junction transmission. It is important to understand the mechanisms that underlie the profound reduction of the functional integrity of the peripheral nervous system to maximize the restoration of movement, particularly should descending neural control be reestablished by a future therapy.

Diagnostic utility of stimulated single‐fiber electromyography of the orbicularis oculi muscle in patients with suspected ocular myasthenia

Stimulated single-fiber electromyography (SSFEMG) is a valuable diagnostic tool in cases of myasthenia gravis with limited disease. From 1990 to 2008 SSFEMG in the orbicularis oculi muscle (OO) was performed in a cohort of 456 patients referred with clinical suspicion of myasthenia gravis (MG) and exclusively ocular symptoms. A diagnosis of MG was made on clinical grounds in 103 patients. In this patient cohort, the specificity of SSFEMG for myasthenia was 97%, and the sensitivity was 80%. MG patients with a normal SSFEMG had a benign clinical course. This study confirms a high specificity and sensitivity of SSFEMG when it is performed on patients suspected to have ocular MG. In such patients, a normal SSFEMG of the OO predicts a benign clinical course.

Workshop on the use of stimulation single fibre electromyography for the diagnosis of myasthenic syndromes in children held in the Institute of Child Health and Great Ormond Street Hospital for Children in London on April 24th, 2009

A meeting to discuss the use of stimulation single fibre electromyography (StimSFEMG) to assist diagnosis of congenital myasthenic syndromes (CMS) took place on 24th April 2009 at the Institute of Child Health in London. Seventeen neurophysiologists with a special interest in electromyography from 15 regional centres attended.

Single fiber electromyographic jitter and detection of acute changes in neuromuscular function in young and adult rats

Introduction Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapted single fiber electromyography (SFEMG) techniques to quantify neuromuscular jitter in adult and juvenile rats after treatment with agents that alter cholinergic neurotransmission. Methods Anesthetized adult and juvenile rats were tested using stimulation SFEMG, recorded in the gastrocnemius muscle, after stimulation in the sciatic notch region. The influence of electrode placement, treatment with decamethonium (to disrupt neuromuscular transmission) or physostigmine (reversible ChE inhibitor), and the impact of varied stimulation frequency were quantified. Results No significant effects of needle placement or criterion amplitude were observed when calculating the mean consecutive difference (MCD). Treatment with decamethonium did not alter MCD values in adult or juvenile rats. However, decamethonium produced an increased blocking of muscle action potentials (MAP) in juveniles. Also, when stimulated at 9.09 Hz, both adult and juvenile animals had a greater decrease in MAP amplitude between the first and fourth responses ( T 1– T 4 decrement) after treatment with decamethonium. Prior to treatment with decamethonium, the T 1– T 4 decrement averaged about 3 fold greater in juveniles than adults, and was larger at 3.03 and 9.09 Hz than with 0.91 Hz stimulation. Treatment with physostigmine resulted in at least 50% inhibition of muscle ChE activity, but produced minimal changes in the MCD values in adults or juveniles. Combined over treatments and stimulation frequencies, the median MCD for juveniles (11.6 µs) was less than that for of adults (18.8 µs). In juveniles, the median MCD increased from 9.3 µs to 13.9 µs as the stimulation rate was increased from 0.91 to 9.09 Hz. This stimulus-dependant change was more evident in juveniles than in adults. Discussion A technique was developed to record stimulation SFEMG and neuromuscular jitter, in vivo, in adult and juvenile rats. The method was sufficiently sensitive to detect age-related differences, potentially allowing developmental processes to be examined. Based on the literature and the current data, the technique appears to be more sensitive to prolonged inhibition of ChE enzymes than the reversible inhibition produced by physostigmine.

Depression of neuromuscular transmission in methylmercury-poisoned rats: a glass microelectrode and single fiber electromyography study.

Changes in neuromuscular transmission were examined in methylmercury (MeHg)-poisoned rats, given a total oral dose of 60 mg CH3HgCl at 5 mg/kg/day. A microelectrode study was done on the 21st day. The mean quantal content and mean values of the immediately available pool of ACh in the MeHg-poisoned rats were reduced as compared to those in the control rats, but the mean values for the release probability of ACh did not differ significantly. Stimulation single fiber electromyography (SFEMG) was done on the biceps femoris muscle at 1, 5, 10 and 20 Hz on the 28th day. Both a significant and consistent increase in jitter were found at increasing stimulation rates in the MeHg-poisoned rats. The SFEMG findings suggest presynaptic involvement due to accelerated depletion of ACh. We confirmed that neuromuscular transmission is depressed in MeHg-poisoned rats in vivo and in vitro.