Single fiber electromyography and measuring jitter with concentric needle electrodes.

This monograph contains descriptions of the single fiber electromyography (SFEMG) method and of the more recently implemented method of recording jitter with concentric needle electrodes (CNEs). SFEMG records action potentials from single muscle fibers (SFAPs), which permits measuring fiber density (FD), a sensitive measure of reinnervation, and jitter, a sensitive measure of abnormal neuromuscular transmission (NMT). With voluntary activation, jitter is measured between two SFAPs with acceptable amplitude and rise time. With activation by axon stimulation, jitter is measured between the stimulus and individual SFAPs. Pitfalls due to unstable triggers and inconstant firing rates during voluntary activation and subliminal stimulation during axon stimulation should be identified and avoided. In CNE recordings, spikes with shoulders or rising phases that are not parallel are produced by summation of SFAPS; these should be excluded and reference values for CNE jitter should be used. CNE and SFEMG have similar and very high sensitivity in detecting increased jitter, as in myasthenia gravis and other myasthenic conditions. However, jitter is also seen in ongoing reinnervation and some myopathic conditions. With SFEMG, these can be identified by increased FD; however, FD cannot be measured with CNE, and conventional electromyography should be performed in muscles with increased jitter to detect neurogenic or myogenic abnormalities. Jitter is abnormal after injections of botulinum toxin, even in muscles remote from the injection site, and can persist for 6 mo or more. This can complicate the detection or exclusion of abnormal NMT.

Single fiber EMG and measuring jitter with concentric needle electrodes.

This monograph contains descriptions of the single-fiber electromyography (SFEMG) method and of the more recently implemented method of recording jitter with concentric needle electrodes (CNE). SFEMG records action potentials from single muscle fibers (SFAPs), which permits measuring fiber density (FD), a sensitive measure of reinnervation, and jitter, a sensitive measure of abnormal neuromuscular transmission (NMT). With voluntary activation, jitter is measured between two SFAPs with acceptable amplitude and rise time. With activation by axon stimulation, jitter is measured between the stimulus and individual SFAPs. Pitfalls due to unstable triggers and inconstant firing rates during voluntary activation and subliminal stimulation during axon stimulation should be identified and avoided. In CNE recordings, spikes with shoulders or rising phases that are not parallel are produced by summation of SFAPS; these should be excluded and reference values for CNE jitter should be used. CNE and SFEMG have similar and very high sensitivity in detecting increased jitter, as in myasthenia gravis and other myasthenic conditions. However, jitter is also seen in ongoing reinnervation and some myopathic conditions. With SFEMG, these can be identified by increased FD; however, FD cannot be measured with CNE, and conventional EMG should be performed in muscles with increased jitter to detect neurogenic or myogenic abnormalities. Jitter is abnormal after injections of botulinum toxin, even in muscles remote from the injection site, and can persist for 6 mo or more. This can complicate the detection or exclusion of abnormal NMT.

Baseline Decrement in Patients with Mild Myasthenia Gravis Predicts Immunomodulation Treatment.

To explore whether higher degrees of electrophysiological abnormalities are associated with a more frequent exposure to a more aggressive treatment regimen, we performed a retrospective chart review of patients attending the neuromuscular clinic from June 2012 to December 2015 and included 87 patients. We compared treatment regimens during the follow-up period between patients with high and low jitter and decrement. Myasthenia gravis patients with high jitter or decrement at baseline were more frequently treated with intravenous immunoglobulins (IVIG) and/or plasma exchange (PLEX) during the follow-up period. In patients with mild disease, IVIG or PLEX treatment was associated with high decrement.

La diminution initiale du potentiel moteur de patients atteints de myasthénie grave peut permettre de prédire le type d'immuno-modulation thérapeutique prodiguée. Afin d'explorer dans quelle mesure des niveaux plus élevés d'anomalies électro-physiologiques peuvent être associés à une exposition davantage fréquente à des régimes de traitement plus vigoureux, nous avons effectué un examen rétrospectif des dossiers de patients, 87 au total, s'étant présentés à une clinique neuromusculaire de juin 2012 à décembre 2015. Nous avons alors comparé les régimes de traitement des patients montrant de basses mesures de gigue (jitter) et une faible diminution d'amplitude du potentiel d'action au cours de leur période de suivi avec les régimes de traitement d'autres patients pour qui ces mesures étaient élevées. Les patients atteints de myasthénie grave (MG) dont les mesures de gigue et la diminution d'amplitude du potentiel d'action étaient initialement élevées ont été plus fréquemment traités, lors d'un suivi, avec des immunoglobulines intraveineuses et/ou des échanges plasmatiques. Chez les patients atteints de la forme bénigne de cette maladie, ces deux traitements ont été associés à une diminution d'amplitude du potentiel d'action plus élevée.

Serial Stimulated Jitter Analysis In Juvenile Myasthenia Gravis.

INTRODUCTION: Clinical and electrophysiological studies to measures disease activity in juvenile myasthenia gravis (JMG) are limited. METHODS: Retrospective review of the clinical profile, Myasthenia Gravis Foundation of America (MGFA) scores, serial stimulated jitter analysis (Stim-JA) of the orbicularis oculi muscle, grip strength, and spirometry of patients with JMG who were followed in a multidisciplinary clinic was performed. RESULTS: Thirteen patients with JMG (9 females) with mean age of 13.2 ± 4.8 years and follow-up duration of 25.3 ± 8.3 months (range, 6-39) with ≥ 2 Stim-JA recordings were included. The mean jitter, mean percentage of apparent single-fiber action potentials (%ASFAP) with increased jitter, and mean %ASFAP with blocking at baseline values (77.3 ± 54.7 µs, 64.3% ± 35.8%, 39% ± 38.6%, respectively) and at follow-up (53 ± 45.4 µs, 51.2% ± 34.5%, 17% ± 29.4%, respectively) were abnormal; however, no statistically significant interval difference was noted. The electrophysiological data correlated significantly with Myasthenia Gravis Foundation of America (MGFA) class. Grip strength and spirometry did not correlate with MGFA class. DISCUSSION: Stimulated jitter values are sensitive biomarkers in JMG. Muscle Nerve 58: 729-732, 2018.

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

INTRODUCTION: 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. METHODS: The e-norms method was used to calculate jitter mean consecutive difference (MCD) descriptive statistics for children <3 years of age. RESULTS: 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. CONCLUSION: 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.

Repetitive nerve stimulation cutoff values for the diagnosis of myasthenia gravis.

INTRODUCTION: Repetitive nerve stimulation (RNS) showing ≥ 10% decrement is considered the cutoff for myasthenia gravis (MG), but this has never been validated. The objective of this study was to find an optimal validated cutoff value for decrement on RNS. METHODS: We performed retrospective chart review of patients who had electrophysiological assessment for possible MG from 2013 to 2015. RESULTS: A total of 122 patients with MG and 182 controls were identified. RNS sensitivities for generalized and ocular MG using the traditional ≥10% cutoff value were 46% and 15%, respectively, for frontalis recordings, and 35% and 19%, respectively, for nasalis recordings. Using a decrement cutoff value of 7% for frontalis and 8% for nasalis increased the sensitivities by 6-11%, with specificities of 95-96%. CONCLUSIONS: For RNS in facial muscles, we suggest a cutoff value of 7-8%, which increases test sensitivity by 6-11%, while preserving high specificity for the diagnosis of MG. Muscle Nerve, 2016 Muscle Nerve 55: 166-170, 2017.

Use of stimulated electromyography in the analysis of the neuromuscular junction in children.

A screening test is required to diagnose disorders of the neuromuscular junction (NMJ) in children. This Review describes the development of stimulation potential analysis with concentric needle electrodes (SPACE). This nomenclature was chosen to distinguish the technique from single-fiber methodology because of the difficulties in identifying single-fiber potentials in most studies, particularly those with the most severe abnormalities of the NMJ. Performed on orbicularis oculi in children with proven or probable disorders of the NMJ, it demonstrated a sensitivity of 84%, specificity of 71%, negative predictive value of 95%, and positive predictive value of 36%. It is well tolerated and within the capability of any clinical neurophysiologist. When combined with a full electrodiagnostic examination, SPACE provides invaluable information about children with NMJ disorders, whose diagnosis often is difficult. Muscle Nerve 56: 841-847, 2017.

Does change in neuromuscular jitter predict or correlate with clinical change in MG?

INTRODUCTION: The objective of this study was to determine if single-fiber electromyography (SFEMG) jitter accurately reflects change in severity in myasthenia gravis (MG). METHODS: We reviewed jitter and outcome data from all MG patients in our clinic who had at least 2 jitter measurements in the extensor digitorum or frontalis muscle. RESULTS: Change in all parameters of jitter measured with SFEMG electrodes predicted clinical change with acceptable accuracy. Absolute and percentage change in mean value of consecutive interval differences were equally accurate in predicting clinical change and were more accurate than change in the proportion of fiber pairs with blocking or normal jitter. CONCLUSIONS: Jitter is a sensitive measure of severity in MG and has a potential role as a biomarker in clinical trials and the clinic. Absolute or percentage change in mean jitter is the best jitter parameter to follow. The accuracy of change in jitter measured with other electrodes has yet to be determined. Muscle Nerve 56: 45-50, 2017.

Electrophysiological testing is correlated with myasthenia gravis severity.

INTRODUCTION: Electrophysiological studies play an important role in the diagnosis of myasthenia gravis (MG). The objectives of this study was to explore the correlation of jitter and decrement with various clinical symptoms and signs and disease severity. METHODS: We performed a retrospective chart review of 75 MG patients who attended the neuromuscular clinic from April 2013 to May 2014. We compared clinical characteristics between patients with high jitter (>100 µs) and decrement (>10%), and patients with lower values to explore the correlations and optimal thresholds of jitter and decrement for different clinical features. RESULTS: High jitter and decrement values were associated with more severe disease, manifested by more frequent symptomatic bulbar and limb muscle weakness, more frequent ocular and limb muscle weakness on examination, higher quantitative MG score, and generalized disease. CONCLUSIONS: The yield of the electrophysiological assessment in MG extends beyond disease diagnosis and correlates with disease severity and the presence of generalized disease. Muscle Nerve 56: 445-448, 2017.

Single-fiber electromyography in the orbicularis oculi muscle in patients with ocular myasthenia gravis symptoms: does abnormal jitter predict response to treatment?

BACKGROUND: Seronegative ocular myasthenia gravis (OMG) is diagnosed by ocular symptoms with supporting SFEMG, typically of frontalis or extensor digitorum muscles. We aimed to determine the sensitivity and specificity of orbicularis oculi SFEMG to diagnose and exclude myasthenia gravis and predict response to therapy. METHODS: Orbicularis oculi SFEMG studies were conducted in 142 consecutive patients with symptoms and/or findings of OMG and negative AChR antibody during the period of 5 years. Retrospective chart review was conducted 2 years after the SFEMG to determine whether treatments were given and responses to treatment. RESULTS: Orbicularis oculi SFEMG was abnormal in 31 patients and normal in 111 patients. Twenty-nine patients with abnormal SFEMG were treated, and 25 had a good response. Twenty-four patients with normal SFEMG received treatment; none responded to treatment or developed generalized myasthenia. CONCLUSION: An abnormal orbicularis oculi SFEMG in patients with seronegative OMG has a high predictive value for response to therapy. Our study findings may affect the treatment decisions in practice and aid better management of myasthenic patients.

Using jitter analysis with concentric needle electrodes to assess disease status and treatment responses in myasthenia gravis.

Objective: This study assesses the utility of jitter analysis with concentric needles to evaluate disease severity in myasthenia gravis (MG), correlate changes in jitter with clinical status as well as identify reasons for any discordance. Methods: We performed a retrospective chart review of 82 MG patients and extracted data on demographics, MG subtype, antibody status, clinical scales, electrophysiology, and interventions at baseline and follow-up. Results: Baseline MGII scores correlated with jitter (r = 0.25, p = 0.024) and abnormal pairs (r = 0.24, p = 0.03). After 28 months, MGII scores correlated with jitter (r = 0.31, p = 0.006), abnormal pairs (r = 0.29, p = 0.009), and pairs with blocks (r = 0.35, p = 0.001). Changes in MGII scores correlated with changes in jitter (r = 0.35, p = 0.002), abnormal pairs (r = 0.27, p = 0.014), and pairs with blocks (r = 0.36, p = 0.001). Conclusions: Concentric needle jitter analysis may have the potential to evaluate baseline and sequential disease severity in MG. Significance: This study highlights the potential for improved MG patient care through precise assessment and management using concentric needle jitter analysis to improve the accuracy of MG diagnosis and monitoring of disease activity.

Novel DPAGT1 Gene Mutation in Two Twins with Congenital Myasthenic Syndrome and a Review of the Literature.

Congenital myasthenic syndromes (CMS) are rare diseases caused by mutation in genes coding for proteins involved in neuromuscular junction structure and function. DPAGT1 gene mutations are a rare cause of CMS whose clinical evolution and pathophysiological mechanisms have not been clarified completely. We present the case of two twins displaying an infancy-onset predominant limb-girdle phenotype and carrying a novel DPAGT1 mutation associated with unusual histological and clinical findings. CMS can mimic paediatric and adult limb-girdle phenotype, hence neurophysiology plays a fundamental role in the differential diagnosis.

Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case-Control Study.

PURPOSE: Much effort has been directed toward studying COVID-19 symptoms; however, the post-COVID-19 phase remains mysterious. The aim of this work was to conduct a clinical and neurophysiological evaluation of physical and mental fatigue in COVID-19 long-haulers and to study whether markers of COVID-19 severity are able to predict the likelihood of developing postinfectious fatigue syndrome (PIFS) in such patients. PATIENTS AND METHODS: This case-control study was conducted on 46 COVID-19 long-haulers who met the criteria for PIFS and 46 recovered COVID-19 subjects without any residuals. Clinical assessment of fatigue was done using a fatigue questionnaire. Repetitive nerve stimulation and single-fiber electromyography were done after excluding neuropathy and myopathy. RESULTS: The median value for physical fatigue was 4 (IQR 2-7), while that for mental fatigue was 2 (IQR 0-3). Each day's increase in the period of COVID-19 illness increased the odds of PIFS in COVID-19 long-haulers 1.104-fold, and each unit increase in ferritin increased the odds of PIFS 1.006-fold. A significant decrement in at least one muscle was observed in 50% of patients. Patients with PIFS had significantly higher mean consecutive difference (MCD) in the extensor digitorum communis than the control group. There were statistically significant positive correlations between MCD values and physical, mental, and total fatigue scores. CONCLUSION: Higher ferritin levels and prolonged COVID-19 infection were independent predictors of PIFS in COVID-19 long-haulers. There was electrophysiological evidence of abnormalities in the peripheral portion of the motor unit in COVID-19 long-haulers with PIFS.

Sustained atypical myokymia of the abductor pollicis brevis with a focal slowing of the median nerve motor axons at the wrist.

OBJECTIVE: We report a case of sustained atypical myokymia associated with short bursts of neuromyotonic discharges involving the abductor pollicis brevis (APB) muscle and describe a useful way of detecting a focal slowing involving a small number of median nerve motor fibers with a concentric needle using the filter setting for single fiber electromyography (EMG). METHODS AND RESULTS: A 62-year-old woman developed right thumb twitches at regular interval of 1.7-3.3 s (0.6-0.3 Hz), which continued for more than four months. Muscle twitches remained the same during altered hand position, psychological stress, or sleep. A concentric needle inserted in the active zone of the APB muscle revealed myokymic bursts with a characteristic of neuromyotonic discharges. Inching study, stimulating at 5 mm increment along the median nerve and recording with a concentric needle using a filter setting for single fiber EMG, revealed a focal slowing of the motor fibers at a point 5-10 mm distal from the distal crease of the wrist, an entrapment site occasionally seen in the carpal tunnel syndrome. One injection of botulinum toxin type A eliminated the myokymia, which then recurred two and a half years later, showing less prominent muscle twitches. CONCLUSIONS: Sustained atypical myokymia seen in our case represented bursts of neuromyotonic discharges originated from a focal demyelinating lesion involving a few median nerve motor fibers.

Botulinum toxin injections associated with suspected myasthenia gravis: An underappreciated cause of MG-like clinical presentation.

INTRODUCTION: The application of botulinum toxin type A (BoNTA) is accelerating, and this includes the uncontrolled cosmetic use of the BoNTA. Diffusion of BoNTA can disturb neuromuscular transmission in several surrounding and distant muscles and result in clinical manifestations similar to myasthenia gravis (MG). CASE PRESENTATIONS: We report two cases of patients referred for neurophysiological evaluation of suspected MG. A 55-year-old female who experienced dysphagia, dysarthria, right-sided ptosis, and neck extensor muscle weakness; and a 46-year-old male who presented with episodic double vision and right-sided ptosis. Both had the history of previous BoNTA use for cosmetic purposes and for the treatment of migraine before the presentation of their symptoms. In both cases examination revealed normal RNS, quite remarkably increased jitter, and signs of denervation and reinnervation in muscles surrounding the injection sites. After extensive neurophysiological evaluations, the primary cause of their symptoms was found to be related to previous BoNTA injections rather than a primary neuromuscular transmission disorder. It could also be concluded that patients do not automatically inform their physicians about cosmetic BoNTA use and they may not be aware of the potential risks associated with BoNTA therapy. CONCLUSIONS: The presented cases illustrate the neurophysiological findings in two patients with suspected MG after the use of BoNTA and emphasize the importance of inquiring about previous BoNTA injections and highlight that it is essential that patients are informed about possible side effects of BoNTA therapy.

Guidelines for single fiber EMG.

This document is the consensus of international experts on the current status of Single Fiber EMG (SFEMG) and the measurement of neuromuscular jitter with concentric needle electrodes (CNE - CN-jitter). The panel of authors was chosen based on their particular interests and previous publications within a specific area of SFEMG or CN-jitter. Each member of the panel was asked to submit a section on their particular area of interest and these submissions were circulated among the panel members for edits and comments. This process continued until a consensus was reached. Donald Sanders and Erik Stålberg then edited the final document.

Selective or predominant triceps muscle weakness in African-American patients with myasthenia gravis.

Myasthenia gravis (MG) can lead to weakness in different patterns of muscle groups. Limb muscle weakness is most typically seen in a limb girdle pattern, although variants exist. In the current study, we aimed to describe a unique MG phenotype consisting of selective or predominant triceps muscle weakness. We performed a retrospective review of MG patients who developed focal or predominant triceps muscle weakness between 2006 and 2016. The clinical, electrophysiological and serological characteristics of these patients were examined. 8 MG patients were identified, including 7 males, all of whom were African-American. Two patients underwent muscle biopsy, and one patient underwent cervical spine decompression surgery. All showed significant improvement following immunosuppressive treatment, although one patient experienced a relapse of muscle weakness. This case series highlights a relatively uncommon MG clinical phenotype of selective triceps muscle weakness, mainly in African-American males, in line with previous literature. Familiarity with this phenotype is important in order to facilitate diagnosis and appropriate treatment for this group, and avoid unnecessary investigations or treatments.

Jitter Values on Voluntary Active Periocular Muscles of Healthy Subjects with Conventional (37 mm) Concentric Needle Electrode.

INTRODUCTION: The aim of this study was to re-evaluate jitter values of healthy subjects in whom pairs of single-fiber-like potentials were recorded from voluntary activated periocular muscles using a disposable 37-mm concentric needle electrode (CNE) with 2-kHz low-cut filtering. METHODS: We reviewed the recordings of 129 subjects (85 women; 44 men; mean age, 43.8±15.3 years). The m. frontalis group included 116 subjects, and the m. orbicularis oculi group included 18 subjects. Jitter values were expressed as the mean consecutive difference (MCD) of 20 different pairs. RESULTS: The mean MCD (n=2680) was 22.5±9.7 µs (range, 5-121 µs), and the upper 95% confidence limit (CL) was 39 µs. The mean of 134 MCD values for each subject was 22.5±3.7 µs (range, 15-33 µs), and the upper 95% CL was 30 µs. The outer limit of the 18th highest MCD values out of 20 recordings for each subject was 31.3±6.5 µs (range, 18-53 µs), with an upper 95% CL of 43.3 µs. CONCLUSION: Using a conventional 37-mm CNE with 2-kHz low-cut filtering may be a cost effective alternative to a single-fiber electrode in periocular muscles if strict criteria are used for acceptable signals. Jitter values of >44 µs that were calculated from single-fiber-like action potential pairs should alert the physician regarding the possibility of neuromuscular junction disorders and constitute an indication for a further diagnostic investigation.

History, Mechanisms and Clinical Value of Fibrillation Analyses in Muscle Denervation and Reinnervation by Single Fiber Electromyography and Dynamic Echomyography.

This work reviews history, current clinical relevance and future of fibrillation, a functional marker of skeletal muscle denervated fibers. Fibrillations, i.e., spontaneous contraction, in denervated muscle were first described during the nineteenth century. It is known that alterations in membrane potential are responsible for the phenomenon and that they are related to changes in electrophysiological factors, cellular metabolism, cell turnover and gene expression. They are known to inhibit muscle atrophy to some degree and are used to diagnose neural injury and reinnervation that are occurring in patients. Electromyography (EMG) is useful in determining progress, prognosis and efficacy of therapeutic interventions and their eventual change. For patients with peripheral nerve injury, and thus without the option of volitional contractions, electrical muscle stimulation may be helpful in preserving the contractility and extensibility of denervated muscle tissue and in retarding/counteracting muscle atrophy. It is obvious from the paucity of recent literature that research in this area has declined over the years. This is likely a consequence of the decrease in funding available for research and the fact that the fibrillations do not appear to cause serious health issues. Nonetheless, further exploration of them as diagnostic tools in long-term denervation is merited, in particular if Single Fiber EMG (SFEMG) is combined with Dynamic Echomyography (DyEM), an Ultra Sound muscle approach we recently designed and developed to explore denervated and reinnervating muscles.

Acrylamide inhibits nerve sprouting induced by botulinum toxin type A.

Botulinum toxin type A is a potent muscle relaxant that blocks the transmission and release of acetylcholine at the neuromuscular junction. Intramuscular injection of botulinum toxin type A has served as an effective and safe therapy for strabismus and focal dystonia. However, muscular weakness is temporary and after 3-4 months, muscle strength usually recovers because functional recovery is mediated by nerve sprouting and reconstruction of the neuromuscular junction. Acrylamide may produce neurotoxic substances that cause retrograde necrotizing neuropathy and inhibit nerve sprouting caused by botulinum toxin type A. This study investigated whether acrylamide inhibits nerve sprouting after intramuscular injection of botulinum toxin type A. A tibial nerve sprouting model was established through local injection of botulinum toxin type A into the right gastrocnemius muscle of Sprague-Dawley rats. Following intramuscular injection, rats were given intraperitoneal injection of 3% acrylamide every 3 days for 21 days. Nerve sprouting appeared 2 weeks after intramuscular injection of botulinum toxin type A and single-fiber electromyography revealed abnormal conduction at the neuromuscular junction 1 week after intramuscular injection of botulinum toxin type A. Following intraperitoneal injection of acrylamide, the peak muscle fiber density decreased. Electromyography jitter value were restored to normal levels 6 weeks after injection. This indicates that the maximal decrease in fiber density and the time at which functional conduction of neuromuscular junction was restored were delayed. Additionally, the increase in tibial nerve fibers was reduced. Acrylamide inhibits nerve sprouting caused by botulinum toxin type A and may be used to prolong the clinical dosage of botulinum toxin type A.