Single-institutional reference values for concentric needle jitter analysis using the extrapolated reference values procedure: Comparison to published reference values.

BACKGROUND: The extrapolated reference values procedure (E-Ref) was used to compare data from a single institution with the recently published reference value (RV) for concentric electrode jitter. METHODS: Data from voluntarily activated concentric needle jitter studies in the frontalis muscle were obtained using retrospective chart review. All measured signals were reviewed for acceptable quality. Cutoff values for increased jitter were calculated using E-Ref, and compared with the published RVs. RESULTS: At total of 1501 apparent single-fiber action potential (ASFAP) pairs were reviewed; 1371 ASFAP pairs were determined to have acceptable quality. The cutoff value identified by E-Ref from all reviewed ASFAP pairs was 36 microseconds and the cutoff for acceptable pairs was 35 microseconds. Using either of these cutoff values (36 or 35 microseconds) did not result in a significant difference in percentage of jitter recordings considered normal when compared with the recently published RV (38 microseconds). DISCUSSION: The single-institution jitter cutoff value obtained by E-Ref gives results that are not significantly different from the reported RV.

Longitudinal neurophysiological assessment of intramuscular type-A botulin toxin in healthy humans.

The aim of this study is to assess the neurophysiological abnormalities of type A botulin toxin-infiltrated human muscle, and their evolution over time. Seried cMAP measurements, 3 and 20 Hz repetitive nerve stimulation, EMG, SFEMG over 3 months from toxin injection. Our findings consist in lack of decrement with 3 Hz repetitive nerve stimulation and facilitation with 20 Hz repetitive nerve stimulation; progressive increasing of jitter; early appearance of fibrillations; small and short motor unit action potential in the first 3 weeks, followed by increasing of MUAP amplitude and duration, with polyphasic morphology. Although claimed as highly specific and sensible, neuromuscular junction facilitation is an inconstant finding in human botulism. Therefore, lack of neuromuscular junction facilitation cannot exclude a diagnosis of botulism. Our findings are compatible with a process of acute denervation followed by distal reinnervation, favored by terminal nerve sprouting.

Clinical and CN-SFEMG evaluation of neostigmine test in myasthenia gravis.

Neostigmine test (NT) is a pharmacological test, demonstrating a clinical improvement in patients affected by myasthenia gravis (MG). We aim to compare clinical evaluation and neurophysiological recordings by concentric-needle single-fiber electromyography (CN-SFEMG) in response to acute administration of neostigmine in ocular and generalized MG patients. Twenty-three MG patients (10 with ocular MG and 13 with generalized MG) were evaluated before and after 90 min neostigmine 0.5-mg administration. Clinical responsiveness was assessed by MG composite (MGC) scale. Neurophysiological evaluation by CN-SFEMG considered analysis of mean value of consecutive differences (MCD), single-pair jitter, and blocks. MGC scores significantly improved after NT in generalized MG patients (MGC 11.1 ± 7.6 vs 9.1 ± 6.7, p = 0.02), whereas the improvement was not significant in the ocular group. CN-SFEMG recordings significantly improved after NT in generalized MG patients (MCD 58.9 ± 18.8 vs 45.9 ± 23.2 µs, p = 0.003; single-pair jitter 49.8 ± 26.9 vs 24.1 ± 26.7%, p = 0.0001; blocks 6.2 ± 9.5 vs 2.6 ± 7.4%, p = 0.03) as well as in ocular MG patients (MCD 50.8 ± 22.7 vs 40.1 ± 22.9 µs, p = 0.01; single-pair jitter 35.9 ± 23.7 vs 20.0 ± 25.1%, p = 0.001). CN-SFEMG is a reliable tool to evaluate responsiveness to acute administration of neostigmine in MG. Moreover, neurophysiological modifications to NT could show subclinical improvement in ocular MG better than that of the clinical scale.

Evidence for dying-back axonal degeneration in age-associated skeletal muscle decline.

INTRODUCTION: Age-associated muscle strength decline is a major contributing factor to increased late-life functional decline and comorbidity, and is strongly associated with early mortality. Although all parts of the neuromuscular system seem to be affected by aging, dying-back of motor axons likely plays a major role. METHODS: We compared the degeneration in ventral roots and neuromuscular junction denervation in young and aged mice and correlated the findings with strength and electrophysiological measures. RESULTS: With normal aging, there is little decline in motor axon numbers in the ventral roots, but the neuromuscular junctions show marked partial denervation that is associated with increased jitter on stimulated single fiber electromyography and a decrease in muscle strength. CONCLUSIONS: These findings suggest that dying-back axonal degeneration may be partially responsible for the electrophysiological and strength changes observed with aging. Muscle Nerve 55: 894-901, 2017.

Diagnostic accuracy of concentric needle jitter in myasthenia: Prospective study.

INTRODUCTION: The aim of this study was to estimate jitter parameters in the orbicularis oculi muscle using a concentric needle electrode (CNE) in patients with myasthenia gravis (MG) and to determine its diagnostic accuracy for jitter analysis (CNEMG-jitter). METHODS: CNEMG-jitter was performed in 20 healthy subjects and 33 MG patients using the voluntary contraction technique. Receiver operating characteristic (ROC) curves were constructed to determine cut-off points with the best sensitivity/specificity combination for jitter analysis. RESULTS: CNEMG-jitter yielded high positivity rates for ocular MG (92.3%) and generalized MG (100%). The ROC curve cut-off point that provided the highest sensitivity without false positives was 24.7 µs for mean jitter and 33.1 µs for the 18th highest value. Sensitivity was 93.9% for both parameters. Diagnostic accuracy of CNEMG-jitter was > 96%. CONCLUSIONS: CNEMG-jitter yielded high sensitivity and specificity rates. Our reference values were lower than previously published values, possibly due to less technical variation between the different recordings. Muscle Nerve 55: 190-194, 2017.

Reference values for jitter recorded by concentric needle electrodes in healthy controls: A multicenter study.

INTRODUCTION: The aim of this study was to create reference values for jitter measured with concentric needle electrodes. METHODS: Operators worldwide contributed recordings from orbicularis oculi (OO), frontalis (FR), and extensor digitorum (ED) muscles in healthy controls. Criteria for acceptable signal quality were agreed upon in advance. Fifteen or 20 recordings of acceptable quality from each muscle were required for voluntary and electrical stimulation recordings, respectively. RESULTS: Recordings from 59 to 92 subjects were obtained for each muscle and activation type. Outlier limits for mean consecutive difference and individual jitter data for voluntary activation were: OO, 31 and 45 µs; FR, 28 and 38 µs; ED, 30 and 43 µs; and for electrical stimulation they were: OO, 27 and 36 µs; FR, 21 and 28 µs; ED, 24 and 35 µs. CONCLUSION: Reference jitter values from concentric needle electrode recordings were developed from signals of defined quality while seeking to avoid creating supernormal values.

Stimulated jitter analysis for the evaluation of neuromuscular junction disorders in children.

INTRODUCTION: Stimulated jitter analysis (stim-JA) using a concentric needle electrode is a technique used to study the neuromuscular junction (NMJ) without voluntary activation. Our objective was to study the diagnostic sensitivity, specificity, and feasibility of stim-JA in infants and children with suspected NMJ defects. METHODS: Sixteen infants and young children ages 2 months to 17 years with suspected NMJ disorders were evaluated using stim-JA over a period of 12 months. RESULTS: Subjects with suspected NMJ defects and abnormal stim-JA subsequently had laboratory confirmation of myasthenia gravis (n = 5) and infant botulism (n = 2). Turnaround time for confirmatory laboratory tests was 6.0 ± 4.3 days, whereas stim-JA results were available immediately. All subjects tolerated stim-JA well without complications or need for sedation. CONCLUSIONS: Stim-JA is a sensitive and safe first-line diagnostic test for evaluation of suspected pediatric NMJ disorders. Stim-JA results precede assay results and may guide early treatment.

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.

Chronic mimics of myasthenia gravis: a retrospective case series.

Myasthenia gravis often presents a diagnostic challenge and may be misdiagnosed, particularly in seronegative disease with active symptoms. We retrospectively evaluated 61 patients following the introduction of single fibre electromyography at our service, and identified 8 mimics which had been inappropriately diagnosed and treated as refractory myasthenia gravis. 6 of these were seronegative, but two had positive acetylcholine receptor (AChR) antibodies. The final diagnoses included one case each of chronic progressive external ophthalmoplegia, chronic ptosis, oculopharyngeal muscular dystrophy, and an undifferentiated disorder suspicious for either a mitochondrial cytopathy or low-grade myositis. Four were diagnosed with functional neurological disorder, one of which had a superimposed thyroid myopathy and orbitopathy. We found the average duration of misdiagnosis was 9 years (SD±5.2, median 11 years), and patients were often exposed to years of unnecessary treatment. All patients had received anticholinesterase therapy, three had immunotherapy, and three surgical interventions were performed including two thymectomies. We found myasthenic mimics should be suspected in disease that is static and treatment refractory, and functional mimics in disease with frequent flares. Thorough neurophysiologic assessment is important, particularly when making a diagnosis of seronegative myasthenia gravis.

Marching band model for simulating a single muscle fiber action potential.

OBJECTIVE: We describe a mathematical model to calculate a single muscle fiber action potential (AP). Based on a marching band pattern, it is an enhancement to our previously described "modified line source" model. METHODS: Calculations were performed using an Excel spread sheet. AP was simulated for a 200 mm long muscle fiber with 60 µm diameter, propagation velocity of 4 m/s, and end-plate located at the center. Several different electrode locations were used to calculate the AP. RESULTS: The AP amplitude was highest at the end-plate where the waveform was biphasic with initial negativity. When the electrode was moved towards the tendon, the amplitude decreased for the first 1.5 mm. The AP was triphasic and its waveform was relatively constant at electrode positions beyond 1.5 mm from the end-plate. It matched the calculations using the modified line source model. When the electrode was near the tendon, the AP amplitude decreased asymmetrically and waveform became biphasic resembling a positive sharp wave. DISCUSSION: The model is conceptually and computationally simple. It simulated the expected AP shape at different electrode positions along the muscle fiber. The waveforms are similar to those obtained from mathematically complex volume conductor models. SIGNIFICANCE: The revised model can be useful for teaching and future simulation studies.

[Acupuncture combined with western medication for ocular myasthenia gravis: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism. METHODS: A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 µs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method. RESULTS: After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 µs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05). CONCLUSION: Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.

Electrodiagnostic Assessment of Neuromuscular Junction Disorders.

Please verify edits, "These techniques", or specify. This article reviews advanced electrodiagnostic techniques used to assess for neuromuscular junction disorders, including repetitive nerve stimulation, conventional or concentric-needle single-fiber electromyography (SFEMG), and stimulated SFEMG. These techniques have high sensitivity but limited specificity. Novel methods currently under investigation are discussed, including vestibular ocular myogenic potential and oculography analysis.

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

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Single-fiber electromyography-based diagnosis of CACNA1A mutation in children: A potential role of the electrodiagnosis in the era of whole exome sequencing.

INTRODUCTION: A loss-of-function mutation in CACNA1A, which encodes P/Q-type Ca channels, causes various diseases. As most of the Ca channels at neuromuscular junctions are of the P/Q type, patients with loss-of-function CACNA1A mutations exhibit disturbed neuromuscular transmission. The associated jitters and blocking in such patients can be detected by single-fiber electromyography (SFEMG). CASES: We report two cases with different phenotypes, which were predicted to harbor loss-of-function mutations of CACNA1A, by using axonal stimulation SFEMG. One case involved a 2-year-old boy with episodic ataxia type 2. The other case involved a 7-year-old girl diagnosed with epileptic encephalopathy. SFEMG results revealed jitters and blocking in both cases. Moreover, whole exome sequencing (WES) revealed a heterozygous CACNA1A mutation, c.5251C>T, p.Arg1751Trp, in the former case and a novel de novo CACNA1A mutation, c.2122G>A, p.Val708Met, in the latter. CONCLUSIONS: Our cases indicate that SFEMG is a potentially useful diagnostic tool for patients with CACNA1A mutation, especially in pediatric cases where trio analysis is difficult or novel mutations are present.

Problems in Comparing Jitter Values Obtained with Voluntary Activation and Electrical Stimulation.

Comparing results from jitter studies performed with voluntary and electrical activation is difficult to perform quantitatively, particularly in complex signals as seen in reinnervation. High jitter values in individual spikes in these multispike signals can be missed with both activation methods, which introduces a bias towards more normal values.With voluntary activation, triggering on a spike from an abnormal end-plate in multispike potentials will overestimate individual jitter values and the number of abnormal jitter values.With electrical stimulation, artefactually-increased jitter may be caused by subliminal stimulation, which causes uncertainty at the stimulation point. Electrical stimulation also may activate many axons, causing signal summation, with erroneous or impossible jitter estimation.Awareness of such pitfalls can improve the correct performance and interpretation of jitter recordings. Quantitative comparisons of results can be made between studies in reinnervated muscle performed with the same activation method, but not between results obtained with different activation methods.

Pitfalls and errors in measuring jitter.

The safety factor of neuromuscular transmission can be assessed by measuring the neuromuscular jitter, which reflects the time variability of processes in the motor end-plate. Jitter is increased in any condition with disturbed end-plate function, such as myasthenic conditions and ongoing reinnervation. Jitter is increasingly being measured with concentric needle (CN) electrodes, which are more prone to artefacts than single fiber EMG recordings. The objective of this review is to identify and demonstrate pitfalls that can be seen with CN jitter measurements, made with both voluntary activation and electrical stimulation. With voluntary activation, errors are caused by poor signal quality; inappropriate time reference points on the signal; an irregular firing rate; and signals with dual latencies, i.e., "flip-flop." With electrical stimulation, additional errors result from insufficient stimulation intensity; from abrupt change in firing rate; and from axon reflexes. Many pitfalls cannot be avoided during recording and can only be detected during post-processing. It is critical to be aware of these artefacts when measuring jitter with CN electrodes.

Deriving muscle fiber diameter from recorded single fiber potential.

OBJECTIVE: The aim of the study was to estimate muscle fiber diameters through analysis of single muscle fiber potentials (SFPs) recorded in the frontalis muscle of a healthy subject. METHODS: Our previously developed analytical and graphic method to derive fiber diameter from the analysis of the negative peak duration and the amplitude of SFP, was applied to a sample of ten SFPs recorded in vivo. RESULTS: Muscle fiber diameters derived from the simulation method for the sample of frontalis muscle SFPs are consistent with anatomical data for this muscle. CONCLUSIONS: The results confirm the utility of proposed simulation method. Outlying data could be considered as the result of a contribution of other fibers to the potential recorded using an SFEMG electrode. Our graphic tool provides a rapid estimation of muscle fiber diameter.

Characterization of patients with ocular myasthenia gravis - A case series.

Ocular myasthenia gravis (OMG) is sometimes difficult to diagnose and is probably both under-diagnosed and misdiagnosed. We studied the epidemiological parameters, relevant serology, electromyographic (EMG) findings, and the relationship between OMG and thymoma, thymus hyperplasia and other autoimmune disorders compared to generalized MG (GMG) in a case control study of 133 patients with MG (32 patients with OMG and 101 patients with GMG). The proportion of OMG among all MG patients was relatively high (24.1%). It affected more males than females and its onset was at an older age. Although anti-AChR Ab was detected in fewer OMG patients compared to GMG patients, the rate of positive serology in OMG patients was higher than previously reported. Male OMG patients had a higher positive serology rate than female OMG patients. OMG patients tended to have less supportive EMG evidence of neuromuscular disorder. Female OMG patients had higher rates of thymus hyperplasia and higher rates of other autoimmune disorders than males. Diagnosing MG in patients with solitary ocular manifestation may be difficult due to lower rates of paraclinic supportive tests. Awareness of the characteristics of OMG is important in order to avoid delayed or misdiagnosis of MG and to prevent avoidable iatrogenic complications.

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.