Fasciculation electromechanical latency is prolonged in amyotrophic lateral sclerosis.

OBJECTIVE: In amyotrophic lateral sclerosis (ALS), motor neurons become hyperexcitable and spontaneously discharge electrical impulses causing fasciculations. These can be detected by two noninvasive methods: high-density surface electromyography (HDSEMG) and muscle ultrasonography (MUS). We combined these methods simultaneously to explore the electromechanical properties of fasciculations, seeking a novel biomarker of disease. METHODS: Twelve ALS patients and thirteen healthy participants each provided up to 24 minutes of recordings from the right biceps brachii (BB) and gastrocnemius medialis (GM). Two automated algorithms (Surface Potential Quantification Engine and a Gaussian mixture model) were applied to HDSEMG and MUS data to identify correlated electromechanical fasciculation events. RESULTS: We identified 4,197 correlated electromechanical fasciculation events. HDSEMG reliably detected electromechanical events up to 30 mm below the skin surface with an inverse correlation between amplitude and depth in ALS muscles. Compared to Healthy-GM muscles (mean = 79.8 ms), electromechanical latency was prolonged in ALS-GM (mean = 108.8 ms; p = 0.0458) and ALS-BB (mean = 112.0 ms; p = 0.0128) muscles. Electromechanical latency did not correlate with disease duration, symptom burden, sum muscle power score or fasciculation frequency. CONCLUSIONS: Prolonged fasciculation electromechanical latency indicates impairment of the excitation-contraction coupling mechanism, warranting further exploration as a potential novel biomarker of disease in ALS. SIGNIFICANCE: This study points to an electromechanical defect within the muscles of ALS patients.

A shortened surface electromyography recording is sufficient to facilitate home fasciculation assessment.

INTRODUCTION/AIMS: Fasciculations are an early clinical hallmark of amyotrophic lateral sclerosis (ALS), amenable to detection by high-density surface electromyography (HDSEMG). In conjunction with the Surface Potential Quantification Engine (SPiQE), HDSEMG offers improved spatial resolution for the analysis of fasciculations. This study aims to establish an optimal recording duration to enable longitudinal remote monitoring in the home. METHODS: Twenty patients with ALS and five patients with benign fasciculation syndrome (BFS) underwent serial 30 min HDSEMG recordings from biceps brachii and gastrocnemii. SPiQE was independently applied to abbreviated epochs within each 30-min recording (0-5, 0-10, 0-15, 0-20, and 0-25 min), outputting fasciculation frequency, amplitude median and amplitude interquartile range. Bland-Altman plots and intraclass correlation coefficients (ICC) were used to assess agreement with the validated 30-min recording. RESULTS: In total, 506 full recordings were included. The 5 min recordings demonstrated diverse and relatively poor agreement with the 30 min baselines across all parameters, muscles and patient groups (ICC = 0.32-0.86). The 15-min recordings provided more acceptable and stable agreement (ICC = 0.78-0.98), which did not substantially improve in longer recordings. DISCUSSION: For the detection and quantification of fasciculations in patients with ALS and BFS, HDSEMG recordings can be halved from 30 to 15 min without significantly compromising the primary outputs. Reliance on a shorter recording duration should lead to improved tolerability and repeatability among patients, facilitating longitudinal remote monitoring in patients' homes.

Accuracy of muscle fasciculations for the diagnosis of later-onset spinal muscle atrophy.

Diagnosis of later-onset spinal muscular atrophy (SMA) can be challenging. This study aimed to evaluate the diagnostic properties of the detection of muscle fasciculations for SMA diagnosis in adolescents and adults with proximal muscle weakness. A cross-sectional diagnostic accuracy study was performed, in which 10 subjects with SMA (5 with type II and 5 with type III) and 9 subjects with genetic muscle diseases were evaluated by physical examination, muscle ultrasound (MUS) and electromyography (EMG). Inter-rater reliability of MUS was higher than physical examination and in a sensitivity analysis of MUS, all SMA subjects and a single patient with genetic muscle disease presented fasciculations in at least 2 different muscle groups, resulting in a sensitivity of 1 (95% CI: 0.69 to 1) and a specificity of 0.89 (95% CI: 0.52 to 1) for SMA diagnosis. Forty-two percent of evaluated subjects did not agree to perform EMG, limiting this method results. Muscle ultrasound presented the best diagnostic accuracy and physical examination combined with MUS seemed to be a good strategy for screening adolescents and adults with proximal muscle weakness for SMA. These results might improve diagnostic guidelines for later-onset SMA, leading to earlier diagnosis, treatment and specific care.

[Cramps and fasciculations: is it amyotrophic lateral sclerosis?] / Crampes et fasciculations : est-ce une sclérose latérale amyotrophique ?

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease of the adult age. It is an aggressive condition with a mean disease duration of only 3 to 5 years, characterized by progressive weakness and atrophy of limb, bulbar, and respiratory muscles. In general, death is caused by chronic hypoventilation due to respiratory insufficiency. No causal treatment is known today, but the two therapeutic agents authorized in Switzerland for the treatment of ALS can slow disease progression significantly. Other important therapeutic strategies include invasive/non-invasive ventilation, pain therapy, as well as physio-, ergo- and speech therapy on a regular basis.

La sclérose latérale amyotrophique (SLA) est la maladie du motoneurone la plus fréquente de l'adulte. C'est une maladie sévère (la survie moyenne est d'environ 3 à 5 ans), caractérisée par une dégénérescence des premier et deuxième motoneurones. Elle se manifeste par un déficit moteur amyotrophiant progressif des membres, de la langue, des muscles bulbaires et respiratoires. En général, le décès est causé par une hypoventilation chronique. Il n'existe actuellement aucun traitement curatif. Les deux médicaments autorisés en Suisse peuvent ralentir significativement la progression de la maladie et plusieurs nouvelles molécules sont à l'essai. Les traitements non médicamenteux/symptomatiques constituent le deuxième pilier de la prise en charge : ventilation non invasive, traitement des symptômes bulbaires, stabilisation du poids, physio et ergothérapie.

Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo / Fasciculations and cramps: physiological bases and clinical approach of a complex phenomenon

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

Fasciculations in Children.

Fasciculations are the most common form of spontaneous muscle contraction. They frequently occur in healthy individuals. However, there are a minority of situations that fasciculations are observed in association with specific neurologic disorders. Publications concerning the evaluation of pediatric patients experiencing fasciculations are limited. These children may undergo invasive or expensive diagnostic investigations that are unnecessary. Moreover, without careful consideration of differential diagnoses, rare neuromuscular disorders that present with fasciculations in the pediatric age group can be under-recognized by pediatric neurologists. This review examines the most important pediatric disorders presenting with fasciculations and other spontaneous muscle contractions to guide pediatric neurologists in evaluating these children.

Benign fasciculations: A follow-up study with electrophysiological studies.

INTRODUCTION/AIMS: Fasciculations can be symptomatic, yet not progress to amyotrophic lateral sclerosis (ALS), a condition categorized as benign fasciculation syndrome (BFS). We aimed to assess electrodiagnostic changes and clinical course over time in patients with BFS. METHODS: This was a retrospective review of medical records of patients who were referred because of a suspicion of ALS or who had directly asked for a consultation because of a personal concern regarding ALS. All clinical and electromyography (EMG) investigations were performed by the same neurologist, following an established protocol. In addition, laboratory testing and imaging studies were performed as determined to be clinically necessary. RESULTS: We included 37 subjects (mean age 46 ± 14.7 y, 29 male, 7 healthcare professionals). Most patients had experienced fasciculations in both upper and lower limb muscles (62.2%); the remaining patients had fasciculations only in their lower limbs. EMG in seven subjects showed chronic neurogenic potentials in addition to fasciculation potentials; all of these were older men. Follow-up data were available in 24 patients (median 4.7 y), 21 with repeat EMGs, including all those with neurogenic EMG changes at baseline (median 6.5 y). Two-thirds of patients reported symptomatic improvement: 57.1% of those with abnormal EMG and 61.1% with normal EMG. The EMG changes were stable. DISCUSSION: Prognosis of BFS is favorable, regardless of minor EMG abnormalities. The latter do not necessarily imply progression to ALS.

Optically pumped magnetometers reveal fasciculations non-invasively.

OBJECTIVE: This proof-of-principle-study evaluated the extent to which spontaneous activity (SA) of the muscle can be detected via non-invasive magnetomyography (MMG) with optically pumped magnetometers (OPM). METHODS: Five patients, who together exhibited all forms of SA (fibrillations, positive sharp waves, fasciculations, myotonic discharges, complex-repetitive discharges) with conventional needle electromyography (EMG), were studied by OPM-MMG and simultaneous surface EMG (sEMG) while at rest, during light muscle activation, and when a muscle stretch reflex was elicited. Three healthy subjects were measured as controls. SA was considered apparent in the OPM-MMG if a signal could be visually detected that corresponded in shape and frequency to the SA in the respective needle EMG. RESULTS: SA in the context of fasciculations could be detected in 2 of 5 patients by simultaneous OPM-MMG/sEMG. Other forms of SA could not be detected at rest, during light muscle activation, or after provocation of a muscle stretch reflex. CONCLUSIONS: Results show that fasciculations could be detected non-invasively via a new method (OPM). SIGNIFICANCE: We show that other forms of SA are not detectable with current OPM and propose necessary technical solutions to overcome this circumstance. Our results motivate to pursue OPM-MMG as a new clinical neurophysiological diagnostic.

Demystifying the spontaneous phenomena of motor hyperexcitability.

Possessing a discrete functional repertoire, the anterior horn cell can be in one of two electrophysiological states: on or off. Usually under tight regulatory control by the central nervous system, a hierarchical network of these specialist neurons ensures muscular strength is coordinated, gradated and adaptable. However, spontaneous activation of these cells and their axons can result in abnormal muscular twitching. The muscular twitch is the common building block of several distinct clinical patterns, namely fasciculation, myokymia and neuromyotonia. When attempting to distinguish these entities electromyographically, their unique temporal and morphological profiles must be appreciated. Detection and quantification of burst duration, firing frequency, multiplet patterns and amplitude are informative. A common feature is their persistence during sleep. In this review, we explain the accepted terminology used to describe the spontaneous phenomena of motor hyperexcitability, highlighting potential pitfalls amidst a bemusing and complex collection of overlapping terms. We outline the relevance of these findings within the context of disease, principally amyotrophic lateral sclerosis, Isaacs syndrome and Morvan syndrome. In addition, we highlight the use of high-density surface electromyography, suggesting that more widespread use of this non-invasive technique is likely to provide an enhanced understanding of these motor hyperexcitability syndromes.

Denny-Brown and Pennybacker: 80 years after their pioneering article on electromyography, fibrillation and fasciculation.

We present a historical review, highlighting the role of Professor Derek Denny-Brown and doctor Joseph Buford Pennybacker in the development of current electromyography (EMG), of the 80 years since the publication of his original report in 1938 on fasciculation and fibrillation potentials and the subsequent studies describing most of the electrical changes necessary to perform and interpret the EMG.

Atypical fibrillation and fasciculation potentials: An exercise in waveform identification and analysis.

No consensus criteria exist for recording and analyzing waveforms in clinical electromyography (EMG). There have been significant technical improvements in recent decades that are under-used in both routine practice and research. In current practice, disciplined techniques in acquisition and analysis of signals are required to appropriately define them. As an example, we describe such an exercise in acquisition and analysis. During a routine study, atypical spontaneous activity was encountered. High-quality digital recordings were stored for off-line analysis. These revealed waveforms that could be isolated and quantitatively defined using basic instrumentation available on most modern EMG systems: "slow" firing fibrillation potentials and a repeating fasciculation potential. Subjective analysis alone could not have identified them. To improve accuracy in identification and understanding of these waveforms, we propose criteria for data collection and signal analysis. This is critical for quality in routine practice, education, and proper reporting of electrophysiological signals.

Peripheral nerve hyperexcitability syndrome: A clinical, electrophysiological, and immunological study.

INTRODUCTION: Peripheral nerve hyperexcitability syndrome (PNHS) is characterized by muscle fasciculations and spasms. Nerve hyperexcitability and after-discharges can be observed in electrophysiological studies. Autoimmune mechanisms play a major role in the pathophysiology of primary PNHS. METHODS: We retrospectively conducted a case-control study recruiting patients with clinical and electrophysiological features of PNHS. Control patients were diagnosed with other neuronal or muscular diseases. Contactin-associated protein2 (CASPR2) and leucine-rich glioma-inactivated1 (LGI1) antibodies were examined. RESULTS: A total of 19 primary PNHS patients and 39 control patients were analyzed. The most common symptoms for the case group were fasciculations (11/19) and muscle spasms (13/19). Case group patients were likely to demonstrate electrodiagnostic findings of nerve hyperexcitability (17/19) and after-discharges in the tibial nerve (19/19). We found high prevalence of CASPR2 (9/19) and LGI1 (6/19) antibodies in the case group. DISCUSSION: Primary PNHS patients were likely to show after-discharges in the tibial nerve. The pathogenesis of PNHS is autoimmune CASPR2 and LGI1 antibodies are possible pathogenic antibodies for primary PNHS.

Denny-Brown and Pennybacker: 80 years after their pioneering article on electromyography, fibrillation and fasciculation / Denny-Brown e Pennybacker: 80 anos da publicação de seu artigo pioneiro sobre eletromiografia, fibrilação e fasciculação

ABSTRACT We present a historical review, highlighting the role of Professor Derek Denny-Brown and doctor Joseph Buford Pennybacker in the development of current electromyography (EMG), of the 80 years since the publication of his original report in 1938 on fasciculation and fibrillation potentials and the subsequent studies describing most of the electrical changes necessary to perform and interpret the EMG.

RESUMO Os autores apresentam uma revisão histórica destacando o papel do Professor Derek Denny-Brown e do doutor Joseph Buford Pennybacker no desenvolvimento da eletromiografia atual, ao longo dos oitenta anos de seu artigo original em 1938, sobre potenciais de fasciculação e fibrilação, e os estudos subsequentes que descreveram a maioria das mudanças elétricas necessárias para realizar e interpretar EMG.

[Fasciculations and cramps: physiological bases and clinical approach of a complex phenomenon]. / Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo.

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

[The cramp-fasciculation-syndrome (CFS)]. / Das Myalgie-Faszikulations-Krampus-Syndrom (MFKS).

The present review focuses on the cramp-fasciculation syndrome, a benign disorder which is regarded as a hyperexcitability syndrome of the peripheral nervous system. The article presents clinical features, pathophysiology, differential diagnosis, therapy and a case report to illustrate the cramp-fasciculation-syndrome.

Fasciculations demonstrate daytime consistency in amyotrophic lateral sclerosis.

INTRODUCTION: Fasciculations represent early neuronal hyperexcitability in amyotrophic lateral sclerosis (ALS). To aid calibration as a disease biomarker, we set out to characterize the daytime variability of fasciculation firing. METHODS: Fasciculation awareness scores were compiled from 19 ALS patients. In addition, 10 ALS patients prospectively underwent high-density surface electromyographic (HDSEMG) recordings from biceps and gastrocnemius at three time-points during a single day. RESULTS: Daytime fasciculation awareness scores were low (mean: 0.28 muscle groups), demonstrating significant variability (coefficient of variation: 303%). Biceps HDSEMG recordings were highly consistent for fasciculation potential frequency (intraclass correlation coefficient [ICC] = 95%, n = 19) and the interquartile range of fasciculation potential amplitude (ICC = 95%, n = 19). These parameters exhibited robustness to observed fluctuations in data quality parameters. Gastrocnemius demonstrated more modest levels of consistency overall (44% to 62%, n = 20). DISCUSSION: There was remarkable daytime consistency of fasciculation firing in the biceps of ALS patients, despite sparse and intermittent awareness among patients' accounts.

Preprocessing surface EMG data removes voluntary muscle activity and enhances SPiQE fasciculation analysis.

OBJECTIVES: Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline. METHODS: Six ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection. RESULTS: Assessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2-13.1 minutes), processing times (10.7-49.5 seconds) and fasciculation frequencies (27.4-71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6-79.4 IQR). CONCLUSION: We hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings. SIGNIFICANCE: Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.