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Estimation of the frequency of the muscular pain-fasciculation syndrome and the muscular cramp-fasciculation syndrome in the adult population.

A nationwide two-phase survey was carried out of the adult population of the Netherlands regarding fasciculation, muscle pain and muscle cramp. We conducted a population-based telephone interview with 780 Dutch adults, followed by a questionnaire covering more clinical details, filled out by 311 subjects, who had been interviewed by telephone previously. From these data the frequencies of fasciculation (men 50%, women 61%), muscle cramp (men 28%, women 42%) and muscle pain (men 48%, women 60%) in the Dutch adult population in 1988 were estimated. The combined occurrence of frequent fasciculation and frequent muscle cramp as well as of frequent fasciculation and frequent muscle pain was reported only sporadically. Although the muscular pain-fasciculation syndrome and the muscular cramp-fasciculation syndrome represent combinations of common neuromuscular phenomena, their occurrence in the general population proved to be rare. This finding supports their clinical identity as distinct motor unit hyperactivity syndromes rather than mere coincidences of fasciculation, muscle cramp and muscle pain.

Adult

The monoclonal antibody 69A1 recognizes an epitope found on neurones with axons that fasciculate but not on those with non-fasciculating processes.

We have previously reported that the cell-type distribution and pattern of expression of the surface antigen recognized by the monoclonal antibody 69A1, suggests that it may be involved during the period of nerve fibre outgrowth and the formation of fibre bundles in the rat (Pigott & Kelly, 1986). In this current study, we have examined the expression of the epitope recognized by antibody 69A1 in regions of the rat central nervous system in which it is possible to distinguish between neurones with axons that fasciculate to form clearly defined fibre tracts and neurones with non-fasciculating processes. We have also examined antibody 69A1 labelling in several regions of the peripheral nervous system. We report that the 69A1 epitope is expressed on neurones with axons that fasciculate but is not found on neurones with short, non-fasciculating axons or on neurones without a morphologically identifiable axon. The antigen 69A1 has been purified and shown to be immunochemically closely related or identical to the L1 antigen.

Animals

Pathophysiology of fasciculations in ALS as studied by electromyography of single motor units.

Electromyographic potentials of fasciculations were studied in ten patients with amyotrophic lateral sclerosis (ALS). The EMG recordings were made from the extensor digitorum brevis muscle. The EMG recording was so selective that only one motor unit potential appeared on maximal voluntary effort and on supramaximal electrical stimulation of the peroneal nerve. In a series of fasciculations, the shapes of the EMG potentials varied, while in a series of voluntary twitch activations of electrical nerve stimulations the EMG potentials were mainly constant. Fasciculations were followed by antidromic impulses in the test unit axon as judged from collision tests, and they persisted after lidocaine blockades of the nerve to the muscle. The findings are compatible with a conclusion of distal multifocal triggering of fasciculation. Fasciculating motor units had voluntary firing properties close to those of normal low-threshold motor units. Widespread fasciculations were abolished by a nonparalytic dose of a synthetic curare derivative (Pavulon) and augmented by administration of neostigmine in two cases. The fasciculations in ALS thus have the same characteristics as experimental fasciculations evoked by cholinesterase inhibitors, and there is reason to believe that the underlying pathophysiological mechanism is similar in the two cases.

Amyotrophic Lateral Sclerosis

Temporal correlation of succinylcholine-induced fasciculations to loss of twitch response at different stimulating frequencies.

STUDY OBJECTIVE: The present study was undertaken to determine the time courses of succinylcholine-induced fasciculations and adductor pollicis single-twitch responses at two stimulating frequencies. DESIGN: A prospective, randomized study. SETTING: The main operating room of a university teaching hospital. PATIENTS: Forty-four patients undergoing general anesthesia and requiring tracheal intubation. INTERVENTIONS: In 22 patients, anesthesia was induced with thiopental sodium, fentanyl, and midazolam and maintained with 70% nitrous oxide in oxygen prior to the administration of succinylcholine 1 mg/kg. In another 22 patients, end-tidal isoflurane 0.75% to 1% was included in the induction regimen. Patients in each group were randomly assigned to receive ulnar nerve stimulation at either 0.1 Hz or 1.0 Hz. MEASUREMENTS AND MAIN RESULTS: The times at which fasciculations were first noticed and no longer visible and the times to 25%, 50%, 75%, 90%, and 100% twitch depression were recorded. These times were compared for the two rates of neurostimulation. With single-twitch nerve stimulation at 1.0 Hz, 100% twitch depression occurred 6 +/- 16 seconds following the end of fasciculations, while at a stimulating frequency of 0.1 Hz, it occurred 52 +/- 32 seconds later (p less than 0.05). At the end of fasciculations, single-twitch depression of 50% or more was noted in only 19% of patients in the 0.1 Hz groups and in all patients in the 1.0 Hz groups (p less than 0.05). In the 0.1 Hz groups, 50% twitch depression occurred 19 +/- 27 seconds after the end of fasciculations, with more than three-quarters of the patients having achieved 50% twitch depression 30 seconds following the disappearance of fasciculations. The addition of isoflurane did not significantly alter any of these times. CONCLUSIONS: The data reveal that cessation of fasciculations may be an inaccurate clinical sign of the readiness for intubation and confirm that standardized methods of neurostimulation are necessary in the pharmacodynamic evaluation of neuromuscular blocking drugs. In settings where profound neuromuscular relaxation is not required, waiting at least 30 seconds beyond the disappearance of fasciculations should provide good intubating conditions.

Adolescent

Voluntary activation and fiber density of fasciculations in motor neuron disease.

Two hundred voluntarily activated motor units and 211 fasciculations were recorded in the biceps of 10 patients with motor neuron disease with the Macro EMG technique. Twenty-two fasciculations, in nine of 10 muscles, had a potential of closely similar shape, amplitude, and area to that of a voluntary unit. Fasciculating units that could not be activated voluntarily had a higher mean number of spikes in their triggering single fiber potentials than units that could only be activated voluntarily, but statistically similar Macro EMG parameters. The mean number of single fiber spikes, and Macro EMG parameters, of fasciculations activated voluntarily, were similar to those of units that were only activated voluntarily. A positive correlation between fiber density and Macro EMG median amplitude and area in individual patients, and between number of single fiber spikes and Macro EMG amplitudes and areas in the pooled data, was found for fasciculations but not for voluntary units. At least 10% of fasciculations in patients with motor neuron disease may originate near or above the point of axonal branching and a proportion of those without evidence of voluntary activation may have a higher number of smaller muscle fibers, or more closely packed muscle fibers, of similar or greater size, than voluntarily activated motor units. Differences in the peripheral microanatomy of a number of fasciculation units not activated voluntarily may underlie ectopic impulse generation in the terminal axonal arborization, endplate zone, or muscle fibers of these units.

Electromyography

Surface EMG in the recording of fasciculations.

The usefulness of multichannel surface recording of fasciculations was evaluated by a retrospective study of 116 patients with various neurological disorders. Eight channels of a conventional electroencephalograph were used with plate electrode recordings from the upper arms and legs. Wide-spread fasciculations (defined as five or more of the eight muscle groups) were recorded in 48 of 54 patients with motor neuron disease, spinal muscular atrophy or postpolio syndrome, but noted on routine clinical examination at presentation in only 6. Eleven of 23 patients with peripheral neuropathy or myelopathy had fasciculations in five or more leads compared to one clinically, and 3 of 39 with other neurological diseases had fasciculations electrically but in only one were they clinically observed. The method is a noninvasive and sensitive adjunct to clinical examination for detecting fasciculations. Its diagnostic value is limited by the relatively high incidence of fasciculations in neuropathies and myelopathies. However, this study suggests that "false negatives" are rare and that the diagnosis of motor neuron disease should be reconsidered when less than five leads shows fasciculations.

Adult

Fasciculations and their F-response. Localisation of their axonal origin.

A fasciculation with an axonal origin may be followed by its own F-response. The time-lapse between these 2 potentials corresponds to the time for the antidromic wave to travel to the alpha-cell and to return to the trigger-point. This relatively stable interval may be compared with the difference between the latencies of the F- and M-responses of the same muscle evoked by distal nerve stimulation. This permits one to localise the origin of the fasciculation on the axon. This method showed that, of 201 fasciculations followed by their F-response, obtained in normal controls and in neurological patients, 97 and 89% respectively had their origin between the muscle and the stimulation site. In this series, the proportion of pathological fasciculations having an origin between the muscle and a point at half the M-latency, is similar to that found in a former study on unselected fasciculations using a collision method (Roth 1982). Comparison between these 2 studies therefore supports the concept that all or almost all fasciculations have an axonal origin.

Axons

Rapid-sequence intubation of head trauma patients: prevention of fasciculations with pancuronium versus minidose succinylcholine.

INTRODUCTION: Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration. Standard rapid-sequence intubation requires a nondepolarizing blocking agent before succinylcholine administration. HYPOTHESIS: Prevention of fasciculations during rapid-sequence intubation of head trauma patients can be accomplished as safely and effectively with minidose succinylcholine as with a defasciculating dose of pancuronium. DESIGN: A prospective, randomized, double-blind study. SETTING: An inner-city county trauma center with 70,000 patient visits per year. PARTICIPANTS: Sequential adult head trauma patients requiring rapid-sequence intubation who had no contraindications to succinylcholine or pancuronium. INTERVENTIONS: Each head trauma patient requiring rapid-sequence intubation who met the inclusion criteria received standard rapid-sequence intubation maneuvers and lidocaine (1 mg/kg) IV. Patients were randomized to receive either minidose succinylcholine (0.1 mg/kg) or pancuronium (0.03 mg/kg) IV one minute prior to the full paralytic dose of succinylcholine (1.5 mg/kg) IV. Fasciculations were recorded using a graded visual scale. RESULTS: Of 46 patients, eight of 19 (42%) in the pancuronium group and six of 27 (22%) in the succinylcholine group experienced fasciculations. No statistically significant difference in fasciculations was detected between the two groups using chi 2 analysis. Complete relaxation of the cords was present in all but two patients, one in each group. No patient in either group experienced emesis or significant dysrhythmias. CONCLUSION: Pretreatment with minidose succinylcholine causes no greater incidence of fasciculations than pancuronium in rapid-sequence intubation of head trauma patients in an ED setting. Thus succinylcholine may be used as the sole paralytic agent in rapid-sequence intubation of head trauma patients.

Adult

Suxamethonium infusion rate and observed fasciculations. A dose-response study.

Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.

Dose-Response Relationship, Drug

Differential effects of neuromuscular blocking agents on suxamethonium-induced fasciculations and myalgia.

The effect of pretreatment with suxamethonium, gallamine or pancuronium on suxamethonium-induced fasciculations and myalgia was studied in a controlled, randomized and double-blind clinical trial. Both fasciculations and myalgia were assessed on a four-point rating scale. There was no significant correlation between fasciculations and postoperative muscle pain at 24, 48 or 72 h, and pretreatment with suxamethonium had no significant effect on fasciculations or myalgia. Gallamine had a more marked effect on fasciculations than pancuronium, and the decrease in the fasciculation score was statistically significant. In contrast, pancuronium had a greater effect on myalgia, and decreased postoperative muscle pain significantly at 24 and 48 h. These differences may reflect the differential activity of gallamine and pancuronium at the neuromuscular junction. Pretreatment had little or no effect on plasma potassium concentrations.

Adolescent

Diazepam does not prevent succinylcholine-induced fasciculations and myalgia. A comparative evaluation of the effect of diazepam and d-tubocurarine pretreatments.

To determine the effectiveness of diazepam pretreatment in preventing succinylcholine (SCh)-induced fasciculations and body pains, 587 patients were randomly allocated to six groups. Patients in Group I received no pretreatment and served as controls. Patients in Groups II and III were pretreated with 0.05 mg/kg of diazepam either 4-5 min (Group II) or 8-10 min (Group III) prior to SCh administration. Patients in Groups IV and V received 0.1 mg/kg of diazepam either 4-5 min (Group IV) or 8-10 min (Group V) prior to SCh administration, while patients in Group VI were pretreated with 0.05 mg/kg of d-tubocurarine (dTc) 4-5 min prior to SCh. The succinylcholine dosage was 1.0 mg/kg in Groups I through V and 1.5 mg/kg in Group VI. Fasciculations, intubation conditions and postoperative body pains were evaluated in all groups. Fasciculations were seen in 90% of patients in the control group and 15% in the dTc pretreatment group, while diazepam was ineffective in altering the frequency or intensity of fasciculations. Conditions for intubation were judged to be clinically adequate in all groups. Body pains were seen in 33% of patients in the control group and 28-36% in diazepam-pretreated groups and in only 8% of patients in the dTc pretreatment group. There was no statistically significant difference in the incidence of body pains by virtue of site of operation, age, sex, and inpatient/outpatient status. It is concluded that the problem of postoperative myalgia is significant and that dTc pretreatment is the effective method for prevention of fasciculations and postoperative myalgia. Diazepam pretreatment was ineffective for the prevention of fasciculations and myalgia.

Anesthesia, General

Involvement of the nerve growth factor-inducible large external glycoprotein (NILE) in neurite fasciculation in primary cultures of rat brain.

The nerve growth factor-inducible large external glycoprotein (NILE) has been found only on the surface of neuronal cells and Schwann cells. Since NILE seems to be concentrated on neurites, we have investigated its possible role in the development of neurites in primary cultures of rat brain. Cultures of embryonic day 14 (E14) whole brain and cultures of postnatal day 5 (P5) cerebellum were grown in the presence of Fab' fragments of antibody against NILE in an attempt to perturb the normal pattern of neurite development. For comparison, cultures were treated with two other reagents that recognize neuronal cell surface molecules: tetanus toxin, which binds to the GD1b and GT1 gangliosides, and Fab' fragments of antibody against neural cell adhesion molecule (N-CAM). Under the conditions used, none of the exogenous reagents affected neurite outgrowth, but specific effects on neurite fasciculation were observed. Anti-NILE inhibited fasciculation in cultures of E14 whole brain but had no effect on fasciculation in cultures of P5 cerebellum. Conversely, anti-N-CAM inhibited fasciculation in cultures of P5 cerebellum, which contain the adult form of N-CAM, but had little effect on fasciculation in cultures of E14 whole brain, which contain the embryonic form of N-CAM. Tetanus toxin had no effect on fasciculation in either culture system. Our results imply that NILE-mediated neurite-neurite interactions are stronger than N-CAM (embryonic)-mediated interactions in the E14 brain cultures, whereas N-CAM (adult)-mediated interactions are stronger than NILE-mediated interactions in the P5 cerebellar cultures.

Animals

Sonographic imaging of muscle contraction and fasciculations: a correlation with electromyography.

Precise quantitation of fasciculations with EMG is difficult because of their random location and discharge frequency in muscle. We studied the clinical value of real-time ultrasound in the study of normal voluntary muscle contraction and in the identification of fasciculations in 22 patients. Sonography effectively imaged fasciculations, demonstrating them in both resting and actively contracting extremity muscles and in less accessible muscles such as the tongue. In two instances ultrasound identified fasciculations not apparent on EMG. Analysis of the video images generated quantitative data on fasciculation duration (averaging 500 msec), size, and location and provided unique insight into the process of normal muscle contraction and motor unit physiology.

Electromyography

Succinylcholine, fasciculations and myoglobinaemia.

The prophylactic effectiveness of a small "self-taming" dose of succinylcholine (0.1 mg X kg-1), of d-tubocurarine (0.05 mg X kg-1), and of pancuronium (0.02 mg X kg-1) on succinylcholine-induced fasciculations and myoglobinaemia was studied in 64 healthy children (ages two to nine years), anaesthetized with halothane, nitrous oxide and oxygen. Serum myoglobin was analyzed by radioimmunoassay and taken as a tracer of muscle damage. No correlation was found between the serum levels of myoglobin and the incidence of muscle fasciculations. Self-taming with succinylcholine decreased the incidence of fasciculations (p = 0.001) but did not decrease the succinylcholine-induced myoglobinaemia (p = 0.224). D-tubocurarine (0.05 mg X kg-1) and pancuronium (0.02 mg X kg-1) both significantly reduced the myoglobinaemia and the fasciculations produced by succinylcholine. The pancuronium pretreated group presented less variable values of serum myoglobin which, when compared to the control group, had a more significant p value (p less than 0.001) than for d-tubocurarine pretreated group (p = 0.003). Muscle fasciculations and increased myoglobin levels were observed in children less than four years old who received succinylcholine. The prophylaxis of acute rhabdomyolytic renal failure due to succinylcholine (seven cases reported in the medical literature) is considered.

Age Factors

Effects of calcium channel blocking agents on neostigmine-induced fasciculations.

Male Sprague-Dawley rats were anesthetized with pentobarbital and prepared for monitoring contractions of the gastrocnemius muscle evoked by stimulation of the sciatic nerve. Animals received atropine prior to a dose of neostigmine of 0.02 mg/kg i.v. The effects on contractile strength and the number of fasciculations in a 2-min period were assessed. Pretreatment with phenytoin, 20 mg/kg, reduced the number of fasciculations to 32% of control without altering contractile strength. Both nifedipine and nitrendipine, 1 mg/kg each, virtually abolished fasciculations without altering twitch strength. Verapamil, 4 and 8 mg/kg, depressed fasciculation frequency to 50% of control without affecting pre-neostigmine twitch height. The dihydropyridine calcium blocking agents did however reduce the neostigmine-induced augmentation of contraction strength. These data suggest that a calcium-mediated current at presynaptic motor endings participates in the generation of repetitive nerve terminal discharges leading to muscle fasciculations.

Animals

Increase in intragastric pressure during suxamethonium-induced muscle fasciculations in children: inhibition by alfentanil.

Changes in intragastric pressure after the administration of suxamethonium 1.5 mg kg-1 i.v. were studied in 32 children (mean age 6.9 yr) pretreated with either physiological saline or alfentanil 50 micrograms kg-1. Anaesthesia was induced with thiopentone 5 mg kg-1. The incidence and intensity of muscle fasciculations caused by suxamethonium were significantly greater in the control than in the alfentanil group. The intragastric pressure during muscle fasciculations was significantly higher in the control group (16 +/- 0.7 (SEM) cm H2O) than in the alfentanil group (7.7 +/- 1.5 (SEM) cm H2O). The increase in intragastric pressure was directly related to the intensity of muscle fasciculations (regression line: y = 0.5 + 4.78x with r of 0.78). It is concluded that intragastric pressure increases significantly during muscle fasciculations caused by suxamethonium in healthy children. Alfentanil 50 micrograms kg-1 effectively inhibits the incidence and intensity of suxamethonium-induced muscle fasciculations; moreover, intragastric pressure remains at its control value.

Alfentanil

Alfentanil inhibits muscle fasciculations caused by suxamethonium in children and in young adults.

The effect of alfentanil on suxamethonium-induced muscle fasciculations was studied in a double-blind study in 34 children (mean age 6.8 years) and in 30 adults (mean age 20 years). After pretreatment with either alfentanil 50 micrograms kg-1 or saline, each patient was anaesthetized with a sleep dose of thiopental followed by suxamethonium 1.5 mg kg-1 for endotracheal intubation. Compared to the control groups, alfentanil significantly decreased the intensity of visible muscle fasciculations caused by suxamethonium. In children, the duration of muscle fasciculations was shorter in the alfentanil than in the control group. In adults, the intensity rather than the duration of fasciculations was attenuated by alfentanil. The inhibition of fasciculations caused by alfentanil was also demonstrated in children in the surface electromyogram recorded on the biceps. There was no circulatory response to endotracheal intubation in the groups pretreated with alfentanil.

Adolescent

[Use of atracurium for the prevention of fasciculations and succinylcholine myalgia in athletes undergoing orthopedic surgery].

The Authors report their clinical experience about the use of atracurium besylate in preventing succinylcholine-induced fasciculations and postoperative myalgias in fifty athletes (ASA class 1), submitted to arthroscopic meniscectomy. The patients were pretreated with atracurium 5 mg i.v. or saline solution in a double-blind fashion. After 2.5 minutes, succinylcholine 1.3 mg/kg was administered, and fasciculations were recorded on a scale ranging from 0 to 3. Twenty-four hours after surgery all subjects were questioned about myalgias occurrence, scored by a 0-3 scale. Fasciculations occurred in all patients who received saline and in 44% of those treated with atracurium. Myalgias on the postoperative day were observed in 80% of patients treated with saline solution, but only in 36% of patients who received atracurium. The difference between atracurium and saline solution was statistically significant (p less than 0.001) either for fasciculations or myalgias incidence. These findings show that atracurium 5 mg i.v. is effective in preventing succinylcholine-induced fasciculations and postoperative myalgias, and suggest atracurium as the drug of choice for this purpose, particularly in muscular subjects.

Adolescent