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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↗

[Real time sonographic imaging of fasciculation].

We studied the clinical value of real time sonographic imaging of fasciculation in patients with neuromuscular diseases, which presented for 4 with amyotrophic lateral sclerosis (ALS), 2 with Kennedy-Alter-Sung syndrome, 1 with Kugelberg-Welander disease, and 1 with n-hexane neuropathy. The ultrasound image of fasciculation showed characteristic of each disease in several features. Analysis of sonographic image revealed that duration, size of fasciculation, and interval of fasciculation in Kennedy-Alter-Sung syndrome and Kugelberg-Welander disease, which is chronic progressive neuromuscular disorders, were longer than that in ALS, n-hexane neuropathy which are acute progressive disorders. We believe the fasciculation image may have significant implications with clinical course. Real time sonography offers a quantitative and qualitative means of investigating fasciculation and is effective to identify pathological information.

Amyotrophic Lateral Sclerosis↗

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↗

The spectrum of ectopic motor nerve behavior: from fasciculations to neuromyotonia.

BACKGROUND: Ectopic impulses in motor nerves generate clinically and electromyographically detectable activity in muscle. These discharges occur in the form of isolated fasciculations, as persistent muscle activity in the form of myokymia and neuromyotonia, or in fulminant contractions of individual muscles in the form of a cramp. In the last 20 years, new studies have helped establish the relationship of fasciculations with cramps and neuromyotonia and have identified common pathophysiologic mechanisms. REVIEW SUMMARY: Current evidence suggests that both cramps and fasciculations originate primarily in the most distal motor nerve terminals. In this portion of the axon, the overlying Schwann cells do not form a myelin sheath and the blood-nerve barrier is relatively porous. The terminal axon is studded with receptors to monitor the release of neurotransmitters. Under certain stresses, reinnervation, ionic imbalances, motor nerve disease, or pharmacologic challenge, ectopic impulses arise and create visible, but sporadic fasciculations. Other circumstances, including muscle shortening and dehydration, give rise to more frequent and localized fasciculations that can erupt into a painful muscle cramp. The most unusual motor ectopic phenomena involves rapidly recurrent discharges in multiple motor nerves, giving rise to grouped fasciculations, including myokymia and neuromyotonia. Recent studies have implicated toxins, and autoimmune and genetic mechanisms in the generation of neuromyotonic and myokymic syndromes. Plasma exchange, carbamazepine, and phenytoin have proven helpful in select cases. CONCLUSION: These findings indicate that motor nerve hyperexcitability is a fruitful subject of clinical and laboratory investigation and that treatment based on underlying mechanisms proves beneficial.

Journal Article↗

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↗

Rocuronium prevents succinylcholine-induced fasciculations.

PURPOSE: The aim of this study was to assess the effect of rocuronium pretreatment at 3 and 1.5 min before succinylcholine administration on fasciculations, neuromuscular blockade and intubating conditions. METHODS: Sixty ASA I or II adults scheduled for elective surgery were anaesthetised with midazolam, fentanyl, propofol, N2O and isoflurane. They were randomised in a double blind manner into three groups: group ROC-3 min (n = 22) received 0.05 mg.kg-1 rocuronium, 3 min before 2 mg.kg-1 succinylcholine; group ROC-1.5 min (n = 20) received 0.05 mg.kg-1 rocuronium 1.5 min before 2 mg.kg-1 succinylcholine; and group NO ROC (n = 18) had no rocuronium before injection of 2 mg.kg-1 succinylcholine. Fasciculations and intubating conditions were evaluated by the same physician who was unaware of the randomisation. Neuromuscular block was measured at the adductor pollicis with an accelerometer. RESULTS: The incidence of fasciculations was lower in the ROC-3 min (9%) and ROC-1.5 min (30%) groups than in the NO ROC group (83%; P < 0.001). The intensity of fasciculations was also less in both pretreatment groups. No statistical difference was noted between pretreatment at 3 and 1.5 min. Intubating conditions, onset time and duration of succinylcholine blockade were comparable in all three groups. CONCLUSION: The incidence and severity of succinylcholine fasciculations can be reduced by giving 0.05 mg.kg-1 rocuronium either 1.5 min or 3 min before succinylcholine. The effects of 2 mg.kg-1 succinylcholine with rocuronium pretreatment, and 1 mg.kg-1 succinylcholine, without pretreatment, are similar with respect to intubating conditions, onset of paralysis and duration of blockade.

Adolescent↗

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↗

Effects of pretreatment with cisatracurium, rocuronium, and d-tubocurarine on succinylcholine-induced fasciculations and myalgia: a comparison with placebo.

STUDY OBJECTIVE: To evaluate the efficacy of cisatracurium, rocuronium, and d-tubocurarine in preventing succinylcholine-induced fasciculations and postoperative myalgia in patients undergoing ambulatory surgery. DESIGN: Randomized, prospective, placebo-controlled trial SETTING: Teaching hospital. SUBJECTS: 80 ASA physical status I and II patients scheduled for elective ambulatory surgery with general anesthesia. INTERVENTION: A standardized balanced anesthetic technique was used for all patients. MEASUREMENTS AND MAIN RESULTS: Patients were randomized to receive cisatracurium 0.01 mg/kg, rocuronium 0.06 mg/kg, d-tubocurarine 0.05 mg/kg, or saline, 3 minutes prior to intravenous (i.v.) succinylcholine 1.5 mg/kg. The intensity of fasciculations and intubating conditions were assessed using a four-point rating scale. In addition, the severity of myalgia was assessed using a four-point rating scale in the postanesthesia care unit and at 24 hours postoperatively. No patient complained of any side effects after the administration of the study drug. Fasciculations were observed less frequently (p < 0.05) in the d-tubocurarine and rocuronium groups compared with the placebo and cisatracurium groups. However, there was no difference between the d-tubocurarine group and the rocuronium group (21% vs. 10%, respectively). Although fasciculations occurred less frequently in the cisatracurium group than in the placebo group (59% vs. 85%, respectively), this difference did not reach statistical significance. There was no difference among the four groups in the intubating conditions or the incidence of postoperative myalgia. CONCLUSION: Pretreatment with rocuronium and d-tubocurarine was superior to cisatracurium in preventing succinylcholine-induced fasciculations. However, pretreatment did not have any effect on the incidence of myalgia after ambulatory surgery.

Adult↗

Effects of high-dose propofol on succinylcholine-induced fasciculations and myalgia.

BACKGROUND: The purpose of this prospective study was to determine the effects of high-dose propofol on the incidence of fasciculations and myalgia, and to evaluate changes in creatine kinase levels following the administration of succinylcholine in 90 women who underwent laparoscopy. METHODS: Patients were randomly assigned to one of three groups. Induction of anesthesia was performed with thiopentone 5 mg kg(-1) in Group I (n = 30), propofol 2 mg kg(-1) in Group II (n = 30), and propofol 3.5 mg kg(-1) in Group III (n = 30). Then succinylcholine 1 mg kg(-1) was administered to the patients for intubation. RESULTS: Fasciculation was absent in 20% of Group III patients, and no vigorous fasciculation occurred in this group. Furthermore, the severity of fasciculation in Group III was significantly lower than in the other two groups (P = 0.01). Seventy per cent of patients had no myalgia in Group III, 39.2% in Group II and 37% in Group I (P = 0.007). Severity of myalgia was also significantly lower in Group III compared with the other two groups (P = 0.011). Post-operative creatine kinase levels were significantly higher than their baseline values in Groups I and II (P < 0.0001). CONCLUSION: Administration of propofol 3.5 mg kg-1 is effective in reducing fasciculations and myalgia after succinylcholine.

Adult↗

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↗

A comparison of tubocurarine, rocuronium, and cisatracurium in the prevention and reduction of succinylcholine-induced muscle fasciculations.

Fasciculations are a common side effect of the use of succinylcholine for tracheal intubation. Many anesthesia care providers prefer to prevent them due to a possible association between fasciculations and increased intracranial and intraocular pressures. The purpose of this study was to compare the effectiveness of tubocurarine, rocuronium, and cisatracurium in the prevention and reduction of succinylcholine-induced muscle fasciculations. The study was a prospective, randomized, double-blind, clinical drug comparison. We randomly assigned 40 subjects to 1 of 4 pretreatment groups. Fasciculations were graded on a 4-point scale. A Kruskal-Wallis analysis of variance, used to analyze data collected from the fasciculation scale, demonstrated there was no statistically significant difference in efficacy between tubocurarine and rocuronium for defasciculation or between cisatracurium and saline for defasciculation. Significant differences were shown between the tubocurarine and cisatracurium groups and between the rocuronium and cisatracurium groups. Rocuronium is equally as efficacious as tubocurarine for defasciculation. Therefore, rocuronium is a valid alternative to tubocurarine for defasciculation. Cisatracurium is inferior to rocuronium and tubocurarine for defasciculation. Therefore, the use of cisatracurium is not recommended for defasciculation.

Adult↗

[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↗

Selective fasciculation as a mechanism for the formation of specific chemical connections between Aplysia neurons in vitro.

Selective fasciculation of growth cones along preestablished axon pathways expressing matching or complementary adhesion molecules is thought to be an important strategy in axon guidance. Growth cone inhibiting factors also appear to influence pathfinding decisions. We have used identified Aplysia neurons in vitro to explore the hypothesis that similar mechanisms could be involved in target selection. Co-cultures of L10 neurons with RB neuron targets or R2 neurons with RUQ neuron targets reliably formed chemical connections. In contrast, co-cultures of L10 with RUQ targets usually failed to form detectable chemical connections unless cell-cell contact was forced during plating by intertwining the major axons. These data suggested that differences in the ability to form cell-cell contacts might underlie the observed synaptic specificity. This notion was supported when fluorescent dye fills of L10 and R2 revealed a positive correlation between the amount of target contact and the frequency of synapse formation: L10-RUQ cultures showed much less target contact than L10-RB or R2-RUQ cultures. To examine the cellular mechanisms of these differences in target contact, presynaptic growth cones were observed as they interacted with target processes. L10-RUQ cultures showed much less fasciculation and more avoidance behavior compared to L10-RB and R2-RUQ cultures. This initial specificity suggested that the differences in amount of target contact arose through selective fasciculation and avoidance rather than through selective elimination after indiscriminate fasciculation. Selective fasciculation and avoidance might, therefore, aid in target selection by regulating the amount of contact between presynaptic processes and potential target cells.

Animals↗

Occurrence of fasciculated microtubules at nodes of Ranvier in rat spinal roots.

Fascicles of microtubules, previously considered to be unique to the initial segments of myelinated axons, were found at nodes of Ranvier of sensory and motor axons in rat spinal roots, though their occurrence was limited to the proximal portion of the axons. No fasciculated microtubules were noticed in the internodes of myelinated axons or in unmyelinated axons. In transverse sections, microtubules in fascicles were characteristically cross-linked by short filamentous strands at a centre-to-centre distance of 36-40 nm. In sensory axons, the density of fasciculated microtubules at the node of Ranvier was 45-48% at the level of the dorsal root ganglion and decreased progressively as thin sections were made more distal to the ganglion in both directions. In motor axons, microtubule-fascicles involved about 24% of the microtubules in the ventral rootlets, but they were rarely seen in distal portions of the ventral roots. No fasciculation of microtubules was discerned in the sciatic and saphenous nerves. These findings suggest that cross-linking protein(s) for fasciculation, which are synthesized in the perikaryon and primarily used for the initial segment, may be further transported to fasciculate microtubules at some proximal nodes of Ranvier.

Animals↗

Succinylcholine: mechanism of fasciculations and their prevention by d-tubocurarine or diphenylhydantoin.

Administration of d-tubocurarine (dTC) or diphenylhydantoin (DPH) was evaluated as a pretreatment to prevent succinylcholine (Sch) evoked fasciculations. Experiments were designed to determine the nature of the drug-drug interactions, sites of interaction, and site of fasciculation suppression. Sch is known to evoke repetitive discharge generation by motor nerve terminals (MNTs). Transmission of these prejunctional discharges causes fasciculations. A cat soleus neuromuscular preparation in situ, which enables recording of nerve action potentials initiated by MNTs, their transmitted muscle action potentials, and the resultant contractile responses, was used to explore Sch effects before and after iv pretreatment with dTC or DPH. dTC is known to act prejunctionally to suppress repetitive discharges initiated by facilitatory drugs and tetanic conditioning of MNTs. Accordingly, pretreatment with dTC 50 micrograms X kg-1 suppressed the Sch-induced MNT repetitive discharging and correspondingly suppressed generalized fasciculations without affecting twitch. This dTC dose, however, also reduced Sch blocking potency by 33%, slowed its rate, and shortened block duration. These latter effects represent competitive postjunctional antagonism. DPH is also known to suppress MNT repetitive discharging. Correspondingly, Sch-induced repetitive firing and ensuing fasciculations were suppressed by DPH (30 mg X kg-1) without affecting twitch. Unlike dTC, this DPH dose increased Sch blocking potency by 50%, increased the initial rate of block, and did not alter block duration. These DPH effects were dose-dependent and within the anticonvulsant range for cats. Therefore, patients with anticonvulsant levels of DPH may not require pretreatment before Sch.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗