Action Potential Decrement Research Articles

Compound Muscle Action Potential Decrement to Repetitive Nerve Stimulation Between Hirayama Disease and Amyotrophic Lateral Sclerosis

To compare repetitive nerve stimulation (RNS) between Hirayama disease (HD) and amyotrophic lateral sclerosis (ALS). The 3-Hz RNS test was performed on bilateral abductor pollicis brevis, abductor digiti minimi, middle deltoid, and upper trapezius muscles in 33 HD patients and 37 ALS patients. In HD patients, none of tested muscles showed any abnormal decrements (≥10%). Significant decrements were observed in 73% of the ALS patients, and decrements were more frequently observed in proximal muscles (deltoid: 70.3%; trapezius: 48.6%). Illness duration did not correlate with decrement percentage in either patient group, and there was no relationship between decrement incidence and ALS diagnostic category (P > 0.05). The significantly different RNS results between ALS and HD patients support the application of RNS, especially performing RNS in proximal muscles, as a supplementary test in distinguishing these two diseases, even in the early stages. These results may also imply a difference in underlying pathophysiology between ALS and HD.

Fast-channel congenital myasthenic syndrome with a novel acetylcholine receptor mutation at the α–ε subunit interface

Congenital myasthenic syndromes (CMS) result from the failure to achieve muscle depolarisation due to disorders in the structure and/or function of the neuromuscular synapse. Mutations of the nicotinic acetylcholine receptor (nAChR) form a major subset of CMS. We describe a patient who presented with recurrent apnoeic crises in the neonatal period requiring ventilator support. Electromyography revealed compound muscle action potential decrement upon repetitive stimulation. Sequencing of nAChR subunit genes revealed two missense mutations. One previously reported null mutation p.εTyr15His, and a second novel missense mutation, p.εThr38Lys, that is well expressed in mammalian cell culture and thus likely to exert its effect via alteration of ion channel kinetics. Functional analysis revealed abbreviated ion channel bursts characteristic of a fast channel CMS. The mutation p.εThr38Lys occurs at the interface between the α and ε subunits of the nAChR pentamer and leads to instability of the open channel. The effects of this mutation on channel function were investigated in relation to other fast channel mutants at an analogous subunit interface within the nAChR pentamer. Fast channel syndromes are frequently characterised by severe myasthenic weakness with apnoeic crises; knowledge of the underlying mutation and its functional consequences can be vital for appropriate therapy and patient management.

Congenital Myasthenic Syndrome: Presentation, Electrodiagnosis, and Muscle Biopsy

We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2-10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies (n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.

Congenital Myasthenic Syndrome: Presentation, Electrodiagnosis, and Muscle Biopsy

We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2–10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies ( n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.

Properties of derived cochlear action potentials in forward tonal masking in guinea pigs.

Chronic experiments on guinea pigs were used to study the characteristics of cochlear nerve action potentials and the derived potential in conditions of forward masking. The auditory nerve action potential was recorded from the round window of the cochlea. The derived potential was obtained by subtracting the action potential recorded with masking from the response obtained in silence. These studies showed that the derived potential showed higher sensitivity to masking than the traditional measure of masking, i.e., the decrement in the amplitude of the auditory nerve action potential. The derived potential reflects not only changes in the action potential during masking, but also changes in its shape. Differences between the derived potential and the action potential decrement provide evidence that the amplitude and time changes in the derived potential provide more complete information on the nature of activity in the auditory fibers.

Transient weakness and compound muscle action potential decrement in myotonia congenita.

Twenty-five Turkish patients with recessive myotonia congenita (RMC), 16 of whom had genetic confirmation, were studied. Nineteen had transient weakness. In the upper extremities, onset age of transient weakness was usually in the early teens. All untreated RMC patients had a compound muscle action potential decrement of > or =25%, usually above 50%, with repetitive nerve stimulation at 10/s for 5 s. Patients with other nondystrophic diseases with myotonia, except 1 patient with dominant myotonia congenita, had no transient weakness and a CMAP decrement below 25%.

Responses of intercostal muscle biopsies from normal subjects and patients with myasthenia gravis

In order to evaluate the mechanisms of weakness in muscles of patients with myasthenia gravis (MG), intercostal muscle biopsies were obtained from 9 normal subjects and 6 MG patients, and the compound muscle action potential (AP) and tension responses to nerve and muscle stimulation, and contracture responses on exposure to caffeine, were monitored in vitro. In normal muscle, on stimulation of the nerve or muscle at 30 to 100 Hz, the AP responses showed decrement in amplitude, one-third of which was attributable to failure of neuromuscular transmission and two-thirds to failure of muscle membrane excitation. On stimulation at 1 to 5 Hz, the AP responses showed very little decrement, while the contractile responses showed significant fade in tension, due to failure of E-C coupling or contractility. In muscle from patients with generalized MG, stimulation of the nerve at all frequencies (1 to 100 Hz) caused much greater decrement in APs and fade in tension responses than in normal muscle, due mainly to failure of neuromuscular transmission. However, at 100 Hz, 40% of the decrement in APs was due to failure of muscle membrane excitation, and at 1 to 5 Hz, 40% of the fade in tension was due to failure of E-C coupling or contractility, as in normal muscle. On direct stimulation the contraction and half-relaxation times were slower and the tetanic tension was smaller than in normal muscle, especially in the MG patient with thymoma. Caffeine-induced contractures were smaller in MG muscle than in normal muscle. These results indicate that while the weakness of MG muscle is due mainly to failure of neuromuscular transmission, it is also partly due to reduced E-C coupling or contractility.

An empirical evaluation of the effects of high-pass noise on the whole-nerve action potential.

A number of methods are presented for evaluating the effect of high-pass noise on the whole-nerve action potential (AP). These methods include measurements of AP thresholds, amplitude-versus-level functions, decrement in AP amplitude-versus-masker level functions, and AP tuning curves. Examinations of threshold shifts as a function of tone-burst frequency and AP amplitude-versus-level with and without the presentation of high-pass noise indicate that basal portions of the cochlear partition can be masked effectively. Decrement in AP amplitude-versus-masker level functions and subsequently constructed AP tuning curves were used to verify that the presentation of high-pass noise did not alter the frequency response of that region of the basilar membrane responding to a 4000-Hz tone-burst probe. As a result, we conclude that high-pass noise may be used to mask the response from remote regions of the cochlea without altering response characteristics from lower frequency regions.