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Mutations in the myelin protein zero gene (MPZ) are associated with certain demyelinating neuropathies, and in particular with Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome, and congenital hypomyelination. MPZ mutations affecting the protein's transmembrane domain are generally associated with more severe phenotypes. We describe a family with mild CMT1B associated with a transmembrane MPZ mutation. Sequence analysis identified a G-to-C transversion at nucleotide 1064, predicting a glycine-to-arginine substitution in codon 163 (G163R) of MPZ. This report furthers the understanding of the clinical and electrophysiological manifestations of MPZ mutations.

This phase I, double-blind, randomized, placebo-controlled study evaluated the safety of single and multiple (daily for 7 days) subcutaneous administrations of recombinant-methionyl human neurotrophin-3 (r-metHuNT3) in healthy human volunteers at seven doses, ranging from 3 to 500 microg/kg/day. No serious or life-threatening adverse events occurred. The most frequently recorded adverse effects were mild injection-site pain, diarrhea, and elevation of liver function tests. No change in neurologic function was noted with these dosing regimens. We conclude that r-metHuNT3 is safe and well tolerated in the dosages used in this study., (Copyright 2000 John Wiley & Sons, Inc.)

Guillain-Barré syndrome (GBS) is recognized clinically by the presence of acute, rapidly progressive weakness, areflexia, and albuminocytological dissociation in cerebrospinal fluid. Although GBS was initially considered to be primarily an acute inflammatory demyelinating polyneuropathy (AIDP), several other subtypes have been recognized: acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), and Fisher syndrome (FS). Because each of these subtypes may have an independent immunopathogenesis and, therefore, may require selective treatments in the future, recognition of these subtypes is important. When using nerve conductions to classify the subtypes, the most easily and confidently identified subtype is AIDP. Therefore, most electrodiagnostic criteria have attempted to identify demyelination in this acute setting, in which physiology is constantly changing. In a single well-defined GBS population, we compared the various published criteria for demyelination in GBS. We reviewed charts of 43 patients with GBS between 1991 and 1996. Applying six available criteria sets, the number of patients categorized as having AIDP ranged from 21% to 72%. Until investigators can agree on a single set of criteria, considerable variability will continue to exist when identifying cases of AIDP.

Diagnosis of multifocal motor neuropathy (MMN), a syndrome characterized by progressive asymmetric weakness with intact sensation, is important because the disorder often responds to treatment. Multifocal partial motor conduction block (PMCB) has been emphasized as a cardinal feature in the diagnosis of this syndrome, but detailed nerve conduction studies are not available. Nine patients, ages 28-58, had chronic, progressive, asymmetric, predominantly distal limb weakness for 5-18 years. Sensation was normal and reflexes were reduced asymmetrically. Although all 9 demonstrated PMCB localized to short nerve segments, additional features of multifocal motor demyelination were present, including temporal dispersion (5 patients), segmentally reduced motor nerve conduction velocity (7 patients), prolonged distal motor latency (4 patients), and prolonged F-wave latency (9 patients). The strength of all patients improved after treatment with human immune globulin. A reduction in the degree of PMCB or an increase in the distal motor amplitude or both accompanied the clinical improvement. These studies suggest that patients with MMN demonstrate widespread evidence of motor demyelination in addition to the well-described PMCB, and that reduction of PMCB accounts for the increase in strength following therapy.

Nerve conduction studies (NCS) are an integral part of the evaluation of amyotrophic lateral sclerosis (ALS) patients and are useful in distinguishing ALS from disorders that mimic it. The question often arises whether in the presence of severe atrophy and reduction of the compound muscle action potential amplitude, abnormal conduction velocity (CV), distal latency (DL), or F-wave latency (F) exceeds what can be expected from ALS alone. To determine the limits of abnormality in classic ALS, we prospectively evaluated NCS data from 61 patients who met a strict clinical definition of ALS. We related CV, DL, and F to distal evoked amplitude (AMP) in peroneal (n = 63 observations), median (n = 50), and ulnar (n = 52) nerves. In nerves with reduced AMP, CV rarely fell to less than 80% of the lower limit of normal, and DL and F rarely exceeded 1.25 times the upper limit of normal. Utilizing the entire data set and regression analyses, 95% confidence limits for expected values for CV, F, and DL as a function of AMP were calculated. These limits thus derived suggest criteria for NCS abnormalities in ALS and may be useful in differentiating ALS from other illnesses.

After nerve transection, the distal stump undergoes Wallerian degeneration (WD). Little information is available concerning sequential changes in nerve conduction measurements during WD in humans. Five patients with nerve injuries were studied temporally. Motor-evoked amplitudes were reduced by 50% at 3 to 5 days after injury; the response was absent by day 9. Sensory-evoked amplitudes were reduced by 50% at 7 days after injury; the response was absent by day 11. Sensory and motor nerves with shorter distal stumps showed earlier loss of amplitude than did those with longer distal stumps. Denervation potentials were seen 10 to 14 days after injury. Our results suggest that WD occurs earlier if the distal stump is shorter, and that motor-evoked responses are affected earlier than sensory-evoked responses. The time-lag between the loss of the motor-evoked response and the appearance of denervation potentials, the latter coinciding with reduction of sensory evoked responses, suggests that failure of neuromuscular transmission precedes axonal loss during WD.

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Electrodiagnosis is confirmed by an increase in compound muscle action potential amplitude during high-frequency repetitive nerve stimulation or following brief exercise. We describe the results of stimulated single-fiber electromyography in 4 patients with disorders of neuromuscular transmission: LEMS (2), LEMS/myasthenia gravis (MG) overlap (1), and MG (1). Stimulated SFEMG was performed in the extensor digitorum communis muscle with axonal intramuscular suprathreshold stimulation at low and high rates. In all 4 patients, a rate dependence of jitter was found. In LEMS and LEMS/MG, jitter and blocking improved with high stimulation rates, as compared with the opposite effect in MG. We conclude that stimulated SFEMG is a valuable technique in the diagnosis of LEMS.

Symmetric sensorimotor polyneuropathy is a common complication of diabetes. Sensory and motor evoked amplitudes and conduction velocities are reduced. Both demyelination and axon loss have been reported in pathologic studies. Conduction block (CB), a manifestation of segmental demyelination, has not been previously studied in diabetic neuropathy. We determined the prevalence of conduction block in patients with diabetes by analyzing electrodiagnostic data from 24 diabetics. Conduction block was defined as a greater than 20% drop in peak-to-peak amplitude, and a less than 15% change in negative-peak duration between proximal and distal stimulation sites. A total of 76 nerve segments were studied. The criteria for conduction block were met in only 6 segments in 6 patients. The mean decrease in peak-to-peak amplitude between stimulation sites was 28% (range 21% to 40%). We conclude that conduction block over long nerve segments is uncommon in diabetic neuropathy, and, if present, suggests that other causes for neuropathy in diabetic patients should be sought.

The nosological distinction between paramyotonia congenita (PC) and hyperkalemic periodic paralysis (HPP) continues to generate debate. Recently, electrophysiological signs thought to be specific for each entity have been described and have been used to bolster the argument that the two disorders are distinct. We report a particularly instructive family wherein individual members had clinical features of either PC or HPP and electrophysiological features of both. We suggest that PC and HPP represent part of the spectrum of a single genetic disorder. Evoked response testing, with exercise and cold provocation, may be useful in determining the physiologic pattern that predominates in any one individual.

Disorders of neuromuscular transmission in infants and children can be divided into two groups. The first group includes conditions similar to those seen in adults: autoimmune myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism. The second includes several disorders that are unique to this age group, such as the congenital myasthenias and infantile botulism. This review discusses the diseases of neuromuscular transmission found in the pediatric population, with emphasis on electrodiagnosis. The distinctive clinical and electrophysiologic features allow the clinician to identify these illnesses correctly, so that appropriate treatment can be instituted or further specialized investigation can be undertaken.

Peripheral neuropathy is a common complication of human diabetes, but its occurrence in spontaneously diabetic monkeys is unknown. Four months after developing diabetes, a 22-year-old female rhesus monkey had nerve conduction studies which were compared with control data obtained from 9 nondiabetic rhesus monkeys. In the diabetic monkey, median and ulnar sensory action potential amplitudes and the median motor distal latency differed from controls by more than two standard deviations. Conduction velocities in the diabetic monkey were less than the mean values in controls, although none were beyond two standard deviations of control means. These electrophysiologic abnormalities are similar to those described in human diabetes and suggest that the spontaneously diabetic monkey peripheral nervous system may be a suitable model of experimental diabetic neuropathy.

Colchicine may produce a neuromuscular disorder even when given in customary doses. We report the electrodiagnostic features in eight pathologically proven cases of colchicine-induced myoneuropathy. Myopathic motor unit potentials and early recruitment were found in proximal limb and truncal muscles, frequently with fibrillations, positive sharp waves, or complex repetitive discharges. These electromyographic findings correlated with the course of the weakness, which rapidly resolved within weeks of drug discontinuation, indicating that the major functional disturbance in the patients was myopathy. The accompanying signs of axonal neuropathy persisted longer, with little functional consequence. Although often misrecognized as polymyositis, colchicine myoneuropathy was identifiable by the rapid clinical and electrophysiologic improvement following drug withdrawal as well as by its distinctive morphology.

Infantile botulism is a recently recognized cause of acute hypotonic paresis and respiratory failure in young infants. Electrophysiological testing has proven useful in early diagnosis in suspected cases by demonstrating abnormal neuromuscular transmission as is known to occur in botulism. Twenty-five infants with bacteriologically proven botulism were studied by uniform methods in our laboratory and characteristic electrophysiological abnormalities were found. Repetitive stimulation at 20 and 50 Hz was the most specific single test; 23 patients (92%) showed incremental responses. Stimulation at low rates was less specific. Concentric needle electromyography provided useful supplemental information. Short-duration, low-amplitude motor unit potentials were prominent in 22 patients (92%) accompanied by abnormal spontaneous activity in 13 patients (54%). Compound muscle action potential amplitudes were usually reduced, but motor and sensory conduction studies were otherwise normal. Electrodiagnostic testing demonstrated one or more characteristic abnormalities in all cases of infantile botulism. This constellation of electrophysiological abnormalities, combined with an appropriate clinical picture, was so distinctive as to allow early presumptive diagnosis of infant botulism, before the results of bacteriological testing were available.

The distribution of muscle involvement, assessed clinically and electromyographically, was analyzed prospectively in 55 consecutive amyotrophic lateral sclerosis (ALS) patients and in 54 patients with other predominantly motor syndromes, some of whom were referred with suspected ALS. In ALS patients, distal limb muscles and thoracic paraspinal muscles were affected most frequently, more so than proximal limb and cranial muscles. The incidence of bulbar symptoms in ALS was greater in women than in men. These patterns suggest selective vulnerability of specific neuronal populations. The vulnerability of truncal muscles, illustrated by thoracic paraspinal wasting or head and shoulder drooping, was a helpful differential sign in diagnosing ALS. Thoracic paraspinal electromyography was especially valuable in distinguishing ALS from other disorders, such as combined cervical and lumbar spondylotic amyotrophy or polymyositis, which may masquerade as ALS. The finding of denervation atrophy on biopsy of thoracic paraspinal muscles was diagnostic in difficult cases. Because the thoracic paraspinal muscles are frequently affected in ALS and spared in spondylotic amyotrophy, their assessment provides a practical strategy in differentiating ALS from other motor syndromes.

We studied the effects of transient focal ischemia on the electrophysiologic function of rat sciatic nerves. Focal and generalized impairment of impulse conduction, measured by falling evoked muscle and nerve compound action potential amplitudes, occurred within 10 minutes of femoral artery occlusion. Conduction failure reached a nadir at 45-60 minutes and then improved to normal within 24 hours. Fastest motor and mixed nerve conduction velocities were reduced less than 15% of baseline values during the period of acute conduction block. There were no detectable morphological abnormalities at the site of conduction failure. Transient ischemia produces reversible conduction block without evident structural changes. The fall in amplitude without significant conduction slowing implies that slower conducting myelinated fibers are relatively more sensitive to the effect of acute ischemia.