Electrophysiologic changes in uremic neuropathy after successful renal transplantation.

The pattern of electrophysiologic abnormalities in uremic neuropathy was studied in 17 patients near the time of successful renal transplantation and for an average of 2 years (4 to 68 months) afterward. Initially, sensory and motor conduction velocities were reduced, distal latencies were lengthened, and evoked action potentials were reduced or dispersed. These abnormalities were most marked in clinically severe neuropathies and were consistent with the combined presence of axonal degeneration and segmental demyelination. Following transplantation, there was a sustained improvement in motor and sensory conduction velocities but less consistent improvement in evoked action potentials. In severe neuropathies, action potentials tended to remain reduced or absent. The results suggest that the main reason for improvement in the neuropathy is segmental remyelination, some fibers remaining degenerate in severe neuropathies. In four patients, late failure occurred in the transplanted kidney, which was accompanied by recurrence of neuropathy. In each patient, a second successful transplant effected improvement for a second time.

Human pneumatic tourniquet paralysis.

A 47-year-old woman experienced loss of strength, sensation, and sweating distal to a pneumatic tourniquet applied to her upper arm during operation for a Dupuytren contracture. Electrophysiologic tests showed a severe conduction block of sensory and motor fibers, well localized to the presumed lower margin of the tourniquet, with little evidence of axonal degeneration. Reversal of block began at 5 weeks and was complete in 6 months, coincident with almost full clinical recovery. Sweating was absent before 5 weeks and then returned, accompanied by a causalgic syndrome that did not disappear until recovery from the electrophysiologic block. The findings in this case correspond closely to pneumatic tourniquet paralysis in baboons, the pathophysiology having been recently defined. The relationship of autonomic changes to the electrophysiologic block suggest a mechanism for this patient's causalgia.

Nerve and muscle biopsy: electrophysiology and morphology in polyneuropathy.

We correlated the results of biopsy of a muscle nerve, a sensory nerve, and tibialis anterior muscle with electrophysiologic studies in 13 patients with sensorimotor polyneuropathy and 6 patients with normal findings. There were significant correlations between teased fiber changes and conduction abnormalities in both muscle nerves and sensory nerves. The density of large myelinated fibers in the lateral fascicle of the deep peroneal (LFDP) nerve correlated significantly with both the motor unit estimate and compound action potential amplitude of the extensor digitorum brevis (EDB) muscle. Other characteristics of the EDB muscle compound action potential related poorly to teased fiber abnormalities. There was good correlation of needle electrode study of the EDB muscle with teased fiber analysis of the LFDP nerve and with the morphology of the tibialis anterior muscle in 75 percent of the cases, and only minor discrepancies in the remainder. These results emphasize the close relationship between certain structural and electrophysiologic changes in subacute and chronic polyneuropathy.

Repetitive phrenic nerve stimulation in myasthenia gravis.

OBJECTIVE: In patients with MG it may be difficult to determine whether respiratory insufficiency is due to a defect in neuromuscular transmission. We therefore studied the clinical value of repetitive electrical stimulation of the phrenic nerve. METHODS: Repetitive phrenic nerve stimulation at 3 Hz was performed in 25 patients with MG. We recorded from the ipsilateral hemidiaphragm with surface electrodes before and after exercising the diaphragm for 10 and 90 seconds. The percent decrement of the negative peak (NP) area between the first and the fifth or sixth diaphragmatic compound muscle action potential (DCMAP) was analyzed and results compared with those from 10 healthy individuals. RESULTS: The mean +/- standard deviation percent change of the NP area in healthy individuals was -2.1 +/- 4.2%, with a normal cutoff of > or = 11%. Twelve patients (48%) had an abnormal decrement of DCMAP--9 had a decrement when the diaphragm was rested, 3 only after fatiguing of the diaphragm. The mean percent change in the 12 patients was 20% at rest, -18% after 10 seconds of exercise, and -23% after 90 seconds of exercise-a pattern consistent with MG. Repetitive stimulation of the accessory nerve with recording of the trapezius CMAP (TCMAP) was abnormal in nine patients (36%). The three patients with abnormal decrement of the DCMAP despite normal TCMAP had symptoms of dyspnea. CONCLUSIONS: Repetitive phrenic nerve stimulation studies are a promising tool in the diagnosis of respiratory muscle weakness in MG and should be part of electrophysiologic studies in patients with undiagnosed respiratory failure.

Peripheral nerve function in sepsis and multiple organ failure.

Forty-three patients who had sepsis and multiple organ failure (critical illness) were studied prospectively to determine the incidence and severity of peripheral nerve function and to correlate such function with a number of variables. Electrophysiologic studies indicated a primary axonal degeneration of motor and sensory fibers in 30 (70 percent). Fifteen (30 percent) had the clinical signs of difficulty in weaning from assisted ventilation, weakness of limb muscles, and reduced or absent deep tendon reflexes. Full recovery from the polyneuropathy occurred among the 23 (53 percent) who survived, except three who had a very severe polyneuropathy. A peripheral nerve function index, computed from electrophysiologic measurements, showed statistically significant (p less than 0.01) negative correlations with the time in the critical care unit, and the serum glucose value; the serum albumin level showed a positive correlation. Multiple regression analyses indicated all three factors accounted for 47 percent (r2 = 0.4678) of all potential variables. In a separate analysis, the nerve function index correlated with the amplitude of the diaphragm compound muscle action potential (p less than 0.01). The results were consistent with the polyneuropathy being due to the same mechanisms that are currently postulated to cause dysfunction in this syndrome of other organ systems (including the neuromuscular respiratory system).

Genotype/phenotype correlations in X-linked dominant Charcot-Marie-Tooth disease.

We have studied the relationship between genotype, clinical phenotype, and pathology in 13 families with dominant X-linked Charcot-Marie-Tooth (CMT) neuropathy. Connexin32 (Cx32) gene mutations were spread throughout the coding region and included eight missense mutations, one 8-bp deletion/4-bp insertion frame shifting mutation, two nonsense mutations, and one deletion of the entire coding sequence. One hundred sixteen affected CMTX patients (53 males and 63 females) and 63 unaffected, at-risk individuals were compared by neurological and electrophysiological examinations and analyzed by gender; nerve biopsies were available from seven index cases. It was found that mutations within all regions of the Cx32 gene coding sequence caused an identical clinical phenotype. Male CMTX patients were affected more severely and showed an age-dependent progression of clinical signs and of the pathology; there was, however, variability in the severity of disease expression, irrespective of age, among males within families of defined genotype. All but 10% of female CMTX patients had only mild signs. Motor nerve conduction velocities were moderately slowed (median nerve MNCV: males 34.5 +/- 6.2 m/sec; females 45.8 +/- 7.3 m/sec), and motor and sensory nerve amplitudes were reduced (median nerve CMAP: males 3.7 +/- 3.7 mV; females 7.8 +/- 3.4 mV), with electromyographic evidence of chronic denervation. Differences were significant between gender and between affected and unaffected individuals. In agreement with the electrophysiological observations, pathological studies showed evidence of paranodal demyelination and of a length-related axonal degeneration in motor and sensory nerve fibers. Correlations between genotype and clinical phenotype suggested that missense mutations located within the second transmembrane domain and/or cytoplasmic loop might be associated with milder clinical phenotype, and therefore might be less disruptive of connexin32 gap junction function. Missense, chain-terminating, or deletion mutations in all other locations of the connexin32 protein caused severe forms of CMTX and disease onset in the first decade. Observed variability of disease severity among males within kinships suggests the influence of other modifying factors.

Neuromuscular complications of sepsis.

Sepsis and multiple organ failure are major problems in medical and surgical intensive care units. Critical illness polyneuropathy occurs in 70% of these patients. Difficulty in weaning from the ventilator is an early sign. Electrophysiological studies are necessary to establish the diagnosis; these studies show an axonal degeneration of peripheral nerve fibres. Recovery occurs in weeks or months, depending upon severity. Muscle biopsy reveals denervation atrophy. Sepsis itself does not induce a neuromuscular transmission defect, but neuromuscular blocking agents may increase the severity of critical illness polyneuropathy. If steroids are used in addition to neuromuscular blocking agents, a severe myopathy may result. Other effects on muscle are cachectic myopathy and panfascicular muscle fibre necrosis. A variety of combinations of these conditions may affect the same patient. Only well-designed prospective studies will determine the true effect of these medications on the neuromuscular system in septic patients.

Neuromuscular disorders associated with failure to wean from the ventilator.

OBJECTIVE: To determine, by retrospective chart analysis, the frequency, type and significance of neuromuscular disorders in patients whose clinical features suggested a neuromuscular cause of failure to wean. BACKGROUND: Failure to wean is a common and difficult problem in critical care units. While a neuromuscular cause may be suspected in some patients, the frequency and type has not been determined utilizing comprehensive electrophysiological studies of limbs and the respiratory system. Such knowledge may aid in patient management and prognosis. METHODS: The clinical setting was a critical care/trauma centre that admits 1500 patients per year, approximately 500 being on ventilators for longer than five days. We analyzed the hospital charts of 40 patients admitted to the unit during three years, whose respiratory assessment suggested a neuromuscular cause for failure to wean from the ventilator. To investigate this possibility, we performed electrophysiological studies of the limbs and also of the respiratory system by phrenic nerve conduction and needle electromyography of the chest wall and diaphragm. The results were compared to 25 healthy controls. RESULTS: 38 of 40 patients (95%) had a neuromuscular disorder: 25--critical illness polyneuropathy, 2--Guillain-Barré syndrome, 4--diabetic and critical illness polyneuropathy, 2--uremic and critical illness polyneuropathy, 10--an abnormality of central drive, 5--unilateral phrenic nerve palsy, 3--a neuromuscular transmission defect, and 5--a primary myopathy. Fifteen (38%) had a combination of disorders. Patients with more severe polyneuropathy took longer to wean, a mean of 136 versus 52 days (p = 0.007). The severity of the polyneuropathy had no effect on mortality. CONCLUSIONS: Electrophysiological studies of limbs and the respiratory system are together valuable in confirming the presence, and identifying the specific type of neuromuscular cause for difficulty in weaning from the ventilator. This information is important in patient management and prognosis.

Clinical and electrophysiological findings in critical illness polyneuropathy.

Sixty two patients with critical illness polyneuropathy (CIP) were studied prospectively to determine the clinical and electrophysiological profile, to assess the prognostic value of respiratory electrophysiology in determining the duration of ventilation and to analyze the role of neuromuscular blocking agents (NMBA) and steroids. Limb motor and sensory nerve conductions, bilateral phrenic nerve onset latencies, bilateral diaphragmatic compound muscle action potentials (CMAP), unilateral diaphragmatic needle electromyography (EMG), limb muscle EMG, time on the ventilator, time in the intensive care unit (ICU), dosage of NMBA and steroids were analyzed in 62 patients. The diagnosis of CIP was made by clinical criteria, electrophysiological criteria and exclusion of any other condition suspicious of an axonal neuropathy. The results of phrenic nerve conduction studies and diaphragmatic EMG were compared to normal mean values in 25 healthy subjects. The most common finding in our study were reduced CMAPs and abnormal spontaneous activity in muscle, occuring in 100%. Forty per cent had reduced CMAPs but normal sensory nerve action potentials (SNAP). These patients had normal CK-levels and normal findings, unspecific changes, type 2 fibre atrophy or denervation atrophy on muscle biopsy. Seventy seven per cent of patients had abnormal diaphragmatic CMAPs and spontaneous activity in the diaphragm indicating denervation of the diaphragm is common in CIP. There was no statistically significant relationship to the dosage of NMBA and steroids, and the respiratory electrophysiological studies, duration of ventilation and stay in the ICU.

Severe axonal degeneration in acute Guillain-Barré syndrome: evidence of two different mechanisms?

Four cases of severe acute Guillain-Barré syndrome (GBS) characterized by severe axonal degeneration are presented. All had electrically inexcitable motor nerves as early as 4 days after onset. The disease was rapid in onset and the residual disability was severe. Two different types of pathology were seen. Nerve biopsies in 3 cases showed severe axonal degeneration without inflammation or demyelination. Autopsy in one of these cases showed that the dorsal and ventral roots were also significantly affected. These cases illustrate the primary axonal form of GBS. Nerve biopsy in the fourth case at day 15 showed marked inflammation and demyelination with axonal degeneration. Contralateral nerve biopsy at day 75 showed almost complete loss of axons. This case illustrates another type of axonal degeneration, that which occurs secondary to inflammation and demyelination.

The cortical representation of somatosensory evoked potentials of the phrenic nerve.

Respiratory electrophysiological studies are of essential value in diagnosing and managing patients with respiratory failure, but assessment of the sensory phrenic nerve fibres has been neglected. We recorded phrenic nerve somatosensory evoked potentials (SSEPs) by combining neurophysiological and neuroimaging techniques in three healthy subjects. Evoked potentials of the phrenic nerve showed the highest amplitude at CP3, determined by the modified 10-20 EEG system, and occurred at a constant latency, PI at 12.0 +/- 0.6 ms, and NI at 17.3 +/- 0.8 ms. Single photon emission computer tomography (SPECT) performed during phrenic nerve stimulation revealed focal neuronal activation in the somatosensory pathways. Intravenously administered Tc-99m Ethyl Cysteinate Dimer (ECD) was used as a blood flow tracer to obtain baseline and activated images. After image registration, baseline images were compared voxel-by-voxel with the activation images. The mean inter-subject summation image of the activated state was compared with that of the baseline state using ten normal subjects. The extent of the total voxel volume increase on the mean images of the 3 activated SPECT images was 0.7%, and a mean signal increase of 22%. For further anatomic localization of regional increases in signal, the magnetic resonance image (MRI) scan of each subject was registered and superimposed on the activated stage SPECT image. This method may be used clinically to study the pathophysiology of impaired central respiratory drive.

Repetitive phrenic nerve stimulation study in normal subjects.

In patients with myasthenia gravis (MG), it may be difficult to determine by clinical methods if respiratory insufficiency is due to a defect in neuromuscular transmission. We therefore studied the technique of repetitive electrical stimulation of the phrenic nerve in 6 healthy subjects. It was easily performed and quite reproducible. Responses at 3-Hz stimulation were recorded from surface electrodes of the ipsilateral hemidiaphragm, before and after exercise. We analyzed the percent decrement of the negative peak (NP) amplitude, area, and duration of the diaphragmatic compound muscle action potential (CMAP) between the first and the fifth or sixth potentials. The mean percentage change of the area was -2.2% (+/-4.3), and in all tests the change was <10.6%, yielding a normal range of <11%. The change in the NP amplitude was 12.1% (+/-8.3); in duration, the change was -8.7% (+/-9.6). Producing diaphragm fatigue did not change these results. The increase in amplitude and decrease in duration with little change in area, termed pseudofacilitation, may be due to shifts in the position of the diaphragm affecting volume conduction. The technique is a promising tool in the diagnosis of respiratory involvement from neuromuscular transmission disorders.

The electroencephalogram in sepsis-associated encephalopathy.

To define the EEG and associated clinical features of septic encephalopathy, we studied 62 patients with positive blood cultures. Patients were divided into three clinical groups: nonencephalopathic (NE), mildly encephalopathic (ME), and severely encephalopathic (SE); the latter two groups had diffuse cerebral dysfunction. EEGs were classified into five groups: normal, excessive theta, predominant delta, triphasic waves, and suppression or burst suppression, in ascending order of severity. The EEG (1) was more sensitive than our clinical criteria for encephalopathy, (2) showed features that were, when considered with clinical and laboratory characteristics, compatible with a potentially reversible encephalopathy, and (3) had well-defined categories that correlated with percent mortality, even within a single clinical group. We conclude that the EEG is a sensitive index of brain function in septic encephalopathy and that it is especially useful in the intensive care monitoring of patients with sepsis.

Distinctive electrophysiological features of denervated muscle in uremic patients.

Abnormal spontaneous activity is a hallmark of acute or subacute denervation of skeletal muscle, particularly in patients with uremic neuropathy. We report 5 patients in whom such activity was unexpectedly minimal or absent.

Neuromuscular complications of sepsis in children.

Sepsis occurs frequently in the pediatric intensive care unit and is a significant cause of morbidity and mortality. Multiple organ systems are adversely affected by sepsis. Approximately 70% of adult patients with sepsis have peripheral nervous system dysfunction on electrophysiologic studies, of whom 30% are symptomatic. Neuromuscular dysfunction in children with sepsis is increasingly reported; however, the incidence remains undefined. Flaccid quadriplegia with the inability to wean from ventilatory support despite full cardiopulmonary recovery is the typical presentation. However, lesser degrees of weakness may be demonstrated with careful evaluation. Electrophysiologic studies often demonstrate the presence of axonal polyneuropathies, abnormalities of neuromuscular transmission, or acute myopathies. Identifiable neuromuscular syndromes in children with sepsis include critical illness polyneuropathy, pure motor polyneuropathy, thick-filament myopathy, and necrotizing myopathy. The common underlying pathogenic process in these syndromes appears to be sepsis, which may be accentuated by the administration of steroids or neuromuscular blocking agents. Recovery in strength usually occurs over a period of weeks to months.

The effect of alterations of uremic retention products upon platelet and peripheral nerve function.

Attempts at the identification of specific uremic toxins have, to date, been unrewarding and yet there is vogue for the measurement of, and the control by devices of hypothetical levels of, "middle molecular weight" toxins. In an attempt to elucidate whether small or middle molecular weight retention products are responsible for uremic platelet and peripheral nerve conduction defects, 14 patients with end-stage renal disease established on hemodialysis were studied using a conventional hemodialyzer and an experimental device which combined hemodialysis and hemoperfusion and which has enhanced in vitro vitamin B12 clearances. With the latter device reduced BUN and creatinine clearances were encountered and over a 2-month treatment period patient's serum BUN rose. In spite of this, there was improvement in the velocity of platelet aggregation to 10 microM adenosine diphosphate and to a standard collagen preparation associated with treatment by the experimental device. There was not, however, any demonstrable influence made on nerve conduction studies. The study suggests that different uremic retention products influence platelet and peripheral nerve function and that further efforts into studying the function of living cells or systems, in uremia might have better yield in the future guidance of the adequacy of dialysis than will the biochemical measurements of various waste products.

Assessment of respiratory function in the intensive care unit.

Disorders of both the central and peripheral nervous systems are important causes of respiratory insufficiency. However, simple clinical observations and pulmonary function measurements may fail to identify the location and type of disorder. This can often be accomplished by the newly-developed technique of phrenic nerve conduction and needle electromyography of the diaphragm which delineate the various disturbances of central drive, axonal or demyelinating neuropathies of the phrenic nerves and certain myopathies. These studies have been preformed safely and with little discomfort on adults, children or infants, and in out-patient and general ward settings. We have found they are of particular value in the intensive care unit.

Peripheral neuropathies associated with chronic renal failure.

A variety of peripheral nerve disorders may be associated with chronic renal failure. The polyneuropathy due to uremic toxins is a distal, motor and sensory polyneuropathy in which there is segmental demyelination, axonal degeneration, and segmental remyelination. The nature of the uremic toxin and the underly mechanism of these changes is unknown. The incidence in patients with "end-stage" renal disease has fallen in recent years, severe cases now being rare, perhaps due to refinements in chronic hemodialysis, transplantation, and other therapies. However, while chronic hemodialysis stabilizes uremic neuropathy, manipulation of hemodialysis schedules may not alter its course, according to current assessment. Successful renal transplantation improves both the clinical and electrophysiological signs, even in severe uremic neuropathy.

Minimum standards for electromyography in Canada: a statement of the Canadian Society of Clinical Neurophysiologists.

BACKGROUND: Electromyography (EMG) is a widely used diagnostic technique for disorders of the nervous system. The Canadian Society of Clinical Neurophysiologists (CSCN) promotes the education, evaluation and standards of EMG in Canada. A statement of practice standards was needed to clarify the position of the CSCN on several issues relevant to the practice of EMG. METHODS AND RESULTS: A subcommittee of the CSCN reviewed current patterns of practice and established guidelines for review by the CSCN. The guidelines developed by the subcommittee were reviewed by the CSCN and adopted as recommendations for EMG practice. The subcommittee was charged with formulation of a document for publication. CONCLUSIONS: This document deals with minimum standards for electromyographer education, laboratory operation, equipment and a variety of special circumstances relevant to the practice of EMG. The standards can be adopted by EMG laboratories to guide quality assurance.