Biomedical subjects

J M Shefner

Publications and source records attributed to J M Shefner.

At least 19 recordsLinked to original sources

PubMed1999

Mice lacking cytosolic copper/zinc superoxide dismutase display a distinctive motor axonopathy.

OBJECTIVE: To characterize the motor neuron dysfunction in two models by performing physiologic and morphometric studies. BACKGROUND: Mutations in the gene encoding cytosolic superoxide dismutase 1 (SOD1) account for 25% of familial ALS (FALS). Transgenes with these mutations produce a pattern of lower motor neuron degeneration similar to that seen in patients with FALS. In contrast, mice lacking SOD1 develop subtle motor symptoms by approximately 6 months of age. METHODS: Physiologic measurements, including motor conduction and motor unit estimation, were analyzed in normal mice, mice bearing the human transgene for FALS (mFALS mice), and knockout mice deficient in SOD1 (SOD1-KO). In addition, morphometric analysis was performed on the spinal cords of SOD1-KO and normal mice. RESULTS: In mFALS mice, the motor unit number in the distal hind limb declined before behavioral abnormalities appeared, and motor unit size increased. Compound motor action potential amplitude and distal motor latency remained normal until later in the disease. In SOD1-KO mice, motor unit numbers were reduced early but declined slowly with age. In contrast with the mFALS mice, SOD1-KO mice demonstrated only a modest increase in motor unit size. Morphometric analysis of the spinal cords from normal and SOD1-KO mice showed no significant differences in the number and size of motor neurons. CONCLUSIONS: The physiologic abnormalities in mFALS mice resemble those in human ALS. SOD1-deficient mice exhibit a qualitatively different pattern of motor unit remodeling that suggests that axonal sprouting and reinnervation of denervated muscle fibers are functionally impaired in the absence of SOD1.

Action Potentials↗

PubMed1999

The cutaneous silent period is mediated by spinal inhibitory reflex.

High-intensity cutaneous stimuli inhibit tonically firing motor neurons resulting in a silent period (CSP) in EMG activity. To determine the central nervous system (CNS) circuitry of this inhibitory reflex, soleus H reflexes evoked by tibial nerve stimuli were conditioned by high-intensity sural stimuli in 5 normal men and 5 men with complete, traumatic cervical myelopathy. The sural-tibial interstimulus interval (ISI) was varied between 0 and 200 ms. In normals, the CSP in the tonically contracted soleus muscle began 90-100 ms after sural stimuli and had a duration of 60-80 ms. In the relaxed soleus, the conditioned soleus H-reflex amplitude was correspondingly reduced at ISIs of 60-120 ms. In patients, conditioned H-reflex amplitude was also reduced over the same ISI range, but the degree of inhibition was significantly less than in normals. These data support the hypothesis that the CSP is mediated by a spinal inhibitory reflex that is subject to supraspinal descending control.

Adult↗

PubMed1999

Amplitude-dependent slowing of conduction in amyotrophic lateral sclerosis and polyneuropathy.

The mechanism of motor nerve conduction slowing in amyotrophic lateral sclerosis (ALS) is thought primarily to be loss of large, fast-conducting motor fibers; this is less certain in axonal polyneuropathy. We compared motor conduction studies in 64 patients with axonal polyneuropathy with 72 patients with ALS. Compound motor action potential amplitude, distal motor latency, and conduction velocity were converted to a percentage of the upper or lower limit of normal and then represented as a square root (SQRT) transformation, plotted with SQRT amplitude as the independent variable and SQRT latency or SQRT conduction velocity as the dependent variables. Regression analysis of the lower extremity nerve data showed that prolongation of latency and slowing of velocity were amplitude-dependent and were virtually identical in ALS and polyneuropathy. In the upper extremity, amplitude-dependent prolongation of latency was similar in both groups, but amplitude-dependent slowing of velocity was seen in ALS and not in axonal polyneuropathy. Our data support the hypothesis that the major mechanism of slowing is similar in both polyneuropathy and ALS and is the loss of large, fast-conducting fibers. However, the presence of distal but not proximal slowing in the upper extremity of axonal polyneuropathy suggests that additional mechanisms may be contributory.

Action Potentials↗

PubMed1999

Reducing intersubject variability in motor unit number estimation.

Motor unit number estimation (MUNE) attempts to directly assess the number of functioning motor units present in a muscle. It is an important addition to the electrodiagnostic evaluation; however, both intrasubject and intersubject reliability must be minimized for this technique to be clinically useful. A number of MUNE techniques have been developed. We propose a change in the way of calculating the MUNE, using the statistical technique described by Daube, and show that this modification reduces intersubject variability and improves test-retest reliability in normal subjects.

Adult↗

PubMed1999

Ulnar neuropathy at the elbow.

Among the entrapment neuropathies, ulnar neuropathy at the elbow is second only to carpal tunnel syndrome in frequency; however, diagnosis and management are considerably more difficult in ulnar lesions than in carpal tunnel syndrome. Electrodiagnosis is the most important means of identifying and localizing ulnar neuropathies at the elbow, but even sophisticated techniques may sometimes fail to confirm diagnosis and localization preoperatively. Mild lesions are best managed conservatively. More severe lesions require surgical intervention. Simple decompression is now preferred over transposition in the majority of cases, but careful correlation of electrodiagnostic abnormalities and findings at surgery are necessary to ensure optimal outcome.

Decompression, Surgical↗

PubMed1999

Neuromuscular disease and hypoventilation.

Alveolar hypoventilation associated with neuromuscular disease can occur in acute and chronic forms. In the acute form, progressive weakness of respiratory muscles leads to rapid reduction in vital capacity followed by respiratory failure with hypoxemia and hypercarbia. Symptoms are those of acute respiratory failure, including dyspnea, tachypnea, and tachycardia. In the chronic form, impairment of the respiratory muscles affects mechanical properties of the lungs and chest wall, decreases the ability to clear secretions, and eventually may alter the function of the central respiratory centers. Symptoms include orthopnea, fatigue, disturbed sleep, and hypersomnolence. Treatment and outcome of the disease's chronic form are dependent on the underlying clinical cause of the alveolar hypoventilation. For chronic but stable diseases such as old polio, quadriplegia, or kyposcoliosis, mechanical support of minute ventilation can reverse symptoms. For chronic and progressive disease such as muscular dystrophy and amyotrophic lateral sclerosis, mechanical support of minute ventilation provides only symptomatic relief and is usually associated with deterioration to the point of complete ventilator dependency for survival. For the chronic progressive forms of alveolar hypoventilation, there is currently a need for quality randomized controlled clinical trials to define physiologic indicators and appropriate timing for mechanical support of minute ventilation.

Acute Disease↗

PubMed1999

Association of cigarette smoking with amyotrophic lateral sclerosis.

We explored the relationship between amyotrophic lateral sclerosis (ALS) and cigarette smoking in a case-control study conducted in New England from 1993 to 1996. Recently diagnosed ALS cases (n = 109) were recruited from two major referral centers. Population controls (n = 256) were identified by random telephone screening. Data were analyzed by logistic regression. After adjusting for age, sex, region and education, ever having smoked cigarettes was associated with an increase in risk for ALS (odds ratio 1.7; 95% confidence interval 1.0-2.8). Average cigarettes smoked per day, years smoked and pack-years were all greater in cases than controls, but dose-response trends were not observed. Similar numbers of cases and controls had ever used alcohol, and only a small, nonsignificant association of drinks per month with ALS was observed. The association of cigarette smoking with ALS was not affected by adjusting for alcohol use. In contrast, the weak relationship of ALS with alcohol use was apparently due to confounding by smoking.

Adult↗

PubMed1998

High-temperature repetitive nerve stimulation in myasthenia gravis.

High temperature enhances the decrement on repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG). However, the limit of this phenomenon at high temperature is unknown. Three-hertz ulnar RNS was performed in 7 patients with MG at a skin temperature of 32 degrees C and then with the hand in a 44 degrees C water bath. At 32 degrees C, the mean decrement preactivation was 5% (range, 0-24%); after 1 min of exercise, the mean decrement reached a maximum of 11% (range, 1-34%) 2 min postactivation. At a hand temperature of 42 degrees C, the mean decrement preactivation was 17% (range, 0-65%); after exercise, the mean decrement reached a maximum of 29% (range, 5-74%) 1 min postactivation. In 3 subjects, RNS was normal at 32 degrees C, but a definite decrement developed with heating. These findings demonstrate that very high temperature can improve the sensitivity of ulnar RNS for postsynaptic neuromuscular transmission defects.

Action Potentials↗

PubMed1998

Root stimulation studies in the evaluation of patients with motor neuron disease.

Nerve root stimulation may be employed in patients with motor neuron disease (MND) to rule out motor neuropathy with conduction block. The diagnostic utility of these studies is unknown, in part because the range of amplitude changes across nerve root segments in patients with active neuronal degeneration has not been well studied. We reviewed root stimulation studies in 32 patients (59 nerves) with MND and found segmental amplitude reduction from 0 to 45%, a range similar to values reported for normal subjects; there was no suggestion of conduction block based on our usual criteria.

Adult↗

PubMed1998

The mixed nerve silent period in normal subjects and patients with amyotrophic lateral sclerosis.

The mixed nerve silent period (MNSP) is the period of motor inhibition observed when the mixed nerve innervating a voluntary activated muscle is electrically stimulated. The etiology of the MNSP is multifactorial, with the early and middle phases likely to be related to the effects of antidromic motor nerve activity on peripheral nerve and spinal interneurons. The terminal portion of the MNSP is mediated primarily by small diameter myelinated afferent fibers. The duration and latency of the MNSP vary as a function of both strength of stimulation and level of voluntary activation. In this study, we varied both stimulus strength and exertion, and compared MNSPs in 6 normal subjects with those obtained from 8 patients with amyotrophic lateral sclerosis (ALS). Differences between patients and control subjects included a longer duration of the MNSP in ALS patients, as well as less complete inhibition in the middle phases of the period. The longer duration of the MNSP may reflect an abnormality of sensory motor processing in ALS patients. The physiology underlying the incomplete inhibition is unclear, but may reflect abnormalities in Renshaw cell function.

Adult↗

PubMed1997

Nerve, muscle, and neuromuscular junction electrophysiology at high temperature.

Although the effect of low temperature on the peripheral nervous system has been systematically studied, the effect of high temperature has not. We investigated the effect of elevating limb temperature from 32 degrees C to 42 degrees C by performing sequential motor studies, antidromic sensory studies, and 3-Hz repetitive stimulation in normal subjects. In addition, we recorded single motor units by using threshold stimulation. On average, motor amplitude and duration decreased by 27% and 19%, respectively, whereas sensory amplitude and duration decreased by 50% and 26%, respectively. Neuromuscular transmission remained normal at 42 degrees C. Single motor unit recordings revealed a reduction in amplitude of 26%, similar to the overall reduction in compound motor amplitude. These findings demonstrate that significant reductions in sensory and motor amplitudes can occur in normal nerves at high temperature; we hypothesize that these changes are secondary to alterations in nerve and muscle ion channel function.

Action Potentials↗

PubMed1996

The critical importance of stimulus intensity in intraoperative monitoring for partial dorsal rhizotomy.

During partial lumbosacral dorsal rhizotomy (PDR), intraoperative dorsal rootlet stimulation (drs) evokes motor responses, presumed to be reflexes, which are used to select rootlets for section. However, dr stimuli may also costimulate ventral root (vr) and evoke an M rather than a reflex response, the two being distinguishable only by comparison of response latencies after drs at two separate sites. In 15 consecutive spastic cerebral palsy patients undergoing PDR, we asked whether reflex and M responses were distinguishable on the basis of stimulus intensity (SI). For soleus H reflexes evoked by percutaneous tibial nerve stimulation, the SI for reflex afferents was usually subthreshold for exciting motor fibers. Similarly, for nerve roots, reflexes were evoked by drs at SIs generally less than that for M responses evoked by vr stimulation (vrs). In contrast, M responses evoked by drs required SIs that were on average 20 times greater. Finally, costimulation of contralateral vr after ipsilateral vrs occurred at SIs shown to evoke M responses after drs. We conclude that: (1) reflex and M responses evoked by drs are distinguishable on the basis of the required SI; and (2) drs employing SIs greater than required for vrs evokes M rather than reflex responses due to costimulation of ipsilateral and contralateral vr.

Cerebral Palsy↗

PubMed1996

Injury zone denervation in traumatic quadriplegia in humans.

In order to obtain an electrophysiological characterization of the injury zone in traumatic quadriplegia, we performed electromyography and nerve conduction studies on the upper limbs of 15 patients with cervical cord trauma. Evidence of significant axonal loss was found in multiple myotomes of all patients. In most cases, the level of the most severe denervation, as determined by the absence or diminution of the compound motor action potential and the density of fibrillation potentials, was 2-5 spinal segments below the clinically and radiologically defined injury levels. In patients with injuries, the rostral extent of which is at C5 or higher, the most obvious clinical and electromyographic denervation was seen in the intrinsic hand muscles (C8/T1), with complete loss of C8/T1 motor axons in a subset of these patients. Our results document that spinal cord trauma can cause loss of motor axons in regions several segments caudal to the rostral level of injury. This finding may have implications for the pathophysiology of secondary injury, for recovery potential, and for the design of rehabilitation strategies.

Action Potentials↗

PubMed1996

Urinary dysfunction in Duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD), sphincter muscles tend to be clinically spared. However, urinary incontinence is occasionally reported, usually late in the course of the disease. We wished to determine the etiology of urinary dysfunction in patients with DMD. Seven boys with DMD and urinary dysfunction were examined by a neurologist and a urologist followed by urodynamic and electrophysiological assessment. Based on the results of these evaluations, patients were defined as having an upper motor neuron (UMN), lower motor neuron (LMN), or myopathic lesion. Five of the patients had UMN abnormalities consisting of either uninhibited contractions or bladder/sphincter dyssynergy. One patient had a LMN lesion with prolonged duration and high-amplitude motor units. No patient demonstrated myopathic motor units. Five boys had undergone spinal fusion for scoliosis. We conclude that urinary incontinence in DMD is most often due to UMN dysfunction and not due to a severe myopathy of the detrusor or external sphincter. The most likely causes of the UMN abnormalities are severe scoliosis or a complication of spinal fusion surgery.

Adolescent↗

PubMed1996

Ulnar neuropathy and dystonic flexion of the fourth and fifth digits: clinical correlation in musicians.

Peripheral nerve lesions are sometimes associated with focal dystonia. We diagnosed ulnar neuropathy in 28 of 73 (40%) cases of occupational cramp in musicians. Focal slowing of ulnar conduction across the elbow was identified in 15 of 19 (79%) patients using the near nerve technique and in 5 of 17 (29%) patients using surface recording. Ulnar neuropathy was present in 24 of 31 (77%) cases with flexion dystonia of the fourth and fifth digits and only 4 of the remaining 42 (10%) cases with other patterns of focal dystonia. Focal dystonia improved in 13 of 14 patients whose ulnar neuropathy improved and appeared or worsened in 2 patients following ulnar nerve injury. These data, together with our recent observation of a dystonic pattern of antagonist bursting in patients with isolated ulnar neuropathy (Muscle Nerve 1995, 18:606-611), suggest that ulnar neuropathy may initiate or sustain a specific dystonia, flexion of the fourth and fifth digits, by inducing a central disorder of motor control.

Adolescent↗

PubMed1996

Coexistent entrapment neuropathies in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To determine the incidence of entrapment neuropathy in patients with amyotrophic lateral sclerosis (ALS). Although it is well known that patients with motor neuron disease may have coexisting focal neuropathies, their prevalence has not been previously determined. METHODS: Electrophysiologic studies (EMG/NCS) were reviewed from 126 patients with ALS seen at a university-affiliated hospital from 1991 to 1994. Every patient had an EMG/ NCS consistent with motor neuron disease (i.e., active and chronic denervation in at least 3 body regions). RESULTS: Forty-three percent (54 patients) had evidence of a neuropathy. Abnormalities included median neuropathy at the wrist in 15 (12%), ulnar neuropathy at the elbow in 18 (14%), nonlocalized ulnar neuropathy in 10 (8%), and peroneal neuropathy at the fibular head in 2 (2%). Furthermore, 9 patients (7%) had a superimposed polyneuropathy. Of these 54 patients, 7 (13%) had clinical symptoms of their neuropathy. CONCLUSIONS: Coexistent focal or generalized neuropathies in ALS are not uncommon. Careful attention to these abnormalities may decrease morbidity in these patients.

Adult↗

PubMed1996

Activity-dependent conduction in single motor units.

Vertebrate sensory and motor axons vary in their responses to submaximal stimuli as a function of time since prior activation. When two equal but submaximal stimuli are presented in pairs, the response to the second stimulus may be greater or less than the response to the first stimulus, depending on the interstimulus interval (ISI). We studied both the supernormal period (ISI between 6 and 25 msec) and the subnormal period (ISI between 25 and 100 msec) under conditions where only single motor axons were stimulated. Twenty single motor units from eight normal subjects were studied. The behavior of single units was very similar to that observed in compound motor action potentials, with the supernormal period lasting approximately 20 msec, followed by a subnormal period lasting at least 80 msec. Surprisingly, a supernormal period could be evoked by a stimulus that did not produce a response in the motor unit being studied; however, the presence of subnormality was dependent on an action potential being generated in response to the first stimulus. Based on these results, we conclude that the supernormal period does not require the opening of voltage-dependent ion channels, in contrast to the later occurring subnormal period.

Action Potentials↗

PubMed1995

The all ulnar motor hand without forearm anastomosis.

Anomalous ulnar innervation of intrinsic hand muscles, inferred in a number of clinical series, has been documented only rarely in electrophysiological studies. Using near-nerve and standard conduction studies we evaluated 2 cases with nearly exclusive ulnar innervation of hand muscles. There was no evidence of anomalous communication in the forearm. Digital sensory fibers were normally distributed in median and ulnar nerves. The anomalous motor innervation most likely results from palmar communication between ulnar and median branches (Riche-Cannieu anastomoses). The normal distribution of digital afferents suggests that such anastomoses are formed primarily by motor axons.

Action Potentials↗