Motor unit number estimation: a technology and literature review.

INTRODUCTION: Numerous methods for motor unit number estimation (MUNE) have been developed. The objective of this article is to summarize and compare the major methods and the available data regarding their reproducibility, validity, application, refinement, and utility. METHODS: Using specified search criteria, a systematic review of the literature was performed. Reproducibility, normative data, application to specific diseases and conditions, technical refinements, and practicality were compiled into a comprehensive database and analyzed. RESULTS: The most commonly reported MUNE methods are the incremental, multiple-point stimulation, spike-triggered averaging, and statistical methods. All have established normative data sets and high reproducibility. MUNE provides quantitative assessments of motor neuron loss and has been applied successfully to the study of many clinical conditions, including amyotrophic lateral sclerosis and normal aging. CONCLUSIONS: MUNE is an important research technique in human subjects, providing important data regarding motor unit populations and motor unit loss over time.

Genotype-phenotype correlations in recessive RYR1-related myopathies.

BACKGROUND: RYR1 mutations are typically associated with core myopathies and are the most common overall cause of congenital myopathy. Dominant mutations are most often associated with central core disease and malignant hyperthermia, and genotype-phenotype patterns have emerged from the study of these mutations that have contributed to the understanding of disease pathogenesis. The recent availability of genetic testing for the entire RYR1 coding sequence has led to a dramatic expansion in the identification of recessive mutations in core myopathies and other congenital myopathies. To date, no clear patterns have been identified in these recessive mutations, though no systematic examination has yet been performed. METHODS: In this study, we investigated genotype-phenotype correlations in a large combined cohort of unpublished (n = 14) and previously reported (n = 92) recessive RYR1 cases. RESULTS: Overall examination of this cohort revealed nearly 50% of cases to be non-core myopathy related. Our most significant finding was that hypomorphic mutations (mutations expected to diminish RyR1 expression) were enriched in patients with severe clinical phenotypes. We also determined that hypomorphic mutations were more likely to be encountered in non-central core myopathies. With analysis of the location of non-hypomorphic mutations, we found that missense mutations were generally enriched in the MH/CCD hotspots and specifically enriched in the selectivity filter of the channel pore. CONCLUSIONS: These results support a hypothesis that loss of protein function is a key predictive disease parameter. In addition, they suggest that decreased RyR1 expression may dictate non-core related pathology though, data on protein expression was limited and should be confirmed in a larger cohort. Lastly, the results implicate abnormal ion conductance through the channel pore in the pathogenesis in recessive core myopathies. Overall, our findings represent a comprehensive analysis of genotype-phenotype associations in recessive RYR1-myopathies.

Use of supramaximal stimulation to predict facial nerve outcomes following vestibular schwannoma microsurgery: results from a decade of experience.

OBJECT: The goal of vestibular schwannoma surgery is tumor removal and preservation of neural function. Intraoperative facial nerve (FN) monitoring has emerged as the standard of care, but its role in predicting long-term facial function remains a matter of debate. The present report seeks to describe and critically assess the value of applying current at supramaximal levels in an effort to identify patients destined for permanent facial paralysis. METHODS: Over more than a decade, the protocol for stimulating and assessing the FN during vestibular schwannoma surgery at the authors' institution has consisted of applying pulsed constant-current stimulation at supramaximal levels proximally and distally following tumor resection to generate an amplitude ratio, which subtracted from 100% yields the degree to which the functional integrity of the FN "dropped off" intraoperatively. These data were prospectively collected and additional variables that might impact postoperative FN function were retrospectively reviewed from the medical record. Only patients with anatomically intact FNs and > 12 months of follow-up data were analyzed. RESULTS: There were 267 patients available for review. The average posterior fossa tumor diameter was 24 mm and the rate of long-term good (House-Brackmann Grade I-II) FN function was 84%. Univariate logistic regression analysis revealed that prior treatment, neurofibromatosis Type 2 status, tumor size, cerebellopontine angle extension, subjectively thinned FN at the time of operation, minimal stimulation threshold, percent dropoff by supramaximal stimulation (SMS), and postoperative FN function all correlated statistically (p < 0.05) with long-term FN function. When evaluating patients with significant FN weakness at the time of hospital discharge, only the percent dropoff by SMS remained a significant predictor of long-term FN function. However, the positive predictive value of SMS for long-term weakness is low, at 46%. CONCLUSIONS: In a large cohort of patients, the authors found that interrogating intraoperative FN function with SMS is safe and technically simple. It is useful for predicting which patients will ultimately have good facial function, but is very limited in identifying patients destined for long-term facial weakness. This test may prove helpful in the future in tailoring less than gross-total tumor removal to limit postoperative facial weakness.

Clinical and electrophysiologic variability in amyotrophic lateral sclerosis within a kindred harboring the C9ORF72 repeat expansion.

Our objective was to characterize the motor neuron disease features within a large c9FTD/ALS kindred. We analyzed clinical, electrophysiologic and neuropathologic data in a c9FTD/ALS kindred of Scandinavian ancestry. Results showed that of six family members affected, three had only ALS, two had FTD and one had FTD and ALS. Each patient with motor neuron disease had a different clinical presentation: one patient had only bulbar symptoms, one had bulbar and limb involvement, one had limb symptoms, and one had primarily upper motor neuron disease. Later in the course of disease, all ALS patients developed bulbar involvement and died from respiratory causes. Survival was uniformly short (two to five years). Electrophysiologic studies recorded progressive lower motor neuron dysfunction except in the patient with predominantly upper motor neuron features. In conclusion, this kindred demonstrates that the presentation of ALS within c9FTD/ALS families may vary considerably and electrophysiologic findings reflect this heterogeneity.

Optimal stimulation settings for CMAP scan registrations.

BACKGROUND: The CMAP (Compound Muscle Action Potential) scan is a non-invasive electrodiagnostic tool, which provides a quick and visual assessment of motor unit potentials as electrophysiological components that together constitute the CMAP. The CMAP scan records the electrical activity of the muscle (CMAP) in response to transcutaneous stimulation of the motor nerve with gradual changes in stimulus intensity. Large MUs, including those that result from collateral reinnervation, appear in the CMAP scan as so-called steps, i.e., clearly visible jumps in CMAP amplitude. The CMAP scan also provides information on nerve excitability. This study aims to evaluate the influence of the stimulation protocol used on the CMAP scan and its quantification. METHODS: The stimulus frequency (1, 2 and 3 Hz), duration (0.05, 0.1 and 0.3 ms), or number (300, 500 and 1000 stimuli) in CMAP scans of 23 subjects was systematically varied while the other two parameters were kept constant. Pain was measured by means of a visual analogue scale (VAS). Non-parametric paired tests were used to assess significant differences in excitability and step variables and VAS scores between the different stimulus parameter settings. RESULTS: We found no effect of stimulus frequency on CMAP scan variables or VAS scores. Stimulus duration affected excitability variables significantly, with higher stimulus intensity values for shorter stimulus durations. Step variables showed a clear trend towards increasing values with decreasing stimulus number. CONCLUSIONS: A protocol delivering 500 stimuli at a frequency of 2 Hz with a 0.1 ms pulse duration optimized CMAP scan quantification with a minimum of subject discomfort, artefact and duration of the recording. CMAP scan variables were influenced by stimulus duration and number; hence, these need to be standardized in future studies.

Myotonia associated with caveolin-3 mutation.

INTRODUCTION: Caveolin-3 is a major component of the caveolae in skeletal and cardiac muscle. Mutations in the caveolin-3 gene (CAV3) lead to a spectrum of clinical phenotypes including limb-girdle muscular dystrophy 1C, distal myopathy, rippling muscle disease, isolated hyperCKemia, and cardiomyopathy. CASE REPORT: A 24-year-old man with myalgia, muscle stiffness, and fatigue has normal strength and prominent myotonic discharges in the gastrocnemius. He also has epilepsy. He harbors a heterozygous CAV3 mutation, p.V57M. He has no mutations in CLCN1 and SCN4A, and he had normal genetic testing for myotonic dystrophy type 1 and type 2. CONCLUSIONS: Mutations in CAV3, and in particular p.V57M in CAV3, previously reported in isolated familial hyperCKemia, can be associated with electrical myotonia.

Electrophysiological testing of spinal accessory nerve in suspected cases of nerve transection.

INTRODUCTION: In this study we sought to determine whether standard electrophysiological testing of the spinal accessory nerve (SAN) accurately identifies patients who would benefit from surgical repair. METHODS: Sixteen consecutive patients sent for surgical evaluation of unilateral SAN injury were studied clinically and electrophysiologically. RESULTS: All patients demonstrated a low-amplitude SAN compound muscle action potential (CMAP) that required a higher stimulus intensity to obtain it than on the unaffected side. Upper trapezius needle electromyography showed dense fibrillation potentials in 16 of 16 nerves, with voluntary motor unit potentials (MUPs) in 5 of 16. Intraoperatively, 12 of 16 nerves were transected; 4 of 16 had neuromas across which there was no nerve action potential. Patients underwent direct repair (6 of 16) or interpositional nerve grafting (10 of 16). Fourteen of 15 patients seen postoperatively had improvement in pain, muscle bulk, and range of motion. CONCLUSIONS: Surgical exploration of the SAN is warranted in patients with clinical signs of severe injury, even when electrophysiological testing shows low-amplitude CMAPs and/or residual MUPs.

Absent, unrecognized, and minimal myotonic discharges in myotonic dystrophy type 2.

The purpose of this study was to describe the frequency of absent, unrecognized, or minimal myotonic discharges (MDs) in myotonic dystrophy type 2 (DM2). We performed a retrospective review of needle electromyography (EMG) data prior to genetic diagnosis in 49 DM2 patients at the Mayo Clinic. MDs were not reported on first or repeat EMG studies (n = 8) and not found in archived recordings of 4 patients (8%); archived EMG recordings (n = 4) confirmed the absence of MDs (n = 2), including 1 patient with normal insertional activity in all muscles, and misinterpretation of MDs as slow fibrillation potentials (n = 1) and complex repetitive discharge (CRD) activity (n = 1). Eight (16%) patients had minimal classic MDs with diffusely increased insertional activity, including waning-only MDs in all patients in this group with archived EMG recordings (n = 5). Diffuse MDs were found in 33 (67%) patients. Absent or minimal MDs do not exclude DM2. Over-reliance on diffuse MDs in patients who present with myopathy may lead to delay in genetic diagnosis of DM2.

Clinical and electrodiagnostic correlates of peroneal intraneural ganglia.

OBJECTIVE: Intraneural ganglia (IG) are an underappreciated but treatable cause of common peroneal neuropathy (CPN). This study was designed to determine if there are clinical measures that distinguish CPN caused by IG from CPN without a clear proximate cause. METHODS: Clinical and electrodiagnostic features of 22 cases of IG were compared in a case-control study to 11 cases of CPN with imaging negative for IG. RESULTS: The IG group had a greater body mass index (30 vs 24; p < 0.005), more pain at the knee (52% of 22 vs 0% of 11; p < 0.005) or in the peroneal distribution (76% of 21 vs 27% of 1; p < 0.02), more frequent fluctuating weakness (48% of 21 vs 4% of 29; p < 0.01) with weight bearing (38%, p < 0.05), or a palpable mass (47% of 20, p < 0.01) at the fibular head. The IG group was less likely to present with a history of weight loss (0% vs 36%; p < 0.01), immobility (0% vs 21%; p < 0.03), or leg crossing (0% vs 80%; p < 0.05). There were no significant electrophysiologic differences. CONCLUSIONS: Presenting clinical features increase the likelihood of intraneural ganglia and may assist selection of patients with common peroneal neuropathy for diagnostic peroneal nerve imaging.

Myotonic dystrophy type 2 with focal asymmetric muscle weakness and no electrical myotonia.

Genetically proven myotonic dystrophy type 2 (DM2) was found in a 61-year-old woman with creatine kinase (CK) elevation and only isolated weakness of one triceps. There was no clinical or electrical myotonia. Electromyography (EMG) showed only scattered fibrillation potentials and short duration motor unit potentials. Muscle biopsy showed nonspecific myopathic features and highly atrophic fibers with nuclear clumps. DM2 should be considered in patients with focal proximal weakness and abnormal EMG without myotonic discharges.

Needle electromyography.

Physiologic assessment of diseases of the motor unit from the anterior horn cells to the muscles relies on a combination of needle electromyography (EMG) and nerve conduction studies (NCS). Both require a unique combination of knowledge of peripheral nervous system anatomy, physiology, pathophysiology, diseases, techniques, and electricity is necessary. Successful, high-quality, reproducible EMG depends on the skills of a clinician in patient interaction during the physical insertion and movement of the needle while recording the electrical signals. These must be combined with the skill of analyzing electric signals recorded from muscle by auditory pattern recognition and semiquantitation.1052 This monograph reviews the techniques of needle EMG and waveform analysis and describes the types of EMG waveforms recorded during needle EMG.

Prospective 15-year study of neuromuscular function in a cohort of patients with prior poliomyelitis.

Poliomyelitis is a monophasic illness affecting lower motor neurons and individuals may describe new problems years after the initial weakness. We have studied 38 people with the post-polio syndrome over a 15-year period assessing a number of neuromuscular measures, including motor unit number estimation (MUNE). Twenty-five individuals reported progressive weakness but there was no objective change in MUNE and other measures. There was an association with reported weakness and initial deficits. There was a slow decline in MUNE values over time in both groups.

Anal sphincter motor unit potential (MUP) differences between sides, between rest and voluntary contraction, and between MUP analysis programs in normal subjects.

Trauma to the external anal sphincter resulting in incontinence is a relatively common disorder. Methods to detect damage include pudendal nerve conduction studies and needle EMG. We have applied a quantitative EMG technique using decomposition-enhanced software to isolate motor unit potentials (MUPs) and their surface representation from an anal probe electrode in healthy nulliparous women. MUPs were readily isolated and metric values compared favorably with those recorded with different software.

Strength, physical activity, and fasciculations in patients with ALS.

Fasciculations are a nearly universal feature in people with amyotrophic lateral sclerosis (ALS). The prognostic value of fasciculations remains uncertain. Twenty-four patients with ALS were evaluated for the effects of atrophy, limb weakness, disease duration, and physical activity on fasciculation frequency (as measured by surface electromyography and clinical counting). Variables were compared by multiple linear regression. As strength of the limb deteriorated, the number of fasciculations in the same limb increased, as long as physical activity was maintained or increased. Fasciculation frequency was not associated with the duration of ALS (r = 0.22; p = 0.30) and was independent of the degree of limb weakness (p>0.05) and limb atrophy (p>0.05). No prediction of disease duration could be made based on fasciculation frequency alone. Fasciculations therefore appear to have diagnostic, but not prognostic, utility in the care of people with ALS.

Motor and somatosensory evoked potentials: their role in predicting spinal cord ischemia in patients undergoing thoracoabdominal aortic aneurysm repair with regional lumbar epidural cooling.

BACKGROUND: Paraplegia is a devastating complication for patients undergoing repair of thoracoabdominal aortic aneurysms. A monitor to detect spinal cord ischemia is necessary if anesthesiologists are to intervene to protect the spinal cord during aortic aneurysm clamping. METHODS: The medical records of 60 patients who underwent thoracoabdominal aortic aneurysm repair with regional lumbar epidural cooling with evoked potential monitoring were reviewed. The authors analyzed latency and amplitude of motor evoked potentials, somatosensory evoked potentials, and H reflexes before cooling and clamping, after cooling and before clamping, during clamping, and after release of aortic cross clamp. RESULTS: Twenty minutes after the aortic cross clamp was placed, motor evoked potentials had 88% sensitivity and 65% specificity in predicting spinal cord ischemia. The negative predictive value of motor evoked potentials at 20 min after aortic cross clamping was 96%. CONCLUSIONS: Rapid loss of motor evoked potentials or H reflexes after application of the aortic cross clamp identifies a subgroup of patients who are at high risk of developing spinal cord ischemia and in whom aggressive anesthetic and surgical interventions may be justified.

Intraneural perineurioma of the radial nerve visualized by 3.0 Tesla MRI.

A progressive radial neuropathy of unknown etiology despite 1.5T magnetic resonance imaging (MRI) and surgical exploration was identified as an intraneural perineurioma by a localized Tinel's sign, an enlarged radial nerve at the spiral groove by 3.0T MRI, and a fascicular biopsy. The distinction between the initial diagnoses of inflammatory, demyelinating polyneuropathy and perineurioma was made by immunohistochemistry and electron microscopy. A slowly progressing, localized mononeuropathy should include perineurioma in the differential diagnosis.

Motor unit number estimates correlate with strength in polio survivors.

Motor unit number estimation (MUNE) has been proposed as an outcome measure in clinical trials for the motor neuron diseases. One major criticism of MUNE is that it may not represent a clinically meaningful endpoint. We prospectively studied a cohort of polio survivors over a period of 15 years with respect to MUNE and strength. We identified a significant association between thenar MUNE and arm strength, extensor digitorum brevis MUNE and leg strength, and the summated MUNE and global strength of the polio survivors. These findings confirm the clinical relevance of MUNE as an outcome measure in the motor neuron diseases and provide further validation for its use in clinical trial research.