Cardiac involvement in the muscular dystrophies.

Cardiac disease is a common clinical manifestation present in a variety of neuromuscular disorders, most notably the muscular dystrophies. Heart disease may produce the presenting or predominant symptoms in these disorders but more often not does not result in clinical features at the time of initial presentation. Cardiac involvement in the muscular dystrophies results from pathologic changes in the myocardium and the cardiac conduction system, leading to cardiomyopathy and/or rhythm disturbances including supraventricular arrhythmias, life-threatening ventricular arrhythmias, and sudden cardiac death. This Review covers the spectrum of cardiac dysfunction in these inherited muscle disorders and proposes practical recommendations for monitoring and management. Muscle Nerve 57: 707-715, 2018.

Electrical impedance myography correlates with standard measures of ALS severity.

INTRODUCTION: Electrical impedance myography (EIM) can be used to assess amyotrophic lateral sclerosis (ALS) progression. The relationship between EIM values and standard assessment measures, however, is unknown. METHODS: EIM 50 kHz phase data from 60 subjects who participated in a longitudinal natural history study of ALS were correlated with handheld dynamometry (HHD), the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and motor unit number estimation (MUNE). RESULTS: Moderate strength correlations between EIM parameters and HHD were observed for both whole-body and individual upper and lower extremity values. Similarly, moderate strength correlations were observed between EIM and ALSFRS-R upper and lower extremity subscores, but not total ALSFRS-R scores. MUNE correlated significantly with single muscle EIM data but not with whole body or upper or lower extremity values. CONCLUSIONS: These results support the concept that EIM can serve as a meaningful measure of disease severity in ALS.

Electrical impedance myography as a biomarker to assess ALS progression.

Electrical impedance myography (EIM), a non-invasive, electrophysiological technique, has preliminarily shown value as an ALS biomarker. Here we perform a multicenter study to further assess EIM's potential for tracking ALS. ALS patients were enrolled across eight sites. Each subject underwent EIM, handheld dynamometry (HHD), and the ALS Functional Rating Scale-revised (ALSFRS-R) regularly. Techniques were compared by assessing the coefficient of variation (CoV) in the rate of decline and each technique's correlation to survival. Results showed that in the 60 patients followed for one year, EIM phase measured from the most rapidly progressing muscle in each patient had a CoV in the rate of decline of 0.62, compared to HHD (0.82) and the ALSFRS-R (0.74). Restricting the measurements to the first six months gave a CoV of 0.55 for EIM, 0.93 for HHD, and 0.84 for ALSFRS-R. For both time-periods, all three measures correlated with survival. Based on these data, a six-month clinical trial designed to detect a 20% treatment effect with 80% power using EIM would require only 95 patients/arm compared to the ALSFRS-R, which would require 220 subjects/arm. In conclusion, EIM can serve as a useful ALS biomarker that offers the prospect of greatly accelerating phase 2 clinical trials.

Electrical impedance myography to assess outcome in amyotrophic lateral sclerosis clinical trials.

OBJECTIVE: Standard outcome measures used for amyotrophic lateral sclerosis (ALS) clinical trials, including the ALS functional rating scale-revised (ALSFRS-R), maximal voluntary isometric contraction testing (MVICT), and manual muscle testing (MMT), are limited in their ability to detect subtle disease progression. Electrical impedance myography (EIM) is a new non-invasive technique that provides quantitative data on muscle health by measuring localized tissue impedance. This study investigates whether EIM could provide a new outcome measure for use in ALS clinical trials work. METHODS: Fifteen ALS patients underwent repeated EIM measurements of one or more muscles over a period of up to 18 months and the primary outcome variable, theta(z-max), measured. The theta(z-max) megascore was then calculated using the same approach as has been applied in the past for MVICT. This and the MMT data were then used to assess each measure's statistical power to detect a given effect on disease progression in a hypothetical planned clinical therapeutic trial. RESULTS: theta(z-max) showed a mean decline of about 21% for the test period, averaged across all patients and all tested muscles. The theta(z-max) megascore had a power of 73% to detect a 10% treatment effect in our planned hypothetical trial, as compared to a 28% power for MMT. These results also compared favorably to historical data for ALSFRS-R and MVICT arm megascore from the trial of celecoxib in ALS, where both measures had only a 23% power to detect the same 10% treatment effect. CONCLUSIONS: The theta(z-max) megascore may provide a powerful new outcome measure for ALS clinical trials. SIGNIFICANCE: The application of EIM to future ALS trials may allow for smaller, faster studies with an improved ability to detect subtle progression of the disease and treatment effects.

Lumbosacral radiculopathy.

Lumbosacral radiculopathy is one of the most common disorders evaluated by neurologists and is a leading referral diagnosis for the performance of electromyography. Although precise epidemiologic data are difficult to establish, the prevalence of lumbosacral radiculopathy is approximately 3% to 5%, distributed equally in men and women. Degenerative spondyloarthropathies are the principal underlying cause of these clinical syndromes and are increasingly commonplace with age. Men are most likely to develop symptoms in their 40s, whereas women are affected most commonly between ages 50 and 60. The clinical presentation and initial management of lumbosacral radiculopathies of various etiologies are discussed.

Prevalence of ulnar neuropathy in patients receiving hemodialysis.

BACKGROUND: Ulnar neuropathy can cause pain, weakness, and sensory changes in the hand and can result in functional impairment. Patients with end-stage renal disease receiving hemodialysis may be predisposed to ulnar neuropathy by factors such as arm positioning during hemodialysis, underlying polyneuropathy, and upper extremity vascular access. OBJECTIVE: To determine the prevalence of clinically evident ulnar neuropathy in a cohort of 102 patients with end-stage renal disease receiving hemodialysis. DESIGN: All eligible patients in a single dialysis unit were screened for symptoms and signs of ulnar neuropathy. Those with at least 1 symptom or sign underwent nerve conduction studies to confirm the presence of ulnar neuropathy. RESULTS: Clinically evident, electrophysiologically confirmed ulnar neuropathy was present in 37 (51%) of the 73 subjects with both screening and nerve conduction study data available. The true prevalence of ulnar neuropathy in this cohort was estimated between 41% and 60%. CONCLUSIONS: There is a high prevalence of ulnar neuropathy in patients with end-stage renal disease receiving hemodialysis, which has not been previously recognized. The high prevalence of ulnar neuropathy in this population suggests that preventative efforts are indicated to prevent this functionally limiting complication.

Vitamin B(12) and methylmalonic acid levels in patients presenting with polyneuropathy.

This study was designed to determine the prevalence of definite vitamin B(12) deficiency (defined as < or =240 pg/ml) and possible vitamin B(12) deficiency (defined as >240 pg/ml and a methylmalonic acid [MMA] level >243 nmol/L) in patients with polyneuropathy and to determine whether patients in both groups respond to vitamin B(12) repletion. We performed a retrospective cohort study of 581 patients presenting with polyneuropathy over a 2-year period; 4% had definite vitamin B(12) deficiency and 32% had possible deficiency as the sole or contributing cause for their polyneuropathy. For those who received treatment with vitamin B(12), subjective improvement was seen in 87% with definite and in 43% with possible deficiency. Possible vitamin B(12) deficiency, defined as an elevated MMA level, is a common finding in patients with polyneuropathy and treatment of these patients with vitamin B(12) may lead to clinical improvement.

Involvement of superficial peroneal sensory nerve in common peroneal neuropathy.

Motor involvement in common peroneal neuropathy (CPN) frequently shows a selective pattern with regard to deep and superficial divisions of the peroneal nerve, by clinical examination and needle electromyography. The involvement of the sensory branch of the superficial peroneal nerve (SPN) has not been well established using nerve conduction studies. Among 42 cases of electrophysiologically defined CPN in 35 patients, 37 (88%) had clinical or electrophysiologic evidence for SPN involvement, but only 20 had diminished superficial peroneal sensory response (SPSR) amplitudes. Many of the cases involving normal SPSRs had significant axonal loss involving deep peroneal motor fibers. Sparing of the superficial peroneal sensory fibers provides further evidence for the selective vulnerability of different nerve fascicles to injury. This is an important pattern to recognize; from a practical standpoint, focal segmental conduction abnormalities in the motor nerve and EMG findings can help to differentiate these lesions from L-5 radiculopathy.

Sural and radial sensory responses in healthy adults: diagnostic implications for polyneuropathy.

We prospectively performed sural and radial sensory nerve conduction studies in 92 healthy subjects, aged between 21 and 88 years, both to determine the lower limits of normal (LLN) and to assess the effects of age and body mass index (BMI) on the sural and radial sensory nerve action potential (SNAP) amplitudes and on the sural/radial amplitude ratio (SRAR). Using the nonparametric bootstrap method to calculate 95% confidence intervals, we found that the 5% LLN values for sural and radial SNAPs were 14 microV and 25.5 microV in subjects aged < or =39 years, 7 microV and 17.4 microV in subjects aged 40-59 years, and 3 microV and 12 microV in subjects aged > or =60 years. The 5% LLN for SRAR for all patients was 0.21. Sural and radial SNAP amplitudes but not SRAR were strongly and inversely correlated with age and BMI. These age-adjusted normal values and revised SRAR will aid in the electrodiagnosis of polyneuropathy.

Diagnostic accuracy of electrodiagnostic testing in the evaluation of weakness.

Electrodiagnostic testing is often used in the evaluation of patients presenting with weakness, but the diagnostic accuracy of the test in this setting is unknown. We prospectively identified 100 patients presenting to our electromyography (EMG) laboratory with the chief complaint of weakness, and compared their referring diagnosis with the electrophysiological diagnosis reached after electrodiagnostic testing. We reviewed each patient's medical record 9 months after EMG to yield a final diagnosis. Electrodiagnostic testing led to a single diagnosis in 79% of the cases; in 31%, this diagnosis was unsuspected by the referring clinician. Adequate follow-up was available for 79% of the patients. The electrodiagnostic testing resulted in a single, correct diagnosis in 73% of the patients and provided more than one possible diagnosis, one of which was correct, in an additional 18%, for an overall diagnostic accuracy of 91% in this group of patients presenting with weakness.

Ulnar neuropathy in the forearm: A possible complication of diabetes mellitus.

Ulnar neuropathy in the forearm is an unusual cause of hand weakness and sensory loss that is most often attributed to compression of the nerve distally within the humero-ulnar arcade (cubital tunnel). An association with diabetes mellitus, however, has not been reported. We identified four patients with type I diabetes mellitus and clinical findings suggestive of ulnar neuropathy in whom electrophysiologic testing revealed partial conduction block or abnormal temporal dispersion within the forearm segment of the ulnar nerve. Although evidence for a mild underlying polyneuropathy was present in three patients, the ulnar nerve abnormalities were disproportionately severe. In all cases, a Martin-Grüber anastomosis was excluded. Whether this lesion is due to an increased propensity to focal compression of the ulnar nerve within the humero-ulnar arcade or whether it represents a localized manifestation of the generalized polyneuropathy remains to be determined.