Jasper R. Daube

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.

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 Methods: In this study, we investigated genotype-phenotype correlations in a large combined cohort of unpublished (n = 14) and previously reported (n = 92) recessive RYR1 cases.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.

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.

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. Muscle Nerve, 2007

The Neurology RRC accredits adult and child neurology training programs and subspecialty training programs in clinical neurophysiology, vascular neurology, neurodevelopmental pediatrics, and pain management. Accreditation of sleep medicine programs will soon begin. The NRRC program accreditation is independent of the ABPN, which certifies individuals who have successfully completed an accredited training program. It is also independent of the AAN, which, among other things, is responsible for continuing education of neurologists who have completed their training. Each functions as an independent body working for the public good. This common philosophy has the ultimate goal of assuring the highest quality of care for patients with neurologic diseases.