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Objective: To evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to reldesemtiv 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Results: Patients (N = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance (p = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R, p = 0.09; muscle strength megascore, p = 0.31). Post hoc analyses pooling all active reldesemtiv-treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). Reldesemtiv was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Conclusions: Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring reldesemtiv for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of reldesemtiv on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898)

The manner in which physicians deliver difficult diagnoses is an area of discontent for patients with amyotrophic lateral sclerosis (ALS). The American Academy of Neurology's Practice Parameter for care of the ALS Patient recommended teaching and evaluating strategies for disclosing the diagnosis (10). Our objective was to examine residents' ability in and perceptions of communicating the diagnosis of ALS. Twenty-two resident physicians were videotaped and rated by two ALS neurologists as they delivered an ALS diagnosis to a standardized patient (SP) during an objective structured clinical examination (OSCE). Residents self-rated immediately after the OSCE, again after viewing their videotape, and completed a survey regarding the OSCE and delivering difficult diagnoses. OSCE performance was suboptimal, particularly for communication skills and empathy. The two examiners' scores correlated except for the empathy subscore. Residents' self-assessments did not align with the examiners' scores either before or after watching their videotape. The survey uncovered residents' apprehension and dissatisfaction with their training in diagnosis delivery. The results highlight a need for resident education in delivering an ALS diagnosis. The lack of correlation between residents' and examiners' scoring requires further study. Evaluation of empathy is particularly challenging. Residents agreed that OSCE participation was worthwhile.

To assess the validity and reliability of an office-based surrogate measure of lumbar spine-stabilization endurance capability; to establish norms and reliability in an asymptomatic group; and to compare their measures with those from a group of chronic mechanical low-back pain patients.: Eight healthy subjects participated in the tool-validation portion of the study that consisted of surface electromyographic (EMG) measurements of core muscle activation during prone and supine bridging. Subsequently, normative and test-retest reliability measures of prone and supine bridging duration were recorded from 43 subjects without back pain and were compared with those of 32 subjects with chronic mechanical low-back pain.: Surface EMG indicated significantly preferential activation of anterior core muscles during prone bridging and posterior core muscles during supine bridging. Mean bridge durations for subjects without back pain were 72.5 +/- 32.6 (mean +/- SD) secs in prone and 170.4 +/- 42.5 secs in supine. They were significantly less in subjects with back pain: 28.3 +/- 26.8 secs in prone and 76.7 +/- 48.9 secs in supine. Test-retest reliability using Pearson's correlation for prone and supine bridging was 0.78 and 0.84, respectively.: Bridging maneuvers seem to be practical, reliable, and valid methods of reflecting lumbar spine-stabilization endurance capability. Prone bridging preferentially challenges core flexors, whereas supine bridging recruits primarily the core extensors; both are compromised in patients with low-back pain.

We report a 64-year-old female with predominantly bulbar amyotrophic lateral sclerosis who experienced 'roaring' in her ears. She was diagnosed with patulous Eustachian tube, which is presumed to occur secondary to bulbar weakness. The roaring adversely affected the management of her ALS by impairing her ability to tolerate BiPaP. A review of the relevant literature is reported.