Improved ALS clinical trials through frequent at-home self-assessment: a proof of concept study.

OBJECTIVE: To determine the potential for improving amyotrophic lateral sclerosis (ALS) clinical trials by having patients or caregivers perform frequent self-assessments at home. METHODS AND PARTICIPANTS: We enrolled ALS patients into a nonblinded, longitudinal 9-month study in which patients and caregivers obtained daily data using several different instruments, including a slow-vital capacity device, a hand grip dynamometer, an electrical impedance myography-based fitness device, an activity tracker, a speech app, and the ALS functional rating scale-revised. Questions as to acceptability were asked at two time points. RESULTS: A total of 113 individuals enrolled, with 61 (43 men, 18 women, mean age 60.1 ± 9.9 years) collecting a minimum of 7 days data and being included in the analysis. Daily measurements resulted in more accurate assessments of the slope of progression of the disease, resulting in smaller sample size estimates for a hypothetical clinical trial. For example, by performing daily slow-vital capacity measurements, calculated sample size was reduced to 182 subjects/study arm from 882/arm for monthly measurements. Similarly, performing the ALS functional rating scale weekly rather than monthly led to a calculated sample size of 73/arm as compared to 274/arm. Participants generally found the procedures acceptable and, for many, improved their sense of control of their disease. INTERPRETATION: Frequent at-home measurements using standard tools holds the prospect of tracking progression and reducing sample size requirements for clinical trials in ALS while also being acceptable to the patients. Future studies in this and other neurological disorders should consider adopting this approach to data collection.

Quantitative muscle ultrasound in upper extremity mononeuropathies.

INTRODUCTION: We assessed the potential use of quantitative ultrasound (QUS) in the evaluation hand muscles affected by upper extremity mononeuropathies. METHODS: The gray scale levels (GSLs) of abductor pollicis brevis (APB), abductor digiti minimi (ADM), and first dorsal interosseous (FDI) of 30 healthy and 30 upper extremity mononeuropathy patients were measured and compared with standard electrophysiological values. RESULTS: Mean GSL was elevated in 34 APBs of carpal tunnel syndrome patients and 18 FDIs of ulnar neuropathy patients (e.g., FDI mean GSL (interquartile range) 31.5 (27.3~43.8) arbitrary units for patients and 24.0(23.0~29.0) for healthy subjects (P = 0.020)). GSL correlated with motor response amplitudes (Spearman's rho (ρ) = -0.39, P = 0.002 in APB, ρ = -0.72, P = 0.002 in FDI, and ρ = -0.43, P = 0.013 in ADM). The APB GSL correlated with electromyographic severity and disease duration (ρ = 0.46, P < 0.001 and ρ = 0.45, P = 0.003). CONCLUSIONS: Muscle QUS may serve as a useful tool in upper extremity mononeuropathy evaluation. Further study of this concept is recommended.

ALS longitudinal studies with frequent data collection at home: study design and baseline data.

OBJECTIVE: To design an ALS clinical study in which patients are remotely recruited, screened, enrolled and then assessed via daily data collection at home by themselves or caregivers. METHODS: This observational, natural-history study included two academic medical centers, one providing overall clinical management and the other overseeing computing and web-services design and management. Both healthy and ALS subjects were recruited on the Internet via advertisement on governmental and foundation websites as well as through Facebook and Google paid advertisements. Individuals underwent screening and enrollment remotely, including signing an electronic informed consent form. Participants were then provided self-measurement equipment and instructed on their use through a series of web-based videos. The equipment included a handgrip dynamometer, spirometer with smartphone connection, electrical impedance myography device, and an activity tracker. ALS Functional Rating Scale-Revised data were also collected. Subjects were asked to collect data daily for three months and twice-weekly for the subsequent six months. RESULTS: One hundred and eleven ALS patients and 30 healthy individuals enrolled in the study from across 41 states (74 men, 62 women). Baseline median ALSFRS-R score was 33. Seventy two percent of the ALS patients sent equipment and 88% of the healthy subjects sent equipment were able to complete a first set of measurements. Expected baseline differences between the ALS patients and healthy participants were identified for all measures. CONCLUSIONS: It is possible to design and institute an at-home based study in ALS patients, using a number of state-of-the-art approaches, including web-based consenting and training and Internet-connected measurement devices.

OBJECTIVE ASSESSMENT OF VOCAL TREMOR.

Detecting early signs of neurodegeneration is vital for planning treatments for neurological diseases. Speech plays an important role in this context because it has been shown to be a promising early indicator of neurological decline, and because it can be acquired remotely without the need for specialized hardware. Typically, symptoms are characterized by clinicians using subjective and discrete scales. The poor resolution and subjectivity of these scales can make the earliest speech changes hard to detect. In this paper, we propose an algorithm for the objective assessment of vocal tremor, a phenomenon associated with many neurological disorders. The algorithm extracts and aggregates a feature set from the average spectra of the energy and fundamental frequency profiles of a sustained phonation. We show that the resultant low-dimensional feature set reliably classifies healthy controls and patients with amyotrophic lateral sclerosis perceptually rated for tremor by speech language pathologists.

Predicting myofiber size with electrical impedance myography: A study in immature mice.

INTRODUCTION: Electrical impedance can be used to estimate cellular characteristics. We sought to determine whether it could be used to approximate myofiber size using standard prediction modeling approaches. METHODS: Forty-four C57BL/6J wild-type immature mice of varying ages underwent electrical impedance myography (EIM) with a needle electrode array placed in the gastrocnemius. Animals were then humanely killed and muscle fixed, stained, and myofiber size quantified. Two different statistical prediction models were then applied. RESULTS: Impedance parameters showed major variation with increasing myofiber size. The prediction models based on EIM data alone were able to predict fiber size, with errors in the range of ±69.05-78.44 µm2 (16.19%-18.40% with respect to the average myofiber size). DISCUSSION: By using well-established statistical models, EIM data alone can provide a satisfactory estimate of myofiber size. Additional study of this approach for approximating myofiber size without the requirement of removing tissue for histological analysis is warranted. Muscle Nerve, 2018.