Dynamic analysis of muscles and the internal structure of the peripheral nerve as biomarkers of amyotrophic lateral sclerosis: A pilot study with ultrasound imaging.

INTRODUCTION: The aim of this study was to determine the behaviour of ultrasound biomarkers of fascicle density and muscle strength in patients with amyotrophic lateral sclerosis (ALS). METHODS: We conducted an observational, cross-sectional pilot study of 14 patients with ALS (28.6% women) and 14 controls. Bilateral cross-sectional ultrasound scans were performed in the abductor pollicis brevis (APB) and tibialis anterior (TA) muscles, with recording of muscle thickness (MT) at rest and in contraction, and the difference in thickness. In the median, sciatic, and common peroneal nerves, we analysed the cross-sectional area (CSA), number of fascicles (NF) and fascicle density (FD). Analyses were nested by laterality. RESULTS: Intra- and interrater agreement regarding NF was very good, with a minimum detectable error of < 0.7%. In patients with ALS, MT was lower in the APB both at rest (P = .003; g-Hedges = 1.03) and in contraction (P = .017; g-Hedges = 0.78) and in TA at rest (P = .002; g-Hedges = 0.15) and in contraction (P = .001; g-Hedges = 0.46), with lower thickening capacity. In the nerves, patients displayed lower CSA, with lower NF and higher FD. Significant correlations were found between MT of the ABP and Medical Research Council (MRC) scores for muscle strength (r = 0.34; r2 = 12%; P = .011) and with revised ALS Functional Rating Scale scores (r = 0.44; r2 = 19%; P < .001). The difference in TA thickening correlated with MRC scores (r = 0.30; r2 = 15%; P = .003) and with revised ALS Functional Rating Scale scores (r = 0.26; r2 = 7%; P = .049). NF in the sciatic nerve showed a significant correlation with MRC scores (r = 0.35; r2 = 12%; P = .008). CONCLUSION: MT measurements derived from dynamic testing together with NF and FD may be useful biomarkers for monitoring patients with ALS and establishing a prognosis.

New insights into the pathophysiology of fasciculations in amyotrophic lateral sclerosis: An ultrasound study.

OBJECTIVE: To describe the fasciculation pattern in ALS and to analyse its clinical and pathophysiological significance. METHODS: Ultrasound of 19 muscles was performed in 44 patients with a recent diagnosis (<90 days) of ALS. The number of fasciculations was recorded in each muscle and the muscle thickness and strength were additionally measured in limb muscles. A subgroup of patients were electromyographically assessed. RESULTS: US was performed in 835 muscles and EMG was available in 263 muscles. US detected fasciculations more frequently than EMG. Fasciculations were widespread, especially in upper limbs onset patients and in the cervical region. Fasciculations' number inversely associated with ALSFR-R and body mass index (BMI) and directly with BMI loss and upper motor neuron (UMN) impairment. Our statistical model suggest that fasciculations increase with the initial lower motor neuron (LMN) degeneration, reach their peak when the muscle became mildly to moderately weak, decreasing afterwards with increasing muscle weakness and atrophy. CONCLUSIONS: Our study suggests that both UMN and LMN degeneration trigger fasciculations causing BMI loss. The degree of LMN impairment could account for differences in fasciculations' rates within and between muscles. SIGNIFICANCE: In ALS, fasciculations could explain the link between hyperexcitability and BMI loss.