Biomarkers in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is neurodegenerative disorder leading to progressive muscle weakness, respiratory dysfunction and death. Despite extensive research of exposome it is still not understood which persons might be affected, what might be the course of the disease. We performed neuromuscular ultrasound (US) for 23 patients with ALS and 33 healthy controls (HC). Nerve cross sectional area (CSA) and echogenicity was evaluated. Mean hyperechoic fraction of white was calculated as a percentage. Muscle echogenicity was evaluated using Heckmatt scale (HS). Disease severity was evaluated using ALS-FRS-R scale, serum‘s concentration of phosphorylated neurofilament heavy chain (pNfH) was analysed. Mean age of patients with ALS was 58.3 (SD 11.4) years, of control group - 53.5 (SD 11.8) years. Increased echogenicity was found in the anterior tibial (AT) (85%), quadriceps femoris (93%), 1st dorsal interosseous (1stDO) (63%), and submental (56%) muscles of ALS patients. Biceps brachii muscle strength of the patients with muscle echogenicity assigned to 1 point by HS was bigger compared to those with muscle echogenicity of 2 points by HS (p<0,001). Also AT muscle strength was bigger of the patients with muscle echogenicity of 1 point by HC compared to those of 3 points by HS (p<0.001). ALS-FRS-R scale score was higher in patients with right 1stDO muscle echogenicity of 1 point compared to those with 3 points (p<0.04). The upper trunk (UT) of the right brachial plexus had a median fraction of white of 34.6% in ALS patients, compared to 17.8% in HC, (p=0.01). Also the left ulnar nerve in the midline of the forearm (FA) had median fraction of white of 66.2 % while corresponding fraction in HC was 77.9%,( p=0.03). Median CSA of the UT of the right brachial plexus was 3.6 mm2 in ALS patients and 5 mm2 in HC (p=0.01). Mild but significant correlation was observed between lower ALS-FRS-R scale score and lower echogenicity of the left UN (r=0.44, p=0.047). Median concentration of pNfH in ALS patients was 43.4 pg/ml, and did not differ between bulbar-onset and limb-onset ALS groups (41.6 pg/ml and 42.5 pg/ml, respectively, (p=0.78)). Our results show that patients with hyperechoic muscles had less strength. Size and US echogenicity changes of peripheral nerves were associated with worse physical function. No differences were found in pNfH concentration according to disease phenotype. Further studies are needed with extended cohort.