Subclinical upper motor neuron involvement at the diagnosis may predict disease progression in a cohort of lower motor neuron syndromes from Southern Italy

Abstract

Background: Only few epidemiological studies on survival of Lower Motor Neuron (LMN) phenotype (LMNP) are available and with controversial results.

Aims: To prospectively evaluate a cohort of LMNP patients and assess the possible contribute on survival or disease's progression according to the presence of subclinical Upper Motor Neuron (UMN) impairment at the diagnosis.

Methods: Forty LMNP among 176 consecutive incident ALS cases observed in our tertiary center from the ALS-Apulia Register were enrolled in the study. Each patient underwent to a neurophysiological study with transcranial magnetic stimulation (TMS) at diagnosis. The primary outcome was the impact of abnormalities at TMS on survival time (from symptoms onset or diagnosis to death, tracheostomy or 30 June 2020, as censoring time). Secondary outcome was time to reach the King's 4 stage.

Results: Approximately one half of LMNP reached the primary outcome during the study period. No difference was found in median survival times and 4 years survival rates according to the presence of TMS impairment. On the other hand, a shorter median time to reach the King's 4 from onset was observed in the group of LMNP with TMS abnormalities (16 months versus 50 months; p = 0.008). Consistently, TMS abnormalities were associated with a 3.5 times higher risk for reaching King's 4 stage (Hazard Ratio: 3.5; 95% Confidence Interval: 1.1-10.9; p = 0.03).

Conclusion: Our data suggest a role of TMS abnormalities as potential indicator of disease progression and multidistrectual involvement in patients with pure clinical LMN phenotype at the diagnosis.

Keywords: Lower motor neuron; Progression; Survival; Upper motor neuron.