Clinical Features and Biomarkers to Differentiate Primary and Amyotrophic Lateral Sclerosis in Patients With an Upper Motor Neuron Syndrome

Background: Differentiation between primary (PLS) and amyotrophic lateral sclerosis (ALS) entails relevant consequences for prognosis and management but is mostly unreliable at early stages. The objectives of the study are: i) to determine the features at onset that could help to differentiate between PLS and ALS; ii) to evaluate the diagnostic performance of an integrated serum biomarker panel; iii) to identify the prognostic factors for patients presenting with an upper motor neuron (UMN)-syndrome. Methods: We selected and retrospectively analyzed the clinical data of patients presenting with UMN-syndrome. At the first evaluation, when available, serum biomarkers were measured using ultrasensitive single molecule array. Results: Study population included 55 PLS and 50 ALS patients. PLS patients presented a longer time to first neurological evaluation (PLS: 35.0 months, IQR: 17.0-38.0; ALS: 12.5 months, IQR: 7.0-21.3; p<0.01) and lower levels of neurofilament light chain (NfL) (PLS: 81.8 pg/mL, IQR: 38.4-111.1; ALS: 155.9 pg/mL, IQR: 85.1-366.4; p=0.01). Two PLS and three ALS patients carried the C9orf72 expansion. NfL resulted an independent predictor of final diagnosis (OR: 1.01, 95%CI: 1.00-1.02; p=0.04) and an independent prognostic factor (HR: 1.01, 95%CI: 1.00-1.01; p<0.01). Conclusions: NfL might help to differentiate PLS from ALS patients and to predict prognosis in patients with an UMN-syndrome.