A long-term prospective study of the natural course of sporadic adult-onset lower motor neuron syndromes.

Objective: To determine the natural course of sporadic adult-onset lower motor neuron syndrome in a long-term prospective study of patients with the syndrome.

Design: Inception cohort with a follow-up of 72 months.

Setting: Three university hospitals in the Netherlands (referral centers for neuromuscular diseases).

Patients: Thirty-two patients were classified as having the following phenotypes according to previously defined criteria: progressive muscular atrophy (PMA; 10 patients), segmental distal muscular atrophy (8 patients), and segmental proximal muscular atrophy (14 patients). A disease duration of at least 4 years was chosen to exclude most patients with amyotrophic lateral sclerosis (ALS).

Main Outcome Measures: Muscle strength, functional impairment, and respiratory function were assessed at 0, 6, 12, 18, and approximately 72 months.

Results: The diagnosis had to be changed to ALS in 3 patients (classified at inclusion as PMA in 2 patients and segmental proximal muscular atrophy in 1) owing to the development of upper motor neuron signs in 2 patients and familial ALS in 1. The remaining 8 patients with PMA showed further deterioration, and the other 24 patients remained more or less stable during long-term follow-up. Respiratory insufficiency developed in 6 of the 11 patients with ALS or PMA, 5 of whom died.

Conclusions: Patients with lower motor neuron syndromes and a disease duration of at least 4 years usually have a favorable prognosis if muscle involvement has a segmental distribution. In patients with a generalized phenotype, progression is relentlessly progressive and eventually leads to death due to respiratory insufficiency.