The discovery of the genetic basis of hereditary lower motor neuron disease (LMND) and the recognition of multifocal motor neuropathy as a distinct clinical entity necessitate a new classification of LMND. To this end, we studied the clinical and electrophysiological features of 49 patients with sporadic adult-onset LMND in a cross-sectional study. Disease duration was more than 4 years to exclude the majority of patients with amyotrophic lateral sclerosis. Based on the pattern of weakness, we identified three groups: 13 patients with generalized weakness (group 1); eight patients with symmetrical, distal muscle weakness (group 2); and 28 patients with non-generalized asymmetrical weakness of the arms in most patients (group 3). Group 3 could be subdivided into patients with weakness in predominantly the distal (group 3a) or the proximal (group 3b) muscle groups, both with disease progression to adjacent spinal cord segments. Distinctive features of group 1 were an older age at onset, more severe weakness and muscle atrophy, lower reflexes, greater functional impairment, more widespread abnormalities on concentric needle EMG, respiratory insufficiency and serum M-protein. In groups 2 and 3, concentric needle EMG findings also suggested a more widespread disease process. Retrospectively, the prognosis of sporadic adult-onset LMND appears to be favourable, because clinical abnormalities were still confined to one limb in most patients after a median disease duration of 12 years. We propose to classify the patients in the different subgroups as slowly progressive spinal muscular atrophy (group 1), distal spinal muscular atrophy (group 2), segmental distal spinal muscular atrophy (group 3a) and segmental proximal spinal muscular atrophy (group 3b). The described clinical phenotypes may help to distinguish between different LMND forms.

To investigate the natural history and prognostic factors in patients with nonhereditary, adultonset progressive muscular atrophy. Design: Inception cohort conducted for 18 months. Settings: Three university hospitals in the Netherlands (referral centers for neuromuscular diseases). Patients: Thirty-seven consecutive patients newly diagnosed (onset of weakness Ͻ4 years) with progressive muscular atrophy enrolled between 1998 and 2001. Main Outcome Measures: Disease progression was measured at 0, 3, 6, 9, 12, 15, and 18 months by the Medical Research Council sum score, number of affected limb regions, and the Amyotrophic Lateral Sclerosis Functional Rating Scale score. Multivariate linear regression analysis was used to identify predictors of poor outcome. Clinical features and classification of phenotype during follow-up were evaluated. Survival analysis was planned after data collection, performed 5 years after the end of the study. Results: Significant decline of muscle strength (mean, 6.01 Medical Research Council sum score points [95% confidence interval [CI], 3.84-8.18]; P value Ͻ.001) and significant increase in the number of affected regions (mean, 0.53 affected region [95% CI, 0.42-0.65]; P value Ͻ.001) and functional impairment (mean, 1.85 Amyotrophic Lateral Sclerosis Functional Rating Scale score points [95% CI, 1.38-2.33]; P value Ͻ.001) were found. Vital capacity (VC) at baseline and decrease of VC during the first 6 months were significantly associated with outcome. Median survival duration after initial weakness was 56 months. Conclusions: This study shows that patients with progressive muscular atrophy have a relentlessly progressive disease course. Patients with a low VC at baseline and a sharp decline of VC during the first 6 months have an especially poor prognosis.

No abstract

Objective:To determine the natural course of sporadic adult-onset lower motor neuron syndrome in a longterm 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).