Verification of propagation hypothesis in patients with sporadic hand onset amyotrophic lateral sclerosis.

Abstract

If lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation at a constant speed, the lesion spread time should be proportional to the anatomical distance. We verify this model in the patients. In 29 sporadic ALS patients with hand onset followed by spread to shoulder and leg, we retrospectively evaluated the inter/intra-regional spread time ratio: time interval of symptoms from hand-to-leg divided by that from hand-to-shoulder. We also obtained the corresponding inter-/intra-regional distance ratios of spinal cord from magnetic resonance imaging of 12 patients, and those of primary motor cortex from coordinates using neuroimaging software. Inter-/intra-regional spread time ratios ranged from 0.29 to 6.00 (median 1.20). Distance ratios ranged from 1.85 to 2.86 in primary motor cortex and from 5.79 to 8.67 in spinal cord. Taken together with clinical manifestations, of 27 patients with the requisite information available, lesion spreading was consistent with the model in primary motor cortex in 4 (14.8%) patients, and in spinal cord in only 1 (3.7%) patient. However, in more patients (12 of 29 patients: 41.4%), the inter-regional spread times in a long anatomical distance of hand-to-leg were shorter than or equal to the intra-regional spread times in a short anatomical distance of hand-to-shoulder. Contiguous cell-to-cell propagation at a constant speed might not play a major role at least in distant lesion spreading of ALS. Several mechanisms can be responsible for progression in ALS.