Differential diagnosis between amyotrophic lateral sclerosis and spinal muscular atrophy by skin involvement

Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) might be clinical variants caused by the same etiology, or different diseases altogether. We studied the skin in 12 patients with ALS and 7 patients with SMA. The "delayed return phenomenon" (DRP) was observed only in ALS patients. On light microscopy, collagen bundles in ALS dermis were seen to be less numerous, thinner and more loosely woven than in SMA. Electron microscopy revealed that in ALS (1) collagen fibers became thinner as the disease lasted longer, and (2) collagen bundles were separated by much more amorphous material. These findings were not observed in SMA. Our observations show that ALS may be distinguished from SMA by the presence of abnormal dermal collagen. Therefore, we suggest that comparable clinical and pathological skin analysis is the most important diagnostic tool in differentiating between ALS and SMA.