OBJECTIVE: To investigate the involvement of the epidermal small sensory fibers in the neurodegenerative process in amyotrophic lateral sclerosis (ALS). METHODS: In the present study, skin biopsies of 28 patients with ALS were obtained at an average of 34 months after disease onset by history. Protein gene product 9.5 (PGP9.5) immunohistochemistry findings were compared to 17 age-matched controls. The primary endpoint of the study was to evaluate the decrease in the density of small intraepidermal nerve fibers and to compare the prevalence of small-fiber neuropathy in patients with ALS and in controls. RESULTS: We found a significant reduction in epidermal nerve fiber density in the distal calf of patients with ALS (4.8 ± 3.7 fibers/mm vs 12.2 ± 4.6 in age-matched controls, p<0.0001). The extent of fiber loss was age-dependent. Also, the number of subjects with small-fiber neuropathy was significantly higher in the ALS group than in the controls (79% vs 12%). Correspondingly, mild sensory symptoms including diffuse dysesthesias, paresthesias, and hypesthesia were found in 7 patients. In 17 biopsies of patients with ALS, but only in 2 controls, we saw larger (>1.5 μm in diameter) focal swellings of epidermal axons resembling spheroids, suggesting trafficking defects. CONCLUSIONS: These results indicate that small, distal epidermal nerve fibers are involved in this disease, supporting the concept of distal axonopathy in ALS.
OBJECTIVE: To investigate the involvement of the epidermal small sensory fibers in the neurodegenerative process in amyotrophic lateral sclerosis (ALS). METHODS: In the present study, skin biopsies of 28 patients with ALS were obtained at an average of 34 months after disease onset by history. Protein gene product 9.5 (PGP9.5) immunohistochemistry findings were compared to 17 age-matched controls. The primary endpoint of the study was to evaluate the decrease in the density of small intraepidermal nerve fibers and to compare the prevalence of small-fiber neuropathy in patients with ALS and in controls. RESULTS: We found a significant reduction in epidermal nerve fiber density in the distal calf of patients with ALS (4.8 ± 3.7 fibers/mm vs 12.2 ± 4.6 in age-matched controls, p<0.0001). The extent of fiber loss was age-dependent. Also, the number of subjects with small-fiber neuropathy was significantly higher in the ALS group than in the controls (79% vs 12%). Correspondingly, mild sensory symptoms including diffuse dysesthesias, paresthesias, and hypesthesia were found in 7 patients. In 17 biopsies of patients with ALS, but only in 2 controls, we saw larger (>1.5 μm in diameter) focal swellings of epidermal axons resembling spheroids, suggesting trafficking defects. CONCLUSIONS: These results indicate that small, distal epidermal nerve fibers are involved in this disease, supporting the concept of distal axonopathy in ALS.
Authors: Janneke G Hoeijmakers; Catharina G Faber; Giuseppe Lauria; Ingemar S Merkies; Stephen G Waxman Journal: Nat Rev Neurol Date: 2012-05-29 Impact factor: 42.937
Authors: A Truini; A Biasiotta; E Onesti; G Di Stefano; M Ceccanti; S La Cesa; A Pepe; C Giordano; G Cruccu; M Inghilleri Journal: J Neurol Date: 2015-02-17 Impact factor: 4.849
Authors: Nan Jiang; Jeffrey P Rasmussen; Joshua A Clanton; Marci F Rosenberg; Kory P Luedke; Mark R Cronan; Edward D Parker; Hyeon-Jin Kim; Joshua C Vaughan; Alvaro Sagasti; Jay Z Parrish Journal: Elife Date: 2019-03-11 Impact factor: 8.140