Mitochondrial loss indicates early axonal damage in small fiber neuropathies.
Evaluation of nerve fibers in the skin provides a useful tool for the diagnosis of small fiber neuropathies (SFNs). Our aim was to determine whether mitochondria are involved in SFN, indicating early axonal damage. We quantified mitochondrial respiratory chain complex IV (OXPHOS) and axonal (PGP 9.5) fluorescence on skin sections from 32 SFN patients and 14 healthy controls. Also, a group of six patients were recruited before and after 30-day treatment with the mitotoxic antibiotic linezolid. We measured the co-localization of OXPHOS within the intraepidermal and subpapillary dermal axons (PGP-immunoreactive [PGP-ir]). SFN patients with relatively preserved intraepidermal nerve fibers (SFN borderline) showed statistically significant reduction of OXPHOS (50.5 ± 33.9 µm(2)  vs. 107.6 ± 81 µm(2)  in controls, p < 0.02). A positive correlation was found between both PGP-ir and OXPHOS in controls (Pearson's coefficient r = 0.59, p < 0.001), whereas such correlation was absent in SFN. With respect to baseline measurements, linezolid therapy increased both PGP-ir and OXPHOS, which could be considered an initial compensatory toxic-induced response. This study set out to identify a possible marker of axonal pre-degenerative state in SFN borderline patients.
Department of Neurology, Hospital Clinic IDIBAPS-Institut d'Investigació Augustí Pi i Sunyer, University of Barcelona, Barcelona, Spain. jcasanovamolla.hj23.ics@gencat.cat
Jordi
J
Casanova-Molla
Merche
M
Morales
Glòria
G
Garrabou
Núria
N
Solà-Valls
Alex
A
Soriano
Maria
M
Calvo
Josep Maria
JM
Grau
Josep
J
Valls-Solé
D000081:Acetamides / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D001706:Biopsy; D042241:Early Diagnosis; D003576:Electron Transport Complex IV / Q000032:analysis; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D023303:Oxazolidinones / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis*; D012867:Skin / Q000294:innervation* / Q000473:pathology
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D003576:Electron Transport Complex IV; D000069349:Linezolid