Disulfiram neuropathy: two cases of distal axonopathy.
BACKGROUND
Disulfiram may cause a peripheral neuropathy that is considered dose- and duration-of-exposure-related. Axonal degeneration has been described as a pathological hallmark of disulfiram toxicity, but experiments have reported a primary toxic effect of the molecule on Schwann cells and myelin.


METHODS
Case 1: At the end of two months of treatment with disulfiram 250 mg/day, a 31-year-old woman complained of weakness in distal segments of the lower limbs associated with burning dysesthesias, numbness and pain in the soles of the feet and the legs below the knees; bilateral walking steppage, reduction in foot strength, absence of ankle jerk and knee tendon reflexes, and tactile stocking pin-pick and vibratory sensory impairment in the lower limbs below the knee. Disulfiram was discontinued and she recovered partially over three months. Case 2: After one month of treatment with disulfiram 1600 mg/day, a 27-year-old man reported walking impairment, distal lower limb weakness and paresthesias. He had unsteady gait with bilateral steppage and foot drop, absence of ankle jerks and overall sensation impairment below the knee. Disulfiram was discontinued and nine months later there was almost complete recovery of motor deficits, only minor motor weakness in distal leg muscles, and no dysesthesia, sensation deficits or areflexia. In both of them clinical and neurophysiological patterns were indicative of a distal axonopathy. DISCUSSION The mechanisms by which disulfiram cause injury in human nerves are unclear, though may involve carbon disulfide. The discrepancy between experimental and clinical observations is still unexplained.


CONCLUSIONS
We report two cases of disulfiram axonal toxicity and the partial response following discontinuation of the drug.
Filosto
Massimiliano
M
University Hospital Spedali Civili, Brescia, Italy. filosto@med.unibs.it
Tentorio
Marta
M
Broglio
Laura
L
Buzio
Serena
S
Lazzarini
Clara
C
Pasolini
Maria Pia
MP
Cotelli
Maria Sofia
MS
Scarpelli
Mauro
M
Mancuso
Michelangelo
M
Choub
Anna
A
Padovani
Alessandro
A
D000328:Adult; D000427:Alcohol Deterrents / Q000009:adverse effects*; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D004221:Disulfiram / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D020127:Recovery of Function; D028761:Withholding Treatment
D000427:Alcohol Deterrents; D004221:Disulfiram