Disulfiram Neuropathy: Two Case Reports

Anh Thu Tran; Richard A. Rison; Said R. Beydoun


J Med Case Reports. 2016;10(72) 

In This Article


Distal axonopathy is considered the hallmark of disulfiram toxicity and was evident in these two cases. Axonopathy is demonstrated by the low CMAPs with relatively normal motor conduction velocities. The length-dependent nature of the disulfiram neuropathy was demonstrated by the severely decreased CMAP in the lower extremities while the upper extremities were spared. Demyelination was not supported by the results of either laboratory studies or electrodiagnostic testing. Studies suggest the causal agent of disulfiram neuropathy is carbon disulfide, which is a by-product of disulfiram metabolization.[1] Ansbacher et al. reported a case in which a sural nerve biopsy demonstrated neurofilamentous distal axonopathy and cited carbon disulfide as the responsible agent. Clinically, disulfiram neuropathy and alcoholic neuropathy can be difficult to distinguish. Some observations that can help distinguish the two include a history of onset that occurs in a matter of weeks in disulfiram neuropathy as opposed to an insidious course over months in alcoholic neuropathy. Additionally, the progression is faster in disulfiram neuropathy.[5] Symptoms of both types of neuropathy can be similar, such as symmetrical distribution, worse severity distally, and depression of ankle jerk reflexes. In contrast to alcohol neuropathy, disulfiram neuropathy results in muscle tenderness as well as disturbances in sweating of distal limbs.[6] In our two cases, our patients presented with distal lower extremity symptoms of predominantly painful sensory complaints. Our patient in case 1 had pre-existing symptoms prior to disulfiram therapy, but experienced an acute worsening of symptoms following disulfiram therapy. Our patient in case 2 had lower extremity symptoms of sudden onset and a temporal relationship with disulfiram therapy. Symptoms in both patients progressed at a faster rate than typically observed with alcoholic neuropathy at a time when both were abstaining from alcohol. Clinically, symptoms improved in both patients after cessation of disulfiram; most notably, our patient in case 2 was free of pain 2 months after stopping disulfiram. Electrodiagnostic tests in both patients demonstrated severe length-dependent axonopathy with low distal CMAPs in their lower extremities but normal CMAPs in their upper extremities. EMG studies showed both active denervation, as evidenced by fibrillation and positive sharp waves, as well as chronic denervation, demonstrated by increased amplitude and polyphasia. Additionally, although the primary complaint was sensory in both patients, their SNAPs were spared. This suggests the involvement of small fiber sensory nerves but the sparing of large fiber sensory nerves. This is in contrast to prior literature that report large fiber involvement in disulfiram neuropathy.[5,6] Unfortunately, both of our patients declined repeat electrodiagnostic testing and hence it was not possible to document a correlation between clinical and electrophysiological findings. Although not routinely performed in the evaluation of disulfiram neuropathy, perhaps sensory nerve biopsies would help elucidate any such correlation.