Neural Toxicity in Tuberculous Patients Treated With Isoniazid (Isonicotinic Acid Hydrazide)

Abstract

IN THIS communication is reported a new syndrome of neural toxicity encountered in a group of tuberculous patients under treatment with isoniazid (isonicotinic acid hydrazide). Although foreshadowed, perhaps, in some of the few papers on the use of the drug in humans, the fully developed syndrome apparently has not previously been encountered or described, and no suggestion of it has appeared in the animal toxicity studies. The patients all had advanced pulmonary tuberculosis and had received a large quantity of the drug. We have examined in detail 14 patients from a larger group of 46 with similar complaints observed in a series of 408 patients receiving the drug.The first complaint was that of a sense of numbness, or lack of feeling, and a tingling, "pins and needles," sensation in the toes and feet, as though the extremity had "been asleep" or was "thawing out from cold." If the drug was withdrawn at this point, the symptoms resolved in a few days. If the drug was continued, the disturbance spread up the legs to the knees, and then, in a few instances, the hands and fingers were similarly affected. As the process advanced, pain and ache in the skin and muscles were experienced, sometimes with a burn¬ ing quality. This was increased by use of the limbs, and in two patients it became severe enough to prevent weight bearing and to interfere with sleep. At this stage the symptoms failed to subside promptly when administration of the drug was stopped. Four patients complained of an electric shock sensation when the limb was touched or moved. Muscular soreness or drawing pain in the calves was another complaint. Two patients also noted loss of balance, and two had weakness of the lower extremities. On the whole the sensory complaints domi¬ nated the picture, and ataxia and weakness were secondary in importance to the continual and disagreeable, if not actually painful, paresthesias of tingling and of burning pain. Nevertheless, the pain was not severe except in two instances, and the patients did not seek analgesics.The location of these aches and pains lay below the knees and in the fingers and hands-in the familiar stocking-glove distribution. The process was bilaterally symmetrical.No bladder or rectal symptoms, no visual symptoms, and no convulsions were encountered. No symptoms referable to the cranial nerves were noted. Several patients complained of dyspnea, and one had transitory dizzness, a symp¬ tom previously reported. Downloaded From: http://archneurpsyc.jamanetwork.com/ by a University of Iowa User on 06/04/2015