An elderly immigrant from the Middle East presents to your office complaining of numbness and tingling of his hands and feet. He was diagnosed with pulmonary tuberculosis several months ago and is currently receiving isoniazid and rifampin. Neurologic testing demonstrates sensory ataxia and decreased pain sensation in the distal extremities. This patient's condition is most likely caused by:

Question

An elderly immigrant from the Middle East presents to your office complaining of numbness and tingling of his hands and feet.  He was diagnosed with pulmonary tuberculosis several months ago and is currently receiving isoniazid and rifampin.  Neurologic testing demonstrates sensory ataxia and decreased pain sensation in the distal extremities.  This patient's condition is most likely caused by:

Quizplus · Accepted Answer

Isoniazid is chemically similar to pyridoxine (vitamin B₆). Because of this similarity, isoniazid can compete with vitamin B₆ in the synthesis of multiple neurotransmitters (including GABA), resulting in defective end products. Isoniazid also increases the urinary excretion of pyridoxine, and a frank deficiency of this vitamin can eventually develop. Vitamin B₆ deficiency most commonly occurs in patients treated with isoniazid who are elderly, those with alcohol use disorder, or who have other comorbidities (eg, kidney or liver dysfunction). When isoniazid neuropathy occurs, it usually clinically manifests as peripheral neuropathy. To prevent these adverse effects, supplemental vitamin B6 is typically prescribed in conjunction with isoniazid. (Choice A) Immune-mediated demyelinization occurs in multiple sclerosis and the Guillain-Barre syndrome. These conditions are not associated with antibiotic therapy of any kind. (Choice B) Bacterial toxin-mediated axonal damage occurs in infections secondary to Corynebacterium diphtheriae, a microorganism that classically causes pseudomembranous pharyngitis. C. diphtheriae synthesizes a potent exotoxin associated with cardiac and neural toxicity. (Choice C) Pyridoxine deficiency, not drug-mediated toxic neuron loss, is responsible for this patient's neuropathy. Drugs known to be directly toxic to nerves include the chemotherapeutic agents that inhibit microtubule formation (eg, vincristine and paclitaxel). (Choice E) There is no evidence or clinical history suggestive of diabetic neuropathy in this patient. The primary cause of diabetic neuropathy is glucose-induced neural toxicity. High concentrations of glucose result in the formation of glycosylation products (eg, hemoglobin A1c) and the accumulation of sorbitol within the nerves, a phenomenon described as metabolic nerve damage. Educational objective: Isoniazid is structurally similar to pyridoxine (vitamin B₆). As a result, this antibiotic increases the urinary excretion of pyridoxine - often causing a frank deficiency of vitamin B₆ - and competes for vitamin B₆-binding sites, leading to the defective synthesis of neurotransmitters like GABA. Isoniazid-induced neuropathy can usually be prevented with pyridoxine supplementation.

An Elderly Immigrant from the Middle East Presents to Your