SIR: Isoniazid (INH) overdose can result in neuropsychological sequelae, including cognitive deficits.1 These deficits are generally regarded as transient and rapidly reversible with pyridoxine.2 We report a case in which, despite appropriate treatment with pyridoxine, INH overdose resulted in Substance-Induced Persisting Dementia.
Mr. A is a 20-year-old, single, white male, with above-average cognitive abilities, as assessed by his scores on the Armed Services Vocational Aptitude Battery (ASVAB) upon entering the Navy. Two years into his service, Mr. A. attempted suicide by overdosing on and estimated 9000 to 12,000 mg of INH.
Mr. A was intubated and treated for persistent seizures. Lavage was initiated, and IV pyridoxine was administered. As sequelae to his overdose, Mr. Anderson developed an acute toxic encephalopathy. At worst, the patient was noted to have fixed and dilated pupils and decerebrate posturing. After treatment in an intensive care unit, Mr. A. recovered medically but was discovered to have significant persisting deficits, specifically retrograde amnesia for 1 and ½ years, previously; anterograde learning difficulties; apraxia; and personality change in the form of a newly acquired passivity.
Repeated psychiatric interviews and neuropsychological testing did not support the diagnosis of a major depressive disorder, conversion disorder, or malingering. Similarly, a thorough work up by infectious disease showed no indications of central nervous system (CNS) tuberculosis or other infectious etiologies.
Formal neuropsychological testing showed impairment in speech initiation and verbal fluency. Tests of attention ranged from severely impaired to low average. Mr. A experienced significant difficulties encoding new verbal information and, to a lesser degree, stored data. Visual memory was below expectations. Fine motor skills were poor. Overall intelligence quotient (IQ) was average but below expectations for his previous baseline.
A neurological examination was negative for evidence of INH-induced peripheral neuropathy but did show changes consistent with a basal ganglia injury. Electroencephalogram (EEG) showed prominent slow delta and scattered theta activity, particularly in the temporal areas. Magnetic resonance imaging (MRI) showed increased signal involving bilateral mesotemporal lobes, which could be consistent with the sort of learning difficulties exhibited.
To target memory problems, Mr. A was treated with continuing PO pyridoxine and donepezil. After 20 days on the inpatient psychiatric service and 2 months of outpatient cognitive rehab, the patient regained function to the point at which he could return to live with his family. Several months later, he was able to obtain a job in a fast food restaurant. One year after the initial overdose, however, he continued to have cognitive difficulties and had not returned to his baseline.
Neuropsychiatric changes are a well-known complication of INH overdose, but it has been assumed that lasting deficits do not result.1,3 The case of Mr. A illustrates that such complications can occur. Persistent seizures, encephalopathy, and other medical consequences that Mr. A suffered as a result of his overdose could have contributed to significant neurotoxicity.3 Long-term, neuropsychiatric screening may, therefore, be warranted in patients who have experienced significant INH overdose.