Amantadine Toxicity Mimicking Holmes Tremor Following Diuretic Dose Escalation: A Case Report

A 69-year-old man with several comorbidities, including hypertension, diabetes mellitus, sequelae of cerebral infarction, and alcoholic liver disease, was admitted to the hospital for transcatheter arterial chemoembolization to treat recurrent hepatocellular carcinoma. Amantadine is eliminated unchanged by the kidneys; even standard therapeutic doses may lead to toxic accumulation when renal function deteriorates. As amantadine neurotoxicity can present with tremor phenotypes resembling cerebellar or Holmes-like tremor, diagnosis is often challenging. In this case, the spironolactone dose was doubled three months before admission, followed by a marked decline in renal function. Two months before hospitalization, the patient developed progressive tremor, gait instability, and dysarthria, and was initially diagnosed with Holmes tremor based on the neurological findings. Although levodopa therapy was initiated, a pharmacist recommended measuring plasma amantadine concentration in light of recent renal impairment. Despite blood sampling 35 hours after the last dose, the amantadine concentration was markedly elevated at 3,935 ng/mL, far exceeding known toxic thresholds. After amantadine discontinuation, plasma concentrations declined, and neurological symptoms gradually improved, with approximately 80% resolution by hospital day nine and complete resolution by six months. Renal function also recovered during follow-up without recurrence of tremor. This case suggests that measuring plasma amantadine concentration should be considered when patients receiving amantadine develop new tremor or gait disturbance in cases with renal dysfunction, while acknowledging the diagnostic uncertainty inherent in single-case observations.