Opsoclonus Caused by Diphenhydramine Self-Poisoning

Abstract

We report a patient who developed opsoclonus together with coma, seizure, autonomic disturbance, and rhabdomyolysis from diphenhydramine overdose. This is the second case report of opsoclonus in this setting (1). A 22-year-old man was found unconscious in bed. Shortly thereafter, he developed a generalized seizure. In our hospital, his body temperature was 36.6°C, blood pressure was 142/90 mmHg, and pulse rate was 153 beats/min. He was unresponsive to painful stimuli. His pupils were dilated and sluggishly reactive to direct light. He had rapid conjugate oscillations of the eyes in the horizontal, vertical, and rotatory planes interpreted as opsoclonus. Abnormal blood test results included hematocrit of 53.1%, white blood cell count of 22,900/mm3, pH of 6.837, anion gap of 33 mEq/L, serum creatinine of 1.32 mg/dL, and creatine kinase of 292 IU/L. Results for plasma glucose, electrolytes, and ammonia were within normal ranges. The Triage Drugs of Abuse Panel (BIOSITE, Inc., San Diego, CA) detected no benzodiazepines or tricyclic antidepressants or their metabolites in the urine. Electroencephalography showed diffuse beta waves without epileptiform activity. Results of brain MRI and lumbar puncture were normal. Several hours after the patient's admission, his serum creatine kinase level rose to 72,312 IU/L, and oliguric acute renal failure occurred. At this time, a family member found empty diphenhydramine packages in the patient's room, suggesting self-poisoning with this agent. We treated the patient with intravenous fluids, furosemide, and 800 mg valproic acid daily. Opsoclonus disappeared on the second hospital day. The patient's level of consciousness returned to normal in tandem with recovery of renal function over several days. There were no residual clinical deficits. After recovery the patient confirmed that he had ingested 3.3 g diphenhydramine in a suicide attempt after conflict with his fiancée. He had been taking the diphenhydramine tablets for insomnia and had purchased multiple packages from several drugstores. High-performance liquid chromatography (HPLC) analysis of the patient's serum 10 hours after he had ingested the diphenhydramine disclosed a serum concentration of 2.61 μg/mL. (In healthy young adults, the mean maximal serum concentration after ingestion of 50 mg diphenhydramine orally is 82.2 ± 31.5 ng/mL [2].) Diphenhydramine is a first-generation antihistamine that can have both excitatory and inhibitory effects on the central nervous system. Its anticholinergic activity can cause autonomic disturbance (3). The previous report of opsoclonus in diphenhydramine poisoning is very similar to ours, in that the patient suffered from opsoclonus, cerebellar ataxia, and mental status changes. The patient confirmed ingestion of 2 g diphenhydramine, and HPLC analysis of the patient's urine confirmed the diagnosis (1). Two reports have described single cases of oculogyric crisis, spasmodic conjugate ocular deviations usually in an upward direction (4,5). Opsoclonus is found mostly in association with viral or paraneoplastic encephalitis, but it may be observed in patients intoxicated with agents such as lithium and organophosphates (6). Lithium may affect the function of glycinergic omnipause neurons, and organophosphate poisoning may affect cholinergic inputs from the pedunculopontine to the fastigial nucleus (6). We speculate that the opsoclonus seen in our patient was caused by the anticholinergic activity of diphenhydramine. Interestingly, oculogyric crisis has been reported not only in an overdose of diphenhydramine but also in an overdose of cetirizine, a second-generation antihistamine with anticholinergic effects (7). In light of the fact that diphenhydramine is widely available, clinicians should recognize its potential to cause opsoclonus. Takashi Irioka, MD, PhD Ayaka Yamanami, MD Department of Neurology and Neurological Science Graduate School, Tokyo Medical and Dental University Tokyo, Japan Naoki Uchida, MD, PhD Mariko Iwase, PhD Hajime Yasuhara, MD, PhD Second Department of Pharmacology Showa University School of Medicine Tokyo, Japan Hidehiro Mizusawa, MD, PhD Department of Neurology and Neurological Science Graduate School, Tokyo Medical and Dental University Tokyo, Japan [email protected]