Pregabalin-associated myoclonic encephalopathy without evidence of drug accumulation in a patient with acute renal failure
A 64-year-old woman was admitted in the Emergency Department (ED) for altered consciousness and abnormal movements. Her medical history included arterial hypertension and type 2 diabetes mellitus. There was no history of epileptic seizures. She was treated since 1 year in the Hematology Department for a multiple myeloma complicated with chronic inflammatory demyelinating polyneuropathy (CIDP). Her current medications included clonazepam, amlodipine, L-thyroxin, metformin, repaglinide, spironolactone, furosemide, minoxidil, irbesartan, hydrochlorothiazide, acyclovir, pantoprazole, and fenofibrate. During the recent hospital stay, the patient started taking pregabalin (75 mg/day for 9 days and then 75 mg bid) to treat CIDP-related pain. At the time of discharge from the hospital, her serum creatinine concentration was 90.2 μmol/l. Five days later, when admitted in the ED, the patient had already received a cumulative dose of 1,350 mg pregabalin for more than 14 days. The last dose of 75 mg had been ingested 36 h before the hospital admission. The medication was stopped by the patient following the symptoms of confusion, speech difficulties, visual hallucinations, and continuous limb and head movements.\nWhen admitted in the ED, the Glasgow Coma Score was 11/15 (E3, V3, M5). Spontaneous myoclonus of the legs was observed, with involuntary movements of the arms and face, which were increased when the patient was stimulated (). She aroused but was unable to speak. The main findings of the laboratory investigations were an acute renal failure, with serum urea, 22.9 mmol/l (normal <8.3); serum creatinine, 451.3 μmol/l (normal <115); and hypercalcemia (total calcium: 3.1 μmol/l). The clearance of creatinine was reduced to 9 ml/min/m2. Acute renal failure was multifactorial: Multiple myeloma, hypercalcemia, and drug interactions. There was no evidence for urinary tract obstruction.\nThe patient was transferred to the intensive care unit. Sedation with benzodiazepines was transiently required to insert venous and arterial catheters, and the intensity of the abnormal movements was decreased. It was not possible to perform an electroencephalogram due to incessant movements of the head. As urine output was maintained, and in the absence of severe metabolic disorders, hemodialysis was not required. Renal function rapidly recovered following fluid therapy. The neurological condition improved after 24 h of supportive care, with a resolution of myoclonus. Confusion and speech disorder persisted for 48 h, but ultimately the patient made a complete neurological recovery, with a total amnesia of the recent events. Pregabalin was not reintroduced. Renal function returned to previous values.\nLater, the results of the toxicological analysis were obtained []. At the time of admission, the concentration of plasma pregabalin was 3.42 μg/ml (therapeutic range: 3-12). The terminal elimination half-life was 11.5 h and was calculated from five consecutive time points up to 31 h after admission. Based on these pharmacokinetic data and considering the delay of 36 h between last drug ingestion and hospital admission, a maximal plasma pregabalin concentration of 13.70 μg/ml could have been reached 12 h after the last drug administration (last theoretical trough concentration).