SUMMARYDose-dependent PR interval prolongation has been reported in preclinical studies of lacosamide (LCM), a recently U.S. Food and Drug Administration (FDA)-approved antiepileptic drug (AED). Here we report a case of second-degree atrioventricular block (AV) block caused by the addition of LCM to other AEDs known to prolong the PR interval, resulting in hypotension and bradycardia, with consequent seizure exacerbation. The patient recovered completely after withdrawal of LCM. This case demonstrates the need for caution and interval cardiac testing when adding LCM to other AEDs known to prolong the PR interval. KEY WORDS: Lacosamide, Heart block, Arrhythmia. Case ReportA 45-year-old man with frontal lobe epilepsy, seizurefree for 1 year, developed palpitations, dyspnea, and exercise intolerance 1 week prior to hospitalization for recurrent seizure. En route to the hospital, he was noted to have bradycardia (44 bpm) with hypotension (83/64 mm Hg).His medical history included craniopharyngioma at age 6, treated with right frontal craniotomy, resection, radiation, and ventriculoatrial shunting. His course was complicated by right eye blindness and panhypopituitarism with diabetes insipidus, hypothyroidism, and adrenal insufficiency. At age 21, he developed acute lymphocytic leukemia, treated with chemotherapy. At age 23, he developed frontal lobe epilepsy featuring generalized tonic-clonic seizures beginning with stereotyped right arm extension. There was no personal or family history of cardiac conduction disorders.His medications included desmopressin, hydrocortisone, levothyroxine, somatropin, alfuzosin, risedronate, Carbatrol 100 mg po qAM and 200 mg po qPM, oxcarbazepine 600 mg po qAM, 600 mg po qPM, and 1200 mg po qHS, and LCM 200 mg nightly. His only medication change over the last year was LCM replacing zonisamide (ZNS) for unclear reasons 3 months previously, reaching 200 mg 2 months prior to presentation.Initial laboratory evaluation with blood counts, electrolytes, and hepatic enzymes was unremarkable; carbamazepine (CBZ) level was 3.8 lg/ml. Head computerized tomography showed stable right frontal encephalomalacia. Electrocardiography (ECG) showed second-degree AV block (Mobitz I/Wenckebach) with frequent dropped beats and bradycardia. A transvenous pacemaker was placed. After three further seizures, Carbatrol was increased to 200 mg twice daily, continuous intravenous lorazepam was added, and he was transferred to our institution.At our institution, physical examination revealed prior craniotomy, depressed consciousness, and right afferent pupillary defect. Echocardiography, urinalysis, urine toxicology, and endocrine evaluation [including sodium, thyroxine, and morning cortisol] were unremarkable. Thyroid-stimulating hormone was undetectable, as expected. His antiepileptic drugs (AEDs) were continued except for ZNS replacing LCM. Initial cardiac monitoring showed a markedly prolonged PR interval, frequent Mobitz I AV block, and right bundle branch block. Continuous videoelectroencephalography (EEG) ...