Abstract Introduction Neuroleptic Malignant Syndrome (NMS) is a potentially life-threatening neurologic emergency classically associated with the use of dopamine-receptor antagonists. However, it is increasingly recognized with the abrupt withdrawal of dopamine-depleting agents. Deutetrabenazine, a vesicular monoamine transporter-2 (VMAT-2) inhibitor used for hyperkinetic movement disorders, can therefore precipitate NMS upon sudden discontinuation, underscoring the need for cautious tapering and heightened clinical awareness of this atypical mechanism. Case Description A 21-year-old woman with autism spectrum disorder, epilepsy, movement disorder, and renal calculi was admitted for management of a urinary tract infection. Her home medications included valproate and zonisamide for epilepsy and myoclonic jerks. She had recently been started on deutetrabenazine for a movement disorder. During hospitalization, valproate was discontinued due to elevated transaminases, and zonisamide was replaced with lacosamide due to concerns for nephrolithiasis. She subsequently developed myoclonic jerks and akathisia, prompting discontinuation of deutetrabenazine. Within 24 hours, she developed a high-grade fever (Tmax 109 °F), tachycardia, generalized rigidity, encephalopathy, followed by cardiac arrest. Return of spontaneous circulation was achieved after one round of CPR, and she was intubated for airway protection. Laboratory evaluation revealed a rising white blood cell count (from 11.6 to 22.8 × 109/L), creatinine (from 1.25 to 2.39 mg/dL), and creatine kinase (800 U/L), consistent with evolving NMS; transaminases were already elevated before the event. Given the recent abrupt discontinuation of deutetrabenazine and the absence of any new dopamine-blocking agents, NMS secondary to deutetrabenazine withdrawal was diagnosed. Dantrolene was administered, resulting in prompt improvement in temperature and hemodynamic stability. Discussion Deutetrabenazine, a VMAT-2 inhibitor commonly used for chorea and tardive dyskinesia, reduces presynaptic dopamine storage and release. However, excessive dopamine depletion may paradoxically cause akathisia or myoclonic jerks. In this patient, myoclonic activity had previously been well controlled with valproate and zonisamide, both of which possess antimyoclonic properties, but resurfaced after their discontinuation, as lacosamide lacks this effect. By altering basal ganglia homeostasis, abrupt interruption of VMAT-2 inhibition can unmask a dopamine-deficient state that clinically manifests as NMS. This case underscores that even brief interruption of VMAT-2 inhibitors can have catastrophic consequences, emphasizing the need for vigilant tapering and early recognition of dopaminergic crisis. This abstract is funded by: None
Lahori et al. (Fri,) studied this question.