(097) What's in a Name? Parkinson-Hyperpyrexia Syndrome in a Patient with Tardive Dyskinesia

‎Background/Significance: Neuroleptic malignant-like syndromes have been reported to occur in the setting of ‎sudden withdrawal of medications used to treat Parkinsonism. Here we describe a case in which a patient with tardive ‎dyskinesia suddenly discontinued amantadine, a pro-dopaminergic medication, resulting in a neuroleptic malignant-‎like syndrome with all hallmark features of neuroleptic malignant syndrome (NMS). The syndrome resolved with re-‎initiation of amantadine.‎

‎

Case: The patient is a 53-year-old female with a history of bipolar 1 disorder, tardive dyskinesia, hypertension, ‎hypothyroidism, hyperlipidemia, fibromyalgia, and migraine who presented with progressive weakness, slurred ‎speech, and decreased alertness after self-discontinuation of amantadine one week prior. The patient was admitted ‎to the medical floor after discovery of bilateral pulmonary emboli on CTA chest, and for ongoing infectious workup ‎after meeting SIRS criteria with fever and elevated white blood cell count.‎

During hospitalization, the patient developed worsening fever with rigidity, lethargy, slurred speech, and tachycardia. ‎Lab work revealed an elevated creatinine kinase and critical hypernatremia. MRI brain showed no evidence of infarct, ‎vEEG was without epileptiform activity, and lumbar puncture results were normal. On day three, low-dose amantadine ‎was reinitiated with mild improvement in lethargy. By day seven the patient returned to her home amantadine dose, ‎which resulted in improvement in fever, rigidity, weakness, hypernatremia, and speech difficulty within two days.‎

‎

Discussion: The patient's syndrome of fever, rigidity, altered mental status, and autonomic instability ‎appeared consistent with NMS. The above symptoms all presented acutely after withdrawal of amantadine. ‎Amantadine improves symptoms of Parkinsonism and movement disorders by functioning as a dopamine agonist as ‎well as a dopamine reuptake inhibitor, thereby increasing amounts of intrasynaptic dopamine. Although there are case ‎reports of amantadine withdrawal leading to neuroleptic malignant-like syndromes, these cases all appear in the ‎context of a patients previously diagnosed with Parkinson's disease, prompting this syndrome to be referred to as ‎Parkinson-Hyperpyrexia Syndrome in the literature.‎

‎Conclusion/Implications: This case marks a rare incidence in which a neuroleptic malignant-like syndrome ‎occurred in a patient with tardive dyskinesia during amantadine withdrawal. This case suggests that the diagnosis ‎referred to as Parkinson-Hyperpyrexia Syndrome in the literature may occur in patients with movement disorders ‎other than Parkinson's disease.‎

‎

References: ‎
‎1. Gurrera, R. J., Caroff, S. N., Cohen, A., Carroll, B. T., DeRoos, F., Francis, A., Frucht, S. J., Gupta, S., Levenson, J. L., ‎Mahmood, A., Mann, S. C., Policastro, M. A., Rosebush, P. I., Rosenberg, H., Sachdev, P. S., Trollor, J. N., Velamoor, V. ‎R., Watson, C., & Wilkinson, J. R. (2011). An International Consensus Study of Neuroleptic Malignant Syndrome ‎Diagnostic Criteria Using the Delphi Method. The Journal of Clinical Psychiatry, 72(09), 1222–1228.‎
‎2. Newman, E. M., Grosset, D. G., & Kennedy, P. G. E. (2009). The Parkinsonism-Hyperpyrexia Syndrome. Neurocritical ‎Care, 10(1), 136–140.‎
‎3. Sakkas P, Davis JM, Janicak PG, Wang ZY. Drug treatment of the neuroleptic malignant syndrome. Psychopharmacol ‎Bull. 1991;27(3):381-384.‎
‎4. Santos, D., Imthon, A. K., Strelow, M. Z., Pille, A., & Schumacher-Schuh, A. F. (2021). Parkinsonism-hyperpyrexia ‎Syndrome After Amantadine Withdrawal. The Neurologist, 26(4), 149–152.‎