Refractory Agitation in Advanced Huntington’s Disease: Palliative Management at End of Life

Key Message : This case highlights the absence of standardized, evidence-based protocols for managing refractory agitation and chorea in advanced Huntington’s disease. Through interdisciplinary collaboration between neurology and palliative care, this report underscores the urgent need for consensus guidelines to ensure comfort, dignity, and ethical decision-making at the end of life.

Abstract:

Background: Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric decline. In advanced stages, refractory agitation and chorea can become profoundly distressing and difficult to control. Despite these challenges, no formalized protocols exist to guide clinicians in the management of end-of-life symptoms specific to HD. Current practice relies largely on individualized, experience-based approaches extrapolated from general palliative care.

Case Description: A 49-year-old male with advanced HD was admitted to the inpatient palliative unit (IPU) for refractory agitation and end-of-life care. Despite maximal oral and IV therapy—including haloperidol, quetiapine, phenobarbital, and scheduled benzodiazepines—his chorea and agitation worsened. Intravenous therapy was initiated with around-the-clock midazolam 4 mg IV every 3 hours and morphine 6 mg IV every 3 hours for comfort and anxiolysis. His home psychotropics were continued. Due to ongoing distress, escalation to a dexmedetomidine infusion and potential initiation of palliative sedation were considered.

Discussion: This case underscores the absence of standardized, evidence-based guidelines for managing refractory agitation and chorea in end-stage HD. Existing literature highlights variability in symptom expression and treatment response, with most data derived from expert opinion or extrapolated neuropsychiatric management. Reports by Armstrong et al. (J Neurol Sci. 2016) and Boersma et al. (Palliat Med. 2019) emphasize this gap, advocating for interdisciplinary approaches that integrate neurology and palliative care. When symptoms remain refractory, ethically guided palliative sedation may be required, consistent with frameworks outlined by Cherny and Radbruch (Lancet Oncol. 2009).

Conclusion: End-of-life care in HD requires collaborative, patient-centered strategies. The lack of formalized protocols for refractory agitation highlights the need for future research and consensus guidelines to optimize comfort and dignity for patients in the terminal stages of neurodegenerative disease.

References: Armstrong MJ, Miyasaki JM. Evidence-based guideline: Pharmacologic treatment of chorea in Huntington disease. J Neurol Sci. 2016;366:161–177.

Boersma I, Miyasaki J, Kutner J, Kluger BM. Palliative care and neurology: Time for a paradigm shift. Palliat Med. 2019;33(5):611–613.

Cherny NI, Radbruch L; Board of the European Association for Palliative Care. European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care. Lancet Oncol. 2009;10(7):622–630