LAUSR

Huntington’s disease is a rare autosomal dominant neurodegenerative disease caused by cytosine-adenineguanine (CAG) trinucleotide expansion of the huntingtin gene on chromosome 4p. Primarily a disease of the central nervous system with accumulation of the huntingtin protein within the cellular nucleus and cytoplasm, the neuronal loss is predominantly located in the caudate and putamen of the basal ganglia. The basal ganglia consist of a group of structures including the globus pallidus, substantia nigra and subthalamic nucleus. Functionally, they are collectively involved in movement, cognition, and emotion. As such, Huntington’s disease is a clinical triad of motor dysfunction (i.e., chorea), cognitive impairment and psychiatric disturbances. In the last decade, it is increasingly recognized that various neurodegenerative disorders including Huntington’s disease can have associated autonomic dysfunction. For example, spinocerebellar ataxias type 2 is also an autosomal dominant disease due to CAG repeat expansion in the ATXN2 gene on chromosome 12q. Similar to Huntington’s disease, symptoms of spinocerebellar ataxias type 2 also include ataxia, chorea, dementia and autonomic dysfunction. In these patients, I-metaiodobenzylguanidine (MIBG) scans showed loss of post-ganglionic myocardial sympathetic nerve fibers with significantly lower early and late heartto-mediastinum (H/M) ratios compared to controls. Similarly, diseases such as Parkinson’s disease and Lewy body dementia (the second most common type of dementia after Alzheimer’s) ‘‘resembles’’ Huntington’s disease as they are also characterized by disturbances in sleep, behavior, cognition, movement and autonomic function. These patients are known to have autonomic dysfunction and abnormal MIBG scans compared to normal controls. There is a strong body of evidence indicating that the autonomic nervous system plays an important role in the genesis of sudden cardiac death. Increased cardiac sympathetic activity without opposing increase in parasympathetic vagal activity can promote ventricular arrhythmias by reducing the ventricular refractory period and ventricular fibrillation threshold, promote triggered activity after potentials, and enhance cardiac automaticity with accelerated generation of action potential in abnormal tissue. Traditionally, autonomic function was frequently assessed by means of heart rate variability (HRV) analysis. Several studies to date have shown increased sympathetic and reduced parasympathetic vagal activities in patients at middle stages of Huntington’s disease, as well as in pre-symptomatic mutation carriers. However, HRV is influenced by age, race, gender, cardiovascular fitness, sleep/wake cycles and drug treatment. In addition, it is only interpretable in patients with predominantly sinus rhythm and have accurate R-wave detection. Ultimately, HRV is an indirect assessment of the autonomic nervous system and does not directly measure absolute sympathetic and parasympathetic activity. In contrast, MIBG scans can directly quantify cardiac sympathetic innervation and Reprint requests: Jeroen J. Bax, MD, PhD, Department of Cardiology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; [email protected] J Nucl Cardiol 2022;29:649–51. 1071-3581/$34.00 Copyright 2020 American Society of Nuclear Cardiology.