Thermoregulatory Dysfunction in Parkinson’s Disease: Mechanisms, Implications, and Therapeutic Perspectives

Highlights What are the main findings? Thermoregulatory dysfunction in Parkinson's disease (PD) arises from combined central and peripheral alpha-synuclein pathology, disrupting hypothalamic integration, sudomotor, vasomotor, and thermogenic pathways. Distinct alterations in sweating, heat and cold tolerance, and crisis syndromes such as parkinsonism-hyperpyrexia and hypothermia underscore the multisystem nature of PD's autonomic impairment. What are the implications of the main findings? Recognizing and managing thermoregulatory dysfunction can improve patient safety, reduce hospitalization risk, and enhance quality of life in PD. Future studies should investigate how PD affects brown adipose tissue (BAT) and shivering thermogenesis, offering potential targets for restoring heat balance and metabolic stability.Highlights What are the main findings? Thermoregulatory dysfunction in Parkinson's disease (PD) arises from combined central and peripheral alpha-synuclein pathology, disrupting hypothalamic integration, sudomotor, vasomotor, and thermogenic pathways. Distinct alterations in sweating, heat and cold tolerance, and crisis syndromes such as parkinsonism-hyperpyrexia and hypothermia underscore the multisystem nature of PD's autonomic impairment. What are the implications of the main findings? Recognizing and managing thermoregulatory dysfunction can improve patient safety, reduce hospitalization risk, and enhance quality of life in PD. Future studies should investigate how PD affects brown adipose tissue (BAT) and shivering thermogenesis, offering potential targets for restoring heat balance and metabolic stability.Abstract Thermoregulatory dysfunction-temperature intolerance and/or inappropriate compensation-is an underrecognized feature of Parkinson's disease (PD) and is linked to poor quality of life. Multiple mechanisms may underlie this dysfunction, including alpha-synuclein deposition in relevant structures, altered functional connectivity in thermoregulatory networks, and disrupted neurotransmitter modulation, on top of the deleterious consequences of aging. Although multiple advanced tests can confirm this dysfunction, diagnosis is largely based on a detailed history. Once this critical symptom is identified, management focuses on crisis prevention and safety, as PD-specific clinical trials are often lacking. This narrative review of the literature addresses mechanisms, clinical expression, diagnostic evaluation, and management of thermoregulatory dysfunction in PD to help guide care for this underappreciated, yet potentially debilitating, non-motor symptom of PD. Future PD-specific trials are needed to further clarify underlying mechanisms and improve treatment options.