Robert S Eisinger, Sarah A Hamimi, Joyce M Lee, Ellie D Gabriel, Casey H Halpern
The hyperkinetic hypothesis alone does not explain post-DBS weight gain. A broader, systems-level framework that integrates motor, metabolic, and neuroendocrine pathways is needed to guide future research and inform therapeutic strategies for addressing weight loss in PD.
OBJECTIVES: Weight loss is a common manifestation of Parkinson disease (PD) and is associated with frailty, morbidity, and mortality. Deep brain stimulation (DBS) often leads to significant postoperative weight gain, which confers a survival benefit. This weight gain has traditionally been attributed to reduced energy expenditure resulting from improved hyperkinetic motor symptoms. We aimed to critically examine the evidence for this hyperkinetic hypothesis and to explore alternative mechanisms.
MATERIALS AND METHODS: We performed a structured narrative review of the MEDLINE and Embase data bases (from inception through December 2025), identifying English-language clinical studies that examined the relationship between motor symptom improvement and postoperative weight changes following DBS in PD.
RESULTS: Correlations between weight gain and improvements in tremor, rigidity, or dyskinesia are inconsistent and often absent, particularly when confounders are controlled. Converging evidence supports alternative mechanisms involving altered resting and total energy expenditure, neuroendocrine dysregulation, and neuromodulation of hypothalamic and limbic circuits that influence appetite and metabolism.
CONCLUSIONS: The hyperkinetic hypothesis alone does not explain post-DBS weight gain. A broader, systems-level framework that integrates motor, metabolic, and neuroendocrine pathways is needed to guide future research and inform therapeutic strategies for addressing weight loss in PD.