Correlation of active contact location with weight gain after subthalamic nucleus deep brain stimulation: a case series

Abstract

Background Weight gain (WG) is a frequently reported side effect of subthalamic deep brain stimulation; however, the underlying mechanisms remain unclear. The active contact locations influence the clinical outcomes of subthalamic deep brain stimulation, but it is unclear whether WG is directly associated with the active contact locations. We aimed to determine whether WG is associated with the subthalamic deep brain stimulation active contact locations. Methods We enrolled 14 patients with Parkinson’s disease who underwent bilateral subthalamic deep brain stimulation between 2013 and 2019. Bodyweight and body mass index were measured before and one year following the surgery. The Lead-DBS Matlab toolbox was used to determine the active contact locations based on magnetic resonance imaging and computed tomography. We also created sweet spot maps for WG using voxel-wise statistics, based on volume of tissue activation and the WG of each patient. Fluorodeoxyglucose-positron emission tomography data were also acquired before and one year following surgery, and statistical parametric mapping was used to evaluate changes in brain metabolism. We examined which brain regions’ metabolism fluctuation significantly correlated with increased body mass index scores and positron emission tomography data. Results One year after surgery, the body mass index increase was 2.03 kg/m2. The sweet spots for WG were bilateral, mainly located dorsally outside of the subthalamic nucleus (STN). Furthermore, WG was correlated with increased metabolism in the left limbic and associative regions, including the middle temporal gyrus, inferior frontal gyrus, and orbital gyrus. Conclusions Although the mechanisms underlying WG following subthalamic deep brain stimulation are possibly multifactorial, our findings suggest that dorsal stimulation outside of STN may lead to WG. The metabolic changes in limbic and associative cortical regions after STN-DBS may also be one of the mechanisms underlying WG. Further studies are warranted to confirm whether dorsal stimulation outside of STN changes the activities of these cortical regions.

Subthalamic deep brain stimulation for refractory Gilles de la Tourette’s syndrome: clinical outcome and functional connectivity

“…In one patient, significant weight gain was observed 6 months after surgery. In some patients with PD and dystonia undergoing STN-DBS, this was also observed [51][52][53]. Certainly, previous studies have suggested a change in body weight as a result of the regulation of diet and metabolism by STN-DBS through diffusion of the electrical pulse to the hypothalamus [54,55].…”

Mechanisms and consequences of weight gain after deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease

“…DBS could therefore influence weight homeostasis by modulating regions that impact reward, appetite, and food intake 23 , 24 , such as the lateral hypothalamus 25 , 26 , the limbic subdivision of STN 27 – 29 , and the medial forebrain bundle 30 . Recent FDG PET studies found a correlation between STN DBS-related weight gain and the engagement of associative and limbic brain areas, but no correlation with sensorimotor regions 4 , 8 , 9 . A recent study showed that DBS of the limbic proportion of the STN leads to increased selective attention for high-calorie foods and a sweet food-seeking-like behavior and, at the same time to a blunted response in the reward system 31 .…”

“…Besides its therapeutic benefits, adverse long-term side effects have been observed, including changes in the metabolic profile, energy homeostasis, endocrine signaling, and eating behavior 3 . In sum, these side effects could lead to an increase in weight together with alterations in body composition 3 , 4 . One predictor for postoperative weight gain appears to be the electrode position and the volume of tissue activated (VTA) within the STN.…”

“…Like other basal ganglia nuclei, the STN can be divided into three functional subregions: sensorimotor, associative, and limbic subdivision, based on its connections to functionally segregated regions of the striatum, pallidum, and cortex 5 , 6 . Previous studies have shown that motor improvement is achieved if stimulation is done by more laterally localized electrodes in the sensorimotor area 4 , 7 – 9 , which leads to less weight gain at the same time 6 , 7 , 10 – 12 . In contrast, more medially located electrodes are associated with greater weight gain and a smaller reduction of motor complications.…”