Effects of subthalamic nucleus deep brain stimulation and levodopa on energy production rate and substrate oxidation in Parkinson's disease

Abstract

Patients with Parkinson's disease (PD) often lose weight, but after subthalamic nucleus deep brain stimulation (STN-DBS), they gain weight. We compared daily energy intake (DEI), resting energy expenditure (REE) and substrate oxidation rates (measured by indirect calorimetry) in nineteen STN-DBS-treated patients (Group S), thirteen others on pharmacologic treatment by levodopa (Group L) and eight control subjects. We also determined the acute effects of STN-DBS and levodopa on REE and substrate oxidation rates. STN-DBS treated patients gained 9·7 (SEM 7·1) kg after surgery, whereas patients on pharmacologic treatment lost 3·8 (SEM 10·0) kg since diagnosis. In STN-DBS-treated patients, REE (216·5 %; P,0·001), lipid oxidation (2 27 %; P, 0·05) and protein oxidation (2 46 %; P,0·05) were decreased, whereas glucose oxidation was elevated (þ81 %; P,0·05) as compared to patients on pharmacologic treatment. Levodopa acutely reduced REE (28·3 %; P,0·05) and glucose oxidation (2 37 %; P, 0·01) with a slight hyperglycaemic effect (after levodopa challenge: 5·6 (SEM 0·8) v. before levodopa challenge: 5·3 (SEM 0·6) mmol/l; P,0·01). Switching 'on' STN-DBS acutely reduced REE (217·5 %; P,0·01) and lipid oxidation (2 24 %; P, 0·001) 30 min after starting stimulation. Fasting glycaemia was slightly but significantly reduced (5·4 (SEM 1·4) v. 5·5 (SEM 1·3) mmol/l; P,0·01). After STN-DBS, the normalization of REE and the reduction in lipid and protein oxidation contribute to the restoration of weight. As levodopa decreases glucose oxidation, the reduction in daily dose of levodopa in STN-DBS-treated patients helps prevent the effect of weight gain on glycaemia.

The pig model in brain imaging and neurosurgery

“…Whether this effect is exclusively due to the decrease in energy expenditure consecutive to the improvement of motor symptoms is still unknown. An additional effect on energy metabolism by current diffusion to the hypothalamus or motivational change by activation of the limbic circuit of the basal ganglia may be hypothesized (Perlemoine et al, 2005;Montaurier et al, 2007).…”

The Role of Ghrelin, Neuropeptide Y and Leptin Peptides in Weight Gain after Deep Brain Stimulation for Parkinson’s Disease

“…Furthermore, a reduction of the total daily dose of L -dopa may have an additional role, via probable lipolytic effects [11] , as well as a central effect on the satiety/appetite hypothalamic centers [12] . Improvement in mood and functional independence may also contribute to WG [5] .…”

“…WG after DBS has been demonstrated in various studies [5][6][7] , but few have examined the etiopathogenetic mechanisms [6,7] . However, 'peripheral' and 'central' mechanisms are currently hypothesized.…”

Evaluation of Metabolic State in Striatal Rat Model of Parkinson’s Disease: before and after Deep Brain Stimulation

“…Body weight variation has been reported in many studies as a non-motor secondary effect of DBS-STN [7][8][9][10]. Studies have shown that weight loss in patients with PD before surgery is a continuous and progressive process that starts years before a formal diagnosis is made, and that surgery modifies this state [11][12][13][14]. Some authors have proposed that PD is associated with profound alterations in energy metabolism that are normalized after DBS-STN [13,15].…”