Mechanisms of body weight gain in patients with Parkinson's disease after subthalamic stimulation

Abstract

Chronic bilateral subthalamic stimulation leads to a spectacular clinical improvement in patients with motor complications. However, the post-operative body weight gain involved may limit the benefits of surgery and induce critical metabolic disorders. Twenty-four Parkinsonians (61.1 +/- 1.4 years) were examined 1 month before (M - 1) and 3 months after (M + 3) surgery. Body composition and energy expenditure (EE) were measured (1) over 36 h in calorimetric chambers (CC) with rigorous control of food intakes and activities [sleep metabolic rate, resting activities, meals, 3 or 4 sessions of 20 min on a training bicycle at 13 km/h and daily EE] and (2) in resting conditions (basal metabolic rate) during an acute L-dopa challenge (M - 1) or according to acute 'off' and 'on' stimulation (M + 3). Before surgery, EE was compared between the Parkinsonian patients and healthy subjects matched for height and body composition (metabolic rate during sleep, daily EE) or matched to predicted values (basal metabolic rate). Before surgery, in Parkinsonian men but not women, (1) daily EE was higher while sleep metabolic rate was lower compared to healthy matched men (+9.2 +/- 3.9 and -8.2 +/- 2.3%, respectively, P < 0.05) and (2) basal metabolic rate (L-dopa 'on') was higher than predicted basal metabolic rate (+11.5 +/- 4.0%, P < 0.05) but was further increased without L-dopa (+8.4 +/- 3.2% vs L-dopa 'on', P < 0.05). EE during daily activities was higher during 'off' periods compared to 'on' periods for both men (+19.3 +/- 3.3%, P < 0.0001) and women (+16.1 +/- 4.7%, P < 0.01). After surgery, there was a 3.4 +/- 0.6 kg (P < 0.0001) body weight increase together with fat mass (P < 0.0001) and fat-free mass (P < 0.05) in Parkinsonian men and a 2.6 +/- 0.8 kg (P < 0.05) body weight increase together with fat mass (P < 0.05) in Parkinsonian women. Sleep metabolic rate increased in men (+7.5 +/- 2.0%, P < 0.01) to reach control values but remained unchanged in women. Daily EE decreased significantly in both men and women (-7.3 +/- 2.2% and -13.1 +/- 1.7%, respectively, P < 0.01) but there was no correlation between daily EE changes and body weight gain. Parkinson's disease is associated with profound alterations in the central control of energy metabolism. Normalization of energy metabolism after DBS-STN implantation may favour body weight gain, of which quality was gender specific. As men gained primarily fat-free mass, a reasonable weight gain may be tolerated, in contrast with women who gained only fat. Other factors such as changes in free-living physical activity may help to limit body weight gain in some patients.

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).…”

Diurnal Variation of Hypothalamic Function and Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease

“…However, STN-DBS can be associated with dysregulation of mood and behavior, for example increased apathy and suicidality, in about 10% of cases [3,4,5]. Many PD patients also experience a noticeable weight gain under STN-DBS, particularly during the first 6 months after surgery [6,7]. …”

Postoperative management of deep brain stimulation in Parkinson’s disease

“…One of the most common chronic side-effects of DBS is weight gain (Moro et al, 1999;Barichella et al, 2003;Krack et al, 2003;Macia et al, 2004;Perlemoine et al, 2005;Kleiner-Fisman et al, 2006;Montaurier et al, 2007;Bannier et al, 2009;Sauleau et al, 2009;Walker et al, 2009;Strowd et al, 2010;Locke et al, 2011;Rieu et al, 2011). Typically, weight gain is maximal in the first year after surgery (Barichella et al, 2003;Macia et al, 2004).…”

“…Different mechanisms may contribute to weight gain. The reduction in energy expenditure related to reduced rigidity, and dyskinesia (Montaurier et al, 2007;Bannier et al, 2009) seem to play a key role. The latter can be even enhanced by reduced activity when apathy occurs (Thobois et al, 2010).…”