Mechanisms of Body Weight Gain in Patients With Parkinson's Disease After Subthalamic Stimulation

C. Montaurier; B. Morio; S. Bannier; P. Derost; P. Arnaud; M. Brandolini-Bunlon; C. Giraudet; Y. Boirie; F. Durif

Disclosures

Brain. 2007;130(7):1808-1818. 

In This Article

Summary and Introduction

Summary

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.

Introduction

Parkinson's disease is a neurodegenerative disorder that mainly affects the nigrostriatal dopaminergic system. Onset is generally between 50 and 65 years of age, and prevalence is 100 to 150/100 000, with the incidence increasing with age. The four cardinal clinical characteristics of Parkinson's disease are bradykinesia, rigidity, rest tremor and postural instability. Dopaminergic therapy such as L-dopa and dopamine agonists usually leads to a dramatic improvement of symptoms, but disease progression nevertheless remains inevitable. Although weight loss is often observed in the evolution of Parkinson's disease, the mechanisms involved remain unknown. For some authors, it results from a decrease in food intakes triggered by a depressive syndrome combining loss of appetite, hypersalivation and dysphagia (Broussolle et al., 1991; Andersson and Sidenvall, 2001; Chen et al., 2003; Lorefalt et al., 2004; Cheshire and Wszolek, 2005; Palhagen et al., 2005). Others underline that an increase in energy expenditure (EE) due to the rigidity or to motor complications such as motor fluctuations and L-dopa-induced dyskinesias (LIDs) should be also considered (Lorefalt et al., 2004). Bilateral Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) is now considered the gold standard surgical treatment for patients presenting Parkinson's disease with intractable motor complications (Krack et al., 2003). Chronic DBS-STN greatly reduces motor fluctuations such as end-of-dose akinesia and on–off phenomena as well as dystonia while off medication. Furthermore, STN stimulation leads to a dramatic improvement in LIDs because it allows a 50% reduction in antiparkinsonian treatment. Consistently with other reports (Moro et al., 1999; Gironell et al., 2002; Barichella et al., 2003; Macia et al., 2004; Tuite et al., 2005; Perlemoine et al., 2005), we have observed body weight gain in ∼30% of our population of patients after DBS-STN implantation, reaching close to 8% of pre-surgery body weight at 3 months post-surgery. Certain patients have presented a weight gain of up to 20 kg within the first 12 months post-surgery. The consequences of DBS therapy-induced weight gain have not been assessed with accuracy, but there is clearly an increased incidence of metabolic and cardiovascular disorders. The underlying mechanisms of body weight gain following DBS-STN remain unknown. Among other hypothesis put forward, Macia et al. (2004) proposed a post-operative decrease in EE. Indeed, the reduction in non-exercise activity thermogenesis due to decreased motor fluctuations and dystonia might be considered as a risk factor for body weight gain. Therefore, Parkinsonian patients presenting severe motor fluctuations may be particularly at risk for post-operative weight regain due to the high pre-operative energy expenditure involved.

The aim of this prospective study was to identify the mechanisms causing body weight gain in patients with Parkinson's disease following DBS-STN. We therefore measured body composition and the various components of daily energy expenditure using whole body indirect calorimetry, at 1 month before and 3 months after DBS-STN implantation, in 24 Parkinsonian men and women.

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