ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 15.3 | DOI: 10.1530/ey.16.15.3

Assessment of safety and outcome of lateral hypothalamic deep brain stimulation for obesity in a small series of patients with Prader-Willi syndrome

Franco RR, Fonoff ET, Alvarenga PG, Alho EJL, Lopes AC, Hoexter MQ, Batistuzzo MC, Paiva RR, Taub A, Shavitt RG, Miguel EC, Teixeira MJ, Damiani D & Hamani C

Children’s Institute, Division of Pediatric Endocrinology, University of Sao Paulo Medical School, Sao Paulo, Brazil

To read the full abstract: JAMA Network Open 2018;1:e185275

The authors describe a small case series of four patients, age range 18–28 years, with Prader-Willi syndrome and obesity. All had received childhood growth hormone therapy, two had previous bariatric surgery, and all had psychiatric comorbidities before the current intervention. All received deep brain stimulation, via electrodes bilaterally implanted in the lateral hypothalamic area, over a 6-month protocol. The intervention was ineffective in reducing body weight or BMI, which actually increased by on average 9.6% and 5.8%, respectively.

It is well recognised that patients with Prader-Willi syndrome invariably develop hyperphagia during childhood, which often leads to severe obesity. Hyperphagia is extremely distressing – even modest hunger is uncomfortable for many of us! Many treatments have been tried to reduce patients with Prader-Willi syndrome but yet without good evidence of effectiveness. The neural mechanism for hyperphagia in this condition is not established; high circulating ghrelin levels are typical and could drive appetite, but patients also have multiple other hormone abnormalities (hypogonadism, growth hormone dysfunction, hypothyroidism, central adrenal insufficiency), as well as behavioural and psychiatric problems.

Deep brain stimulation (DBS) is widely accepted to be an effective treatment for advanced stages of Parkinson’s disease, and other types of movement disorders. Its use in other conditions, such as obsessive-compulsive disorder, is being explored. The rationale for deep brain stimulation as an intervention in severe obesity is that it mimics the reward circuitry stimulated by binge-like feeding. Unfortunately no such benefits were obvious in this small case series, but the paper highlights the importance of reporting negative findings. Results of studies of other interventions, such as GLP-1 receptor agonists, are eagerly awaited.