Disorders of hypothalamic function: Insights from Prader-Willi syndrome and the effects of craniopharyngioma.

Either physical damage or being born with a specific genetic abnormality can impact on the functioning of the hypothalamus, resulting in diverse physical manifestations and/or specific behavior disorders. The impact of physical damage due to craniopharyngioma (CP) and/or surgery to remove a craniopharyngioma is compared and contrasted with the impact resulting from the genetic abnormalities associated with Prader-Willi syndrome (PWS). Similarities between PWS and CP posttreatment include hyperphagia and weight gain, low growth hormone levels, low bone density in adults, hypogonadism, disturbed temperature regulation, disturbed sleep and daytime sleepiness, memory difficulties, and problems with behavior and with peer relationships. These disturbances are an indication of the hypothalamus's central role in homeostasis. Most of the abnormalities appear to be more severe postoperatively in people with CP. Differences include higher ghrelin levels in PWS, complete absence of pituitary hormones in many cases of CP, higher incidence of thyroid dysfunction in CP, "growth without growth hormone" in obese children with CP, different types of diabetes (diabetes insipidus in CP and diabetes mellitus in PWS), and evidence of developmental delay and low IQ in people with PWS.

Transcutaneous vagus nerve stimulation (t-VNS): A novel effective treatment for temper outbursts in adults with Prader-Willi Syndrome indicated by results from a non-blind study.

Temper outbursts are a severe problem for people with Prader-Willi Syndrome (PWS). Previous reports indicate that vagus nerve stimulation (VNS) may reduce maladaptive behaviour in neurodevelopmental disorders, including PWS. We systematically investigated the effectiveness of transcutaneous VNS (t-VNS) in PWS. Using a non-blind single case repeat measures modified ABA design, with participants as their own controls, t-VNS was evaluated in five individuals with PWS [three males; age 22-41 (M = 26.8)]. After a baseline phase, participants received four-hours of t-VNS daily for 12 months, followed by one month of daily t-VNS for two-hours. The primary outcome measure was the mean number of behavioural outbursts per day. Secondary outcomes included findings from behavioural questionnaires and both qualitative and goal attainment interviews. Four of the five participants who completed the study exhibited a statistically significant reduction in number and severity of temper outbursts after approximately nine months of daily four-hour t-VNS. Subsequent two-hour daily t-VNS was associated with increased outbursts for all participants, two reaching significance. Questionnaire and interview data supported these findings, the latter indicating potential mechanisms of action. No serious safety issues were reported. t-VNS is an effective, novel and safe intervention for chronic temper outbursts in PWS. We propose these changes are mediated through vagal projections and their effects both centrally and on the functioning of the parasympathetic nervous system. These findings challenge our present biopsychosocial understanding of such behaviours suggesting that there is a single major mechanism that is modifiable using t-VNS. This intervention is potentially generalizable across other clinical groups. Future research should address the lack of a sham condition in this study along with the prevalence of high drop out rates, and the potential effects of different stimulation intensities, frequencies and pulse widths.