Hypersomnolence in Prader Willi Syndrome

Abstract

Background: Children with Prader Willi syndrome (PWS) are at risk of sleep disordered breathing involving central and obstructive components. PWS patients are known to have abnormal responses to hypoxia and hypercapnoea, an increased incidence of Obstructive Sleep Apnoea [OSA] and hypersomnolence when older not explained by obesity alone. As infants, many present with delay in central control of breathing during sleep. Hypersomnolence and indeed narcolepsy have been reported in this group of patients. Modafinil is a wake promoting agent but a pharmacological profile that is distinct from sympathomimetic amines, which increase wakefulness by other mechanisms. Modafinil does not bind to most of the potentially relevant receptors for sleep/wake regulation, including those for noradrenaline, serotonin, dopamine, GABA, adenosine, histamine‐3 and benzodiazepines. Methods: Polysomnography (PSG) and multiple sleep latency testing [MSLT] was performed on PWS children attending a multidisciplinary clinic. Children who met criteria for narcolepsy were treated according to narcolepsy guidelines. Those who were hypersomnolent were assessed and three patients were trialed on Modafinil (a novel wake promoting agent). Results: Three children were studied, aged 7–13 years. Two were treated within a placebo controlled cross‐over design. There was a significant difference in behavioural parameters as measured by teacher and parent. The other had significant hypersomnolence with a BMI in the obese range. Treatment resulted in a dramatic improvement in behaviour, activity and BMI. Conclusion: Children with Prader Willi syndrome and hypersomnolence may benefit from treatment with modafinil.