Seventeen children and young adults with the Prader-Willi syndrome were investigated. Twelve of 17 subjects had excessive daytime sleepiness as determined by their own or parental report, a high Epworth Sleepiness Scale score or a short mean sleep latency. Night sleep disturbances were reported in seven subjects with snoring, mouth-breathing, breath-holding and occasional nocturnal enuresis. Polysomnography showed abnormalities of sleep structure with rapid eye movements without reduction in muscle tone at sleep onset in 12 subjects, and a high respiratory event index with frequent brief apnoeas, particularly in REM sleep, in 16 subjects. Most apnoeas were not accompanied by arousals. Seven subjects, all of whom were obese, were considered to have symptomatic sleep apnoea and were treated with continuous positive airway pressure (CPAP) but this was poorly tolerated in two. Five subjects continued CPAP over a 6-month period resulting in subjective improvement in excessive daytime sleepiness in 3. Excessive daytime sleepiness occurs in approximately two-thirds of subjects with the Prader-Willi syndrome. It is mainly of central origin but obstructive sleep apnoea may increase sleepiness, particularly in obese subjects.

Obesity, short stature, hypotonia and excessive daytime sleepiness are characteristic features of the Prader-Willi syndrome. Excessive daytime sleepiness has been attributed to obstructive sleep apnoea (OSA). To investigate the role of anatomical factors in OSA in the Prader-Willi syndrome, clinical and ENT assessment, radiology of the upper airway and polysomnography including sleep oximetry were done in 14 subjects. Excessive daytime sleepiness was present in eight of 14 subjects as determined by a mean sleep latency to non-rapid eye movement stage I-II of < 5 min and/or self-rating sleepiness score > 9 (Epworth Sleepiness scale). Seven subjects were snorers or mouth breathers and dental abnormalities were present in 11. Sleep apnoea, as determined by a combined apnoea-hypopnoea index of more than 10 respiratory events per hour was present in 12 of 14 subjects. On clinical assessment, the nasopharynx, oropharynx and hypopharynx were small in one subject. No subject had redundant pharyngeal mucosa or an enlarged tongue. However, radiological studies performed in the awake supine posture showed a slight reduction in the cross-sectional area in nine subjects at the oropharyngeal level and in four subjects at the nasopharyngeal level as compared with normal control subjects. Sleep apnoea and minor radiological evidence of narrowing of the upper airway are common in the Prader-Willi syndrome, although clinical otolaryngological examination is often unremarkable. Excessive daytime sleepiness occurs in approximately 50% of all patients with Prader-Willi syndrome. Although obstructive sleep apnoea is one important factor related to sleepiness, an additional central disturbance of sleep mechanisms is present.

Subjective evaluation of the effect of treatment of excessive daytime sleepiness (EDS) with dexamphetamine and of cataplexy with clomipramine was made in 124 subjects with the narcoleptic syndrome. Drug effects were evaluated by self-report of the propensity to EDS and cataplexy as determined by the Epworth Sleepiness Scale and a rating scale of anticipation-associated loss of postural motor tone during long-term therapy. The effects of dexamphetamine alone (60 subjects), clomipramine alone (16 subjects) and combined dexamphetamine-clomipramine treatment (48 subjects) were evaluated. Self-reports indicated that the propensity to EDS was reduced by approximately 20% by dexamphetamine (mean dosage 16 mg/24 h, range 5-60: mean treatment period 21 years, range 2-45). The propensity to cataplexy was reduced by 23% by clomipramine (mean dosage 64 mg/24 h, range 25-125: mean treatment period 14 years, range 1-24). Dexamphetamine alone, in addition to reducing the propensity to EDS also reduced the propensity to cataplexy. Clomipramine alone reduced cataplexy, but not EDS. Combined dexamphetamine-clomipramine treatment caused a reduction in the propensity to EDS and cataplexy of similar magnitude to that caused by dexamphetamine alone. Less than 10% of all subjects with the narcoleptic syndrome reported a daytime sleep propensity in the normal range whilst on dexamphetamine and no subject on clomipramine reported complete control of cataplexy. Long-term treatment with dexamphetamine was associated with weight increase more commonly than weight loss. Weight gain was reported by two-thirds of subjects taking clomipramine alone. Reports of weight loss were as common as reports of weight gain by subjects on combined dexamphetamine-clomipramine treatment. Constipation, dry mouth and impaired sexual function were reported by 25%, 38% and 19% (respectively) of subjects on clomipramine. This retrospective long-term self-report study investigated the propensity to, rather than the frequency of, episodes of EDS and cataplexy in subjects with the narcoleptic syndrome. This study suggests that long-term drug treatment in the narcoleptic syndrome results in only minor reduction in attack propensity, in contrast to the findings of many previous short term objective studies, which suggest 50-80% reduction in attack frequency. Major factors limiting response to dexamphetamine in the narcoleptic syndrome include physician prescription of sub-optimal drug dosages, and a low index between the limited therapeutic efficacy and frequent side-effects of this drug.

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