The clinical diagnosis of the narcoleptic syndrome.

Sleep-wake habits and control of postural muscle tone were investigated by self-report questionnaire in 183 subjects considered to have the narcoleptic syndrome, 62 subjects with hypersomnia and 10 with obstructive sleep apnoea. Results were compared with those in a group of 188 control subjects with normal sleep wake habits. Excessive daytime sleepiness, determined by the Epworth Sleepiness Scale (ESS), was five times greater in the narcoleptic syndrome than in control subjects (score range 0-24, mean scores +/-SD 19.6+/-3.0; and 4.5+/-3.3 respectively; P<0.001). The propensity to cataplexy, as determined by a rating scale developed to estimate the likelihood of loss of postural tone in response to sudden emotional stimuli, including laughter, was 10 times greater in narcoleptic syndrome than in control subjects (postural atonia total score range 0-600; mean + SD 334+/-122 and 28+/-45, respectively; P<0.001). Narcoleptics had more disturbances of night sleep than controls with episodes of muscle jerking, sleep walking, sleep talking and sleep terrors, as well as sleep paralysis, and higher insomnia self-rating scores. Sleep latency from bedtime to sleep-onset time was shorter in narcoleptics than controls. The hypersomniac group of 62 subjects was heterogeneous. Subsequent investigation showed that 18 subjects (29%) had idiopathic hypersomnia, four (6%) 'incomplete' narcolepsy without cataplexy and 10 (16%) hypersomnia accompanying a mood disorder. The mean ESS scores in this group and in subjects with obstructive sleep apnoea were comparable to those of the narcoleptic syndrome subject group. Mean postural atonia scores were similar to those of control subjects.

Striatal dopamine D2 receptors in patients with narcolepsy measured with PET and 11C-raclopride.

We investigated in vivo D2 receptor binding using 11C-raclopride and PET in the striatum of 17 subjects with the narcoleptic syndrome. Putamen and caudate nucleus 11C-raclopride uptake was comparable in the total patient group and controls, and the tracer uptake was similar in the HLA-DR2-positive (n = 12) and HLA-DR2-negative (n = 5) narcoleptic subjects. There was a significant increase in 11C-raclopride uptake in the putamen of narcoleptic subjects older than 31 years (n = 11) when compared with age-matched controls (n = 15). There was no evidence of involvement of the striatal D2 dopaminergic neurotransmitter system in the basic pathophysiology of the narcoleptic syndrome despite an age-related increase in putaminal 11C-raclopride uptake.

The delayed sleep phase syndrome: clinical and investigative findings in 14 subjects.

Fourteen subjects are described in whom a clinical diagnosis of the delayed sleep phase syndrome was made. The condition is multi-factorial, dependent on lifestyle, mood and personality, as well as on familial factors but no single factor in isolation is sufficient to explain the delay in sleep timing. Refusal to attend school may be important in some instances but will not explain cases with delayed age of onset. In half the subjects the delay in sleep phase started in childhood or adolescence. The syndrome causes severe disruption to education, work and family life. Polysomnography, motor activity monitoring of rest-activity cycles, plasma melatonin profiles and urinary melatonin metabolite excretion are normal. Different patterns of sleep phase delay seen in the syndrome include stable, progressive, irregular and non-24 hour sleep-wake cycles. These patterns may result from different social and other Zeitgebers ("time-markers", for example sunrise, sunset) in the normal environment. Treatment by forced sleep-wake phase advance or with melatonin resulted in a partial sleep-phase advance but this was not maintained on stopping treatment.