One case of agrypnia (4 months without sleep) in a morvan disease, favourable action of 5-hydroxytryptophane
A 27-year-old man entered the HôpItal. Neurologique with a complaint of muscular fasciculations, insomnia, distal pain and diarrhea. A diagnosis of "chorée fibrillaire de Morvan" was made. This disease, with a proposedly viral aetiology, exhibits some neurological similarities with the Pink-Disease which might be induced by chronic mercury intoxication.
The polygraphic recordings in the initial period confirmed the total insomnia. A 9 month follow-up study was undertaken. The patient was either under placebo or under 5-HTP treatment. Except for the fasciculations and distal paraesthesias, no obvious troubles were observed during day-time. In spite of total lack of sleep, the patient never felt sleepy nor tired. None of the physical signs described during sleep-deprivation experiments were noticed. During the day no agitation or memory and/or intellectual disorders were present; some particular symptoms occurred at night: between 9 and 11 p.m., dramatic hallucinatory episodes, accompanied by aggravation of distal pain and vasoconstriction, were regularly observed (hallucinatory-distalgic syndrorme). During these episodes, lasting from 20 min to 1 h, auditory, visual, olfactory and somaesthetic hallucinations could occur while the polygraphic recordings showed either wakefulness or descending stage I.
These hallucinations were markedly enhanced by tryptophan loading, and disappeared under high doses of 5-HTP (from 2 to 12 g/day) which restored normal sleep stages.
Another type of hallucination, short-lasting with vocalization, occurred during brief episodes of stage I sleep or waking.
5-HTP given at large doses first improved the patient's condition dramatically. After 5-HTP withdrawal there was a gradual worsening of our patient's condition. 5-HTP therapy was again attempted but was then ineffective in reversing the symptoms and the patient died after 11 months of sickness. The neuropathology demonstrated no specific lesions.
No irritative or focal signs were noticed on the EEG data of more than 110 polygraphic recordings (representing 82,854 min). Some special qualitative signs were occasionally observed: blepharospasms and lack of alpha blocking during wakefulness.
During the initial period, an average of 26 min of stage I over 5 nights was recorded, reaching 40 min (stage 1) over 4 other nights during a placebo period. This insomnia was unaffected by the classical hypnotic drugs. A slight, but significant increase in Total Sleep Time (TST) followed electroconvulsive therapy. L-tryptophan given orally (12 g/day) during 5 consecutive days was completely ineffective (48 min stage I per night), in spite of a normal increase in urinary 5-HIAA (14.48 mg/24 h). The hallucinatory episodes were strongly enhanced by this aminoacid.
Low doses of oral DL-5-HTP (below 2 g/day) led to no changes in sleep but sedation and clinical improvement were obvious.
Higher doses of this drug (from 2 to 12 g/day) restored gradually stages III and IV sleep. Most of the time, the sleep periods occurred within 50 min after the drug administration. TST was markedly increased and paradoxical sleep (PS) reappeared during several consecutive nights (r TST/5-HTP=0.4482, P < 0.001; r 5-HTP/III+ IV=0.6099, P < 0.001; r 5-HTP/PS=0.6134, P < 0.001; n = 54). At that time urinary 5-HIAA was directly correlated with 5-HTP doses (r 5-HTP/5-H IAA = 0.9156, P < 0.001; n = 30).
During the terminal phase of the disease, however, when 5-HTP became ineffective, there was a decrease in urinary 5-HIAA.
The mechanisms of this dramatic insomnia and beneficial effects of 5-HTP are discussed in relation with the serotoninergic theory of sleep.
The origin of the hallucinations and the differences between this total-long-lasting absence of sleep (agrypnia) and the sleep-deprivation experiments are also discussed.