Yasuo Hishikawa

ELECTROENCEPHALOGRAPHIC STUDY ON NARCOLEPSY.

Abstract A total of 124 EEG examinations were performed in 75 narcoleptic patients. The routine EEGs were normal (abnormal slow waves being observed in less than 10%). The majority of the patients fell in drowsy state and sleep in the early part of the examination and about a half of them did so even during overbreathing. Polygraphic recording of the EEG, EKG, eye movements and respiratory movements were obtained in 34 examinations performed in 21 narcoleptics. An EEG pattern resembling that of drowsy state was found in 18 records in association with rapid eye movements (REM) at the sleep onset or several minutes after the onset. The patients often experienced sleep paralysis and/or hallucinations exclusively in the sleep onset REM period. During a cataplectic attack lasting for a brief period of about 30 sec, low voltage alpha rhythm was observed. Two other recordings obtained soon after the onset of and during cataplectic attacks which lasted several minutes indicated that the patients fell in the REM period soon after the onset of the attacks. The patients experienced hallucinations and/or dreams in the later parts of the attacks, which corresponded to the REM period. It would thus seem that cataplectic attacks are experienced in the transitional state from wakefulness to the REM period. The patients were in a similar or slightly higher level of consciousness in the early part of the sleep onset REM period than in drowsy state. In the REM period occurring several minutes after the sleep onset, they were in sleep, the depth of which corresponded to the sleep stages with spindles and high voltage slow waves. When the EEG pattern of the other sleep stages were observed, they were really in sleep, the depth of which was comparable to that of normal persons in the corresponding sleep stages. The EEG response to arousing stimuli were much decreased in the REM period as compared with those observed in the other sleep stages. In the early part of the sleep onset REM period as well as in the other part of the REM period the flash stimuli induced little or no EEG responses, although in the former period the patients were conscious of the stimuli and later recollected the correct number of them. In other sleep stages than the REM period the patients responded to and remembered only those but not all stimuli that induced marked arousal response in their EEGs. In conclusion, the basic disturbances characterizing narcoleptics are a persistent and intense inclination to fall in sleep and to fall into the REM period of sleep directly from wakefulness and at the sleep onset. Both, but predominantly the former, characterize sleep attacks, and the latter is manifested as cataplectic attacks, sleep paralysis and hypnagogic hallucinations. Narcolepsy is considered to be a disease not related to epilepsy.

Photosensitive epilepsy: Relationships between the visual evoked responses and the epileptiform discharges induced by intermittent photic stimulation ☆

Abstract In fifteen patients with photosensitive epilepsy the characteristics of the EEG epileptiform discharges induced by intermittent photic stimulation (IPS) were investigated. In all the patients generalized EEG epileptiform discharges were induced by IPS. In eight of them (1st group) the discharges appeared first in the occipital area, whereas in the remaining seven patients (2nd group) they occured simultaneously over all head regions or appeared earlier over the anterior areas of both sides. Averaged visual evoked responses (VERs) to single flashes of light in the patients were similar morphologically to those of normal subjects. In these, the VER recorded from the mid-occipital area consisted of 4–6 rhythmic wavelets occurring within 100 msec from the flash and of larger deflexions following such wavelets. The initial component of the response is positive and has a peak latency of 20–27 msec. In six patients of the 1st group certain components of the VER were extraordinarily augmented. The earliest spikes of the EEG epileptiform discharges appearing first over the occipital regions were interpreted as unusually augmented VERs. The photosensitivity of the patients decreased remarkably during drowsiness. No epileptiform discharges were induced during slow wave sleep. In the REM stage of sleep the discharges were on the contrary as promptly induced as in the waking state. This phenomenon did not seem to be due to pupillary miosis. Monocular stimulation markedly reduced the epileptogenic effect of IPS as compared to binocular stimulation. Background illumination appeared to modify the epileptogenic effects of IPS. Ophthalmological examination revealed incomplete red-green color blindness in one patient and quadrantic hemianopsia in another. In the remaining subjects no pathological conditions of the retina were found. Some considerations on the neural mechanisms involved in epileptic photosensitivity are presented.

The effect of imipramine, desmethylimipramine and chlorpromazine of the sleep-wakefulness cycle of the cat ☆

Abstract The effects of imipramine, desmethylimipramine and 3hlorpromazine upon the sleep-wakefulness cycle were studied in 5 adult cats, with doses of 2 and 4 mg/kg. Imipramine and desmethylimipramine at either dosage had an inhibitory effect upon the REM period of sleep. Imipramine at both dosages and desmethylimipramine at the dose of 4 mg/kg had a hypnotic effect, prolonging the time spent in sleep and decreasing the number of awakenings. Chlorpromazine at both dosages had a hypnotic effect, and at the dose of 4 mg/kg had an inhibitory effect upon the REM period, which was, however, less pronounced than that of the other two drugs. Chlorpromazine at the dose of 2 mg/kg had no significant effect upon the REM period, but in 4 out of 5 cats the period appeared earlier than under control conditions. The inhibitory effect of imipramine and desmethylimipramine upon the REM period is considered to be an important mechanism by which these drugs produce favorable effects upon some of the narcoleptic symptoms other than sleep attacks.

The nature of sleep attack and other symptoms of narcolepsy

Abstract The electroencephalogram, electro-oculogram and electromyogram of the mental muscle were simultaneously recorded in eighteen narcoleptics and thirty controls under each of the following three conditions in the daytime, on different days: (I) lying on a bed: bed(1); (II) sitting on a stool, then, on a chair, and finally, lying on a bed: stool(2), chair(2) and bed(2); (III) sitting on a chair: chair(3). Recording in each posture was performed for about 50 min and 152 recordings, 81 in the narcoleptics and 71 in the controls, were obtained. Under every condition, the narcoleptics fell asleep with a shorter latency and spent in sleep a larger percentage of recording time than the controls, and sleep of the narcoleptics was deeper than that of the controls. Sleep of the narcoleptics was deeper and more stable under bed(1) and bed(2) than under chair(2) and chair(3), and the latter than under stool(2) condition. Similar relations were found in the controls. The REM stage of sleep occurred in variable number of narcoleptics with sleep attack and other main symptoms under different conditions. It occurred in fifteen of eighteen narcoleptics under bed(1), in eleven of eighteen narcoleptics under both chair(2) and bed(2), in five of nine narcoleptics under chair(3) and in only two of eighteen narcoleptics under stool(2) condition. Latency of the REM stage was 29 min and 34.5 min respectively under stool(2). Under the other conditions this stage occurred at the onset of, or soon after the onset of sleep in most cases. These and other findings would suggest that, during sleep under unstable and uncomfortable conditions, narcoleptics are completely or incompletely deprived of the REM stage, and that, during sleep in the following period under stable and comfortable conditions, they tend to show a compensatory increase in its amount. Cataplexy of brief duration occurred in one narcoleptic under chair(2). Sleep paralysis, hallucinations and/or dreams were experienced by twelve narcoleptics; under stool(2) by one, under chair(2) by four and under bed(2) by seven. All of the twelve patients showed the REM stage under these conditions. In conclusion, a marked tendency to fall asleep in narcoleptics brings about sleep attack, and another tendency to fall in the REM stage at the sleep onset brings about cataplexy, sleep paralysis and hypnagogic hallucinations.

Treatment of narcolepsy with imipramine (Tofranil) and desmethylimipramine (Pertofran)

Abstract In 23 narcoleptic patients, the action of desmethylimipramine and/or imipramine (25–50 mg a day in the majority of the cases and 75–150 mg a day in a few cases) on their clinical symptoms was studied. Desmethylimipramine produced good results in the relief of cataplectic attacks, sleep paralysis and hypnagogic hallucinations, but it had little if any effect upon the sleep attacks. The same results were obtained by the use of imipramine. Undesirable side-effects were minor as a rule, and were less frequent in the case of desmethylimipramine than of imipramine. Accordingly, desmethylimipramine appeared more suitable for practical use than imipramine. It is recommended that desmethylimipramine should be used in combination with one of the analeptic drugs (amphetamine, ephedrine, methylphenidate, pipradrol), which are the most effective medicaments at present available for attacks of irresistible sleep. The possible neuropharmacological mechanisms of the striking effects of desmethylimipramine and imipramine upon the narcoleptic symptoms, are discussed on the basis of recent work.

Sleep satiation in narcoleptic patients

UNLABELLED Polygraphic sleep recording was performed in 20 narcoleptics with one or more of the auxiliary symptoms, 4 narcoleptics with only sleep attacks and 10 normals during one night and into the following day. Total sleep time in the narcoleptics did not differ significantly from that in the normals. Sleep of the narcoleptics with auxiliary symptoms was unstable with frequent awakening. The temporal organization of the REM--NREM sleep cycle was irregular in the narcoleptics with auxiliary symptoms, compared with those in the other two groups. Percentage of Stage 1 was significantly larger in the narcoleptics with auxiliary symptoms than in the other two groups and percentage of Stage 2 was smaller. Percentage of Stage 4 was smaller in the narcoleptics with auxiliary symptoms than in those with only sleep attacks. Percentages of Stages 3 and REM did not differentiate the three groups. Spindle density during Stage 2 did not differentiate the three groups. Sleep onset Stage REM was frequently observed exclusively in the narcoleptics with auxiliary symptoms. Excluding the instances showing sleep onset Stage REM, mean latency of initial episodes of REM sleep in the three groups was shorter after daytime sleep onset than after nighttime sleep onset. In the narcoleptics with auxiliary symptoms, no significant correlation was found between the percentage of Stage REM and clinical findings. CONCLUSIONS the sleep attacks in narcoleptics are due to an ill-timed, strong tendency to fall asleep (including both REM and NREM sleep), and it is therefore suggested that they are manifestations of their disturbed circadian rhythm of sleep--wakefulness cycle.

H-REFLEX AND EMG OF THE MENTAL AND HYOID MUSCLES DURING SLEEP, WITH SPECIAL REFERENCE TO NARCOLEPSY.

Abstract The activity of the mental and hyoid muscles, and the H-reflex were examined during nocturnal sleep and daytime naps of narcoleptic and normal subjects. The continuous, tonic EMG discharges, which were observed in all subjects in the awake state, decreased in parallel with deepening of sleep but disappeared only during the rapid eye movements (REM) period, which occurred at the sleep onset in narcoleptics and late in nocturnal sleep in normal and narcoleptic subjects. During the REM period, only transient, phasic EMG discharges of low voltage were occasionally observed. The H-reflex also decreased in amplitude when the subjects fell asleep. The degree of its decrement was slight in the drowsy stage and was greater in light and deep sleep. During the REM period which occurred at the sleep onset in narcoleptics and late in nocturnal sleep in normal and narcoleptic subjects, the decrement was most prominent and consistent and the H-reflex reflex would completely disappear. The sleep onset REM period was examined in four narcoleptics, two of which experienced sleep paralysis in this period. It is concluded that sleep paralysis is not a part of the hypnagogic hallucinations often experienced by narcoleptics but a real experience of paralysis resulting from a dissociation between the level of consciousness and the somatic muscle and reflex activities in the sleep onset REM period.

Effect of butyrolactone and gamma-hydroxybutyrate on the EEG and sleep cycle in man.

Abstract The purpose of the present paper is to compare a sleep state induced by butyrolactone and sodium γ-hydroxybutyrate with natural sleep in man with the aids of the EEG, electro-oculogram and EMG of the mental muscle. The following results were obtained: 1. (1) The i.v. administration of 20–30 mg/kg of butyrolactone and sodium γ-hydroxybutyrate induced in man a peculiar state without marked change in consciousness and with high voltage slow waves in the EEG. 2. (2) When butyrolactone was administered at night, just prior to bed-time, the spindle and delta stages of sleep occurred earlier, the duration of the spindle stage became shorter and the delta stage tended to last longer than in the control night. The latency to the onset of the initial REM period calculated either from the start of the injection or from the onset of sleep did not differ significantly.

A neurophysiological study of sleep paralysis in narcoleptic patients.

Abstract Behavioral response by pressing a switch placed in the hand and EEG arousal response to external stimuli (calling the subject by name 3–5 times at short intervals) were studied in the REM period in nocturnal sleep. Subjects consisted of eight normal controls and eight narcoleptics with sleept paralysis and other narcoleptic symptoms in addition to sleep attacks. All the vocal stimuli, with a few exceptions, were perceived by the subjects. Narcoleptics and controls, when stimulated in the REM period occurring more than 1 h after the sleep onset (the non sleep-onset REM period), responded to most of the stimuli by pressing the switch. In the REM period occurring at the sleep onset (the sleep-onset REM period), in which narcoleptics experienced sleep paralysis, they frequently failed to show a behavioral response (statistically significant). EEG arousal response was more marked in the controls than in the narcoleptics. In the narcoleptics it was more prominent in the non sleep-onset REM period than in the sleep-onset REM period. Based on these findings it is suggested that a dissociation between perception or consciousness level and somatic motor function occurring in narcoleptics in the sleep-onset REM period produces sleep paralysis. Possible neurophysiological mechanisms related to the occurrence of this dissociation in the sleep-onset REM period and of this sleep state in narcoleptics are discussed.

Modification of photosensitivity in epileptics during sleep.

Abstract In eleven patients with photosensitive epilepsy, photosensitivity during various phases of sleep and wakefulness was investigated. During the waking state, epileptiform discharges were promptly induced by intermittent photic stimulation (IPS) in all of the patients. During non-REM sleep, five patients showed no evidence of photosensitivity. The remaining six patients showed some EEG evidence of sensitivity to IPS, but this was reduced remarkably as compared with that in the waking state in five of them. The induced discharges during non-REM sleep were usually most prominent on the anterior regions and were found only in the first cycle of nocturnal sleep. In one patient, prominent epileptiform discharges were induced during non-REM sleep both in the first and last cycles, but IPS failed to induced paroxysmal discharges during non-REM sleep in the other cycles of nocturnal sleep. During REM sleep, all patients except one who was treated with anticonvulsants showed prominent photosensitivity, although this was in many instances relatively reduced as compared with that in the waking state. In some cases the induced discharges were of larger amplitude in the posterior than in the anterior region. Possible explanations for previous conflicting reports on this subject are discussed.