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A putative flip-flop switch for control of REM sleep.

Rapid eye movement (REM) sleep consists of a dreaming state in which there is activation of the cortical and hippocampal electroencephalogram (EEG), rapid eye movements, and loss of muscle tone. Although REM sleep was discovered more than 50 years ago, the neuronal circuits responsible for switching between REM and non-REM (NREM) sleep remain poorly understood. Here we propose a brainstem flip-flop switch, consisting of mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum. Each side contains GABA (gamma-aminobutyric acid)-ergic neurons that heavily innervate the other. The REM-on area also contains two populations of glutamatergic neurons. One set projects to the basal forebrain and regulates EEG components of REM sleep, whereas the other projects to the medulla and spinal cord and regulates atonia during REM sleep. The mutually inhibitory interactions of the REM-on and REM-off areas may form a flip-flop switch that sharpens state transitions and makes them vulnerable to sudden, unwanted transitions-for example, in narcolepsy.

Animals↗

Intrinsic dreams are not produced without REM sleep mechanisms: evidence through elicitation of sleep onset REM periods.

The hypothesis that there is a strict relationship between dreams and a specific rapid eye movement (REM) sleep mechanism is controversial. Many researchers have recently denied this relationship, yet none of their studies have simultaneously controlled both sleep length and depth prior to non-REM (NREM) and REM sleep awakenings, due to the natural rigid order of the NREM--REM sleep cycle. The failure to control sleep length and depth prior to arousal has confounded interpretations of the REM-dreams relationship. We have hypothesised that different physiological mechanisms underlie dreaming during REM and NREM sleep, based on recent findings concerning the specificity of REM sleep for cognitive function. Using the Sleep Interruption Technique, we elicited sleep onset REM periods (SOREMP) from 13 normal subjects to collect SOREMP and sleep onset NREM (NREMP) dreams without the confounds described above. Regression analyses showed that SOREMP dream occurrences were significantly related to the amount of REM sleep, while NREMP dream occurrences were related to arousals from NREM sleep. Dream properties evaluated using the Dream Property Scale showed qualitative differences between SOREMP and NREMP dream reports. These results support our hypothesis and we have concluded that although 'dreaming' may occur during both REM and NREM periods as previous researchers have suggested, the dreams obtained from these distinct periods differ significantly in their quantitative and qualitative aspects and are likely to be produced by different mechanisms.

Adolescent↗

Hallucinations and pathological visual perceptions in Maupassant's fantastical short stories--a neurological approach.

Maupassant excelled as a realist writer of the nineteenth century, with fantastical short stories being an outstanding example of his literary genius. We have analysed four of his fantastical stories from a neurological point of view. In "Le Horla," his masterpiece, we have found nightmares, sleep paralysis, a hemianopic pattern of loss and recovery of vision, and palinopsia. In "Qui sait" and in "La main" there is also an illusory movement of the objects in the visual field, although in a dreamlike complex pattern. In "Lui," autoscopy and hypnagogic hallucinations emerge as fantastical key elements. The writer suffered from severe migraine and neurosyphilis involving the optic nerve, which led to his death by general paralysis of the insane (GPI). Visual loss and visual hallucinations affected the author in his last years, before a delirant state confined him to a nursing home. Our original hypothesis, which stated that he could have translated his sensorial experiences coming from this source to his works, had to be revised by analyzing some of his earliest works, notably "Le Docteur Héraclius Gloss" and "La main d'écorché" (1875). We found hallucinatory symptoms, adopting the form of autoscopy and other elaborated visual misperceptions, in stories written at age 25, when Maupassant was allegedly healthy. Therefore, we hypothesize that they may be related to his hypersensitive disposition, assuming that no pathology is necessary to experience such vivid experiences. In addition, Maupassant's abuse of drugs, as illustrated in "Rêves," could have provided an additional element to outline his painstaking visual depictions. All these factors, in addition to his up-to-date neurological knowledge and attendance at Charcot's lectures at "La Salpêtrière," armed the author for repetitive and enriched hallucinatory experiences, which were transferred relentlessly into his works from the beginning of his career.

Fantasy↗

Alien abduction experiences: Some clues from neuropsychology and neuropsychiatry.

INTRODUCTION: Many thousands of people around the world firmly believe that they have been abducted by alien beings and taken on board spaceships where they have been subjected to painful medical examination. METHOD: Given that such accounts are almost certainly untrue, four areas of neuroscience are considered with respect to possible clues that may lead towards a fuller understanding of the alien abduction experience. RESULTS: First, it is argued that sleep paralysis may be implicated in many such claims. Second, research into false memories is considered. It is argued that abductees may be more prone to false memories than the general population. Third, evidence is considered relating to the mental health of abductees. It is concluded that there is currently no convincing evidence for higher rates of serious psychopathology amongst abductees compared to the general population. However, abductees do seem to show higher levels on some potentially relevant measures (e.g., tendency to dissociate). Finally, claims that alien abduction experiences may be linked to abnormal activity in the temporal lobes is considered. CONCLUSION: Although the neurosciences provide many clues to the nature of this bizarre experience, further research is required before a full understanding will be attained.

Journal Article↗

Pharmacokinetics of gammahydroxybutyrate (GHB) in narcoleptic patients.

Sodium gammahydroxybutyrate (GHB) is an endogenous compound that has been under investigation in the management of narcolepsy for about two decades. The data confirm that GHB treatment decreases daytime sleepiness and episodes of cataplexy, sleep paralysis, and hypnagogic hallucinations. The current study evaluated the pharmacokinetics of GHB, given twice in one night to six narcoleptic patients who had been chronically taking GHB nightly on a similar basis. Results confirmed earlier reports and showed nonlinear pharmacokinetics. Maximum concentrations were reached in 40 +/- 6.2 and 35.7 +/- 7 minutes after the first and second dose respectively. Mean AUCinf was 17731.6 +/- 4867 mg/mL/m. Mean GHB T1/2 was 53 +/- 19 minutes. GHB elimination appears to be capacity-limited in some patients when administered at a fixed dose of 3 g twice nightly at a 4-hour interval.

Brain↗

The clinical spectrum of narcolepsy with cataplexy: a reappraisal.

In the absence of a golden standard for the diagnosis of narcolepsy, the clinical spectrum of disorder remains controversial. The aims of this study were (1) to determine frequency and characteristics of sleep-wake symptoms in patients with narcolepsy with cataplexy, (2) to compare clinical characteristics with results of ancillary tests, and (3) to identify factors that discriminate narcolepsy from other conditions with excessive daytime sleepiness (EDS). We prospectively studied 57 narcoleptics with cataplexy, 56 patients with non-narcoleptic hypersomnia (H), and 40 normal controls (No). Based on suggested and published criteria, we differentiated between narcoleptics with definite cataplexy (N) and narcoleptics without definite cataplexy (possible cataplexy, NpC). Assessment consisted of questionnaires [all patients and controls, including the Ullanlinna Narcolepsy Score (UNS)], polysomnography (all patients), multiple sleep latency test (MSLT) and human leukocyte antigen typing (in most narcoleptics). A new narcolepsy score based on five questions was developed. Data were compared with those of 12 hypocretin-deficient narcoleptics (N-hd). There were significant differences between N and NpC (including mean sleep latency on MSLT), but none between N and N-hd. A score of sleep propensity during active situations (SPAS) and the frequency of sleep paralysis/hallucinations at sleep onset, dreams of flying, and history of sleep shouting discriminated N from H and No (P < 0.001). Cataplexy-like symptoms in H (18%) and No (8%) could be discriminated from 'true' cataplexy in N on the basis of topography of motor effects, triggering emotions and triggering situations (P < 0.001). Our narcolepsy score had a similar sensitivity (96% versus 98%) but a higher specificity (98% versus 56%) than the UNS. Analysis of co-occurring symptoms in narcolepsy revealed two symptom complexes: EDS, cataplexy, automatic behaviors; and sleep paralysis, hallucinations, parasomnias. Low/undetectable cerebrospinal fluid hypocretin-1 levels and a history of definite cataplexy identify similar subgroups of narcoleptics. Specific questions on severity of EDS (SPAS score) and characteristics of cataplexy allow the recognition of subgroups of narcoleptics and their differentiation from non-narcoleptic EDS patients, including those reporting cataplexy-like episodes. The existence of co-occurring symptoms supports the hypothesis of a distinct pathophysiology of single narcoleptic symptoms.

Adult↗

Mazindol in the treatment of narcolepsy.

Thirty-four subjects with the narcoleptic syndrome were treated with mazindol 3--8 mg daily for 1 year. Treatment cuased a sustained improvement in narcolepsy, but had no effect on cataplexy or sleep paralysis. The response to mazindol was excellent in six subjects, good in 14, moderate in 12 and poor in two. No cardiovascular effects, haematological toxicity, tolerance or dependence occurred. Mazindol 6 mg had the same effect on narcolepsy as d-amphetamine 50 mg, but caused less side effects.

Adolescent↗

Symptomatic cataplexy.

The case is described of a man who developed attacks of cataplexy, narcolepsy, and sleep paralysis because of microglioma which infiltrated the walls and floor of the IIIrd ventricle and the upper brain stem. The mechanisms by which the pathology is related to the symptoms are discussed.

Adult↗

Narcolepsy-cataplexy and loss of sphincter control.

We describe the case of a 34-year-old man who presented intermittent faecal incontinence as a manifestation of cataplexy. The patient's sleep history was positive for the full narcoleptic tetrad (sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations) while extensive neuropsychiatric work up was negative for any neurologic or psychiatric illness. Repeat polysomnograms (including a polysomnogram with a full seizure montage) were positive for pathologic sleepiness, but there was no evidence of a seizure disorder. The course of the patient's symptomatology and the favourable response of his symptoms to stimulants and imipramine support the theory that his intermittent loss of sphincter control is part of his narcolepsy-cataplexy.

Adult↗

Problems in the differential diagnosis of narcolepsy versus schizophrenia.

The authors discuss the problems of accurately diagnosing narcolepsy when patients manifest the auxiliary symptoms of this disorder, i.e., cataplexy, hypnagogic hallucinations, and sleep paralysis, which conclude that misdiagnosis of narcolepsy can be avoided if clinicians are aware that this illness can simulate a psychiatric disorder and if they give careful attention to the histroy of the patient's illness.

Adult↗

Opening and closing mechanisms of the larynx.

Opening and closing of the larynx are determined by the intrinsic and extrinsic muscles acting on the elastic forces in the tongue, pharynx, larynx, and trachea. The pharynx is opened or closed by two mechanisms: (1) Contractions of the cricothyroid and of the intrinsic muscles of the larynx open and close the vocal cords. (2) The false cords, ventricle, and true cords accordion open or close in a bellows mechanism. We conclude that the posterior cricoarytenoid opens the laryngeal airway. The cricothyroid together with the posterior cricoarytenoid accentuates this opening. The larynx is also opened by the geniohyoid, mylohyoid, sternothyroid, and middle constrictor. The thyrohyoid, cricothyroid, sternohyoid, and inferior constrictor close the laryngeal airway. Abnormalities in the soft tissues of the neck or of the innervation of the larynx, pharynx, and neck muscles may severely interfere with patency of the laryngeal airway. This occurs in such conditions as vocal cord paralysis, sleep apnea, multiple sclerosis, amyotrophic lateral sclerosis, spastic dysphonia, mandibular fractures or hypodevelopment, and cerebrovascular disease.

Animals↗

Continuous cataplexy in a patient with a midbrain tumor: the limp man syndrome.

A patient with glioblastoma of the rostral brainstem and hypothalamus exhibited bilateral internuclear ophthalmoplegia and vertical nystagmus; he suffered episodes of cataplexy, narcolepsy, and sleep paralysis. A peculiar fluctuation of posture and tone ("limp man syndrome") proved to be a manifestation of continuous cataplexy, as documented by H-reflex recordings. This is the first report of a remarkable movement disorder caused by continuous, fluctuating, partial cataplexy, and is the second report of an association between cataplexy and a tumor of the rostral brainstem.

Adult↗

The psychosocial problems of children with narcolepsy and those with excessive daytime sleepiness of uncertain origin.

BACKGROUND: Narcolepsy is a predominantly rapid eye movement sleep disorder with onset usually in the second decade but often in earlier childhood. Classically it is characterized by combinations of excessive sleepiness especially sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. The psychosocial effects of this lifelong condition are not well documented, especially in children. This study aims to describe the psychosocial profile of a large group of children with narcolepsy compared with other excessively sleepy children and controls. METHODS: We used an international cross-sectional questionnaire survey of children aged from 4 to 18 years who had received from a physician a diagnosis of narcolepsy compared with age- and gender-matched controls. Assessments were made of behavior, mood, quality of life, and educational aspects. RESULTS: Recruited children were separated into those who met conventional criteria for narcolepsy (n = 42) and those whose primary complaint was excessive daytime sleepiness without definite additional features of narcolepsy (excessive daytime sleepiness group; n = 18). Compared with controls, children with narcolepsy and also those with excessive daytime sleepiness alone showed significantly higher rates of behavioral problems and depression. Again, to a significant extent, their quality of life was poorer and they had more educational problems. The children with narcolepsy and the excessive daytime sleepiness group were indistinguishable from each other on these measures. CONCLUSIONS: A range of psychosocial problems can be identified in children with narcolepsy. The origins of these problems are unclear. The similar profiles of difficulties in the narcolepsy and excessive daytime sleepiness groups suggest that excessive sleepiness is the main cause. Clinicians and others responsible for the care of such children need to be mindful of the importance of early detection, intervention, and, ideally, the prevention of these problems.

Adolescent↗

Childhood onset of narcolepsy-cataplexy syndrome in Turkey: clinical and genetic study.

Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal manifestations of rapid eye movement (REM) sleep including cataplexy, sleep paralysis and hypnagogic hallucinations. It is known to be complex disorder in which both genetic predisposition and environmental factors play a role. In humans, susceptibility to narcolepsy is tightly associated with a specific HLA allele, DQB1*0602. In this report, we took advantage of the ongoing genetic study in Turkish narcoleptic patients to document clinical and genetic data of eight patients whose onset of symptoms were in the childhood period.

Adolescent↗

Current concepts in narcolepsy.

Narcolepsy, a disabling disorder, has been underdiagnosed. The classic tetrad of symptoms includes sudden sleep attacks, cataplexy, sleep paralysis, and hypnogogic hallucinations. Diagnosis and treatment will restore a normal quality of life.

Amphetamines↗

[Dr. John Baptiste Edouard Gélineau].

With this brief review we honor the memory of the great French doctor Jean Baptiste Edouard Gélineau. Dr. Gélineau was born on December 23, 1828 at Blaye, Gironde, close to the Bordeaux region. His name is connected with the first clinical description of the disease for which he, both by the right of the primacy as well as ad valorem of his first two names, coined the name "narcolepsy". He was the first to notice the intrinsically evanescent symptoms of narcolepsy, such as excessive daytime somnolence, imperative sleep habits and cataplexy or "astasia" as he called it, and incorporate them into a single clinical syndrome. In 1881 Gélineau discussed Kaffe's case of "maladie du sommeil" as a proof of the existence of the new disease described a year before. As a good clinical observer Gélineau noticed the close relation of emotional engagement and astasia. His attitude was that narcolepsy was a nosologic entity, a disease sui generis, but admitted that it could appear purely as a symptom only. This was in discordance with the views in England where (in 1928) Dr. Samuel Alexander Kinnier Wilson repudiated such convictions; in 1930 Lhermitte still shared the same opinion. Gélineau differentiated narcolepsy from epilepsy with the elegance of clinical reasoning. Overall, Gélineau described three elements of the narcoleptic pentade. Sleep paralyses were first described by Mitchell in 1876, and were first attributed to narcolepsy by Wilson in 1928; in 1930 Lhermitte first described hypnapompic, and Daniels, in 1934, hypnagogic sleep paralysis. Hypnagogic hallucinations were described by Maury in 1848 and subsequently by de Saint Denis in 1867. In twenties they were thoroughly studiesed during the epidemic encephalitis and after the Big War in 1922 by Levy. The life story of Dr. Gélineau covers multivarious activities. As a young student of the Rochefort Navy Medical School he took part in the fight against colera which deluged the city of La Rochelle. In 1849 he became the "Intern" of the Navy Hospital and next year a "Surgeon of the Third Class". As a Navy surgeon he visited French colonies in the Indian ocean: first the Reunion island and then Mayotte island of the Commores Archipelago. Of this period he wrote "Voyage a i'lle de la Réunion", memoirs published much later, in 1905, in which he described colonial life and abolition of slavery. The story of Elise, a beauteous Creole woman, a concubine of a young naval Commander, who delivered a child that soon died, inexorably points to the autobiographic character of his work. He defended a doctoral thesis "Aperçu Medical de I'lle de Mayotte" at Montpellier University School of Medicine in 1858, using the data collected during his year-and-a-half stay on a Mayotte island; at that time he was a "Navy Surgeon of the Second Class". For his dedication in fighting against epidemics that broke out during the French-German war in 1870 he was nominated for the Legion of Honor, but received it only later. In 1871 Gélineau introduced "Doctor Gélineau's tablets" for the treatment of epilepsy (contained bromide and arsenic). He was a member of the Société de Médicine, Société d' Hypnologie, La-Société Française d' Hygiène, and a few others. After retirement at the age of 72, Gélineau switched to wine production, continuing the family tradition; for the quality of his Bordeaux wines he was awarded gold medals at the Anvers and Paris Exhibitions. Dr. Gélineau died on March 2, 1906, at Argeles Gazost in Pyrnees honored by the titles of Chevalier de la Légion d' Honneur, Officier d'Academie and Commander of Nichan of the Ottoman Empire.

Epilepsy↗

[Narcolepsy].

Narcolepsy is a disorder of sleep with uncontrolled sleepiness and cataplexy. Its prevalence in Japanese is estimated to be 0.16-0.59%. The handicap of narcoleptic patients is even larger than that of epileptic patients. The etiology is still unknown, however, a tight association between specific HLA (DR15 and QQ6) or its genotypes (DRB1*1501, DRB5*0101, DQB1*0602, DQA1*0102) and narcolepsy was recently established. This finding raises the possibility that narcolepsy might be an immunological disorder. At present, any concrete evidence supporting this possibility is lacking. Methylphenidate and pemoline are used for controlling excessive daytime sleepiness. Some tricyclic antidepressant such as clomipramine and imipramine are effective in controlling cataplexy, sleep paralysis and hypnagogic hallucination.

Antidepressive Agents, Tricyclic↗