Kleine-Levin syndrome is a rare pathology of the central nervous system, occurring with transient periods of sleep and wakefulness disorders. Hypersomnia is characteristic during the attack — the patient sleeps 18 hours a day. Short intervals between sleep are accompanied by a strong feeling of hunger, changes in behavior and psyche. The diagnosis is established according to clinical criteria, taking into account the results of somnological, neurological examination. The treatment is under development. In order to shorten hypersomnic episodes, it is possible to use psychostimulants, lithium preparations for the relief of mental disorders.
ICD 10
G47.8 Other sleep disorders
General information
The first description of the disease is dated 1786. The observation of several patients suffering from attacks of hypersomnia in combination with uncontrolled appetite is given in the work of the German psychiatrist V. Kleine in 1825. In 1936, the description of the disease was supplemented by the American neurologist M. Levin. In honor of the researchers of the phenomenon in 1942, the pathology was named Kleine-Levin syndrome. Due to the peculiarities of the clinical picture, the name “sleeping beauty syndrome” is used in popular scientific literature. The prevalence of the disease is 1-2 cases per 1 million population. In most cases, the syndrome manifests in the puberty period, boys get sick more often than girls.
Causes
The etiofactors leading to the development of the disease have not been determined. Due to the examination of patients using positron emission tomography, the leading role of dysfunction of the reticular formation, the thalamus, was established. An important function of the reticular formation is the regulation of sleep-wake cycles. Its close connection with the neuroendocrine system (hypothalamus, pituitary gland) explains the characteristic debut of symptoms during the hormonal restructuring of the body.
Traumatic brain injuries, viral infections, severe stress, hyperthermia of unknown origin are considered trigger factors. There are cases of diseases of members of the same family, indicating a possible genetic determinism of pathology. Most authors believe that the disease is based on a hereditary predisposition, which is realized under the influence of triggers against the background of endocrine restructuring.
Pathogenesis
It is suggested that the pathogenetic basis of the disease is autoimmune mechanisms. According to this theory, Kleine-Levin syndrome is an autoimmune encephalitis with an isolated lesion of the hypothalamus, developing as a result of acute respiratory infections. A number of studies have shown the leading pathogenetic role of cerebral orexin neuropeptides. The hypothalamic neurons responsible for the synthesis of orexins are connected by axons to almost any part of the brain. Orexin-producing cells activate neurons that produce monoamines. The latter have an exciting effect on the cerebral cortex and thalamus. Thus, orexins maintain a state of wakefulness. Inhibition of orexin-producing neurons leads to drowsiness, transition to a sleep state.
Symptoms
The basis of the clinical picture is paroxysmal periods of hypersomnia (increased drowsiness), lasting from several days to 5-6 weeks. During the hibernation period, the duration of sleep is 18-20 hours, the patient wakes up only to recover the natural needs of the body. It is extremely difficult to wake up a sleeper, such a violent awakening is dangerous by the high aggressiveness of the awakened one. After an independent transition to a waking state, the patient does not feel rested and well-rested, as with a full sleep. A few hours later, he falls asleep again. In the intervals between sleep, the patient is tormented by a strong feeling of hunger, there is no control of eating behavior.
Bulimia leads to eating everything edible that the patient is able to find. Food consumption occurs without taste preferences, the compatibility of products is not taken into account, the feeling of saturation does not occur for a long time. During such wakefulness, mental changes are possible: aggressiveness, hypersexuality, emotional lability, psychomotor agitation, narrowing of consciousness, hallucinations, schizophrenic symptoms. Hypersomnia is accompanied by symptoms of autonomic dysfunction: increased sweating, cyanosis of the distal extremities, nasolabial triangle, the appearance of dark circles under the eyes.
In typical cases, Kleine-Levin syndrome occurs with complete amnesia of the hypersomnic period. Finally awakened patients believe that they have woken up after a normal night’s sleep. Periods of hibernation are observed 2-3 times annually. They completely turn off the patient from social and family life, deprive him of the opportunity to study, conduct professional activities. Between bouts of hypersomnia, the patient’s well-being is not disturbed, he is physically and mentally healthy. Bulimia can result in excessive body weight gain with the development of obesity.
Diagnostics
Verification of the diagnosis is based mainly on clinical symptoms with typical attacks of hypersomnia, including episodes of prolonged sleep, alternating with short periods of wakefulness, occurring with bulimia, mental disorders of varying severity. A distinctive feature of hypersomnia is the absence of enuresis. The neurologist’s examination does not reveal significant deviations in the neurological status. Instrumental surveys are of auxiliary importance, include:
- Electroencephalography. In most cases, the study reveals a diffuse nonspecific slowing of the main rhythm. It is possible to register symmetrical low-amplitude peaks of temporal, temporal-parietal localization.
- Polysomnography. There is a shortening of the 3-4 phases of sleep, a decrease in the delay period of the sleep phase, the time of REM latency. A decrease in the average latency of less than 10 minutes indicates an average severity of hypersomnia, less than 5 minutes. — about serious violations.
- PET-CT of the brain. In the inter-criminal period corresponds to the norm. In the hypersomnia phase, it reveals a sharp decrease in perfusion in the hypothalamus, thalamus, and reticular formation.
Diagnostic search is carried out with the participation of a somnologist, an epileptologist, an infectious disease specialist, a psychiatrist. It is necessary to differentiate Kleine-Levin syndrome from depression, narcolepsy, lethargic encephalitis, somnambulism. Narcolepsy is characterized by short episodes of hypersomnia (no more than 2-3 hours), the ability to wake up a sleeper, and a cheerful state of health after waking up. Hypersomnia in encephalitis occurs with the presence of neurological symptoms: oculomotor disorders, ataxia, extrapyramidal disorders.
Treatment
Specific therapy has not been developed. The rarity of pathology causes the complexity of clinical trials, as a result of which there are no drugs with reliably proven effectiveness. Symptomatic therapy has 2 main directions:
- Treatment of drowsiness. It is aimed at reducing the duration of periods of hibernation. It is carried out by the appointment of psychostimulants: methylphenidate, ephedrine, D-amphetamine.
- Relief of mental disorders. It is carried out between episodes of pathological sleep to reduce bulimia and other psychopathological symptoms. In the literature on clinical neurology, there is an indication of the prospects of prescribing lithium preparations. The use of antidepressants, neuroleptics, tranquilizers proved ineffective.
Prognosis and prevention
Kleine-Levin syndrome is characterized by a benign course. Over time, hypersomnia periods are shortened, intercalary intervals are lengthened, and gradual spontaneous recovery is observed. The duration of the course of the disease is 10-14 years, the maximum experience of the disease described in the literature is 18 years. The presence of a symptom of hypersexuality may be a prognostic sign of a prolonged course of the syndrome. Since the etiopathogenesis of the disease remains unclear, its prevention has not been developed.
