Kleine–Levin syndrome

Kleine-Levin syndrome (KLS) is a rare intermittent neuropsychiatric disorder (approximately 3 cases per million) that predominantly affects adolescents and young adults. It is characterised by symptomatic periods (“crises” or “episodes”) lasting from one to several weeks and involving severe hypersomnia associated with cognitive, behavioural and psychiatric disorders. 

The episodes are separated by intercritical periods lasting from several weeks to several months, with a return to normal functioning. 

The course is variable, with an average of approximately twenty episodes, and is often favourable: the disorder frequently disappears after the age of thirty. 

This favourable prognosis should not obscure the fact that some patients experience very distressing episodes (severe derealisation, sometimes serious behavioural disorders involving hyperphagia, hypersexuality, aggression, delusions or suicidal thoughts), prolonged episodes (lasting more than a month) or very frequent episodes, which affect their academic, professional and family life. 

Furthermore, around one third of young people develop, as a result of recurrent episodes, persistent mild cognitive impairment between crises, sleep disorders, anxiety or disord

The classic presentation is that of a previously healthy adolescent who suddenly begins sleeping continuously (18 hours or more per day), stays in their room, lying down, confused, slowed down and apathetic (for example, no longer using their mobile phone), and experiences derealisation (the feeling of being in a dream). The episode lasts one or two weeks, after which the young person returns completely to normal. During the episode, varying degrees of severe anxiety, sadness, disinhibited behaviour (megaphagia, hypersexuality, rudeness) or delusions may also occur. Since the first episode is often triggered by an infection or alcohol use, the doctor often suspects a viral illness or substance use, performs a brain MRI (which is normal), sometimes a lumbar puncture (also normal), or recommends seeing a child and adolescent psychiatrist. A recurrence of the same symptoms weeks or months later should suggest Kleine–Levin syndrome.

The diagnosis is primarily clinical: a description, observation, or video recording of the episodes by the family, and exclusion of more common alternative diagnoses. However, frequent abnormalities may be observed on EEG during an episode and on functional brain imaging (PET scan), even during asymptomatic periods: hypometabolism of the posterior association cortex or hippocampus in 70% of cases. Predisposing factors include male sex and neonatal disorders. The cause is unknown, but certain indirect findings suggest that this is a recurrent inflammatory encephalopathy.

General management

- Explanation of the disease: current knowledge and patient association.

- Reduction of factors that trigger episodes: no alcohol or cannabis, sufficient and regular sleep, barrier measures, prevention (seasonal influenza and COVID-19 vaccination, and treatment of infections).

- In the event of an episode: keep the patient at home, resting in bed in a quiet environment and often in the dark, under the supervision of the family, ensuring that he or she drinks enough and eats a little. Urination is maintained. Never drive a vehicle during an episode (risk of an accident). Bring the patient home if an episode begins abroad.

- Hospitalisation: only if there is a risk to the patient or others (severe delirium, suicidal thoughts, aggression).

Drug treatment

This is selected and regularly reassessed by the neurologists responsible for the patient’s care. No treatment is also an option. However, on a case-by-case basis, depending on the degree of disability—particularly if the episodes are frequent (> 3/year), prolonged (> 1 month), or involve significant psychiatric symptoms—the following is recommended:

Lithium at a therapeutic dose: beneficial in more than 83% of cases. It requires drinking plenty of water, regular monitoring of blood lithium levels, TSH and creatinine levels, and an annual reassessment of its effectiveness. Please note that this disease is unrelated to bipolar disorder. Lithium is then gradually discontinued after 3 years without an episode.

Treatment during an episode: a methylprednisolone infusion of 1 gram/day for 3 consecutive days may be started, with antacid cover.