History
In 1815, there was a report of a young man who showed excessive appetite and prolonged sleep after experiencing a fever; this may have been an early description of the condition. Another case with similar symptoms was described by Brierre de Boismont in 1862.Five patients with symptoms of persistent sleepiness were described in detail in 1925 by Willi Kleine, a neurologist from Frankfurt. This report was followed four years later by details of a similar case by New York-based psychiatrist Max Levin. In 1935, Levin published information about several more cases, including one described by Kleine. Levin noted that some patients displayed an intense appetite in addition to their persistent tiredness. MacDonald Critchley, who first wrote about the condition in 1942, described 11 cases he had examined and reviewed 15 other published cases in a 1962 publication. In the report, which included patients he had examined in the Royal Navy during World War II, he observed that irritability and depersonalization often occurred while patients were awake. He named the condition Kleine–Levin syndrome and noted four common traits: hypersexuality, adolescent onset, spontaneous resolution, and compulsive eating. He believed that the condition only affected males, but later studies showed some female patients. In the 1970s, several psychoanalytic and psychodynamic explanations for the condition were proposed. In 1980, a Hawaiian–Caucasian family was found in which nine family members had the condition.Diagnostic criteria for KLS was established by Schmidt in 1990, and the International Classification of Sleep Disorders further refined them.
Evidence for their role includes lesions found in autopsies. CSF samples from KLS patients indicate that the condition has a different cause than influenza-associated encephalopathy. Triggers of KLS may also affect the blood-brain barrier, which could play a role in the condition. There is limited evidence of what role hypocretin may play, although it often influences hypersomnia.Androgen might (indirectly) block melatonin receptors, possibly by means of vasodilation, and cause cholinergic abnormalities in some cases of Kleine–Levin syndrome.Because KLS occurs at a much higher rate in Jews and in some families, it is likely that there is some genetic component in addition to environmental factors. Genetic studies hold promise for understanding the disease, but they have yielded inconsistent results and few patients are available for testing.Epilepsy and depression do not appear to cause KLS. The conditions rapid onset after infections indicates that the immune system is not to blame.One study has suggested a link to the gene LMOD3 on chromosome 3. Diagnosis
KLS can be diagnosed when there is confusion, apathy, or derealization in addition to frequent bouts of extreme tiredness and prolonged sleep. The earliest it can be diagnosed is the second episode, this is not common. The condition is generally treated as a diagnosis of exclusion. Because KLS is rare, other conditions with similar symptoms are usually considered first.MRIs can determine if the symptoms are caused by certain brain disorders, stroke, and multiple sclerosis. Lumbar puncture can determine if encephalitis is the cause. KLS must be differentiated from substance abuse by toxicology tests.