Kleine-Levin Syndrome in 120 Patients: Differential Diagnosis and Long Episodes

ObjectiveKleine-Levin syndrome is a rare disease characterized by recurrent episodes of hypersomnia with behavioral and cognitive disturbances. We aimed at describing the diagnosis procedure, risk factors, and severe forms. MethodsIn consecutive patients referred for suspected Kleine-Levin syndrome, we detailed differential diagnoses, and atypical and secondary cases, compared typical patients with healthy subjects, and examined the characteristics of patients with prolonged (>30 days) episodes. ResultsAmong 166 referred patients, 120 had typical primary Kleine-Levin syndrome (syndrome secondary to brain diseases; n=4, atypical syndrome, n=7; differential diagnoses that were mostly psychiatric, n=29; incomplete information, n=6). The prevalence in France was 1.8 per million. The patients were often male (64%) and had more frequent birth and developmental abnormalities (45%) than controls (despite normal karyotypes), and most (80%) had teenage onset, with no difference between patients with prolonged (n=34) and short (n=85) episodes. In patients with prolonged episodes, the durations of the first episode (3233 vs 11 +/- 6 days) and subsequent episodes were longer (mean episode duration=23 +/- 19 vs 10 +/- 3 days) and the disease course tended to be longer (9 +/- 6 vs 6 +/- 4 years). During episodes, patients with prolonged episodes had shorter sleep time, higher levels of anxiety, increased agitation, and more feelings of disembodiment and amnesia. Between episodes, they were more tired, needed more naps, fell asleep more rapidly, and had higher anxiety/depression scores. InterpretationMental disorders are frequent differential diagnoses of Kleine-Levin syndrome. One-third of patients have prolonged (>1 month) episodes with more frequent immediate and long-term consequences of the disease, prompting therapeutic trials. Ann Neurol 2015. Ann Neurol 2015;77:529-540