Systematic Assessment of Dysexecutive Syndrome, Hypersomnolence and Dysautonomia in Kleine-Levin Syndrome.

BACKGROUND

Kleine-Levin Syndrome (KLS) is a neurological disorder of unknown pathophysiology. It is characterized by relapsing-remitting episodes of hypersomnia, with cognitive symptoms and behavioral disturbances. The diagnosis relies on clinical criteria, which require further standardization. Our main objective was to better phenotype and systematically quantify the severity and impact of cognitive and behavioral symptoms, hypersomnolence and dysautonomia in a well-characterized population of KLS patients.

METHODS

Forty-three consecutive KLS patients diagnosed in a National Reference Center for Rare Hypersomnias underwent a standardized clinical and polysomnographic evaluation and completed validated questionnaires with their relatives. The Behavioral Dysexecutive Syndrome Inventory (BDSI) assessed their behavior during most episodes. The Idiopathic-Hypersomnia Severity Scale (IHSS) assessed different hypersomnolence components (inertia, sleepiness, prolonged sleep), and the Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT) assessed dysautonomia. The latter two scales were completed twice to differentiate symptoms during and between episodes.

RESULTS

During symptomatic periods, behavioral changes were observed in all BDSI domains, more than half of patients showing reduced activities and apathy, anticipation-organization-initiation difficulties, disinterest, irritability-aggression, perseveration-stereotypies, and sexual or eating disorders. IHSS scores were severe and higher during episodes (42.6 ± 5.8 vs. 15.6 ± 9.8, p < 0.0001), and each item higher. The SCOPA-AUT scores were higher during episodes (12.1 ± 8.5 vs. 8.5 ± 8.2, p = 0.0001), particularly in the cardiovascular, pupillomotor, and thermoregulation domains.

CONCLUSIONS

Our findings suggest the relevance of the BDSI for the evaluation of dysexecutive behavioral symptoms in KLS. The IHSS would be useful for phenotyping hypersomnolence and the SCOPA-AUT for assessing dysautonomia during episodes. Future studies could combine the BDSI with imaging and other biomarkers to explore the neuroanatomical correlates of this enigmatic disorder.