Interest in Kleine-Levin syndrome has been recently rejuvenated with the use of SPECT studies and the reports of familial cases including 2 multiplex families and of one case of monozygotic twins concordant for Kleine-Levin syndrome. Next steps should be linkage analysis and the new generation exome sequencing to identify a potential mutation, CSF hypocretin-1 measurements during both symptomatic periods and asymptomatic intervals, and, in view of the autoimmune hypothesis, the screening of CSF for the presence of autoantibodies directed against neurons in presumed affected neuroanatomical regions.