Conclusion

Narcolepsy is genetically complex and environmentally influenced. Although the HLA DQB1*0602 remains the unique established genetic risk factor, future studies may focus in identifying new genetic susceptibility factors, environmental factors and the study of gene-environment interactions, involving in hypocretin cell death. The cause of this focal neurodegeneration remains a mystery although an autoimmune hypothesis is likely. A transient and focal inflammatory process targeting hypocretin neurons may have occurred around disease onset and disappeared shortly thereafter.

Further studies that focus on reactivity of serum and/or CSF to other components of the hypocretin neurotransmission system, and on T-cell autoimmune response directed against neuroantigens are warranted. Finally, the efficacy of immune-based therapies in narcolepsy needs to be confirmed in larger double blind placebo controlled trials.

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