Immunotherapy in Narcolepsy

Narcolepsy type 1 (NT1) is a chronic and disabling sleep disorder due to the loss of hypocretinergic neurons in the lateral hypothalamus pathophysiologically linked to an autoimmune process. Current treatment is symptomatic, and no cure is available to date. Immunotherapy is considered a promising future therapeutic option, and this review discusses the rationale for immunotherapy in narcolepsy, current evidences of its effects, outcome measures, and future directions.

A limited number of case reports and uncontrolled small case series have reported the effect of different immunotherapies in patients with NT1. These studies were mainly based on the use of intravenous immunoglobulin (IVig), followed by corticosteroids, plasmapheresis, and monoclonal antibodies. Although initial reports showed an improvement of symptoms, particularly when patients were treated close to disease onset, other observations have not confirmed these results. Inadequate timing of treatment, placebo effects, and spontaneous improvement due to the natural disease course can account for these contrasting findings. Moreover, clear endpoints and standardized outcome measures have not been used and are currently missing in the pediatric population. On the basis of the available data, there are no enough evidences to support the use of immunotherapy in NT1. Randomized, controlled studies using clear endpoints and new outcome measures are needed to achieve a definitive answer about the usefulness of these treatments in narcolepsy.