Symptoms of narcolepsy in relation to pandemrix vaccination and CSF-hypocretin-1 levels

Introduction The incidence of narcolepsy increased in Finland, Sweden, Norway, Ireland, UK and France after the H1N1 influenza vaccination (Pandemrix) campaign in 2009–2010. The increase has been noted especially in people aged Materials and methods In all 89 [45 post- (19 men, 26 women) and 44 pre-Pandemrix (19 men, 25 women)] patients with diagnosed narcolepsy (ICSD-2 criteria) were clinically examined. A modified Basic Nordic Sleep Questionnaire was used. PSG, MSLT and/or hcrt measurements were done. Results All subjects with Pandemrix-association (post-PDRX) and 95% without association (pre-PDRX) were HLA-DQB1 ∗ 06:02 positive. Median ages at diagnosis were 16.4 and 26.5years, respectively. 34 (77%) and 25 (68%), respectively, had onset at age P =0.001). Hcrt levels were similar, mean 44.7pg/ml vs 48.3pg/ml and median 3pg/ml (0–264) vs 27pg/ml (0–313). SL in MSLT was shorter in post-PDRX (median 2.4min vs 3.6min, P =0.028). There were no significant differences in occurrence of CPL (88% vs 86%), hypnagogic hallucinations (58% vs 71%) or sleep paralysis (42% vs 39%) at diagnosis. There were no differences in ESS, Ullanlinna Narcolepsy Scale (UNS), Skogby Excessive Daytime Sleepiness Scale (SEDS), Rimon's Brief Depression Scale (LKDA) or WHO Well-Being Scale (WHO5). Hcrt correlated with shorter SL in MSLT ( r =0.362, P =0.012, Pearson correlation), diagnostic delay ( r =0.299, P =0.032) and REM-latency in PSG ( r =0.564, P =0.010) but not with sleep efficiency, ESS, UNS, WHO5, LKDA or number of CPL per week. CPL at time of diagnosis was present in 41/47 (87%) of subjects with hcrt ⩾ 110pg/ml ( P =0.012). Conclusion Pre- and post-Pandemrix narcolepsies do not differ significantly. Hypocretin-1 levels correlated poorly with most symptoms. In sum our results implicate that also non-hypocretin-related mechanisms play an important role in narcolepsy. Acknowledgement This study has been funded by the Academy of Finland grant 260603.