Course and severity of post-H1N1 narcolepsy type 1: a long-term prospective cohort study

Objective: The narcolepsy type 1 (NT1) phenotype severity is heterogeneous, and the disease course is largely unknown. The 2009-10 H1N1-(Pandemrix(R))-vaccinations were followed by increased numbers of possibly more severe post-H1N1 NT1 cases but long-term prospective data on large, vaccinated cohorts are missing. Methods: 130 consecutive post-H1N1 NT1 cases (113/130 Pandemrix(R) -vaccinated) were prospectively followed up after approximately 5.5 years. Epworth Sleepiness Scale (ESS), cataplexy, hypnagogic hallucinations, sleep paralysis, PSG, MSLT, and BMI were evaluated. Phenotype severity predictors (hypocretin-1 deficiency severity <40 vs. 40-150 pg/ml; Pandemrix(R)- vaccination; disease duration) were tested in age and sex-adjusted multivariable regressions. Results: From baseline to follow-up, phenotype severity overall improved (milder symptoms, higher mean MSLT sleep latency (SL) and fewer SOREMPs, all p<0.001). Follow-up phenotype severity was strongly predicted by the same baseline measures. Females had worse ESS and cataplexy, men had higher BMI, and young individuals had lower mean MSLT SL and more SOREMPs. Severe hypocretin deficiency (<40 pg/ml) predicted baseline PSG SOREMPs and lower MSLT SL. Vaccinated individuals had more severe baseline PSG/MSLT measures but greater long-term symptom improvement, and vaccination no longer predicted PSG/MSLT severity at follow-up. Conclusion: The best prognostic factor for long-term NT1 phenotype severity is the earlier phenotype severity. Hypocretin deficiency severity also predicts parts of short-term but not long-term phenotype severity. Pandemrix(R)-vaccination is associated with initially more severe phenotype but larger long-term improvement i.e. a different clinical course than in unvaccinated NT1, although medication effects cannot be excluded. Our findings underscore heterogeneity in NT1 phenotype and disease trajectories.