AS03 adjuvant influenza vaccine will increase the incidence of narcolepsy, clinically much like sporadic circumstances

Immunization with the AS03 adjuvant H1N1 influenza vaccine was associated with an increased incidence of narcolepsy, but the vaccination-associated narcolepsy had clinical features similar to sporadic narcolepsy, according to study results published in the Journal of Clinical Sleep Medicine.

In this retrospective study, researchers from 3 different hospitals in Ireland reviewed documented cases of narcolepsy in adults and children referred to a sleep disorders clinic between 2009 and 2016. A total of 40 patients in the study had vaccine-related narcolepsy, while 14 patients had sporadic narcolepsy.

The 54 patients who participated in the study underwent polysomnography and multiple sleep latency tests overnight. The baseline assessments included collecting demographic information, narcolepsy-specific clinical information, and assessing symptom severity. Most patients also underwent brain MRI, hypocretin level assessment, and human leukocyte antigen typing.

All cases showed abnormal levels of hypocretin, with 21 patients having hypocretin levels less than 50 pg / ml and 3 having levels less than 110 pg / ml. The mean age of the entire cohort was 13.5 years.

Approximately 74% (n = 40) of patients had narcolepsy induced by the AS03-adjuvanted H1N1 influenza vaccine. The median time from onset of symptoms to diagnosis of narcolepsy for the entire cohort was 112 weeks, while the median time from vaccination to onset of symptoms was 26 weeks.

Compared to adults, children had a lower frequency of hypnagogic hallucinations (67% versus 17%; P = 0.018). Adults and adolescents also reported more frequent sleep paralysis than children (75% and 38% versus 0%; P <0.0005). The median sleep latency was significantly shorter in children than in adults (1.75 versus 4 minutes; P = 0.011).

The study researchers found no differences between vaccine-related and sporadic cases in terms of the core characteristics of narcolepsy. However, cases of narcolepsy induced by the vaccine had significantly longer median polysomnographic latency (10.5 versus 5 minutes; P = 0.043) and longer stage 2 sleep (209.6 ± 44.6 versus 182, 3 ± 34.2 minutes; P = 0.042). than sporadic cases.

Limitations of this study included the lack of an age-matched control arm and the small group of sporadic narcolepsy cases.

The researchers in this study concluded that they believe that both vaccine-related and sporadic narcolepsy cases “share the same underlying pathophysiological mechanisms, albeit triggered in different ways”.


Ferguson D., Wrigley S., Purcell E. et al. Single-center analysis of patients with H1N1 vaccine-induced narcolepsy and sporadic narcolepsy over the same period. J Clin Sleep Med. Published online December 8, 2020. doi: 10.5664 / jcsm.9052

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