Immunization with the AS03-adjuvanted H1N1 influenza vaccine was associated with an increased incidence of narcolepsy, but narcolepsy associated with vaccination had similar clinical features as 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 adult and pediatric narcolepsy cases 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 overnight polysomnography and multiple sleep latency tests. Baseline assessments included the collection of demographic information, narcolepsy-specific clinical information, and symptom severity assessment. Most patients also underwent brain MRI, assessment of hypocretin levels, and human leukocyte antigen typing.

All cases demonstrated abnormal hypocretin levels, with 21 patients presenting with a hypocretin level of less than 50 pg/mL and 3 having a level of less than 110 pg/mL. The median age of the entire cohort was 13.5 years.

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

Compared with adults, children had a lower frequency of hypnagogic hallucinations (67% vs 17%, respectively; P =.018). Adults and teenagers also reported more frequent sleep paralysis than children (75% and 38% vs 0%, respectively; P <.0005). The median sleep latency duration was significantly shorter in children than adults (1.75 vs 4 minutes, respectively; P =.011).

Study researchers found no differences between vaccine-related and sporadic cases in terms of core narcolepsy features; however, cases of narcolepsy triggered by the vaccine had significantly longer median polysomnography latency (10.5 vs 5 minutes, respectively; P =.043) and longer stage 2 sleep (209.6±44.6 vs 182.3±34.2 minutes, respectively; P =.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 of this study concluded that they believe both vaccine-related and sporadic narcolepsy cases “share the same underlying pathophysiological mechanisms albeit triggered in different manners.” 


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

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