Immunological Events Indicated in Onset of Hypersomnolence Disorders, Study Finds

Multiple immunological events have been connected to the onset of narcolepsy type 1 (NT1), such as various respiratory and nonrespiratory infections, influenza, and the H1N1 influenza vaccine, according to a recent study published in Sleep Medicine.¹

Daytime Sleepiness, Hypersomnolence Model | image credit: Andrey Popov - stock.adobe.com

NT1, narcolepsy type 2 (NT2), and idiopathic hypersomnia are 3 conditions within a group of disorders referred to as central disorders of hypersomnolence. Although the underlying pathophysiology of many of these conditions is still unknown, the central disorders of hypersomnolence are characterized by excessive or variable degrees of daytime sleepiness.² NT1 can also cause sleep paralysis, nocturnal sleep disruptions, and sleep-related hallucinations, but it is distinguishable from other central disorders of hypersomnolence because bouts of cataplexy (emotionally induced loss of muscle control, usually associated with positive emotions like laughing) can occur. Additionally, NT1 stands out because affected individuals report nocturnal awakenings and lower sleep efficiency at higher rates compared with those impacted by NT2 or idiopathic hypersomnia.

Incidence rates of NT1 increased in the wake of the H1N1 pandemic of 2009-2010.¹ As the present authors note, this trend sparked interest for researchers to investigate the potential influence of environmental factors or immunological events in the development of narcolepsy. This increase was not observed in cases of NT2 or idiopathic hypersomnia but the authors cite previous research that found a cohort with idiopathic hypersomnia all registered positive results for Epstein-Barr virus (EBV). By analyzing individuals impacted by hypersomnolence disorders, the authors contended, insights could be derived to improve clinical understandings of the possible relationship between immunologic events or environmental factors and the manifestation of these conditions. To expand knowledge in this area, researchers investigated the distribution of these events and factors in NT1, NT2, and idiopathic hypersomnia.

Participants were recruited from Sleep-Wake Center SEIN Heemstede, a tertiary clinic in the Netherlands, and were diagnosed with a hypersomnolence disorder between January 2010 and January 2020. Histories of individual infection with and vaccination against influenza were also gathered.

In total, 87 individuals with idiopathic hypersomnia, 18 with NT2, and 194 with NT1 were eligible for inclusion in this study.

The history of infection or influenza vaccination was known in 149 and 142 of the individuals with NT1, respectively. Prior to their development of NT1, 87 of the 194 participants (44.8%) had a prior infection or influenza vaccine. In 46 of the 149 patients with a known infection (30.9%), 13 reported having the flu (8.7%), 12 having EBV (8.1%), and 11 and 10 having other nonrespiratory or respiratory infections (7.4% and 6.7%, respectively). Of these 46 individuals, the researchers found that the rapid onset of NT1 occurred for 36 (78.3%) within 1 year following their infection.

In the 142 patients with NT1 and known vaccination histories, 44 (31%) had received the influenza vaccine. The H1N1 influenza vaccination of 2009-2010 had been administered in 33 (23.2%) participants in this group. The rapid onset of NT1 in the year following vaccinations was reported by 15 of the 44 individuals who had the influenza vaccine (34.1%) and 15 of the 33 who received the H1N1 vaccine (45.5%).

The onset of hypersomnolence disorders was frequently reported following immunologic events across all groups but, as the researchers note, was more commonly seen in patients who went on to develop NT1. NT1 was linked closer to the flu and H1N1 vaccinations whereas EBV and other nonrespiratory and respiratory infections were more commonly linked to NT2 and idiopathic hypersomnia.

“Infections and influenza vaccinations were often reported within days to weeks of hypersomnolence symptom onset, making a causal relationship plausible,” the authors concluded. “Our study opens a new research path into possible immunological pathophysiology underlying non-hypocretin-1 deficient central hypersomnolence diagnoses, including EBV and other respiratory infections.”

References

1. Gool JK, Zhang Z, Fronczek R, Amesz P, Khatami R, Lammers GJ. Potential immunological triggers for narcolepsy and idiopathic hypersomnia: Real-world insights on infections and influenza vaccinations. Sleep Med. 2024;116:105-114. doi:10.1016/j.sleep.2024.02.033

2. Trotti LM. Central disorders of hypersomnolence. Continuum (Minneap Minn). 2020;26(4):890-907. doi:10.1212/CON.0000000000000883