Autonomic Dysfunction Could Be Associated With Idiopathic Hypersomnia, According to Review

A review published in the Journal of Clinical Sleep Medicine found that the relationships between autonomic dysfunction and idiopathic hypersomnia (IH) and between sleep disturbances and postural orthostatic tachycardia syndrome (POTS) are poorly understood. The authors of this review wrote that it was important to recognize the autonomic comorbidities with IH and POTS. The aim of this review was to summarize the current literature on these relationships and highlight gaps in the current knowledge.

Symptoms of autonomic nervous system dysfunction are common in patients with IH. The review cited a study that featured 138 patients with IH and 81 controls that used online surveys to assess excessive daytime sleepiness, insomnia quality of life, and autonomic symptoms, using the Composite Autonomic Symptom Score-31. The score assesses autonomic functions in 6 different domains: secretomotor, vasomotor, pupillomotor, gastrointestinal, orthostatic intolerance, and urological. Patients with IH had a higher autonomic symptom burden in all 6 domains. This positively correlated with sleepiness and negatively correlated with quality of life.

The researchers wrote that the involvement of the autonomic nervous system during sleep could help understand the autonomic dysregulation in patients with IH. In non-REM cycles of sleep, the sympathetic nervous system has decreased activity while the parasympathetic nervous system has increased activity. This occurs through the ventrolateral preoptic nucleus of the hypothalamus.

According to the researchers, the nucleus of the solitary tract is the regulator of blood pressure and is the main contributor to the baroreceptor reflex. The pons, which is responsible for REM sleep, has glutamatergic connections to the nucleus of the solitary tract, which suggests 1 mechanism of blood pressure regulation while asleep. Going to sleep brings blood pressure down by 10% to 20% compared with baselines during the day.

The authors noted that these neuroanatomical pathways could underlie the coexistence of daytime sleepiness and autonomic dysfunction in patients with IH. However, the mechanism of autonomic dysfunction in patients with IH is unknown. Some research has postulated that it may be due to reduced physical activity or immune dysregulation.

The researchers cited a study on 84 participants with autonomic dysfunction and 100 controls. The results of the study identified that orthostatic intolerance had a strong and independent association with lack of physical activity and deconditioning. In a separate study with 83 pediatric patients with primary hypersomnia, 33 demonstrated orthostasis. Of the 33 who demonstrated orthostasis, 11 had IH while the rest had narcolepsy, secondary hypersomnia, or periodic hypersomnia.

The relationship between immune dysregulation and IH is supported by the discovery of higher prevalence of autoinflammatory conditions in IH patients and the finding that autonomic dysregulation may be immune mediated in certain neuroimmunological conditions.

IH-related autonomic disfunction and POTS have an intriguing overlap, according to the researchers. Both of these conditions are associated with Ehlers-Danlos syndrome (EDS). Patients with POTS often complain of EDS. Persistent EDS was reported in 40% of patients with POTS, EDS at least once weekly was reported by 22% of patients with POTS, and 20% reported EDS at least once a month.

Patients with POTS also experienced increased heart rate in sleep (r = 0.291), especially in non-REM sleep (r = 0.275) and while awake in the supine position (r = 0.518). Some patients with POTS also had nocturnal tachycardia and increased autonomic arousals.

In a study cited by the researchers of this review, 25 patients with POTS and 31 control patients filled out the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale questionnaires. Patients with POTS scored significantly higher on the Pittsburgh Sleep Quality Index (median [IQR], 8 [4-13] vs 4 [3-5]) compared with the control group. Patients with POTS also scored higher on the Epworth Sleepiness Scale, although these results did not reach significance.

On a polysomnography in that same study, patients with POTS had a higher mean heart rate in both REM and non-REM sleep and a higher percentage of stage N2 sleep than the control group (42.45% vs 36.70%). Patients with POTS also had poor sleep efficiency and complain of insomnia.

More research will be required to evaluate the role of intravenous immunoglobulin treatment (IVIG) in the treatment of daytime sleepiness in these patients, as a small, recent case series identified IVIG as a treatment that could improve autonomic symptoms and fatigue for patients with POTS.

“As we learn more about the pathophysiology of IH as well as that of POTS, we will be able to come up with better theories for the mechanism of autonomic dysfunction in these patients,” the researchers wrote. “For now, it is important to recognize autonomic comorbidities with IH and sleep disturbances in POTS.”

Reference

Adra N, Reddy M, Attarian H, Sahni A. Autonomic dysfunction in idiopathic hypersomnia: an overlooked association and potential management. J Clin Sleep Med. 2022;18(3):963-965. doi:10.5664/jcsm.9818