Linking To And Excepting From “Frequency and severity of autonomic symptoms in idiopathic hypersomnia”

Posted on April 8, 2025 by Tom Wade MD

In addition to today’s resource, please see:

  1. “Idiopathic Hypersomnia” From StatPearls
    Posted on December 15, 2023 by Tom Wade MD
  2. The Multiple Sleep Latency Test From AASM’s Sleep Education Site
    Posted on July 9, 2023 by Tom Wade MD
  3. Links To Sleep Diary Web Page And To A Printable Two Week Sleep Diary From Sleep Education
    Posted on July 10, 2023 by Tom Wade MD
  4. Links To And Excerpts From “Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management”
    Posted on August 2, 2022 by Tom Wade MD

Today, I review, link to, and excerpt from Frequency and severity of autonomic symptoms in idiopathic hypersomnia [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. J Clin Sleep Med. 2020 May 15;16(5):749-756. doi: 10.5664/jcsm.8344. Epub 2020 Feb 10.

There are 120 similar articles in PubMed.

The above article has been cited by 11 articles in PubMed.

The questionnaires uses in this study include:

  • Compass-31
    • Orthostatic intolerance
    • Vasomotor
    • Secretomotor
    • Gastrointestinal
    • Bladder
    • Pupillomotor
    • Total weighted score
  • Epworth Sleepiness Scale
  • Fatigue Severity Scale
  • Morningness-Eveningness Questionnaire
  • Restless Legs Syndrome-single item (years)
  • STOP-Bang
  • Insomnia Severity Index
  • RAND-36
    • Physical functioning
    • Role limitations due to physical health
    • Role limitations due to emotional problems
    • Energy/fatigue
    • Emotional well-being
    • Social functioning
    • Pain
    • General health

All that follows is from the above article.

In conclusion, we found that autonomic symptoms are common in IH, with the greatest symptom burden in the orthostatic and vasomotor domains. In addition, ANS symptom burden correlates moderately with higher levels of sleepiness and fatigue and is inversely correlated with quality of life. Future analysis will focus on objective autonomic testing to help identify symptomatic domains, with the goal of more focused therapeutic targets for patients with IH.

Abstract

Study Objectives:

We aimed to quantify the symptoms of autonomic nervous system dysfunction in a large online cohort of patients with idiopathic hypersomnia, and to determine how the severity of these symptoms interacts with sleepiness, fatigue, and quality of life.

Methods:

One hundred thirty-eight patients with idiopathic hypersomnia and 81 age- and sex-matched controls were recruited through the website of the Hypersomnia Foundation, a US-based patient advocacy group. Twenty-four patients with confirmed idiopathic hypersomnia were selected by the study investigators as a comparison group. All participants completed a battery of online sleep, autonomic, and quality of life questionnaires including the composite autonomic symptom score-31 (COMPASS-31).

Results:

Online and confirmed patients reported significantly higher COMPASS-31 scores (median [interquartile range]) (43.6 [33.6–52.7] and 32.9 [21.7–46.8] vs 17.6 [11.7–27.9], P < .001), with the greatest symptom burden in the orthostatic and vasomotor domains. Online and confirmed patients reported more sleepiness (Epworth sleepiness scale), whereas only online patients reported more fatigue (Chalder fatigue scale). Both the Epworth sleepiness scale and Chalder fatigue scale positively correlated with COMPASS-31 scores. Patients reported lower quality of life as reflected by lower scores across all domains of the RAND 36-item health survey, which was negatively correlated with COMPASS-31 scores.

Conclusions:

Symptoms of autonomic nervous system dysfunction are common in idiopathic hypersomnia. In addition, autonomic nervous system symptom burden was positively correlated with sleepiness and negatively correlated with quality of life.

Citation:

Miglis MG, Schneider L, Kim P, Cheung J, Trotti LM. Frequency and severity of autonomic symptoms in idiopathic hypersomnia. J Clin Sleep Med. 2020;16(5):749–756.

Keywords: idiopathic hypersomnia, autonomic, orthostatic intolerance, POTS, syncope, fatigue

BRIEF SUMMARY

Current Knowledge/Study Rationale: The prevalence of autonomic nervous system dysfunction in idiopathic hypersomnia is unknown. Prior publications have described various symptoms of autonomic nervous system dysfunction in idiopathic hypersomnia; however, exploration of the character and severity of autonomic nervous system dysfunction in a large cohort of patients with idiopathic hypersomnia is lacking.

Study Impact: We provide the results of the first large-scale online study in idiopathic hypersomnia assessing the character and severity of autonomic nervous system dysfunction in this population, laying groundwork for future explorative studies. In addition, we correlate the severity of these symptoms with both excessive daytime sleepiness and worse quality of life.

INTRODUCTION

Idiopathic hypersomnia (IH) is a potentially debilitating central nervous system (CNS) hypersomnia of unknown etiology. Although the cardinal features of IH include excessive daytime sleepiness, lack of cataplexy, and unrefreshing sleep that is often prolonged, it has been our experience that many patients with this condition also report symptoms of autonomic nervous system (ANS) dysfunction. Prior publications have described temperature intolerance, orthostatic intolerance, and Raynaud’s phenomenon in patients with IH,, and more recent heart rate variability studies have demonstrated markers of increased parasympathetic tone during wake and sleep. However, further exploration of ANS dysfunction in this population is lacking, with prior studies being limited to case series without healthy controls, survey-based studies with limited focus on ANS dysfunction, or small case-control heart rate variability (HRV) studies. ANS dysfunction has been well described in type-1 narcolepsy (NT1), another CNS hypersomnia, which may be related to the underlying pathophysiology of hypocretin cell loss. As the etiology of IH is not currently known, formally evaluating autonomic dysfunction as an associated feature of this disease would be of great value to further characterize its pathophysiology. We aimed to quantify the frequency and severity of ANS symptoms in a large online cohort of patients with IH, and to determine how the burden of these symptoms interacts with sleepiness, fatigue, and quality of life.

METHODS

Patient selection

Online patients and controls were recruited through the website of the Hypersomnia Foundation, a US-based patient advocacy group. This method of convenience sampling is often necessary to recruit sufficient numbers of participants in the case of rare diseases, such as IH. A similar strategy of convenience sampling was performed to recruit the control group, which consisted of patients’ spouses, friends, and nonblood relatives. All online participants self-reported a diagnosis of IH made by a physician and verified that this diagnosis was supported by polysomnogram and multiple sleep latency (MSLT) testing.*

*A Multiple Sleep Latency Test (MSLT) is a daytime nap study used to assess excessive daytime sleepiness, particularly in diagnosing narcolepsy and idiopathic hypersomnia, by measuring how quickly and how often someone falls asleep during multiple nap opportunities.

An additional cohort of carefully phenotyped patients with confirmed IH were recruited as a validation group by the investigators at the sleep centers of Stanford (MGM, PK, LS, JC) and Emory (LMT).All confirmed patients were diagnosed by two of the study investigators (MGM, LMT) using current American Academy of Sleep Medicine criteria (mean sleep latency ≤8 minutes on MSLT with <2 sleep-onset rapid eye movement periods, or total sleep time ≥11 hours confirmed by 7-day actigraphy).6. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014. [Google Scholar][Ref list]Participants were excluded if they had untreated obstructive sleep apnea (OSA) or systemic exertional intolerance disease/chronic fatigue syndrome (SEID/CFS), such that self-reported diagnoses of OSA or SEID/CFS resulted in survey termination. We chose to exclude those with a pre-existing diagnosis of SEID/CFS due to the high rate of coexisting autonomic impairment in this patient population and concerns of biasing the data set.Controls were excluded if they had a pre-existing diagnosis of any CNS hypersomnia. Online patients were excluded from final analysis if they reported any symptoms of cataplexy or an average total sleep times less than 7 hours nightly (atypical in IH). Participants with clear outlier and implausible data (eg, total sleep time 25 hours) were also excluded from the final data set. Patients were not excluded if they were previously diagnosed with an autonomic disorder. In order to maintain consistency, we also included controls if they reported a pre-existing autonomic diagnosis.

Questionnaires

All participants completed a survey consisting of basic demographic information, a sleep questionnaire consisting of 7 hypersomnia-specific questions (supplemental material), the composite autonomic symptom score-31 (COMPASS-31), the Epworth Sleepiness Scale (ESS), the Chalder fatigue scale (CFQ), the morningness-eveningness questionnaire self-assessment (MEQ-SA), the STOP-Bang questionnaire, the insomnia severity index (ISI), the restless leg syndrome (RLS)–single item (RLS-SI) screen, and the RAND 36-item health survey (RAND-36). Data were collected via the online Research Electronic Data Capture platform.

The COMPASS-31 is a widely used patient questionnaire that provides an abbreviated quantitative assessment of the severity and distribution of autonomic symptoms. This questionnaire generates a weighted score from 0 to 100, and questions fall into one of six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor function. Higher scores indicate greater symptom severity, with controls reporting a mean score of 8, and patients with mild, moderate, and severe autonomic dysfunction reporting mean scores of 15, 29, and 46, respectively (W. Singer, personal correspondence, May 2019). This questionnaire has proven to have good internal validity as well as good correlation with autonomic cardiovascular reflex testing in various patient populations.–

The ESS is a 24-point scale that quantifies the likelihood of dozing in various situations over the preceding 4 weeks. Scores ≥10 suggest excessive daytime sleepiness. The MEQ-SA is a 19-item form that is used to predict circadian preference in individuals. Scores range between 16 and 86, with scores ≤41 indicating “evening” chronotypes, ≥59 indicating “morning” chronotypes, and scores 42–58 indicating “intermediate” chronotypes. The CFQ is an 11-item questionnaire used to assess physical and mental fatigue validated in patients with SEID/CFS. Scores range from 0 to 33, with higher scores reflecting greater fatigue. A score ≤14 is considered normal, and a score >28 indicates significant fatigue, as experienced by those with SEID/CFS., The RAND-36 is a health-related quality of life survey of 36 items that generates a numerical score from 0 to 100 for 8 different scales: physical functioning, role limitations caused by health problems, role limitations caused by emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health perceptions. Higher scores define a more favorable health state. The ISI is a 7-item questionnaire assessing severity and impact of insomnia symptoms over the preceding month. Questions 1–3 address features unique to insomnia (difficulty falling asleep, staying asleep, and waking earlier than intended), whereas questions 4–7 address the effects of sleep disruption on quality of life. The total score ranges from 0 to 28, with ≤7 indicating the absence of insomnia, 8–14 subthreshold insomnia, 15–21 moderate insomnia, and ≥22 severe insomnia. The RLS-SI is a single-item question developed by the RLS Study Group: “when you try to relax in the evening or sleep at night, do you ever have unpleasant, restless feelings in your legs that can be relieved by walking or movement?” The STOP-Bang questionnaire is a widely used 8-item form that screens for obstructive sleep apnea, where a score of ≥3 indicates an increased risk.

Statistical analysis

The primary outcome measure was defined as the total weighted COMPASS-31 score. Secondary outcomes included COMPASS-31 domain scores and correlations between total weighted COMPASS-31 score and ESS, CFQ, and RAND-36 domain scores. Categorical variables are presented as percentages, and continuous variables as median and interquartile range for non-Gaussian variables, as confirmed by the Shapiro-Wilk test for normality.

RESULTS

See article for details of this section.

Online and confirmed patients reported significantly higher COMPASS-31 scores, with the highest scores reported by online patients (43.6 [33.6–52.7] and 32.9 [21.7–46.8] vs 17.6 [11.7–27.9] online controls; P < .001) (Table 2, Figure 2). When compared with controls, online patients reported higher scores in all 6 autonomic domains, whereas confirmed patients reported higher scores in the orthostatic and vasomotor domains only (P < .001 for both) (Figure 3). Symptoms of sympathetic impairment were just as common as parasympathetic impairment (diarrhea vs constipation) in most domains, although it should be noted that the COMPASS-31 was not designed to make this distinction but rather to quantify the severity of autonomic impairment by subdomain.

Table 2.

Questionnaire results.

Online Patients (n = 138) Confirmed Patients (n = 24) Online Controls (n = 81) P Pairwise Comparison Summary
COMPASS-31
 Orthostatic intolerance 22.2 (13.3–26.7)* 17.8 (0–22.2)† 0 (0–13.3) < .001 OP&CP>OC
 Vasomotor 0 (0–3)* 0 (0–3)† 0 (0–0) < .001 OP&CP>OC
 Secretomotor 7.5 (3.8–9.4)* 7.5 (3.3–9.4) 3.8 (1.9–5.6) < .001 OP>OC
 Gastrointestinal 11.9 (8.6–14.0)* 8.6 (7.6–11.1) 8.6 (5.4–11.9) < .001 OP>OC
 Bladder 1.1 (0–2.2)* 0 (0–1.1) 0 (0–1.1) < .001 OP>OC
 Pupillomotor 2.7 (1.9–3.5)* 2.1 (1.4–3.2) 1.15 (0.7–1.9) < .001 OP>OC
 Total weighted score 43.6 (33.6–52.7)* 32.9 (21.7– 46.8)† 17.6 (11.7– 27.9) < .001 OP&CP>OC
Epworth sleepiness scale 16 (12–19)* 13 (8–16.5)† 6 (4–8) < .001 OP&CP>OC
Fatigue severity scale 30 (24–34)*§ 17 (13–28) 15 (13–18) < .001 OP>CP&OC
Morningness-eveningness questionnaire 44 (38–51)* 54 (43–62) 55 (46–62) < .001 OP>OC
Restless legs syndrome–single item (years) 29 26 25 .657 N/A
STOP-Bang 1 (1–2) 1 (0–1) 1 (0–2) < .001 N/A
Insomnia severity index 9 (7–12)*§ 5 (1–7) 4 (2–7) < .001 OP>CP&OC
RAND-36
 Physical functioning 65 (45–80)* 80 (58–95) 90 (80–95) < .001 OP<OC
 Role limitations due to physical health 25 (0–25)*§ 75 (25–100) 100 (75–100) < .001 OP<CP&OC
 Role limitations due to emotional problems 50 (0–100)* 100 (50–100) 100 (75–100) < .001 OP<OC
 Energy/fatigue 10 (5–20)* 50 (15–56) 55 (40–65) < .001 OP<OC
 Emotional well-being 60 (44–76)* 66 (60–80) 72 (60–80) < .001 OP<OC
 Social functioning 44 (25–63)* 75 (50–100) 75 (63–100) < .001 OP<OC
 Pain 68 (45–90)* 85 (68–90) 90 (68–90) < .001 OP<OC
 General health 35 (25–60)* 60 (38–79) 70 (60–80) < .001 OP<OC

Values are presented as the median (interquartile range) or percentage. Comparisons of results for questionnaires between groups using Kruskal-Wallis test. Post hoc pairwise comparisons were only performed with the Wilcoxon rank sum test for measures demonstrating significant groupwise differences with a Bonferroni-corrected threshold of α = 0.00086. *Significant difference between online patients and online controls. †Significant difference between confirmed patients and online controls. §Significant difference between online patients and confirmed patients. CP = confirmed patients, OC = on-line controls, OP = on-line patients, N/A = not applicable.

 

This entry was posted in Autonomic Dysfunction, Autonomic Nervous System, Autonomic Nervous System Testing, COMPASS-31, Idiopathic Hypersomnia. Bookmark the permalink.