Patient-reported Autonomic Symptoms Do Not Correlate With Objective Dysfunction

Few centers in the U.S. can provide objective, quantitative testing for the assessment of dysautonomia. Patient-reported symptom questionnaires are often used as a surrogate, even when not validated for the suspected diagnosis.

Now, researchers have confirmed in a large cohort what previous research suggested: a lack of correlation between subjective dysautonomia and standardized objective testing. Peter Novak, MD, PhD, director of the Autonomic Laboratory at Brigham and Women’s Faulkner Hospital, William J. Mullally, MD, associate chief of Clinical Neurology at Brigham and Women’s Faulkner Hospital, and colleagues published the findings in Scientific Reports.


The retrospective study included 2,627 patients who underwent autonomic testing between 2017 and 2023 at Brigham. All completed the Survey of Autonomic Symptoms (SAS), a 12-item questionnaire (11 items for women). 564 patients also completed the Composite Autonomic Symptom Score–31 (COMPASS-31), which the clinic began using in 2022.

Autonomic test results were graded on the Composite Autonomic Severity Score (CASS) and the QASAT (quantitative scale for grading cardiovascular reflex results, sudomotor test results, and skin biopsies). QASAT allows a choice of sudomotor tests; this study used electrochemical skin conductance.


Correlations were strong between subjective instruments and objective instruments:

  • SAS vs. COMPASS-31: r, 0.74 (P<0.001)
  • CASS vs. QASAT: r, 0.81 (P<0.001)

However, the more critical relationships were absent: there was no correlation between SAS and QASAT or between COMPASS-31 and CASS.

The mismatch between subjective and objective results was apparent in all conditions the researchers selected for specific investigation: peripheral autonomic neuropathy (n=463), hypermobile Ehlers–Danlos syndrome (n=213), postural tachycardia syndrome (n=211), mast cell activation syndrome (n=172), post-treatment Lyme disease syndrome (n=163), preload failure (n=120), myalgic encephalomyelitis/chronic fatigue syndrome (n=95), neurogenic orthostatic hypotension (n=86), type 2 diabetes (n=71), post-acute sequelae of COVID-19 (n=61), and hereditary alpha tryptasemia (n=45).

Guidance for Physicians

SAS was designed to detect mild dysautonomia in patients with early diabetes, but in this study it strongly correlated with COMPASS-31 when applied to patients either with or without diabetes. Because SAS is simpler and shorter than the more general COMPASS-31, it should be considered a reliable alternative.

At this time, however, subjective questionnaires cannot be recommended as a replacement for autonomic testing. The lack of correlation here between subjective and objective instruments highlights that some patients overestimated their symptoms and some underestimated their deficits.

Patients who overestimate their symptom burden may represent a population with idiosyncratic dysautonomia, an intriguing issue for further study. Still, the workup should always explore factors potentially contributing to subjective dysautonomia. Examples are hypocapnic cerebral hypoperfusion and orthostatic cerebral hypoperfusion syndrome as well as comorbidities including depression, anxiety, stress, fatigue, central sensitization and mast cell disorders.

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