Definition and Overview
The autonomic function test battery is a diagnostic protocol that systematically evaluates sympathetic and parasympathetic function through multiple standardized tests [2]. Because the complex functions of the autonomic nervous system cannot be adequately assessed by a single test, complementary tests are combined for comprehensive evaluation.
The autonomic reflex screen (ARS) developed by Low et al. at Mayo Clinic is the most widely used standard protocol [1]. This protocol includes deep breathing test with heart rate variability, Valsalva maneuver test, tilt table test (or active standing test), and QSART.
Component Tests
Heart Rate Variability Tests (Parasympathetic Assessment)
The deep breathing test measures heart rate fluctuation (E:I ratio) during 6 deep breaths per minute. The difference between maximum and minimum heart rate during breathing is the normal response; a diminished difference suggests parasympathetic (vagal) dysfunction [4].
The Valsalva ratio is the maximum heart rate during the Valsalva maneuver divided by the minimum heart rate after the maneuver, serving as an indicator of parasympathetic function. Values below the age-adjusted lower limit of normal are considered abnormal [4].
The 30:15 ratio is the R-R interval ratio of the 15th and 30th heartbeats after standing. It evaluates the reflex response of heart rate increase (15th beat) followed by decrease (30th beat) immediately after standing, reflecting parasympathetic function.
Blood Pressure Response Tests (Sympathetic Adrenergic Assessment)
Blood pressure responses during the Valsalva maneuver assess sympathetic adrenergic function. Late phase II (IIb) blood pressure recovery and phase IV blood pressure overshoot are normal responses; loss of this pattern indicates sympathetic dysfunction [1].
The tilt table test or active standing test measures blood pressure changes over 3 minutes after standing. A drop in systolic blood pressure of 20 mmHg or more, or diastolic blood pressure of 10 mmHg or more, upon standing is diagnostic of orthostatic hypotension.
QSART (Sympathetic Cholinergic/Sudomotor Assessment)
The quantitative sudomotor axon reflex test (QSART) quantifies sweat output by stimulating eccrine sweat gland axon reflexes via acetylcholine iontophoresis [3]. Measurements are taken at four sites -- forearm (proximal), proximal leg, ankle, and dorsal foot -- to assess the distal-to-proximal functional distribution of sympathetic cholinergic fibers.
CASS (Composite Autonomic Scoring Scale)
The composite autonomic scoring scale (CASS) quantifies battery test results on a 0-to-10 scale, representing the severity of autonomic dysfunction as a single composite score [1].
CASS comprises three subscores: cardiovagal score (0-3 points) based on deep breathing test, Valsalva ratio, and 30:15 ratio; adrenergic score (0-4 points) based on orthostatic blood pressure response and Valsalva blood pressure response; and sudomotor score (0-3 points) based on QSART.
A CASS of 0 is normal, 1-3 indicates mild, 4-6 moderate, and 7-10 severe autonomic dysfunction [1]. CASS is valuable for longitudinal tracking of autonomic dysfunction and monitoring treatment response.
Pre-Test Preparation
Standardized preparation is required for accurate test results [2]. Caffeine beverages (coffee, tea, energy drinks) and alcohol should be avoided starting the day before testing. Fasting for at least 3 to 4 hours on the test day is recommended. Medications affecting the cardiovascular system (beta-blockers, alpha-blockers, anticholinergics, tricyclic antidepressants) should be discussed with the attending physician regarding temporary discontinuation. Smoking is prohibited on the test day. The patient should rest in the supine position for at least 30 minutes before testing.
Clinical Applications
Diabetic autonomic neuropathy: used for diagnosis and severity assessment of cardiac autonomic neuropathy, incorporating the 5 tests recommended by the ADA [4]. POTS and orthostatic hypotension: orthostatic blood pressure and heart rate responses enable accurate subtype classification and mechanism evaluation. MSA vs. Parkinson's disease differentiation: the pattern and extent of autonomic involvement aids in distinguishing these conditions. Small fiber neuropathy: QSART detects early damage [3]. It is also used for evaluating autoimmune autonomic ganglionopathy.