David S. Younger, MD
Noninvasive ART techniques are designed to detect and quantitate autonomic failure by evaluation of sudomotor, cardiovagal, and adrenergic autonomic function and the effectiveness of treatment thereof.
QUANTITATIVE SUDOMOTOR AXON REFLEX TEST (QSART) 
Postganglionic sympathetic sudomotor axons innervate sweat glands of the epidermis with the neurotransmitter acetylcholine (ACh). Testing of sweat gland function commences with the application of a 10% saline AChR solution applied iontophoretically to the skin. An electrical impulse is generated antidromically to a branching point along the postganglionic sympathetic sudomotor axon from which it travels orthodromically to the nearest sweat gland. The activated sweat gland releases sweat that is quantified by a sudorometer, the commercially available FDA-approved model which is known as a Q-Sweat apparatus.
Dorsum of the foot (sural nerve), distal leg (saphenous), proximal leg (peroneal), and medial forearm (ulnar)
Similar sweat volumes measured on all recording sites indicate normal responses. Men show greater sweating than women; however, both decline with age.
Reduced, excessive, or persistent sweating patterns
The silastic imprint technique records directly from the sweat gland bypassing the nerve by the application of 1% pilocarpine or acetylcholine so that there is no dependence on an axon reflex.
SYMPATHETIC SKIN RESPONSES (SSR)
The sympathetic skin response evaluates sudomotor function by measuring changes in skin resistance following stimuli delivered at random intervals and with increasing intensity.
SSR measurements are made along the palms and soles via surface electrodes.
Readily elicitable, amplitude in hands > foot
A difference of 50% or more from side to side, or absent response; both are considered abnormal.
THERMOREGULATORY SWEAT TEST (TST)
The thermoregulatory sweat test examines efferent sympathetic cholinergic pathways. Alizarin red, cornstarch, and sodium carbonate in a ratio of 50:100:50 grams respectively is dusted over the body to identify sweat production signaled by a change in color from white to red, while in a temperature- and humidity-controlled chamber used to control core body temperature. Areas of hypo- or anhidrosis, or hyperhidrosis, are documented by anatomical drawings or photography.
Homogeneous sweating
Distal, segmental, regional, focal, mixed, and global sweat loss patterns
The heart rate (HR) response to deep breathing (HRDB) is assessed by continuous ECG of a respiratory frequency of six cycles per minute.
- Age 20–39 (14–41 bpm), 40–59 (10–33 bpm), ≥60 (7–27 bpm)
- Acceleration of heart rate during inspiration and deceleration during expiration
Reduced HRDB is an early sign of autonomic dysfunction and potentially associated with increased cardiovascular risks.
This maneuver consists of forced expiration for 15 seconds against a fixed resistance, maintaining an expiratory pressure of 40 mm Hg. The calculated Valsalva ratio (VR) is a measure of peripheral adrenergic function, based upon conduction through the baroreflex arc along sympathetic adrenergic and parasympathetic cardiovagal pathways. Patients are instructed to forcefully blow into a mouthpiece attached to a manometer maintaining an expiratory pressure of 40 mm Hg for 15 seconds. Four phases of the VM response are recognized. Beat-to-beat continuous BP is obtained using a Finometer-based servoplethysmograph that generates reliable waveforms for digital data acquisition and computerized waveform display. Four hemodynamic phases are produced for analysis. Phase I coincides with mechanical compression of the aorta leading to a brief decrease in HR and increase in BP. The early phase II (IIE) response coincides with the progressive fall of BP, venous return, and cardiac output compensated by baroreflex-mediated tachycardia. The late phase II (IIL) response coincides with the restoration of BP to resting levels due to increasing peripheral resistance. Phase III coincides with a decrease in BP and increase in HR. The phase IV response coincides with a BP overshoot as venous return and cardiac output return toward normal in spite of increased peripheral vasoconstriction and baroreflex-mediated bradycardia. The VR is an index of tachycardia during phase II and bradycardia during phase IV.
- Adrenergic overactivity: Reduced pulse pressure, increased phase IV
- Adrenergic failure: Increased fall of BP, reduced or absent late phase II, reduced phase IV
- Cholinergic failure: Flat HR response
BP and HR are recorded continuously before, during, and after 5–10 minutes of 70 degrees automated tilting before returning to the supine position.
HR increment >10 and <30 bpm, stable BP, and cerebral blood flow
- Orthostatic intolerance (OI): HR increment >30 bpm and <120 bpm, pulse pressure reduced <50% of baseline
- Postural tachycardia syndrome (POTS): Heart rate >120 bpm, pulse pressure falls >50% of baseline, >10% reduction of cerebral blood flow
- Syncope: Rapid fall of BP with brady- or tachycardia and cerebral hypoperfusion
- Orthostatic hypotension: Sustained fall of BP >30/10 mm Hg for 3 minutes with or without OI
Power spectrum of R-R intervals, beat-to-beat variation, etc., are sensitive methods for evaluation of HR variability.
- Loss of consciousness, dizziness, lightheadedness, orthostatic and postprandial intolerance
- Painful small fiber neuropathies, diabetic neuropathy, sweating disturbance
- CNS neurodegenerative conditions including Parkinson disease, multiple system atrophy
Non-invasive and reproducible
Interpretation may be limited in older people with anticholinergic, sympatholytic, and sympathomimetic medications. Withdrawal of these medications for 24 hours may be indicated. HR variation is reduced by aging, tachycardia, hypocapnia, and anticholinergic medications.
HUT may induce orthostatic hypotension, syncope with tachy-, bradycardia, or rarely sinus arrest. Risks of stopping cardioactive medications such as beta-blockers.
Caution needed for tilt testing of older people with cardiac disease and pacemakers.
Preparation/Special Instructions for Patients
No caffeine or cigarettes for 8 hours and 1 hour after meal. No lotion. Patient should be well hydrated.
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