Autonomic Testing

SWEAT TESTING

The thermoregulatory sweat test consists of the visual detection of skin humidity in response to warm external temperature. A dye that changes color when moist is painted or sprinkled onto the patient’s skin, and the ambient temperature is raised by 1° C by a heat cradle over the torso. As the patient starts to sweat, the dye changes to a dark purple color. This test measures abnormalities in the sweat pathways at all levels (afferent, central, and efferent). The quantitative sudomotor axon reflex test (QSART) evaluates postganglionic sudomotor cholinergic fibers more objectively. It involves the iontophoresis of acetylcholine, resulting in an axon reflex: an impulse travels antidromically to reach a branch point and then orthodromically to the sweat gland, stimulating the release of acetylcholine from the nerve terminal to evoke the sweat response. A multicompartment sweat capsule is attached to the skin to measure the sweat response at standardized sites. Abnormality indicates that postganglionic sudomotor sympathetic axons are dysfunctional. QSART is usually normal in preganglionic lesions. The sympathetic skin response (a voltage change at the skin surface after an electrical stimulus) also reflects postganglionic sudomotor function, with results correlating with those of other sweat tests.

CARDIOVAGAL TESTING

Cardiovagal function is assessed by measuring the heart rate response to deep breathing, the Valsalva maneuver (VM), and standing. For the heart rate response to deep breathing, the patient inspires and expires deeply at six breaths per minute, and the difference between the maximum and minimum heart rate response is calculated. For VM, the subject makes a forced expiration to maintain a column of mercury at 30 to 40 mm for 15 seconds, and the ratio of the maximum heart rate during the maneuver to the lowest rate occurring within 30 seconds of its conclusion is determined. Concurrent measurement of beat-to-beat blood pressure (BP) enables quantification of baroflex sensitivity. There are four main phases to the response to the VM; during phase I, there is a transient rise in BP due to increased intrathoracic and intraabdominal pressure. In early phase II (II_e), the reduced venous return results in a fall in BP followed by a compensatory increase in heart rate and peripheral resistance, resulting in an increase in BP in the late phase II (II_L). During phase III, there is a transient decline in BP from a reduction in intrathoracic pressure, and in phase IV, the BP overshoots due to normalized venous return and cardiac output in the presence of persistently increased peripheral resistance. Late-phase II (II_L) is a function of alpha-adrenergic and phase IV of beta-adrenergic responses; they can be used to assess sympathetic adrenergic integrity. Abnormality may lead to an excessive decline in blood pressure in phase II, with no BP overshoot in phase IV.

On standing, the heart rate increases, peaking at about the 15th beat after standing, and then declines to reach a stable state at about the 30th beat. The ratio of the R-R interval at the 15th and 30th beats after standing provides a test of parasympathetic (vagal) function. It is age dependent, but in young adults, a ratio of less than 1.04 is abnormal. The biphasic response that occurs on standing is not present with passive tilt.

HEAD-UP TILTING

Patients with sympathetic dysfunction have a progressive decline in blood pressure during head-up tilt to 70 degrees. The heart rate response is also usually attenuated and does not compensate fully for the fall in blood pressure. If the patient is being evaluated for neurocardiogenic syncope or delayed orthostatic hypotension, prolonged tilting beyond 10 minutes, often for about 45 minutes, is needed.

ISOMETRIC HANDGRIP

During sustained handgrip, sympathetic outflow increases due to muscle contraction, increasing the BP. For testing purposes, a 30% maximal contraction for 3 to 5 minutes is required; diastolic BP usually increases by more than 15 mm Hg.

NEUROCHEMICAL TESTING

Measurement of supine and upright plasma norepinephrine levels provides a measure of postganglionic release of norepinephrine; levels usually double on standing. With preganglionic lesions, supine levels are normal, but there is a limited rise or no change in the standing level. In postganglionic lesions of the sympathetic system, both supine and standing values are low.

¹³¹I-labeled metaiodobenzylguanidine (MIBG) scintigraphy is useful in evaluating cardiac sympathetic innervation.

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