Autonomic testing has a key role in the evaluation of patients with diabetes mellitus who are troubled by orthostatic intolerance, syncope, flushing, bladder and bowel dysfunction, gastrointestinal tract distress, painful feet, anhidrosis, or hyperhidrosis. Signs and symptoms of cardiovascular autonomic neuropathy include:
Paola Sandroni, M.D., Ph.D., of the Department of Neurology at Mayo Clinic says: "Heart rate variation that normally occurs with deep breathing, a test specific for vagal function, and the Valsalva maneuver, which elicits activation of parasympathetic [vagal] and sympathetic cardiovascular responses, may be absent in patients with even early diabetic autonomic neuropathy.
"Advanced autonomic neuropathy in patients with diabetes may cause cardiac denervation and lead to fixed heart rate, painless myocardial infarction, and increased risk of death. Central and peripheral cardiovascular sympathetic denervation may result in postural hypotension due to the lack of vasoconstriction in peripheral and splanchnic vascular beds."
Peripheral autonomic neuropathy results from loss of sympathetic vascular innervation, leading to vasoconstriction failure, abnormal local reflex vascular control, and increased peripheral blood flow through arteriovenous shunts. Furthermore, sympathetic fibers innervating sweat glands are lost. Signs and symptoms of peripheral autonomic neuropathy include venous prominence, peripheral edema, dry skin, pruritus, and poor wound healing—all of which may lead to foot ulcers.
In the 29 years since neurologist Phillip A. Low, M.D., founded the autonomic testing laboratory at Mayo Clinic, he and his colleagues have established the norms and national standards for quantified evaluation of autonomic function. In conjunction with the thermoregulatory sweat test (TST) and under the direction of fellow neurologist Robert D. Fealey, M.D., since 1980, routine autonomic evaluation includes noninvasive tests of sudomotor, cardiovagal, and adrenergic function.
Because test results are quantifiable, responses from the 3 systems can be compared to determine selective or relative autonomic dysfunction, or both. For example:
This latter condition is a more benign disorder that does not progress to widespread autonomic failure and for which symptomatic and sometimes specific treatment is available. Only by testing all 3 systems can such diagnostically informative patterns emerge.
Dr. Low explains: "Autonomic testing helps determine presence, severity, distribution, and localization of autonomic dysfunction. It can distinguish primary from secondary autonomic disorders, true autonomic neuropathy from conditions that mimic it, and psychogenic from organic conditions. It can help differentiate progressive diseases and serve to monitor disease progression and response to treatment."
The quantitative sudomotor axon reflex test (QSART) evaluates postganglionic sudomotor function. TST evaluates preganglionic and postganglionic function over the anterior body surface. When assessed together in the same patient, TST and QSART can differentiate preganglionic from postganglionic lesions.
For QSART, a stimulus solution of acetylcholine is applied with iontophoresis to evoke an axon reflex-mediated sweat response. Recording sites include:
TST uses a dedicated heat- and humidity-controlled cabinet to produce a whole-body sweat response that can be quantitated as a percentage of body-surface sweating versus not sweating.
Distribution of abnormal sweat responses is diagnostically important for various conditions such as peripheral neuropathy. For example, small-fiber neuropathy with the symptom of burning feet can be associated with idiopathic disease and also with diabetes. In such cases, the most distal sites may have abnormal QSART and TST responses, with more proximal sites becoming involved as the disease progresses.
Using a 10-point composite autonomic severity score that they developed, Drs. Sandroni, Low, and Fealey found that sudomotor testing is highly sensitive in identifying clinical distal small-fiber neuropathy in patients who have normal or unrelated abnormalities on electromyographic testing.
Dr. Sandroni notes: "This is a condition for which we get a lot of referrals. It is very difficult to diagnose unless carefully controlled sudomotor testing is done."
Cardiovagal and adrenergic function tests
The 2 main tests of cardiovagal function in the autonomic test sequence are heart rate response to deep breathing and the Valsalva ratio, which involves several calculations and up to 4 maneuvers.
The Valsalva ratio measures beat-to-beat blood pressure. Once an invasive technique, its measurement can now be done with a recording device placed on the patient's finger. Heart rate, systolic blood pressure, and diastolic blood pressure are displayed continuously on a computer screen.
Valsalva maneuver is measured during 4 main physiologic phases. Drs. Low and Sandroni and their colleagues have validated the use of the phases in evaluating adrenergic function.
Beat-to-beat blood pressure under various laboratory conditions is a proven method of testing adrenergic function for many conditions, including orthostatic hypotension (OH).
OH is well recognized as a potential consequence of chronic diabetes and is recognized increasingly as a common disorder among elderly persons. Some OH symptoms (e.g., fatigue, impaired concentration) can be subtle and make OH difficult to diagnose.
Even when mild, OH symptoms can be debilitating and markedly affect activities of daily living. Severe, sustained OH can induce syncope with resultant falls and injury. In younger patients, symptoms may include palpitations, anxiety, and nausea and may be indicative of autonomic neuropathy.
Adrenergic testing helps distinguish OH syncope from psychogenic disorders and from other conditions that induce loss of consciousness, such as seizures and transient ischemic attacks. Autonomic tests can determine OH severity, an important factor when considering behavioral, pharmacologic, and nonpharmacologic treatments.
In discussing the value of Mayo's autonomic testing laboratory, Dr. Low notes that "it highlights the complexity of the autonomic system." He continues: "Although we can't dissect all aspects of autonomic function, what we can do is detect deficits that may have gone undiagnosed, determine whether problems are benign or represent true autonomic failure, and, if so, quantify its severity and distribution."