The Utility of Autonomic Testing

Syncope, flushing, bladder and bowel dysfunction, dizziness, endocrine dysfunction, Parkinson-like symptoms, gastrointestinal tract distress, painful feet, orthostatic intolerance, extreme fatigue, tachycardia, cognitive dysfunction, anhidrosis, and hyperhidrosis — these are some of the symptoms and conditions that can benefit from autonomic testing.

Referrals for autonomic evaluation across Mayo Clinic's three sites are increasingly coming from outside the field of neurology as well as from within it. The growing number of referrals from disciplines such as cardiology, endocrinology, dermatology, gastroenterology, internal medicine, and urology may be a function of wider appreciation for the utility of autonomic testing for differential diagnosis and management.

Example of autonomic test result

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In the 27 years since he founded the autonomic testing laboratory at Mayo Clinic in Minnesota, neurologist Phillip A. Low, M.D. and his colleagues have established the norms and national standards for quantified evaluation of autonomic function. In the late 1990s, through the American Academy of Neurology, they generated the CPT codes for reimbursement. In conjunction with the thermoregulatory sweat test (TST), under the direction of fellow neurologist Robert D. Fealey, M.D. since 1980, a strong battery of autonomic tests has been available at Mayo Clinic in Minnesota for many years.

Routine reimbursable autonomic evaluation includes tests of sudomotor, cardiovagal, and adrenergic function. The tests are noninvasive. Because test results are quantifiable, responses from the three systems can be compared to determine selective and/or relative autonomic dysfunction. For example, a patient might have moderate involvement of the cardiovagal system and severe involvement of adrenergic function without impacting sudomotor function. Or both the cardiovagal and adrenergic systems may be normal in the face of isolated anhidrosis, suggesting the possibility of chronic idiopathic anhidrosis, 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 three systems can such diagnostically informative patterns emerge.

Autonomic testing helps to determine the 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 to differentiate progressive diseases and serve as a means of monitoring disease progression and response to treatment.

As an example, recent evidence from studies by Paola Sandroni, M.D., Ph.D., a neurologist specializing in autonomic dysfunction at Mayo Clinic in Minnesota, Dr. Low, and their colleagues demonstrates that combined and detailed autonomic tests of symptoms and severity can distinguish multiple system atrophy from Parkinson disease (PD) and from PD with autonomic failure. Although autonomic disturbance is common in PD, its severity is more variable in PD than in multiple system atrophy, which is characterized by generalized autonomic failure affecting blood pressure, thermoregulatory sweating, bladder and erectile function, as well as cerebellar, extrapyramidal and corticospinal function. Without autonomic testing, it can be difficult to distinguish the two diseases, a distinction that has major consequences for prognosis and management.

Routine Tests of Autonomic Function

Sudomotor Tests
The quantitative sudomotor axon reflex test (QSART) is used to evaluate postganglionic sudomotor function. The TST is used to evaluate both preganglionic and postganglionic function over the entire anterior body surface. When evaluated together in the same patient, TST and QSART can differentiate preganglionic from postganglionic lesions. For QSART, a stimulus solution of acetylcholine is applied using iontophoresis to evoke an axon reflex-mediated sweat response. Recording sites include the forearm, proximal leg, distal leg, and proximal foot. The TST utilizes 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 and not sweating.

The distribution of abnormal sweat responses is of diagnostic importance for a number of 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. As Dr. Sandroni notes, "This is a condition for which we get a lot of referrals. It is very difficult to diagnose it unless carefully controlled sudomotor testing is done."

Cardiovagal and Adrenergic Function Tests
The two 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 four maneuvers. The measure used for Valsalva ratio is beat-to-beat blood pressure. Once an invasive technique, measurement of beat-to-beat blood pressurecan now be done with a recording device placed on the patient's finger. Heart rate, systolic blood pressure and diastolic blood pressure are continuously displayed on a computer screen. The 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 PD and diabetes and is increasingly recognized as a common disorder among the elderly. Symptoms of OH such as fatigue and impaired concentration can be subtle and difficult to diagnose. Even when mild, symptoms of OH can be debilitating and markedly affect activities of daily living. Severe and 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 also determine severity of OH, 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 goes on to say, "Although we can't dissect all aspects of autonomic function, what we can do is detect deficits that may have gone undiagnosed, determine if the problems are benign or represent a true autonomic failure, and, if so, quantify its severity and distribution."