Help Available for Hard-to-diagnose Conditions 

This article originally appeared in Pathways, a magazine published for physicians and the community by UMass Memorial Medical Center.

When a patient presents with a history of fainting or any orthostatic symptoms, a diagnostic work up to rule out cardiac etiologies and seizure disorders is appropriate. If this process yields no definitive answer, dysfunction of the autonomic nervous system (ANS) may be the culprit. Now, thanks to an investment in state-of-the-art equipment, autonomic function testing (AFT) is available at UMass Memorial Medical Center. In fact, the Medical Center is home to one of only a handful of comprehensive AFT labs in the United States.

Autonomic function testing, under the direction of Peter Novak, MD, PhD, center, and Lan Qin, MD, PhD, right, includes the tilt-table test, which measures heart rate and beat-to-beat blood pressure.

"There are thousands of patients who suffer from conditions relating to autonomic dysfunction," explained Peter Novak, MD, PhD, a board-certified neurologist who heads the AFT Lab at UMass Memorial. "But they can be very hard to diagnose because disturbances in ANS function can produce a wide variety of symptoms. These include syncope, dizziness, chronic pain, bladder urgency or frequency, fatigue, nausea, palpitations, abnormal sweating, bloating or cramping after meals, constipation, or skin color changes.

"Many patients and their doctors are frustrated when these symptoms become disabling, and there are no definitive answers as to what is causing them," he continued. "With AFT, we can accurately and reliably establish whether dysfunction of the autonomic nervous system is the cause, providing answers so that appropriate treatment can be given."

"Syncope is a fairly common clinical symptom," noted Lan Qin, MD, PhD, a board-certified neurologist and fellowship-trained neurophysiologist at the Medical Center. "Abnormalities of the autonomic nervous system can be found in 75 percent of syncope patients who don't have heart diseases or seizure disorders. We would not be able to accurately diagnose this group of patients without AFT."

Specialized Testing Provides Objective Measurement

AFT entails several specialized tests to monitor blood pressure, blood flow, heart rate, skin temperature and sweating. By measuring these functions, it is possible to evaluate quantitatively the functioning of the autonomic nervous system and correlate signs and symptoms of possible autonomic dysfunction with this objective measurement in a way that is clinically useful. Tests include:

• The tilt-table test which measures heart rate and beat-to-beat blood pressure response to tilt-up for evaluation of orthostatic hypotension
• The heart rate response to deep breathing (HRDB) test, used to evaluate cardiovagal function
• The Valsalva maneuver, where a patient blows into a tube to increase pressure in the chest, used to measure heart rate and beat-to-beat blood pressure changes and to evaluate the cardiovagal and peripheral adrenergic function
•  Sudomotor testing, including the quantitative sudomotor axon reflex test, which measures skin vasomotor function by assessing the small autonomic nerve fibers which control the sweat glands, and the thermoregulatory sweat test, a test of sympathetic nerves that supply the skin, which evaluates and documents neuropathic disturbances that may be associated with pain.

The Value of Skin Biopsy Testing

In addition, the UMass Memorial Autonomic Function Testing Laboratory offers skin biopsy testing to detect small-fiber neuropathy. Dr. Qin explained why this testing is very important:

"Because one of my practice areas is neuromuscular diseases, I see a lot of patients with neuropathy," she said. "Conventional electromyography usually can detect large-fiber neuropathy, so an EMG study for patients with small-fiber neuropathy could be normal, especially in the early stages.

"It is important to detect small-fiber neuropathy early because studies show that it could be the first sign of diabetes," she continued. In fact, one study showed that in 40 percent of patients with small-fiber neuropathy diagnosed only after skin biopsy, oral glucose tolerance testing revealed a previously undetected impaired glucose tolerance.

"Early detection of small-fiber neuropathy leads to early screening for diabetes or glucose intolerance, and early lifestyle or pharmacological interventions," she added.

In addition, skin biopsy testing demonstrates small-fiber neuropathy in restless legs syndrome and erythromelalgia. Plus, in systemic diseases, such as lupus, sarcoidosis, Sjögren's syndrome, celiac disease and hypothyroidism, skin biopsy testing has enabled correlations between neuropathic symptoms and small-fiber degeneration.

Indications for AFT

When is a referral for AFT appropriate? "In general, when an autonomic abnormality is suspected, or if it is unclear whether a common condition, such as chronic fatigue or orthostatic symptoms, are neurological or not, laboratory evaluation of the autonomic nervous system is appropriate," Dr. Novak said.

For example, sexual dysfunction may be the manifestation of disorders affecting the ANS. AFT directly estimates the extent of involvement of the sympathetic and parasympathetic nervous systems - particularly important in evaluating patients with erectile dysfunction who may have both organic (such as those with diabetes) and psychogenic etiologies.

In addition, disorders of bowel motility, such as achalasia, intestinal pseudo-obstruction, chronic recurrent abdominal pain, and unexplained diarrhea or constipation, are increasingly linked to generalized autonomic abnormalities. Urinary frequency or retention may be an early symptom of ANS disease. Sweating abnormalities, such as hyperhidrosis or heat intolerance, are measured directly by AFT that includes quantitative sweat monitoring. And silent cardiac ischemia in diabetic patients may be due to autonomic impairment, but because moderate dysautonomia may produce few symptoms, it can remain undiagnosed without AFT.

Postural orthostatic tachycardia (POTS) syndrome, common in young women, occurs when unexplained tachycardia accompanies orthostatic symptoms. Correctly recognizing the problem can prevent unnecessary procedures such as radiofrequency ablation or pacemaker placement. What is more, chronic fatigue syndrome may result from chronic orthostatic hypotension. AFT can identify patients who will benefit from treatment of orthostasis, enabling many to resume a normal lifestyle.

The Ultimate Benefit

Providing timely, accurate diagnostic information to identify the most appropriate therapy is the ultimate benefit of AFT, Drs. Novak and Qin emphasized. "It's gratifying to be able to give patients and their physicians answers to previously unexplained problems so that they know what is going on and what to do about it," Dr. Novak said. AFT also can be used to monitor the response to therapy.

"AFT is noninvasive and painless, except for the skin biopsy, which is nothing more than a big scratch," he added. "Testing is done on an outpatient basis and takes only about 60 to 90 minutes, depending on the number of studies administered. And it is covered by insurance."