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Autonomic Function Testing

When President George W. Bush experienced an episode of syncope after choking on a piece of pretzel in January, the public's attention was directed toward the medical evaluation of episodic loss of consciousness. Various talking heads on the TV news programs offered the opinion that the President should undergo a thorough medical evaluation for syncope, and that evaluation should include a "tilt-table test." Many physicians have heard of this type of test, but few are aware that it is part of a larger battery of tests that can be done to evaluate the function of the autonomic nervous system (ANS).

The ANS is distributed throughout the body. It subserves the vegetative functions of the body, and it is under the control of the most primitive part of the brain. The most rostral part of the brain involved in integration and control of autonomic function is the hypothalamus. Descending neural input from centers in the hypothalamus travel through a variety of pathways in the brainstem and spinal cord. Descending sympathetic input travels through the intermediolateral cell column in the thoracic spinal cord, and parasympathetic outflow travels through cranial nerves and sacral nerve roots. Both sympathetic and parasympathetic efferent activity travels along unmyelinated axons in peripheral nerves. Virtually every organ in the body receives innervation through the ANS, and a balance of sympathetic and parasympathetic input is usually the rule. This balance is a part of the regulatory control of integrative and vegetative function of most organ systems. Diseases affecting any level of the neuraxis can have impact on the ANS and cause symptoms of autonomic dysfunction.

Symptoms of Failure

Failure or dysfunction of some portion of the ANS can thus affect various bodily functions, and a variety of symptoms may be attributable to autonomic dysfunction. Common symptoms of autonomic dysfunction are listed in the table. The autonomic symptoms recognized by clinicians most commonly are those which relate to failure of cardiovascular control. The heart and great vessels receive a significant amount of autonomic innervation, and the control of heart rate and blood pressure through the baroreflex arc constitute an important part of the regulation of the circulation. A number of disease processes can affect the cardiovascular portion of the ANS. Common disorders such as diabetes mellitus can have an early effect on the ANS through the evolution of peripheral neuropathy. Other peripheral neuropathies that have prominent autonomic dysfunction include autonomic neuropathy, uremic neuropathy, and other degenerative axonal neuropathies.

A variety of central nervous system diseases have autonomic dysfunction as the main or only feature of the disease. The symptoms can range from minimal to quite severe.

Benign diseases include the various fainting sydromes associated with vasovagal hyperreflexia. These range from common faints to micturition syncope. More severe disorders include multiple system atrophy (or Shy-Drager syndrome), pure autonomic failure, postural orthostatic tachycardia syndrome (POTS), and medication side-effects. Patients with other neurodegnerative diseases such as amyotrophic lateral sclerosis and multiple sclerosis have also been found to have some features of autonomic dysfunction.

Table 1
Common Symptoms of Autonomic Dysfunction
· Postural hypotension
· Syncope
· Decreased sweating/heat intolerance
· Hyperhidrosis - focal or diffuse
· Constipation/diarrhea
· Impotence
· Dry eyes/mouth
· Failure of accommodation

Assessment

Since many of the disorders of ANS function are manifested by effects on heart rate and blood pressure, several techniques have been devised for assessment of these functions. The variation of heart rate in response to regular deep breathing is familiar to clinicians as "sinus arrhthymia." The dynamic response of heart rate and blood pressure to forced exhalation against a closed glottis, the Valsalva maneuver, is also familiar to most clinicians. The autonomic assessment used most frequently in daily practice is the assessment of blood pressure and pulse rate in response to postural change, often described in a short-hand fashion as "orthostatics." All of these tests can be done at the bedside using equipment available in every hospital and physician's office. The heart rate can be assessed by recording the electrocardiogram, and blood pressure can be recorded with the use of a sphygmomanometer. Rough estimates of variations in the pulse rate and blood pressure can be made, but more detailed observations require the use of more elaborate equipment and procedures.

Autonomic function testing laboratories have evolved over the years from rather crude elaborations of the bedside testing described above. Equipment has been developed that allows for detailed and rather elaborate analysis techniques. As noted above, the testing modalities available most widely are those that record heart rate and blood pressure. Testing protocols which allow for evaluation of both the sympathetic and parasympathetic arms of baroreflexes have been devised, and many are now relatively standardized. The measurement of heart rate continues to be based on a rather straight-forward recording of the electrocardiogram. The instantaneous heart rate is measured from the interval between successive R-waves, or R-R interval. Blood pressure measurement, as performed by the familiar sphygmomanometer method is accurate and reproducible, but the cycle time required to make measurements does not allow one to assess dynamic changes. Instantaneous measurements of blood pressure have heretofore required the insertion of an arterial cannula. The difficulty and discomfort associated with insertion of an arterial line have limited the application of this type of measurement technique, but noninvasive techniques have been developed which make the more invasive approach unnecessary. Plethysmographic recording of arterial blood pressure pulse waves from a digit or from the radial pulse at the wrist can now be done quickly and easily, with minimal discomfort for the patient. This advance allows for instantaneous recording of blood pressure and pulse rate, and standardized tests of baroreflex function are now possible on a routine basis.

Tilt-Table Testing

Autonomic function testing has been offered as a testing option through the Department of Neurology EMG laboratory for the past year. Most patients are referred to the laboratory for a tilt-table test. The indication for such testing is usually episodic alteration of consciousness, most often associated with assumption of an upright position from a horizontal or seated position. As noted above, tilt-table testing is part of the evaluation of syncope. It is performed by having the test subject lie on a motor-driven tilt table. The heart rate and blood pressure are monitored for 5 to 15 minutes while the patient lies quietly. Once stable recordings are made, the head of the table is tilted up to 60o, and the heart rate and blood pressure are monitored for up to 40-45 minutes. A normal response is a brief, transient decrease in blood pressure accompanied by an increase in heart rate. There is a return to near-baseline rates and pressures, and this is maintained throughout the period of tilting.

Several abnormal patterns can be recognized. Patients who experience neurocardiogenic syncope will have normal initial responses, but develop bradycardia and progressive hypotension after 15-20 minutes of tilting. Patients with multiple system atrophy or pure autonomic failure exhibit no change in heart rate in response to tilting, but their blood pressure progressively declines throughout the period of tilting. In POTS, a pattern of marked increase in heart rate without an associated change in blood pressure is observed. The patients who have this entity may also exhibit posturally mediated syncope, and there is some overlap between POTS and the controversial disorders, chronic fatigue syndrome and fibromyalgia. In all of the disorders described here, postural light-headedness or syncope can occur.

Valsalva Maneuver

In addition to tilt-table testing, the baroreflex arc can be assessed by having the patient perform paced deep breathing and Valsalva maneuver while blood pressure and heart rate are recorded. When a normal individual takes regular, deep breaths at a rate of 5-6 breaths per minute, the heart rate and blood pressure are entrained in a sinusoidal fashion (Figure 1). The degree of heart rate variation is a mainly a measure of parasympathetic tone on the cardiac conduction system. The degree of heart rate variation is averaged over 5 breathing cycles and is compared with age-adjusted normal values.

The Valsalva maneuver is performed by having the patient forcibly exhale into a manometer. The object is to increase intrathoracic pressure, and it is standardized by asking the patient to achieve a pressure of 40 mm Hg. An artifactual increase in the exhaled pressure is avoided by introducing a small air leak in the manometer system. This prevents the patient from generating pressure from the buccal muscles and insures that the exhaled pressure comes from contraction of the expiratory muscles. The exhaled pressure is maintained for 15 seconds and

then is released rapidly. The normal response is a dynamic interaction between pulse rate and blood pressure. An example of a recording from a normal individual is shown in Figure 2. The normal response is a decrease in blood pressure during the forced exhalation, which is accompanied by a reflex increase in heart rate. After release of the pressure, there is first a rebound in the blood pressure followed by a reflex slowing of the heart rate. The ratio of the fastest heart rate during the Valsalva maneuver to the slowest heart rate after its release is calculated as a "Valsalva ratio." This value can also be compared with age-adjusted norms. The heart rate and blood pressure changes which occur during the Valsalva maneuver are largely under the control of the sympathetic nervous system.

This battery of tests can thus be used to dissect the baroreflex arc and assess the balance between the sympathetic and parasympathetic nervous system. The testing can be applied to many disorders which may have a component of sympathetic dysfunction. Testing is done typically with the patient in a fasting state or after only a light meal to minimize pooling of vascular volume in the splanchnic circulation. Since some medications can introduce artifactual changes in autonomic function, patients are asked to hold all medications on the day of testing, but this is done in consultation with the patient's physician. If it would be dangerous to withhold a specific medication, the testing is done with the use of that drug in mind. Testing typically requires 60 to 90 minutes.

Figure 1
Normal Recording

Figure 1: An example of a recording made in a normal subject in response to paced breathing at a rate of 6 breaths per minute. The top traces show the systolic and diastolic blood pressure wave forms of a plethysmographic recording made from the radial artery at the wrist. The bottom trace is the instantaneous heart rate displayed as the R-R interval in milliseconds. Paced breathing started at the first triangle on the horizontal axes, and it stopped at the second triangle. The normal response is a sinusoidal entrainment of the heart rate and blood pressure.

 

Figure 2
Normal Recording

Figure 2: A recording of the Valsalva maneuver in a normal subject. The display of blood pressure and pulse is the same as in Figure 1. The Valsalva maneuver begins at the first triangle on the horizontal axis, and it is rapidly released at the second. See the text for an explanation of the response.

Lawrence H. Phillips, II, M.D., lhp3n@virginia.edu

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