Name: Quantitativa test autonomici (Video) | JoVE Journal
Uploaded: 2011-07-19T15:00:00.000+00:00
Duration: 11 min 40 s
Description: Impara il test quantitativo delle funzioni autonomiche per valutare la disautonomia. Questo protocollo standardizzato analizza i domini cardiovagale, adrenergico e sudomotore usando punteggi compositi di gravità.

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Author thanks to Dr. Lan Qin and Shane Stanek for help with collection of data.

<ol><li>Low, P. A., Denq, J. C., Opfer-Gehrking, T. L., Dyck, P. J., O'Brien, P. C., Slezak, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effect+of+age+and+gender+on+sudomotor+and+cardiovagal+function+and+blood+pressure+response+to+tilt+in+normal+subjects%5BTitle%5D)+AND+%22Muscle+Nerve%22%5BJournal%5D)">Effect of age and gender on sudomotor and cardiovagal function and blood pressure response to tilt in normal subjects.</a> Muscle Nerve. 20, 1561-1568 (1997).</li>
<li>Low, P. A., Denq, J. C., Opfer-Gehrking, T. L., Dyck, P. J., O'Brien, P. C., Slezak, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effect+of+age+and+gender+on+sudomotor+and+cardiovagal+function+and+blood+pressure+response+to+tilt+in+normal+subjects%5BTitle%5D)+AND+%22Muscle+Nerve%22%5BJournal%5D)">Effect of age and gender on sudomotor and cardiovagal function and blood pressure response to tilt in normal subjects.</a> Muscle Nerve. 20, 1561-1568 (1997).</li>
<li>Low, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Composite+autonomic+scoring+scale+for+laboratory+quantification+of+generalized+autonomic+failure%5BTitle%5D)+AND+%22Mayo+Clin+Proc%22%5BJournal%5D)">Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure.</a> Mayo Clin Proc. 68, 748-752 (1993).</li>
<li>Low, P. A. Laboratory evaluation of autonomic function. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aLow%2C+PA+%22Clinical+Autonomic+disorders%22">Clinical Autonomic disorders</a>. Low, P. A. , Lippincott-Raven. Philadelphia. 179-209 (1997).</li>
<li>Low, P. A. Laboratory evaluation of autonomic failure. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aLow%2C+PA+%22Clinical+Autonomic+disorders%22">Clinical Autonomic disorders</a>. Low, P. A. , Lippincott-Raven. Philadelphia. 179-209 (2008).</li>
<li>Novak, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Assessment+of+sympathetic+index+from+Valsalva+maneuver%5BTitle%5D)+AND+%22Neurology%22%5BJournal%5D)">Assessment of sympathetic index from Valsalva maneuver.</a> Neurology. , Forthcoming (2011).</li>
</ol>

No conflicts of interest declared.

Pitfalls 
Completing the autonomic testing is in most of patients straightforward and can be done within 1 hours. Particular pitfalls of each step of testing is discussed below.
Equipment, data acquisition and processing of autonomic signals. 
There are number of pitfalls related primarily to data quality. Inadequate cleaning of skin can lead to excessive noise in ECG signal that can render detection of R wave difficult. Improper placement of the blood pressure sensor my give false high or low values. Transcranial Doppler signal of high quality can be difficult to get in elderly patients due small bone window. Software for data processing may not be robust enough to distinguish artifacts at the blood pressure, for example in Parkinson patients with tremor.
Deep breathing
<ol>
 <li>Anxiety and abnormal respiratory pattern can affect the results of deep breathing. Subject should be well relaxed during the testing. A good marker of anxiety is the heart rate profile. If subject is anxious, the heart rate can be elevated. Before starting deep breathing test, make sure that the heart rate is not trending up or down, if this happened wait until the mean heart rate remains flat.
 The resting respiratory pattern should be normal, e.g there should be no hyperventilation (as measured by end tidal CO2) or tachypnea (respiratory rate is above 11 per minute).</li> 
 <li>The deep breathing test has limited usefulness in certain cardiac dysrythmia for example in atrial fibrillation or when the heart rate is controlled by pacemaker because the vagal nerve modulation of the heart will be override by either the heart-generated rhythm or by a pacemaker. Basic knowledge of cardiac rhythm abnormalities is recommended.</li>
 <li>Improper detection of R waves due artifacts will obviously cause errors in results. This can happened if the R waves are too small to be reliably detected, or if the ECG background is noisy for example due poor skin contact.</li> 
</ol>
Valsalva maneuver
Valsalva maneuver requires considerable cooperation from the subjects Many elderly or frail patients cannot perform the Valsalva maneuver correctly. Most common reason is weakness of the mouth muscles that results in air leak during the respiratory strain. In this case it is effective to gentle seal the air leak around the tube with fingers6. 
Evaluation of adrenergic functions cannot be done in a square-wave variant of Valsalva maneuver (Figure 10). This response is rare but can be seen in healthy subjects or in patients with congestive heart failure.
Tilt testing
Number of medication can affect the tilt test rendering interpretation of the test difficult. It is not always practical to discontinue medication before testing.
It may be difficult to obtain good quality recordings in movement disorders patients, for example in Parkinson patients with tremor.
Sudomotor testing (QSART)
<ol>
 <li>Incomplete removal of oily surface or too much skin irritation can affect sweat output.</li>
 <li>Leaks if the capsule is not watertight or pain due too much tight capsule </li>
 <li>Commonly used medication has anticholinergic effect that interferes with the sweat test. In many cases, is in impractical to discontinue these medications rendering interpretation of results difficult.</li>
</ol>
Grading of autonomic impairment using the Composite Autonomic Severity Score (CASS).
Generation of CASS score is quite cumbersome because it involves multiple comparisons in both absolute and percent values. Unfortunately, there is no commercial software that enables to calculate the score automatically. At UMASS, we use proprietary software that generates the CASS score automatically. Example of CASS scores is on the Table 8.

<table><tbody><tr><td colspan="4">Table 9: Recommended equipment.</td></tr><tr><td>Motorized tilt table</td><td>WR Medical Electronics Co.</td><td></td><td>Any table with smooth movement reaching 70 degree within 5-10 seconds</td></tr><tr><td>ECG monitor</td><td></td><td></td><td>Any device with analog output</td></tr><tr><td>Noninvasive beat-to-beat blood pressure monitor</td><td>Finapres Medical Systems</td><td></td><td>Several models are available, all are similar</td></tr><tr><td>Q-Sweat</td><td>WR Medical Electronics Co.</td><td></td><td></td></tr><tr><td>Transcranial Doppler</td><td></td><td></td><td>Any device with analog output</td></tr><tr><td>&lt;a href="http://www.adinstruments.com/products/hardware/research/Data*Acquisition*Systems/" target="_blank"&gt;Recording system&lt;/a&gt;</td><td><a href="http://www.adinstruments.com/" target="_blank"><img src="/img/new_window.png"> ADInstruments</a></td><td></td><td>Simple programming</td></tr><tr><td>Recording system</td><td>Labview</td><td></td><td>Complex programming</td></tr><tr><td>Recording system</td><td>Matlab</td><td></td><td>Complex programming</td></tr><tr><td>Recording system</td><td>WR Medical Electronics Co.</td><td></td><td>Ready to use, but limited flexibility</td></tr><tr><td>CO2 monitor</td><td></td><td></td><td>Many models used for sleep studies</td></tr><tr><td>Respiratory monitor</td><td></td><td></td><td>Simple thermistor attached to a recording system</td></tr></tbody></table>

quantitative autonomic testing

Quantitative Autonomic Testing

Disorders associated with dysfunction of autonomic nervous system are quite common yet frequently unrecognized. Quantitative autonomic testing can be invaluable tool for evaluation of these disorders, both in clinic and research. There are number of autonomic tests, however, only few were validated clinically or are quantitative. Here, fully quantitative and clinically validated protocol for testing of autonomic functions is presented. As a bare minimum the clinical autonomic laboratory should have a tilt table, ECG monitor, continuous noninvasive blood pressure monitor, respiratory monitor and a mean for evaluation of sudomotor domain. The software for recording and evaluation of autonomic tests is critical for correct evaluation of data. The presented protocol evaluates 3 major autonomic domains: cardiovagal, adrenergic and sudomotor. The tests include deep breathing, Valsalva maneuver, head-up tilt, and quantitative sudomotor axon test (QSART). The severity and distribution of dysautonomia is quantitated using Composite Autonomic Severity Scores (CASS). Detailed protocol is provided highlighting essential aspects of testing with emphasis on proper data acquisition, obtaining the relevant parameters and unbiased evaluation of autonomic signals. The normative data and CASS algorithm for interpretation of results are provided as well.

Standardized, comprehensive and fully quantitative testing of autonomic functions is described. The autonomic tests consist of evaluation of all three major autonomic domains including cardiovagal, adrenergic and sudomotor. The severity and distribution of dysautonomia is quantitated using Composite Autonomic Severity Scores.

Disorders associated with dysfunction of autonomic nervous system are quite common yet frequently unrecognized. Quantitative autonomic testing can be ...

The overall goal of this procedure is to describe standardized quantitative testing of autonomic functions. The presented protocol evaluates all three major autonomic domains, cardio vagal adrenergic, and pseudo-motor. Finally, the severity and distribution of dysautonomia is quantitated using composite autonomic severity scores.Several assessments are used to accomplish this. The first assessment, the deep breathing test checks cardio vagal function or parasympathetic function. The second assessment, the Valsalva maneuver checks both cardio vagal and adrenergic function.The third assessment, the tilt test checks primarily adrenergic function. The final assessment, the sweat response test checks post ganglionic sympathetic pseudo-motor function. Ultimately, these assessments can demonstrate not only the presence or absence of autonomic failure, but also the severity and distribution of autonomic failure.This test method can help answer the key questions such as, does the patient suffer for this autonoma? Does the patient have autonomic neuropathy? These methods also help address whether the DYS autonoma is clinically relevant.Help determine the distribution and severity of autonomic failure and help determine how to treat the failure. Demonstrating the procedure will be changed Static A technician from my laboratory For the deep breathing test have the patient lie down. Then attach the ECG electrodes.Next, attach the respiratory probe and the blood pressure probe. Blood pressure monitoring is not necessary for deep breathing, but it is customary to attach the blood pressure probe now as it can take some time for the blood pressure to settle. Next, instruct the subject to relax and obtain one minute of baseline breathing.Make sure that the R wave on the ECG is well differentiated. Begin the deep breathing test by instructing the subject to perform six deep breaths through the nostrils. With the mouth closed, the six deep breaths should be continuous.With each inhalation lasting five seconds and each exhalation lasting five seconds, monitor the end tidal carbon dioxide to rule out hyperventilation. After completing the deep breathing test, calculate the respiratory sinus arrhythmia. The amplitude of the respiratory sinus arrhythmia is defined as the difference in heart rate between the end of expiration and the end of inspiration.The typical approach is to average the respiratory sinus arrhythmia amplitudes over six respiratory cycles. In this example, the average respiratory sinus arrhythmia is 21.9 beats per minute. This next figure shows a normal response to a deep breathing test.The depressed respiratory sinus arrhythmia shown in this next figure indicates a moderate abnormality of the cardiova functions. This figure shows essentially a fixed heart rate during the deep breathing. This is consistent with severe cardiova failure.The next test to be demonstrated is the Valsalva maneuver. Use a five to 10 milliliter plastic syringe for the mouthpiece and attach it to the pressure gauge. There should be a small air leak in the tubing to prevent closure of the glottis.Let the subject practice several Valsalva maneuvers to become comfortable with the procedure. This allows the subject to learn how much pressure to use and how to create a proper seal with the lips. Wait approximately one minute to allow the subject to relax.Then instruct the subject to take a deep breath and blow into the syringe for 15 seconds, tell the subject to watch the expiratory pressure and to adjust the strains so as to keep the expiratory pressure at 40 millimeters of mercury. As the subject is blowing into the syringe, give the subject feedback about how many seconds are left. Allow the subject to rest for three minutes following the Valsalva maneuver.Then repeat the Valsalva maneuver two more times. If the Valsalva maneuver shows a square wave response and no heart failure is suspected, turn the table up 30 degrees. This changes the Valsalva maneuver to the more common four-phase pattern.To evaluate the Valsalva maneuver, select the recording that has the most differentiated phases with the least movement artifact. The Valsalva maneuver yields two measurements, the Valsalva ratio based on heart rate changes and the Valsalva response based on blood pressure changes. The Valsalva ratio is defined as the maximum heart rate during the Valsalva maneuver, which is 121.2 beats per minute.In this figure divided by the lowest heart rate obtained within 30 seconds of the peak heart rate, which is 78.2 beats per minute in this figure for this example, the Valsalva ratio is 1.55. This figure shows typical blood pressure responses to the Valsalva maneuver. In a healthy subject, the mean blood pressure is calculated from the systolic and diastolic blood pressure.The Valsalva response is divided into four phases. The next few figures show how to measure changes in blood pressure during phase two and phase four. The baseline blood pressure is the blood pressure just before the Valsalva maneuver is commenced.The blood pressure at the end of phase two and the overshoot during phase four are important markers for sympathetic adrenergic dysfunction. Subtract the diastolic pressure from the systolic pressure to get the pulse pressure. The minimum pulse pressure is obtained during the phase two.The pressure recovery time is calculated from the systolic blood pressure. This figure shows a normal Valsalva response. The blood pressure in both late phase two and phase four exceed the baseline blood pressure of 96.8 millimeters of mercury.This figure shows a moderately abnormal Valsalva maneuver. The mean blood pressure at the end of phase two is significantly below baseline. Phase four, however, is normal.This figure shows a severely abnormal Valsalva maneuver. The mean blood pressure at the end of phase two is still below baseline and the phase four overshoot is missing. Note also the supine hypertension that typically accompanies severe generalized autonomic failure.Prior to performing the tilt test, record the blood pressure from the brachial artery with the subject in the supine position. In addition, record the blood pressure using op press. Ensure that the blood pressure has a well-defined dichotic notch and there is no drift of the baseline.Next, acquire five to 10 minutes of baseline blood pressure. Begin the tilt test by tilting the patient up to a 70 degree angle. The transition should be smooth and should take five to 10 seconds.Obtain the blood pressure from the brachial artery every minute for 10 minutes. Observe the subject for the presence of any discomfort, chest pain, shortness of breath, dizziness, lightheadedness, or syncope. Be prepared to terminate the tilt if any serious event occurs during the tilt.After 10 minutes, tilt the patient back to a supine position. Measure the blood pressure within one minute. Again, the normal response of the heart rate to a tilt is an increase of 10 to 30 beats per minute with the maximal heart rate less than 120 beats per minute.The normal response of the blood pressure to a tilt is a drop of less than 20 millimeters of mercury of the systolic blood pressure or a drop of less than 10 millimeters of mercury of the diastolic blood pressure. This figure shows severe progressive orthostatic hypotension during the tilt test. To prepare for the pseudo-motor testing, follow the manufacturer's directions to assemble the four capsules, which will be used for stimulation and recording.Use alcohol to vigorously clean the four recording sites on the subject's skin. One recording site is on the medial forearm. 75%of the distance from the ulnar epicondyle to the PIM bone.Use an elastic binder to secure the capsules in place. The capsules should be watertight but should not cause substantial discomfort. The next recording site is on the proximal leg, five centimeters distal to the fibular head laterally.The third recording site is on the distal leg, five centimeters proximal to the medial maus medially. The final recording site is on the proximal foot over the extensor digitorum muscle. Next, place a ground for stimulation about five centimeters next to each capsule and attach the stimulators.Then fill the capsules with 10%acetylcholine diluted in sterile water. Note that water not saline is used. Start the sweat recording and verify on the Q sweat machine that no leak is present.A leak is easily detected by a large increase in baseline. Sweat recording in the case of a leak. Fix the capsule placement.Wait until the baseline sweat is flat below 100 nanoliters per minute, and all channels give similar baseline sweat output. The difference between the channels should be less than 15%Once the baseline sweat is stable, set the current to two milliamps on all four stimulators and begin stimulation. Turn on the marker on the Q sweat machine.The subject will feel a mild tingling during the stimulation. Continue the stimulation for five minutes, then switch off the stimulation. The stimulation stops automatically after five minutes.Continue recording the sweat for another five minutes. After the end of stimulation, obtain the latency and volume of the sweat response for each recording site as shown here. This figure shows a normal sweat response.This figure shows a moderately abnormal sweat response. This figure shows a severely abnormal sweat response. Grading of autonomic impairment in each domain is done.Using the composite autonomic severity score. Refer to included tables for details of grading. The results of this test, can IV diagnosis, for example, confirming diagnosis of autonomic neuropathy or diagnosis of autonomic failure in Parkinson disease.The results of the testing can point to a specific deficit in a particular domain, and as such can have direct implications for the therapy. For example, whether it is justified to suppressor medication if orthostatic hypotension is being detected. Another important aspect of the testing is the ability to detect autonomic failure due to the side effect of commonly used medication.

Research

JoVE Journal

Medicine

We describe a "gold standard" for evaluating orthostatic tolerance (OT) using tilt testing with combined lower body negative pressure (LBNP). This can be combined with non-invasive evaluations of cardiovascular reflex control. Normal and abnormal responses are defined.

Tilt Testing with Combined Lower Body Negative Pressure: a "Gold Standard" for Measuring Orthostatic Tolerance

Measurement of autonomic nervous system activity usually confines the researcher and participant to the laboratory, which may provide an intimidating environment to children. The VU University Ambulatory Monitoring System (VU-AMS) device can record cardiac autonomic control in any setting. The VU-AMS proved very amenable to testing in children.

Measuring Cardiac Autonomic Nervous System (ANS) Activity in Children

The catheter of a telemetry device is implanted into the abdominal aorta in order to continuously collect beat-by-beat hemodynamic data from animals pre and post-high thoracic spinal cord transection. A novel JAVA software was employed to analyze hemodynamic parameters as well as frequency and intensity of spontaneous episodes of autonomic dysreflexia.

Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device

We describe the methods for continuous monitoring of the autonomic nervous system under resting and challenge conditions with 18 month old children. Results revealed that this protocol can produce meaningful physiological responses in both branches of the autonomic nervous system and elicit significant individual variability in patterns of responses.

Measuring Cardiac Autonomic Nervous System (ANS) Activity in Toddlers - Resting and Developmental Challenges

The goal of this procedure is to demonstrate a battery of quantitative techniques for sensory and pain measurement in humans. The equipment and techniques described are commonly found in pain clinics or are easy to obtain.

A Protocol of Manual Tests to Measure Sensation and Pain in Humans

By assessing pain in response to repetitive or different types of standardized stimuli, dynamic quantitative sensory testing (QST) can reveal changes in the central processing of pain. We present methods to optimize and individualize two dynamic QST measures: temporal summation (TS) and conditioned pain modulation (CPM).

Dynamic Quantitative Sensory Testing to Characterize Central Pain Processing

A validated computerized battery of neuropsychological and neurophysiological tests is used to study pharmacodynamic effects on the central nervous system of newly developed drugs in early phase development. To demonstrate the test battery, the acute effects of mecamylamine and the reversal of these effects by two agonist drugs are described.

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development

Persistent postsurgical pain may be related to changes in pain processing. By assessing pain in response to standardized stimuli, changes in pain processing can be elucidated. We present methods to obtain pain thresholds to different stimuli and a measure of endogenous analgesia in patients undergoing breast cancer surgery.

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

The ValsalvaAnalyzer software includes functions to analyze continuous beat-to-beat electrocardiogram and blood pressure (BP) measurements recorded during the Valsalva maneuver (VM). The computed clinical biomarkers and estimated model outputs provide insight into sympathetic and parasympathetic regulation of heart rate and BP during the VM.

Software for Analysis of Heart Rate and Blood Pressure Time-series Data from the Valsalva Maneuver

This protocol aims to provide a standardized and reproducible head-up tilt test to evaluate cardiovascular autonomic dysfunction, particularly orthostatic hypotension, in patients with neurodegenerative diseases, ensuring reliable assessment under controlled testing conditions and with continuous blood pressure monitoring.

A Standardized Head-Up Tilt Test Protocol to Assess Cardiovascular Autonomic Dysfunction in Neurodegenerative Diseases

Impara il test quantitativo delle funzioni autonomiche per valutare la disautonomia. Questo protocollo standardizzato analizza i domini cardiovagale, adrenergico e sudomotore usando punteggi compositi di gravità.

Quantitative Autonomic Testing

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