Autonomic dysfunction can occur as a result of many diseases that affect autonomic pathways. The clinician’s role is to seek out symptoms of dysautonomia Necessary to determine if these symptoms are really due to involvement of autonomic systems. ee etl eee caeIntroduction The oonceptnek famtegene begat igth century . These original tests were developed over time . Widely used in clinical practice for 50 years Decades of extensive experience and thousands of studies published on its use.1. To evaluate the severity and distribution of autonomic function 2. To diagnose limited autonomic neuropathy 3. To diagnose and evaluate orthostatic intolerance 4. To monitor the course of dysautonomia 5. To monitor response to treatment 6. As an instrument in research studies1, Cardiovagal innervation (parasympathetic innervation): heart rate (HR) response to deep breathing, Valsalva ratio, and HR response to standing (30:15 ratio) 2. Adrenergic: beat-to-beat blood pressure (BP) responses to the Valsalva maneuver, sustained hand grip, and BP and HR responses to tilt-up or active standing 3. Sudomotor: quantitative sudomotor axon reflex test (QSART), thermoregulatory sweat test (TST), sympathetic skin response (SSR).Beat to beat heart rate analysis Heart rate documented on ECG or on EMG equipment For ECG in EMG Low filter 1-5 Hz; High filter 500Hz Slow oscilloscope sweep time(o.2-1 secs) Sensitivity- 0.5 mv Active electrode midline posteriorly between inferior angle of scapula; reference mid axillary line~ Heart rate is inversely related to RR interval ~ Heart rate(R-R/min)= sweep speed(mm/s)+RR interval x60 _ BP sphygmomanometer Beat to beat BP measurement formerly required invasive intra arterial measurement; but plethysmographyThe variation of heart rate with respiration is known as sinus arrhythmia Inspiration > increases the heart rate Expiration > decreases the heart rate This is also called Respiratory Sinus Arrhythmia (RSA) This is an index of vagal control of heart rateSTEDLeIWaUuUOn ae pTDRN Te]ba ay ‘ A e Due to changes in vagal control of heart rate during respiration Probably due to following mechanisms Influence of respiratory centre on the vagal control of heart rate Influence of pulmonary stretch receptors on the vagal control of heart rateConnect the ECG electrodes for recording lead II Ask the subject to breath deeply at a rate of six breaths per minute for 3 cycles (allowing 5 seconds each for inspiration and expiration)Deep breathing Time [sec]iatereeIUUt Record maximum ante minimum cheat rate with each respiratory cycle Average the 3 differences Normal > 15 beats/min Borderline = 11-14 beats/min Abnormal <10 beats/minProcedure 5 Ce a i od Determine the expiration to inspiration ratio (E:I ratio) Mean of the maximum R-R intervals during deep expiration to the mean of minimum R-R intervals during deep inspirationsits = bi longest RR interval (expiration)An immediate response with an abrupt fall in systolic and diastolic blood pressure and a visible acceleration of heart rate (first 30 s), a phase of early stabilization, which occurs after approximately 1-2 min, a response to prolonged orthostasis lasting for more than 5 min. during the phase of stabilization , acceleration of heart rate by about 10-15 beats per minute and a slight decrease in systolic blood pressure, while diastolic pressure increases by approximately 10 mmHglecoceEvaluation of changes in heart rate (30/15 ratio) is performed during the initial phase of adaptation to orthostasis . On standing the heart rate increases until it reaches a maximum at about 15" beat (shortest R-R interval after standing) after which it slows down toa stable state at about 30!" beat (longest R-R interval after standing)Heart rate response to standing from supine postureSion i) Lae) The ratio of R-R cara corresponding to the 30" and 15" heart beat > 30:15 ratio RR interval at 30" beat 3Zo0u5ratio= = ------------------------------ RR interval at 15'" beat This ratio is a measure of parasympathetic response30:15 ratio — RR interval at 30" beat 30:15 ratio = a eee eee cae RR interval at 15‘* beat Normal > 1.04 Borderline =1.01-1.04 Abnormal =<1.00i Fluctuations of blood pressure are assessed based on somewhat later responses to standing (first 4 min) they are expressed as the difference between the baseline supine and the minimal blood pressure after standing up. A decline in systolic blood pressure by more than 20 mmHg and by more than 10 mmHg for diastolic blood pressure is considered abnormal- OH- fall of 20 mm Hg systolic or 10 mm Hg diastolic BP on standing- AAS ;AAN 1996 ~ 30mmHg systolic; 20 mmHg diastolic BP- McLeod and Tuck, 1987 ~ Diagnostic criteria of POTS include a) a sustained increase in heart rate (HR) of 30 beats per minute (bpm) or greater during 10 minutes of assuming an upright position, __b) noassociated hypotension, and - c) symptoms of orthostatic intolerance, which must be present for at least three months. In severe forms of the disease, HR may increase to more than 120 bpm on standing.Assesses integrity of the baroreceptor reflex Measure of parasympathetic and sympathetic function It is “forced expiration against a closed glottis”/alsalva ManoeuvrePerform the Valsalva manoeuvre (forced expiration against a closed glottis) by asking the subject to breathe forcefully into a mercury manometer and maintain a pressure of 40 mmHg for 15 seconds Record the ECG throughout and for 30 seconds after the procedureValsalva Manoeuvre 4 phases Phase I Phase II Phase III Phase IVFour Phases‘i ‘i Phase | - Onset of straining Time (sec) 3s 3 & —& = ! i. =z g = : £ ‘. i Time (sec)Phase II - Phase of straining Blood Pressure (mmHg) phos cee Time (sec) Time (sec)Mechanism ~ Early part * venous return decreases with compression of veins by increased intrathoracic pressure> central venous pressure decreases > BP decreases ~ Latter part » drop in BP in early part will stimulate baroreceptor reflex > increased sympathetic activity > increased peripheral resistance > increased BP ( returns to normal ) » Heart rate increase steadily throughout this phase due to vagal withdrawal in early part & sympathetic activation in latter partPhase III - Release of straining ? a 2 3 E Time (sec) Time (sec)Mechanical displacement of blood into pulmonary vascular bed, which was under increased intrathoracic pressure > BP decreasesPhase IV — further release of strain . * Time (soc) 2 = = g 3 a =. 2. 2 @ if =. 5 = Time (sec)Mechanism — Due to increase in venous return, stroke volume and cardiac outputPhaseI Increase in BP Phase II Decrease in BP, Tachycardia Phase III Decrease in BP Phase IV Overshoot of BP, BradycardiaMeasure of the change of heart rate that takes place during a brief period of forced expiration against a closed glottis Ratio of longest R-R interval during phase IV (within 20 beats of ending maneuver) to the shortest R-R interval during phase II Average the ratio from 3 attemptsValsalva Ratio Longest RR Valsalva Ratio = ee ae ee Shortest RR Values :> 1.4 » morethani.21 > normal ~ lessthan1.20 abnormalCe Valsalva maneuver evaluates 1. sympathetic adrenergic functions using the blood pressure responses 2. cardiovagal (parasympathetic) functions using the heart rate responses4. Cold pressor test Submerge the hand in ice cold water(1 minute) diastolic pressure by >15 mmHg HR>10/min 5. Isometric handgrip test isometric pressing of a handgrip dynamometer at approximately one third of the maximum contraction strength for 3-5 min. Blood pressure measurements are taken at the other arm at 1 min interval Rise of DBP>15/min ee eaSai lereel) reneTable 2: Tilt-table testing for evaluation of syncop: Indications. Tit-table testing Is warranted Recurrent syncope or single syncopal episode in a high-risk patient Whetner or not the medical history Is suggestive of neurally mediated (vasovagal) origin, and (1) no evidence of structural cardiovascular disease or (2) suuctural cardiovascular disease Is present. but other Eauses of syncope have been excluded by appropriate testing, Further evaluation of patients in wnom an apparent cause has been established (0.g., asystole. atrioventricular block). but In whom demonstration of susceptibility to neurally mediated syncope would Sffect treatment plans Part of the evaluation of exercise-induced oF exercise-associated syncope Reasonable differences of opinion exist regarding the utility of tit-table testing Differentiating convulsive syncope from seizures Evaluating patients (especially the elderly) with recurrent unexplained falls Assessing recurrent dizziness or presyncope Evaluating unexplained syncope in the setting of peripheral neuropathies or dysautonomias Follow-up evaluation to assess therapy of neurally mediated syncope Tut-tabie testing not warranted Single syncopal episode, without Injury and net In high-risk setuing with clear-cut vasovagal clinical features Syncope in which an alternative specific cause has been established na in which additional demonstration of neurally mediated Susceptibility would not alter treatment plans Potential emerging indications Recurrent idiopathic vertigo Recurrent transient Ischemic attacks Chronic fatigue syndrome Sudden infant death syndrome (SIDS)Contraind Sees aay Tey + Patient refusal + Morbid obesity (technicians cannot tilt safely) + Unable to stand for long periods due to pain + Pregnancy + Recent (within 6 months) myocardial infarction or stroke/TIA « A known tight stenosis anywhere (eg heart valve, LV outflow obstruction, coronary or carotid/cerebrovascular artery)Fast 2 or more hrs Rest supine 20-45 minutes Stop drugs affecting cvs or autonomic function; minimum of 5 half life pretest Minimize lower limb movements Get the baseline blood pressure from the brachial artery. Acquire the 5-10 minutes baseline Tilt angle and durationTilt patient up. The tilt should be done at 70 degree. The transition from supine to tilt position should smooth and of duration 5-10 seconds. Obtain the blood pressure from a brachial artery every minute. Observe subject for the presence of any discomfort, chest pain, shortness of breath, dizziness, lightheadedness, syncope Be prepared to terminate the tilt of any serious event occurs during the tilt based on clinical judgment. The tilt can be continued if no obvious abnormalities are detected but a clinical history is strongly suggestive of dysautonomia or blood pressure instability. Tilt the patient back.- The normal responses in heart rate during the tilt is heart rate increment within 10 - 15 beats per minute. _ At the same time the maximal heart rate should be less than 120 beats per minute. » Normal responses in the blood pressure during the tilt modest rise of diastolic blood pressure ; slight fall of <10 mm Hg in SBP.PHYSIOLOGICAL BASIS OF HUT about 300 to 800 mL of blood is forced downward to the abdominal area and lower extremitiesSy ac penne fg) Ha te Dita od presure nen Ha sszesseeg Twain Time i Ig. 1: Responses to heac-upright tilt-table testing. A: Normal response Is characterized by absence of significant decrease in blood pressure (more than 20 mm Hg systolic or 10 mm Hg diastolic), absence of significant and sustained increase in heart rate [more than 30 beats/min) and absence of orthostatle symptoms. B: Postural orthostatic tachycardia syndrome (POTS) Is charac Jerized by significant and sustained increase in heart rate. C: Neurocardiogentc syncope Is characterized by significant and sud- Hon docroase in blood pressure, frequently associated with suddon bradycardia. D: Dysautonomic response Is characterized by Jmmodiato, progressive and significant decroaso in blood pressure, froquently without appropriate incroase in heart rato.From studies HUT testing (2 occasions), with a known time interval,an average reproducibility of 81% However, as Behzad and collaborators and other authors highlighted, negative results are much more reproducible than positive ones (about 95% and 50% respectively). depends strongly on population selection as it is increased in patients with severe and frequent orthostatic symptoms.~ Studies assessing the ability of the HUT test to diagnose neurocardiogenic syncope averaged a sensitivity of 35% without pharmacologic stimulation ~ 57% with pharmacologic stimulation ~ Studies using HUT testing within the boundaries set by the American College of Cardiology guidelines averaged a sensitivity of 65%- The specificity of the HUT test for neurocardiogenic syncope 92% on average without pharmacologic stimulation ~ 81% with pharmacologic stimulation - Two investigator-HUT test-American College of Cardiology guidelines-both yielded a specificity of 100%.Table 1 Classification of vasovagal syncope induced by head-up tilt table testing Type Classification®* Type 1 Mixed Ventricular rate during syncope 240 bpm or falls to <40 bpm for <10 stasystole for <3 s. BP falls prior to heart rate. Type 2A Ventricular rate during syncope Cardioinhibitory <40 bpm for > 10 sec or asystole for >3s. BP falls prior to heart rate. Type 2B Ventricular rate at syncope Cardioinhibitory <40 bpm for > 105s or asystole for >3 s. BP falls to <80 mmHg systolic at or after rapid fall in heart rate (as above). Type 3 Heart rate does not fall more Pure vasodepressor than 10% from its peak at syncope. Fall in BP precipitates syncope.- Thermoregulatory sweat testing (TST) is used » evaluate the integrity of central and _ peripheral sympathetic sudomotor pathways from the CNS to the cutaneous sweat glands » The temperature is adjusted to 45-50 °C with a relative humidity of 35-40%.Camera Infrared heaters Thermometer \ \ Temperature probes, A TST chamber is temperature and humidity controlled. Ceiling mounted infrared heaters control the patient's temperature. The patient is placed in the supine position. Oral and cutaneous temperature probes are attached. During the application of the indicator dye. the patient's eyes, nose and mouth should be protected. To achieve even distribution of the indicator powder. an atomizer should be used. The test is started by increasing the room temperature. Oral temperature must rise at least 1.0°C above baseline temperature or to 38 °C (whichever is higher). At the end of the test pictures are taken and used to generate a topographical map of the sweat pattern,~ Sweat produces a change in local pH resulting in the indicator dye changing color » marking the location of sweat production (sweat has a PH of 4.5-5.5 at low sweat rates of 15-100nL/gland per hour). - Two common indicators include alizarin red powder (alizarin red, corn starch, sodium carbonate, 1:2:1) and iodine corn starch.~ Maximal sweating is achieved within 30-65 minutes. » Heating time should not exceed 70 minutes to avoid hyperthermia » Sweating causes the indicator to change its color (from yellow to dark red for alizarin red and from brown to purple with iodine). - Digital photographs are taken and a sweat density map is generated on standard anatomical drawings ~ Data are expressed as TST% which is the measured area of anhidrosis divided by the area of the anatomic figure, multiplied by 100~ Normal sweating patterns are generally symmetric but vary in quantity . Asymmetric sweat patterns and anhidrotic areas (focal, segmental, regional, length dependent) are noted. » The TST% can provide a general index of severity of the autonomic failureNormal sweat pattems show a sweat response present over the entire body that may be variable in intensity (A). In (B), a length dependent neuropathy from diabetes with stocking and glove distribution loss is seen. A patient with a complete myelopathy at T9 is shown in (C). Lesions to individual nerves can show focal or dermatomal sweat defects. A patient with a right T10 radiculopathy and a left lateral femoral cutaneous neuropathy can be identified in (D). A patient with complete anhidrosis secondary to pure autonomic failure is- Limitations ~ TST can localize specific areas of sudomotor dysfunction but can not differentiate preganglionic from postganglionic lesions » In combination with a test measuring postganglionic sudomotor function (QSART, silicone impression) the site of a lesion can be separated: » preganglionic lesions show an abnormal TST, while the QSART, or silicone imprints are normal. - A postganglionic lesion will be abnormal in all testsQuantitative sudomotor axon reflex Quantitative sudomotor axon reflex test (QSART) is used to evaluate postganglionic sympathetic cholinergic sudomotor function Axon-reflex mediated sweat response over time and has achieved widespread clinical use.Cholinergic agonists (such as acetylcholine) applied through iontophoresis (shown with the black arrow) bind to muscarinic receptors causing local sweat production (dashed arrow). The cholinergic agonist simultaneously binds to nicotinic receptors on nerve terminals of sudomotor fibers and an impulse travels antidromically. At branch points this impulse travels orthodromically to a neighboring population of eccrine sweat glands causing an indirect axon mediated sweat response (dotted arrows).Clean the recording sites vigorously with the alcohol. Recording sites are1) the medial forearm (75 % distance from the ulnar epicondyle to the pisiform bone); 2) the proximal leg (5 cm distal to the fibular head laterally); 3) the distal leg (5 cm proximal to the medial malleolus medially 4) proximal foot over the extensor digitorum brevis muscle. Place the ground for stimulation about 5 cm next to the capsule.Data acquisition Hygrometer Heat exchanger lontophoresis box An overview of the QSART testing procedure: A multi-compartmental sweat capsule has an outer ring (A, 1.5mm wide) for iontophoretic stimulation and an inner compartment (C, lem Giameter) for measuring humidity. The stimulation and recording site: are separated by a small compartment (B, 1 Smm wide) to prevent direct stimulation of the sweat glands and leakage of the iontophoresis fluid. Dry nitrogen gas is released at a steady rate of flow (ypically 100 cc/min) controlled through a flow meter. The gas flows through a temperature controlled heat exchanger and inte the sweat capsule (C). Upon exiting the capsule the gas flows back through the heat exchanger and to a hygrometer, where change: in humidity are recorded on 2 compute:- Wait until the baseline sweat is flat, below 100 nanoliters/minute and all channels give similar baseline sweat output (difference < 15 %,) ~ Start stimulation at current 2 mA for 5 minutes, turn on the marker. ~ Record another 5 minute of the sweat (total 10 minutes), turn on the marker. » Obtain the latencies and volumes at each sitei dip ane ee a ieeeS| 4\@fo af aa Figure 23. Drifing baseline of spontaneoes sweating.Figure 24. Placement of markers of stimulation and recordingsFigure 25. Principles of measurement of latency and sweat volume,1 (Sls rose 0:00.00 Figure 26. Normal QSART, CASS-sudomotor score= 0, 59 y/o man.~ In normal individuals, the sweat output starts with a delay of 1-2 minutes. - The sweat output increases for up to 5 minutes after stimulation until it reaches the inflection point and decreases slowly. ~ While males and females have similar latency the sweat output differs. » Mean sweat output for males is 2-3 ul/cm2 (approximate range 0.7-5.4 pl/cm2) and » females 0.25-1.2 l/cm2 (approximate range 0.2-3 pl/cm2) with some variation depending on the site of stimulation ~ Sweat response can be absent, decreased or increased.longer latency of the sweat onset can be seen as well as a lack of recovery, the “hung up” response Increased sweat production is often a sign of axonal excitability, seen in conditions such as diabetic neuropathy, reflex sympathetic dystrophy and other small fiber neuropathies. In diabetic neuropathy, especially during early stages, a length-dependent pattern of sweat reduction can be seenFigure 30. Moderately abnormal, QSART CASS-sudomotor = 2. 64 y/o woman,QSART measures the postganglionic sudomotor response and will be unable to detect preganglionic lesions. QSART is also time-consuming, requires special equipment and is not widely availablemeasure of electrodermal activity Generated in deep layer of skin Reflex activation of sweat glands via cholinergic sudomotor sympathetic efferent fibres. Provides a surrogate measure of sympathetic cholinergic sudomotor function.Historical aspects » (SSR) is a change in skin potential following arousal stimulation, described by Tarchanoff (1890). » Method introduced by Sahani in 1984 and later by Knezevic and BjadaSSR is a change in potential recorded from surface of skin, representing sudomotor activity Can be evoked by different stimuli Acoustic; TMS C7, brain; startle; laser skin; reflex hammer percussion on sternum Resende et al deglutition; blinking; — skeletal movements; biting; light stimuli; vocalization; sphincteric contraction Stimulus modality determine the afferent tractoriginate from the hypothalamus and descend uncrossed along the lateral column of the spinal cord to form asmall bundle between the pyramidal tract and the anterior-lateral tract. Terminates on sympathetic preganglionic neurons in the intermediolateral cell column. Myelinated sympathetic fibres from intermediolateral nucleus in Ti- L2 of spinal cord Paravertebral sympathetic ganglia Post ganglionic by non myelinated( type c); innervating sweat gland ayRoom temperature should be comfortable and the skin surface temperature 32@C. potentials are increased during psychological stress and may contaminate the evoked SSR. situation during recording has to be relaxed, without acoustic disturbancesRecording is done from glabrous skin and is referenced against hairy skin whose sweat glands are not typically active at normal ambient temperatures. The surface Ag-AgCl electrodes are placed on the palm (active) and referenced against the volar forearm or dorsum of the hand (indifferent); and on the sole of the foot (active) and referenced against the shin or dorsum of the foot (indifferent)The recording time should nee 5410 s, the lower frequency limit 0.142 Hz (better,1 Hz), and the upper limit 10042000 Hz (not critical). Amplification should be 0.0543 mV/division.~ Electrical stimulation is carried out with a constant current stimulus (0.2 ms, supramaximal, 10+30 mA). ~ Typically the median, posterior tibial, peroneal, sural or supraorbital nerves are stimulated at a strength at least three times the sensory threshold. - it is applied at irregular time intervals and at a frequency of approximately 1/min to avoid habituation.~ If electrical stimulation at one site does not evoke an SSR, other sites of stimulation should be tried ~ If the response to electrical stimulation is absent » response to acoustic stimuli or to an inspiratory gasp should be tried (Shahani et al. 1984).- In normal subjects, transcranial magnetic stimulation of the motor strip ~ elicited palmar and plantar SSRs similar - both in latency and amplitude to those evoked by median nerve stimulation. Normal results ~ The shape of the SSR is variable. - The shortest latency to onset and the maximum peak to trough amplitude of at least 5 recordings is used.Elstim. r. Med. nerve Elstim. r. Tee nerve Acoustic stim. Elbow Popliteal by magnetic stimulator if 1.5 sec 2.1 sec Fig. 1. Typical simultaneous recording of SSR from both hands and feet, Average latencies of 4 recordings are indicated, Electrical stimulation at elbow and popliteal fossa causes only minor latency differences. The click of a magnetic stimulus, coil 40 cm apart from the subject, elicits a reproducible SSR.Latency » The latency of the SSR includes 4. afferent conduction (about 20 ms), 2.central processing time (a few milliseconds), 3.and efferent conduction in pre- and slow conducting postganglionic autonomic nerve.- The mean conduction velocity of sudomotor nerve fibers is about 1+2 m/s. ~ Conduction in post- ganglionic C fibers as well as activation time of sweat glands include about 95% of the SSR latency ~ of around 1.5 s at the hands and 2s at the feet. » differences in fast afferent conduction are not relevant for the SSR latency and the site of stimulation is also not significant~ Amplitude Measurements in theory should reflect the density of spontaneously activable sweat glands. - interaction of the two components, sweat gland and epidermal, makes the absolute amplitude of the evoked EDA difficult to interpret. - the reproducibility of the electri-cally evoked SSR is poor. » Age- latency; amplitude ~ SSR evoked by an auditory stimulus has less inter and intrasubject latency and waveform variability than the inspiratory gasp induced response.~ Still no consensus about the evaluation and processing » Qualitative evaluation accepts only the absence of SSR as a pathological sign » Quantitative evaluation- different opinionSSR is a poor test of sympathetic sudomotor function. No close correlation between presence or absence of SSR and the severity of autonomic dysfunction. polyneuropathy, erectile dysfunction, —_ central degenerative diseases, multiple sclerosis(50%), brain infarction, reflex sympathetic dystrophies, spinal and peripheral nerve lesions.Table Evaluation summary of autonomic fncton tests Test Cardiovagal beat ate Adcenergic Sudomotor Skin vasomotor Neurogeni flare Application Diagnosing and monitoring the course of autonomic neuropathy Diagnosing and monitonng the course of autonomic neuropathy ‘Diagnosing autonomic neuropathy Quiltyof ——— Stengih of Rating Evidence Ratings Evidence (cas Ratings Established 10 B Established lt Established Investigational InvestigationalDistal small fiber neuropathy Sympathetic sudomotor fibers are affected, so that QSART will show abnormalities at the feet and normal sweating more proximally thermoregulatory sweat test shows anhidrosis that is confined to the distal feet confined or becomes generalized. diabetes or amyloidosis can start with DSFN and progress, while others do not: od e.g: Autonomic neuropathies and multiple system atrophy. widespread loss of sweating, cardiovagal failure is present, and OH with impaired baroreflexes is seenSelective chronic idiopathic anhidrosis, gastroparesisRecent studies indicate that MSA is distinguishable from PD using autonomic tests. PD is characterized by a length-dependent involvement of postganglionic sudomotor fibers MSA is characterized by widespread, early and preganglionic autonomic failure. MIBG or fluorodopa scan of the heart, which images postganglionic adrenergic innervation, is typically defective in PD and normal in MSA~ PD case showed very distal anhidrosis, affecting only parts of the toes, and did not progress over time. ~ Incontrast, MSA causes widespread anhidrosis. » If both QSART and TST are performed, normal QSART volume in an anhidrotic region indicates that the lesion is preganglionic in site.- Plasma norepinephrine measured with the subject supine and after a period of standing provides another method of studying adrenergic function. - A normal response consists of doubling of NE on standing. - The patient with generalized postganglionic adrenergic failure, as in pure autonomic failure (PAF), will have low supine NE. - The patient with preganglionic lesion, as in MSA, will typically have normal supine values (since the postganglionic fibers are intact) but a failure to increment on standingMishra and kalita: clinical neurophysiology D. Clausa,* and R. Schondorf: Sympathetic skin response; 1999 International Federation of Clinical Neurophysiology. Kucera p, Goldenberg Z, Kurca E: SSR: Review of method and its clinical use;Bratisi Lek Listy 2004 Ben M.W. Illigens, MD and Christopher H. Gibbons, MD MMSc:Sweat testing to evaluate autonomic function; Clin Auton Res. 2009 April Peter Novak:Video Article Quantitative Autonomic Testing; 201 Journal of Visualized ExperimentsThanksModel Coverage Policy September 2, 2014 Christopher H. Gibbons, MD, FAAN William P. Cheshire Jr., MD, FAAN Terry D. Fife, MD, FAAN Background The conceptual framework for autonomic testing began at the turn of the 19" century with a number of experiments in basic neurophysiology. These original tests were developed over time into a rigorously defined, standardized series of autonomic tests that are useful in the clinical assessment and care of patients with suspected autonomic disorders. Autonomic testing has been widely used in clinical practice for 50 years, with decades of extensive experience and thousands of studies published on its use. Comprehensive textbooks have been published on the purpose and methodology of autonomic testing.~* Autonomic testing is an umbrella term that covers testing of the various branches of the nervous system: the sympathetic, parasympathetic, and enteric. It should be noted that the autonomic nervous system extends to nearly every organ system in the body; so many organ specific tests are in