History  &  physical exam  and then  autonomic testing

       End  organ function evaluation (homeostatic  control)

       No  direct  pathway  assesment  such as EDX

       First cardiac study

       There are 3 noninvasive or minimally invasive approaches to evaluating  ANS:

       R-R interval variability (HRV)

       Baroreflex sensitivity (BRS)

       Bedside AFT (eg, VM, tilt testing,…)


       Time domain → mean R-R interval (HR) ± SD

       Frequency domain →  spectral analysis

                               HF:  parasympathetic activity

                               LF:  Sympathetic activity as modulated by Parasympathetic activity

       Instantaneous measurements of  BP: insertion of an arterial cannula.

       noninvasive techniques :  FINAPRESS

Baroreflex  Sensitivity

       BRS  is  a  measure  of  PNS  input  to  sinus  node

        Measuring  reflex ↑ in R-R interval in response to an ↑ in BP by IV injection of an -agonist(phenylephrine) 20-30 mmHg ↑ in systolic BP

       Generally  a  linear  relationship  exists  between  increase  in (R-R interval and systolic BP)

       Slope is used to quantify  sensitivity  of arterial baroreflex, Repeated 3-5 times to an average slope (typically steep form in healthy  case)

       BRS  decreases (i.e., flatter slope) with sympathetic  dominance  and increases (i.e., steeper slope)  with  parasympathetic  dominance. (FINAPRES)

       pressure changes →sensed in aortic arch/carotid sinus → brain stem nucleus tractus solitarius →(baroreflex mediated) changes in  PNS/SNS  outflow →result in early change in HR and later change in peripheral vascular tone.

Autonomic function test

Parasympathetic  testing:

       Early changes in HR are due exclusively to changes in PNS tone to heart, (good measure of PNS function)

       Patients are asked to perform 3 different maneuvers(metronomic breathing, Valsalva, stand up)  which change BP and HR response to each maneuver is measured

       Sympathetic  testing

Two components of SNS function are routinely measured in  autonomic laboratory

       Vasomotor function:  is measured by evaluating  BP response to maneuvers described above, metronomic breathing, Valsalva, stand up/heads up tilt

       Sudomotor function:  is measured by quantitative sudomotor axon reflex testing (QSART), thermoregulatory sweat testing (TST), or sympathetic skin response (SSR)

Metronomic  breathing

       patient is asked to ‘breath in…’ and ‘breath out…’ at a steady rate of 6 breaths/min that results in a slowly fluctuating  BP that decreases with inhalation and increases with exhalation due to changes in intrathoracic pressure. These  BP changes result in HR  fluctuation via  baroreflex. Maximum HR variation between inhalation and exhalation and ratio of HR during exhalation to inhalation (E:I ratio) are measured.(RSA)

       Advantages of this test are its simplicity, reproducibility, and sensitivity for PNS dysfunction.

Valsalva maneuver

       forcibly exhale into a manometer- 40 mmHg  for 15 seconds and then is released rapidly

        Initially there is a transient ↑ in BP due to ↑ ITP (phase I)  followed by a steady ↓ in BP as cardiac return falls (Phase II early) → baroreflex mediated ↑ in HR, peripheral vasomotor tone that eventually begin to ↑ BP  towards baseline (phase II late)

       With release of V there is a transient ↓ in BP caused by↓ITP during inhalation (phase III). Rapidly cardiac output returns to baseline. However, peripheral vasomotor tone remains elevated resulting in a transient overshoot in BP following VM(phase IV).

       fast HR during VM is caused by near complete removal of PNS tone.

       transient overshoot in BP following VM (phase IV) leads to  suppression of HR.

        PNS function →ratio of fastest HR during maneuver/slowest HR  following  it

        vasomotor (SNS)dysfunction→ incomplete recovery of BP during phase II,Lack of phase IV  BP overshoot

Stand-up  test

       stand up as rapidly as possible from a lying position → transient decline in BP followed by a brief overshoot in BP. initial fall in BP causes a baroreflex mediated increase in HR which peaks at approximately 15th beat after standing. subsequent overshoot in BP results in a baroreflex mediated suppression of HR which is maximal at approximately  30th beat following standing.

       PNS function is measured by taking a ratio of HR at 30/15

Sudomotor  Function

       Best measured with QSART(rate of sweating is measured at baseline and after application of a cholinergic agonist)This test can help differentiate central/peripheral ANS dysfunction that has a high sensitivity in detecting small fiber involvement in neuropathy and  a objective evidence of small fiber neuropathy.         

Quantitative Sudomotor Axon Reflex Testing

Thermoregulatory Sweat Test

       During this test, patient is coated with a powder that changes color when sweat, then enter a chamber with slowly increasing temperature. It causes body temperature to increase 1 to 1.5 degrees C, which makes most people sweat. Digital photos document results. sweat pattern may help confirm a diagnosis of autonomic neuropathy or other causes for decreased or increased sweating.

       TST assesses both central and peripheral aspects of  efferent  SNS, from hypothalamus to sweat glands. It is a well-standardized test and evaluates  distribution of sweat by a change in color of an indicator powder on skin after exposure to infrared light. TST is semiquantitative (percentage of anterior body anhidrosis) and has a high sensitivity.

Sympathetic Skin Response

       abnormal (reduced amplitude or absent) (between 500 µV-3 mV, p-p)

       only a portion of response ( early fast changes) is due to sweating, whereas rest of response (later changes) is due to skin potential changes that are present in congenital absence of sweat glands.[51]

       active on palm sole/reference  on  dorsum

       latencies are not meaningful.[44]

        amplifier: low-frequency filter (0.1–0.5 Hz). High-frequency filter (500 - 1,000 Hz)


       Pupil  is  innervated  by  both  SNS/PSNS.

       principle of dynamic infrared pupillometry consists of quantifying change of  pupil diameter during  course of a light reflex and dividing it into several kinetic parameters, which are analyzed separately  that reflect activity of  two branches of ANS in response to a light stimulus, resulting in pupillary constriction and redilation phases.

Assessment of Myocardial Sympathetic Innervation

      Imaging of myocardial sympathetic innervation with various radiotracers [e.g., I123 meta-iodobenzylguanidine (MIBG)] has recently evolved as a potentially exciting new noninvasive methodology for determination of autonomic dysfunction.14

      reduced uptake of MIBG in diabetic autonomic neuropathy and may be a more sensitive15 and specific indicator of abnormal innervation than  standard CVRT.

      currently a research tool.

      SCREENING — ADA recommends screening for DAN at time of diagnosis of type 2 DM and 5 years after  diagnosis of type 1 DM [42].

      Screening should include a history and PE for signs of autonomic dysfunction

      Tests of HRV may be indicated, including expiration to inspiration ratio, response to VM, and response to standing

      If initial screening is negative, it should be repeated annually

If initial screening is positive - alert to search for associated risk factors of cardiovascular disease and implementation of an intense program to reduce these factors and thereby reduce risk of mortality

ANS Testing

      Six challenges include:

      A)resting (initial) baseline,

      B)parasympathetic challenge of deep breathing

      C)return to baseline,

      D)sympathetic challenge of a series of short VM

      E)return to baseline,

      F) Quick postural change (seated to standing) followed by quiet standing

      FDA Clearance

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                دکتر  علی اوشیب نتاج        متخصص طب فیزیکی و توانبخشی

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برچسب‌ها: اتونومیک نوروپاتی, تست های تشخیصی, AUTONOMIC STUDY, diabetic neuropathy, autonomic neuropathy, blood pressure, فشارخون
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Clinical Manifestations

       Cardiovascular: Resting tachycardia, Exercise intolerance/Orthostatic tachy-bradycardia syndromes/Cardiac denervation, painless MI/Orthostatic hypotension/Intra-perioperative CV  instability/Sudden death

       Gastrointestinal: Esophageal dysfunction/Gastroparesis diabeticorum /Diarrhea/Constipation/Fecal incontinence

       Genitourinary: Erectile dysfunction/Retrograde ejaculation/Cystopathy /Neurogenic bladder

       Neurovascular: Heat intolerance/Gustatory sweating/Dry skin/Impaired skin blood flow(red- white)

       Metabolic: Hypoglycemia unawareness

       Pupillary/ lacrimal gland: Decreased diameter of dark adapted pupil/Argyll-Robertson type pupil

Effects  of  DAN  on exercise risk

       Silent  MI

       Resting tachycardia/decreased maximal responsiveness

       Orthostasis/hypotension with exercise

       Exaggerated  BP responses with supine position and exercise

       Cardiovascular/cardiorespiratory instability

       Abnormal systolic ejection fractions at rest/exercise

       Poor exercise tolerance

       Failure of pupil adaptation to darkness

       Gastroparesis/diabetic diarrhea


       Decreased  hypoglycemia  awareness

       Heat  intolerance  due  to  defective  sympathetic  thermoregualtion  and sweating  (prone to dehydration)

       Susceptibility  to  foot  ulcers/limb  loss  due  to  disordered  regulation  of cutaneous  blood  flow


       Reprinted with permission from  American Diabetes Association, Health Professional's Guide to Diabetes and Exercise, p. 190

مازندران بابل میدان کشوری کنار بیمارستان بهشتی ساختمان رضا

                دکتر  علی اوشیب نتاج        متخصص طب فیزیکی و توانبخشی

                      01112288978     ---------        09357807071

برچسب‌ها: اتونومیک نوروپاتی, تست های تشخیصی
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