Autonomic Function Testing

There are many tests of autonomic function. They are imployed on a case by case basis to diagnose autonomic neuropathy, to distinguish between causes of autonomic failure, diagnose POTS, distinguish between causes of Parkinsonism among other indications.
Physiologic:
Baroreceptor function testing:

  • Beat to beat heart rate HR variation a.k.a. HR response to deep breathing, HRDB:
  • R-R is monitored on 60 second ECG monitoring, with 5 respiratory cycles (5s expiration, 5s inspiration)

Deep breathing while supine for 3 minutes:

  • Expiration:inspiration ratio, E:I: 16-20 y.o. >1.23, 76-80 y.o. >1.05
  • Heart rate response to deep breathing (HRDB) is Abnormal in parasympathetic cardiovagal dysfunction:
  • HR response to the Valsalva manoeuvre a.k.a. Valsalva ratio, VR:
    • Recumbent patient maintains 30-50mmHg of pressure on exhalation into a bugle with air leak
    • VR= maximum HR with valsalva/minimum HR within 30 seconds of maximum
    • VR is Abnormal in vagal disorders (Parasympathetic cardiovagal dysfunction)

Beat to beat BP respone to Valsalva manoeuvre:

  • BP is measured Beat to Beat noninvasively or invasively. Then a Valsalva manoeuvre is performed
  • Normal: increase in HR (i.e. decrease in RR interval) & fall in BP during Valsalva.. After the manoeuvre ends the HR drops (i.e. increased RR interval) & BP overshoots baseline.
  • Abnormal= more prominent & longer decreased BP during Valsalva, loss of overshoot of BP & relative bradycardia= baroreflex-sympathoneural dysfunction
  • Tests the baroreflex cardiovagal gain= baroreceptor sensitivity

Tilt tablet testing: HR and blood pressure BP response to Tilt table:

  • Normal: transient drop in BP, recovery withing 1 minute
  • Abnormal: persistent drop in BP, indicates baroreflex-sympathoneural dysfunction
  • In simple faints (a.k.a. neurally mediated syncope a.k.a. Vasovagal syncope a.k.a. neurocardiogenic syncope a.k.a. vasodepressor syncope):
    • After tilt up there is a period of normal BP & HR. Then a sudden drop in BP & HR with recurrence of syncopal symptoms.
  • In autonomic failure:
    • After tilt up there is a progressive gradual drop in BP & HR with recurrence of syncopal symptoms.
  • In Parkinson’s disease:
    • Upright tilt: BP declines progressively (not suddenly) until syncope occurs. No acute bradycardia

BP response to isometric Hand Grip:

  • Normal: increase BP

Abnormal: indicates sympathetic noradrenaline abnormality

  • Forearem impedance plethesmography:
  • Cuff is inflated above venous pressure but below diastolic pressure, measures flow and therefore forearm vascular resistance
  • Normal: increase forearm resistance in response to stimulus
  • Abnormal: absent or attenuated response, failure of reflexive sympathoneural function

Power spectral analysis of HR variability:

  • Interbeat intervals are analyzed by Power spectral analysis at frequency of breathing (at high frequency)
  • Power peak is measured~ respiratorysinus arrhythmia
  • Power peak is low or absent in Cardiovagal failure

Schirmer test:

  • Quantifies Production of tears

Sudomotor tests= Sympathetic cholinergic function testing:

  • Women sweat less than men.
  • Combination of the below can differentiate between preganglionic and postganglionic lesions
  • Thermoregulatory sweat testing TST:
    • Stimulus: increased environmental temperature
    • Measurement: skin humidity (by powders that change colour)
    • Abnormal: in any lesion of the thermoregulatory pathway
  • Sympathetic skin response:
    • Stimulus: electricity, startle
    • Measurement: skin electrical conductance changes
    • Abnormal: in any lesion of the thermoregulatory pathway
  • Quantitative sudomotor-axon-reflex testing QSART:
    • Tests a reflex that is mediated completely by sympathetic axons; stimulus–> antidromic axon travel–> branch point–> orthotromic axon travel–> ACh release–> sweat
    • Stimulus: Iontophoresis of acetylcholine (10% of acetylcholine with a 2mA current for 5 minutes)
    • Measurement: Sweat response over 5 minutes
    • Abnormal test: lesion of postganglionic sudomotor nerve axon e.g. small fibre neuropathy or transynaptic defect with preganglionic nerve deficits (Sympathetic Cholinergic dysfunction)

Neurochemical:
Plasma norepinephrine (noradrenaline) & epinephrine (adrenaline) supine & standing:

  • Supine levels:
    • Low in:
      • Pure autonomic failure, small fibre peripheral neuropathy
    • Normal in:
      • Multiple system atrophy
  • Standing levels:
    • Low in: central & peripheral causes of orthostatic hypotension
    • Normal: 2 to 3 fold increase in NE
    • Elevated: elevated NE & adrenaline levels on standing occurs in POTS

Plasma norepinephrine NE (noradrenaline):

  • Produced by sympathetic nerve cells
  • Increased:
    • Many causes of increased noradrenaline (norepinephrine NE)
    • Tricyclic antidepressants TCAs
  • Low:
    • Undetectable in Dopamine beta-hydroxylase deficiency
    • Low in pure autonomic failure

Plasma dihydroxyphenylglycol DHPG:

  • Reflects the amount of adrenaline turnover/reuptake into cells.
  • High:
    • Increased stimulation of intact sympathetic nerves
  • Low:
    • Undetectable in Dopamine beta-hydroxylase deficiency
    • Low in pure autonomic failure
    • Tricyclic antidepressants TCAs

Plasma epinephrine (adrenaline) & metanephrine:

  • Produced by adrenal medulla Chromaffin cells. Reflects activity of adrenal medulla
  • High:
    • High activity of adrenal medulla
  • Low:
    • Low activity of adrenal medulla

Neuroimaging:
Cardiac SPECT MIBG, 123I- labelled Metaiodobenzylguanidine, 123I-MIBG:

  • Reduced uptake i.e. cardiac denervation:
    • Pure autonomic failure PAF
    • Parkinson’s disease
    • Familial amyloidotic polyneuropathy FAP
    • Diabetes mellitus
  • Intact cardiac innervation:
    • Multiple systems atrophy
    • Autoimmune autonomic ganglionopathy

PET scan:

  • Reduced uptake i.e. cardiac denervation:
    • Pure autonomic failure PAF
    • Parkinson’s disease
    • Familial amyloidotic polyneuropathy FAP
    • Diabetes mellitus
  • Intact cardiac innervation:
    • Multiple systems atrophy
    • Autoimmune autonomic ganglionopathy
    • Chromium labelled RBCs or 131I-Albumin:
    • Blood volume measurement

Tests by functional systems:
Sympathetic noradrenergic/adrenergic:

  • Plasma norepinephrine (noradrenaline)
  • Plasma dihydroxyphenylglycol DHPG
  • Beat to beat BP respone to Valsalva manoeuvre: (part of baroreceptor reflex testing)

Sympathetic cholingergic:

  • Sudomotor tests:
    • Thermoregulatory sweat testing
    • Sympathetic skin response
    • Quantitative sudomotor-axon-reflex testing QSART
  • Parasympathetic:
    • Beat to beat heart rate HR variation a.k.a. HR response to deep breathing, HRDB
    • HR response to the Valsalva manoeuvre a.k.a. Valsalva ratio, VR

Causes of baroreceptor reflex dysfunction (Barorefex-sympathoneural & Baroreflex-Cardiovagal):

  • Parkinson’s disease
  • Multiple systems atrophy
  • Pure autonomic failure
  • Dopamine beta-hydroxylase deficiency

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