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
- Low in:
- 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