Autonomic Neuropathy


Autonomic neuropathy/autonomic failure/autonomic dysfunction


Autonomic dysfunction may be central (CNS) or peripheral (PNS)

Clinical features:

Helps define distribution and extent of disease:

  • Sympathetic, parasympathetic
  • Adrenergic, cholinergic

Helps define presents of associated CNS disease
Helps define associated systemic disease

Autonomic function testing:

Baroreceptor function testing a.k.a. Cardiovagal testing by HR variability:
  • Beat to beat heart rate HR variation (the main test):
    • 60 second ECG monitoring, with 5 respiratory cycles (5s inspiration, 5s inspiration)
    • Expiration:inspiration ratio, E:I: 16-20 y.o. >1.23, 76-80 y.o. >1.05
    • Abnormal in parasympathetic dysfunction
  • HR response to the Valsalva manoeuvre a.k.a. Valsalva ratio, VR (another good test):
    • 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
    • Abnormal in vagal disorders (Parasympathetic cardiovagal dysfunction)

Beat to beat BP respone to Valsalva manoeuvre: (tests the baroreceptor reflex)
HR and blood pressure BP response to standing
BP response to Hand Grip
HR response to IV phenyephrine


Plasma norepinephrine (noradrenaline) and epinephrine (adrenaline) supine and standing
Plasma norepinephrine (noradrenaline):

  • Undetectable in Dopamine beta-hydroxylase deficiency
  • Low in pure autonomic failure

Plasma dihydroxyphenylglycol DHPG

  • Undetectable in Dopamine beta-hydroxylase deficiency
  • Low in pure autonomic failure

Plasma epinephrine (adrenaline) and metanephrine

Sudomotor tests= Sympathetic cholinergic function testing:

Thermoregulatory sweat testing TST
Sympathetic skin response
Quantitative sudomotor-axon-reflex testing QSART


For cardiac innervation:

  • Cardiac SPECT MIBG, 123I- labelled Metaiodobenzylguanidine, 123I-MIBG:
  • Reduced uptake i.e. cardiac denervation. Normal i.e. intact cardiac innervation
  • PET scan

Cardiac denervation:

  • Pure autonomic failure PAF
  • Parkinson’s disease
  • Familial amyloidotic polyneuropathy FAP
  • Familial amyloidotic polyneuropathy FAP
  • Diabetes mellitus

Intact Cardiac innervation:

  • Multiple system atrophy
  • Autoimmune autonomic ganglionopathy

MRI: for features of associated CNS disease

Investigations to consider:

  • FBC
  • Fasting blood glucose/glucose tolerance test: diabetes mellitus
  • HIV testing
  • SPEP
  • Fat/rectal/gingival biopsy: Amyloidosis

Paraneoplastic antibodies:

  • Antineuronal (anti-Hu), anti neuronal nicotinic ACh receptors,  ANNA-1, Purkinje cell cytoplasmic antibodies PCA-2, collapsing response-mediator protein CRMP-5
  • Anti-P/Q type calcium channel

Screen for neoplasms:

  • CT thorax +abdomen: small cell lung cancer, pancreatic adenocarcinoma

Autoimmune conditions:

  • Schirmer test, Anti-Ro/SS-A, anti-La/SS-B,
  • Anti-rheumatoid factor,


  • Nerve conduction studies NCS: Lambert Eaton syndrome

Autonomic function testing and Quantitative sensory testing
Genetic testing for autonomic neuropathies
Leukocyte alpha-galactosidase: Fabry disease

Causes of autonomic neuropathy:



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