2. Outline Of Presentation
• Anatomical and functional Overview
• Classification of ANS disorders
• Historical keys and Examination findings
• Bedside Assessment Tests Of ANS
• Parasympathetic and Sympathetic functions
• Functional Autonomic Disorders
• Structural Autonomic Disorders
• Peripheral Efferent , Afferent
• Central
• Management Strategies
• Non-Pharmacological
• Pharmacological
• Recent Advances
3. Pioneers
JOHN LANGLEY
i) Mapped 3 distinct divisions in
system.
ii) Coined term ‘AUTONOMIC’
CLAUDE BERNARD
i)Theory of chemical synapse
transmission.
ii)Described fundamental role of
ANS in maintaining Homeostasis
(la fixite du milieu interior)
4. Definition
• The term autonomic nervous system, meaning
“self- driven,” The innervation of each end-organ
is highly tailored to a balance between the
primary needs of the organ itself and the
importance of some degree of control in daily
function.
10. Heart Rate Variation During Respiration
(Parasympathetic function tests)
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
11. Sinus Arrhythmia
• 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
12. • Record maximum and minimum heart rate with each
respiratory cycle
• Average the 3 differences
15 beats/min- Normal >
- Borderline =
- Abnormal<
11-14 beats/min
10 beats/min
E:I ratio = longest RR interval
(expiration)
shortest RR interval (inspiration)
Normal E:I ratio = 1.2
13. Heart Rate Variation During Postural
change
Changing posture from supine to standing leads
to an increase in heart rate immediately, usually
by 10- 20 beats per minute
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 to a stable state at about 30th beat
14. The ratio of R-R intervals corresponding to the 30th and
15th heart beat 30:15 ratio
30:15 ratio = RR interval at 30th
• RR interval at 15th beat
This ratio is a measure of parasympathetic response
• Normal > 1.04 = 1.01-1.04
Abnormal =<1.00
15. Valsalva Maneuver
(Parasympathetic function tests)
The Valsalva maneuver consists of respiratory
strain which increases intrathoracic and
intraabdominal pressures and alters
hemodynamic and cardiac functions
Valsalva maneuver evaluates
• - 1. sympathetic adrenergic functions
using the blood pressure responses
-2. cardiovagal (parasympathetic)
• functions using the heart rate responses
16. The patient is supine or with head slightly elevated to about 30°.
• Most labs have the patient strain against 40 mmHg applied for 15 s by blowing into a mouthpiece
attached to a sphygmomanometer.
• The system should have a slow leak to ensure the patient strains continuously
Following cessation of the Valsalva strain, the patient relaxes and breathes at a normal comfortable rate.
The ECG is monitored during the strain and 30-45 s following its release.
The maximal heart rate of phase II actually occurs about 1 s following cessation of the strain The
minimal heart rate occurs about 15-20 s after releasing the strain.
The ratio of the maximal-to-minimal heart rate is determined as a simple ratio. •
After a brief rest, the maneuver is repeated until three ratios are determined.
18. Phase I – Onset of straining
Transient increase in BP which lasts for a
few seconds
- HR does not change much
19. Phase – II – Phase of straining
• Early part - drop in BP lasting for about 4 seconds
• Later part - BP returns to normal
20. Mechanism
Early part
-venous return decreases with compression of veins by increased
• intrathoracic pressure central venous pressure decreases BP
decreases
• Later 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
21. Phase III - Release of straining
Transient decrease in BP lasting for a few
seconds
Little change in heart rate
Mechanical displacement of blood into pulmonary
vascular bed, which was under increased
intrathoracic pressure BP decreases
22. Phase IV - further release of
strain
BP slowly increases and heart rate
proportionally decreases
BP overshoots
Occurs 15-20 s after release of strain and lasts for about
a minute or more
Due to increase in venous return, stroke volume and
cardiac output increases
♦ Phase I Decrease in BP
♦ Phase II Decrease in BP, Tachycardia
♦ Phase III Decrease in BP
♦ Phase IV Overshoot of BP, Bradycardia
23. Valsalva Ratio
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
Values
• more than 1.21 normal
• less than 1.20 abnormal
24. Valsalva Tracing of Autonomic
Dysfunction Patient
• Absent indulation of heart rate
• During strain, there is no increase of heart rate; after release
of the strain. there is no reflex: brad/cardia
25. Blood pressure response to sustained
hand grip (Sympathetic Function test)
• Sustained hand grip causes reflex increase in heart rate
& cardiac output without changing systemic vascular
resistance.
• Diastolic BP thus normally increases.
• BP is measured every min for 5 min.
• The initial diastolic BP is substracted from the diastolic
BP just before release.
• The normal value is difference of >16mm Hg.
26. Cold Press Test
Submerge the hand in ice cold water(4oC)
This increases
- systolic pressure by about 20 mmHg
- diastolic pressure by 10 mmHg
27. Thermoregulatory sweat Test
The TST is a sensitive semiquantitative test of
sweating
After a color indicator (quinizarin powder or
povidone-iodine) is applied to the skin,
the environmental temperature is increased until
an adequate core temperature rise is attained
(usually a 2°C rise in core temperature or a core
temperature of 38.5°C, whichever is less)
the presence of sweating causes a change in the
indicator
29. TST
Estimating the percent of anterior surface anhidrosis
quantitates the results, and the sweat rates may be
measured
• Some characteristic patterns of anhidrosis include
(1)the peripheral pattern of distal anhidrosis, seen in distal small-fiber
neuropathy and length-dependent axonal neuropathy;
(2)the central patterns of distal sparing or segmental involvement,
generally seen in MSA or PD; and
(3)a sudotomal pattern suggesting involvement at the root or ganglion
level, seen in disorders involving nerve roots or specific ganglia, such as
diabetes, Sjögren disease, and pure autonomic failure.
• The TST pattern is therefore helpful in distinguishing
between postganglionic, preganglionic, and central lesions.
31. Common Abnormal TST Pattern
Small Fibre
Neuropathy
Unilateral Spinal
Cord injury
(T10 here)
Radiculopathy,
Herpes zoster
or Diabetic
Patients
Chronic
Idiopathic
Anhydrosis,
MSA
32. Quantitative Sudomotor Axon Reflex
Test
The physiological basis of the QSART is elicitation of an
axon reflex mediated by the postganglionic sympathetic
sudomotor axon
Acetylcholine (ACh) activates the axon terminal.
The impulse travels antidromically, reaches a branch-
point, then travels orthodromically to release ACh from
the nerve terminal.
ACh traverses the neuroglandular junction and binds to
M3 muscarinic receptors on eccrine sweat glands to
evoke the sweat response.
The QSART specifically evaluates the functional
status of postganglionic sympathetic axons.
33. QSART
Current is applied to one compartment of a
multicompartmental sweat cell,
the sweat response is recorded from a second
compartment with a sudorometer.
The multicompartmental sweat cells are attached to sites
on the upper and lower limbs.
This distribution permits the detection of dysfunction
localizable to one specific peripheral nerve territory or of
a length-dependent autonomic neuropathy.
An absent response indicates a lesion of the
postganglionic axon.
37. TST/QSART benefit in Localization
(MSA)
• A) Preganglionic – TST absent, QSART Normal
• B) Postganglionic – Both QSART, TST Reduced
38. Tilt Table Testing
Subject patients to head-up tilt at angles of 60 to 80
degrees ,
induce either syncope or intense presyncope with
reproduction of presenting symptoms.
Passive tilt tests simply use upright tilt for up to 45
minutes to induce vasovagal syncope (sensitivity ≈ 40%,
specificity ≈ 90%).
Provocative tilt tests use a combination of orthostatic
stress and drugs such as isoproterenol, nitroglycerin, or
adenosine to provoke syncope with a slightly higher
sensitivity but reduced specificity.
42. Reflex Syncope
Transient loss of consciousness due to loss of brain
perfusion as a protective reflex occurs at least once
in 50% of healthy young adults, usually as an
emotional faint with a well-recognized
precipitating stimulus.
The loss of consciousness is also short, usually less than 20
seconds, and recovery is very fast.
43. The guidelines divide syncope in 4 groups:
(1)vaso-vagal: produced by either orthostatic stress or
emotionally mediated (fear, blood phobia, etc.);
(2)situational: can be triggered by exercise,
defecation, post-prandial, visceral pain cough, etc.;
(3) carotid sinus syncope and
(4) atypical without an apparent trigger or with an
atypical presentation
44. Syncopal Migraine
Headache with migrainous features immediately
prior to or after the syncopal spell
increased duration of loss of consciousness (up
to 15 minutes in this series),
and longer time to full recovery
prompt response to anti-migrainous medications
such as verapamil and topiramate
45. Carotid Sinus Hypersensitivity
Defined as an asystole of 3 seconds, a fall in
systolic pressure of 50 mm Hg, or both in
response to carotid artery massage in a patient
with otherwise unexplained dizziness or syncope
35 to 100 patients per million per year present
diagnosis is by manual massage of the carotid
sinus
• Longitudinal massage should be performed for 5 seconds
• Hypotension, bradycardia, or both may dominate the clinical
picture
46. Postural Tachycardia Syndrome
Defined as an increase of at least 30 bpm on
standing (> 40 bpm in subjects <19 yrs of age) ,
associated with symptoms of sympathetic
activation
Orthostatic symptoms include light-headedness,
palpitations, tremulousness, visual changes,
discomfort or throbbing of the head, poor
concentration, tiredness, weakness, and
occasionally fainting
an elevated plasma norepinephrine
concentration of 600 pg/mL or more on
47. POTS
4 : 1 female preponderance
typically in the 15- to 45-year age group
propranolol 10 to 20 mg three times daily; increased
dietary salt; fludrocortisone 0.1 mg orally daily;
clonidine 0.05 mg once or twice daily; and midodrine 5
mg orally twice daily.
49. Functional Gastrointestinal Disorders
Frequent symptom of nausea.
Hyperalgesia is very common, from increased
rectal sensation to distention of anal balloons to
increased sensitivity and discomfort with normal
physiological functions
The role of either increased intestinal bacterial in
the foregut (small-bowel bacterial overgrowth)
or altered bacteria is well documented.
IBS is defined as 3 months of abdominal discomfort
relieved by a bowel movement or associated with a
change in bowel movement frequency or consistency and
occurs in 10% to 20% of the general population.
51. Autonomic Storm and Takotsubo
Cardiomyopathy
Autonomic storms result in acute alterations in body
temperature, blood pressure, heart rate, respiratory rate,
sweating, and muscle tone.
a massive catecholamine surge occurs that can induce
seizures, neurogenic pulmonary edema, and myocardial
injury
(heightened activity of diencephalic or brainstem
sympathoexcitatory pathways appears to be the major
substrate of these episodes.)
52. Takotsubo “Broken Heart” Syndrome
It mimics myocardial infarction and is characterized by
chest pain and shortness of breath. It was described
initially in Japan as tako tsubo (octopus trap) syndrome
and in the United States as apical ballooning syndrome
or broken heart syndrome
Diagnosis is from nonspecific ST–T abnormalities, ST
elevation, or QT prolongation with large negative T
waves, often occurring over days in succession
Plasma and urinary catecholamines are typically elevated
Treatment is supportive, and while 95% of patients
experience complete recovery, approximately 10% will
have recurrence over a 4-year period.
54. FAMILIAL DYSAUTONOMIA
(Riley- Day Syndrome)
Ashkenazi Jewish extraction carrying mutations
in the IB kinase-associated protein gene
(IKBKAP)
FD is part of a group of disorders termed
hereditary sensory and autonomic neuropathies
(HSANs) and is classified as HSAN I
pathophysiology originates from loss of afferent
nerve function, particularly baroreceptor
information
55. Preventive and supportive strategies
• Maintaining eye moisture,
• fundoplication with gastrostomy to provide
nutrition and avoid risk of aspiration,
• use of central agents such as benzodiazepines,
clonidine, or carbidopa to control vomiting and
the dysautonomic crisis,
• fludrocortisone and midodrine to combat
cardiovascular lability
56. Baroreceptor Reflex
• .
Cardioregulatory
and vasomotor
centers in the
medulla
oblongata
Carotid sinus baroreceptors
Aortic arch
baroreceptors
Sympathetic
vessels
nerves
Sympathetic
chain
57. Braoreflex Failure
Acute baroreflex failure
display stress-induced systolic blood pressure surges of more
than 300 mm Hg
hypertensive crisis
bilateral destruction of baroreflex afferent function
results in concomitant destruction of much efferent
vagal function
if the baroreflex failure occurs with relative sparing
of the parasympathetic efferent vagal fibers, sleep or
sedation may lead to malignant vagotonia with
severe bradycardia and hypotension and episodes of
sinus arrest
58. • chronic baroreflex failure
Abnormalities in the vascular baroreceptors, the
glossopharyngeal or vagal nerves, or their brainstem
connections
• Trauma from injury, tumor, radiation, surgical
intervention, or
• brainstem stroke
60. Pure Autonomic Failure
Synucleinopathy with synuclein found within Lewy bodies
confined to autonomic ganglia, presenting in mid- to late life
The initial feature in men is impotence, but OH usually brings
patients to the physician.
OH is worst in the morning and improves as the day
progresses.
Supine hypertension may occur during the night while supine.
Meals,exercise, fever, or environmental heat worsen OH.
PAF patients suffer from profound OH with a decrease in
systolic blood pressure of 50 mm Hg and sometimes more
than 100 mmHg.
Urinary hesitancy, urgency, dribbling, and occasional
incontinence may also occur related to specific bladder
dysfunction.
61. Causes
Diabetes or metabolic syndrome , Sjögren
syndrome, paraneoplastic autonomic neuropathy.
Collagen vascular disorders such as lupus or
rheumatoid arthritis
Infectious causes include herpes zoster, Lyme
disease, and syphilis.
infiltrative disorders such as α-galactosidase
deficiency (Fabry disease), porphyria, heavy
metal poisoning
62. Drug-Induced Dysautonomia
mechanisms :
blood volume depletion-hyperadrenergic orthostatic
hypotension.
sympathoplegic effects causing impairment in maintenance
of vascular resistance, venous tone, or cardiac output -
hypoadrenergic orthostatic hypotension ;
and direct vasodilatation, which lowers vascular resistance
or venous tone
sedatives, hypnotics, antidepressants, diuretics,
antihypertensive drugs, or nitrates , Oncological
agents such as vincristine and cisplatin ,
zonisamide,
63. Dopamine β-Hydroxylase Deficiency
selective absence of norepinephrine and all its metabolite
absent sympathetic noradrenergic function but normal
• parasympathetic and sympathetic cholinergic functions
Symptoms in the perinatal period include
• vomiting, dehydration, hypotension, hypothermia, and profound
hypoglycemia requiring repeated hospitalization.
• Exercise capacity is poor.
By early adulthood,
profound orthostatic hypotension,
greatly reduced exercise tolerance, ptosis of the eyelids, and supine
nasal stuffiness.
Presyncopal symptoms include dizziness, blurred vision, dyspnea,
nuchal discomfort, and chest pain.
64. • Biochemical features
minimal or undetectable plasma, CSF, and urinary
norepinephrine and epinephrine and a fivefold to tenfold
elevation of plasma dopamine
lack urinary normetanephrine, metanephrine, and
• vanillylmandelic acid.
65. Menkes kinky hair Syndrome (X-Linked
Copper Deficiency)
DBH deficiency -copper-containing enzyme, and
congenital disorders of impaired copper metabolism
stubby, tangled, sparse hair (often white or gray in
color), pudgy cheeks, spasticity, seizures, hypothermia,
retarded growth, and decreased visual function.
Subdural hematoma, jaundice, and osteoporosis
Administration of droxidopa (l-threo-3,4-
dihydroxyphenylserine), or LDOPS alleviates OH
67. Multiple system atrophy
• Progressive neurodegenerative disorder
encompassing
• autonomic,
• extrapyramidal,
• cerebellar, and
• pyramidal features
• Pathological hallmark of MSA is neuronal loss
and gliosis within multiple sites in the brain,
intermediolateral columns, and the Onuf
nucleus, with characteristic glial cytoplasmic
inclusions (GCIs) containing α-synuclein and
ubiquitin
68. Glial cytoplasmic inclusions (GCIs)
MSA vs PD
1. Shape: GCIs tend to be irregular in outline, in contrast
to the target-shaped concentric circular Lewy bodies of
PD.
2. Cellular location: GCIs are in glia, whereas Lewy
bodies are in neurons.
3. Neuraxis location: GCIs dominate in the basal ganglia
and pons, whereas Lewy bodies occur in midbrain,
cortex, and autonomic ganglia.
69. Parkinson Disease
Lewy bodies of PD directly involve ganglia, and
hence postganglionic neurons, with degeneration
of peripheral autonomic fibers
Reduction in axon reflex sweating more frequently in PD
than in MSA
Peripheral predilection in PD is the basis for the
denervation seen on metaiodobenzylguanidine
(MIBG) scanning of the heart, diagnostic test to
distinguish PD from MSA
70. Autonomic changes in Spinal Cord
Transection
• First, a transient state of decreased excitability occurs,
known as Spinal Shock. It may last for days to weeks.
• The phenomenon of Autonomic dysreflexia can occur
with stimulation below the lesion.
– Dramatic rise in blood pressure.
– Marked reduction in flow to periphery.
– Flushing & sweating in areas above the lesion.
– In addition there may be contraction of bladder & bowel,
skeletal muscle spasm & penile erection.
• Bladder & bowel distension can elicit Mass Reflex.
71. Horner’s syndrome
• Characterized by-
Constriction of the pupil
Enophthalmos
Drooping of eye lid
Anhydrosis on affected side of face
• Occurs due to-
Damage of stellate ganglia
Paralysis of Cervical Sympathetic nerve trunk
73. Nonpharmacological
Interventions
• Treatment - primarily nonpharmacological.
• Crossing legs with forward leaning – but increase postural
instability.
• Squatting is another powerful pressor maneuver
• water aerobics or water jogging in shoulder deep water if
orthostasis is advanced.
• Orthostatic (standing) training- leaning patients upright
with the upper back against a wall and the feet away from
the wall about 1 foot (mimicking a 70-degree angle) for 10
to 20 minutes once or twice a day
• Support garments over the lower part of the body benefit
patients by acutely increasing blood pressure.
74. Dietary Measures
• Sodium- Chronically increasing dietary salt, aiming to raise
urinary sodium to 185 mmol in a 24-hour urinary collection
• Patients with OH need between 6–10 g of sodium and 2–3 L
of water
• Patients with POTS will usually require 2 g at 8 am and 2 g
at 2 pm. The duration of action is 4 to 5 hours
• Water Drinking- effect of water is greatest in the hour after
ingestion and is almost gone 90 minutes. Effect starts 5
minutes after drinking water and peaks at about 40 minutes
• Food Ingestion- Ingestion of a meal, particularly one rich in
carbohydrate, significantly lowers blood pressure.
76. Fludrocortisone
• MOA- peripheral vascular resistance, enhanced pressor
response to norepinephrine, and extravascular fluid
accumulation (edema) in the legs which limits blood pooling.
• It rapidly absorbed after oral ingestion and plasma half-life of
2 to 3 hours but biological half-life is much longer (several
days) because of nuclear changes in sodium handling.
• POTS - start with a half tablet (0.05 mg) every other day.
effect requires several days to weeks to reach its peak
• Weight is a good guide to the required dose, weight gain due
to fluid retention should be limited to 5 to 8 pounds.
• S/E – hypokalemia, supine hypertension
77. Midodrine
• Its prodrug hydrolyzed in the liver to its active form,
desglymidodrine - peripherally active α1 adrenoceptor
agonist.
• 2.5 to 10 mg every 3 to 4 hours, up to a maximum of 60
mg/day.
• peak effect of oral midodrine occurs 1 hour after
administration, duration of action is 4 to 6 hours.
• S/E - piloerection (goose flesh on scalp) and urinary
retention, Supine Hypertension
78. Droxidopa
• Droxidopa was just approved by the FDA in 2014 for
neurogenic orthostatic hypotension.
• MOA- It converted in the body directly to norepinephrine
by l-aromatic amino acid decarboxylase within the nerve
terminal. maximum effect of the drug occurs 5 hours after
ingestion
• Droxidopa is particularly beneficial in patients with DBH
deficiency also have role in PAF and MSA but limited role
in PD.
79. Pyridostigmine
• MOA- increase neuromuscular junction neural traffic at
the nicotinic receptor on the muscle, increase in blood
pressure is greater in the standing position than in the
lying position- so No supine hypertension.
• Begins with 30 mg 3 times daily
80. Supine Hypertension Rx
• Best treated with postural measures, avoiding the flat
position and sleeping with the head of the bed raised 30
to 45 degrees with the help of an electric bed or mattress
• Bed time clonidine or Ramipril
84. What we have learnt?
• Overview of anatomic and functional organization of the
sympathetic and parasympathetic system.
• Clinical features of various disorders of autonomic
nervous system, including autoimmune autonomic
ganglionopathy
• Bedside Diagnostic tests of various disorders of ANS
• Diagnostic approach to orthostatic hypotension and
implement nonpharmacologic and pharmacologic
strategies for its management.
• Recent advancement in Diagnostic modalities and
treatment