Disorders of the Autonomic Nervous System

1. Disorders of the Autonomic
Nervous System

2. AUTONOMIC NERVOUS SYSTEM
• The autonomic nervous system (ANS) is a division of
the peripheral nervous system that supplies smooth
muscle and glands, and thus influences the function
of internal organs.
• The autonomic nervous system has three branches
1. Parasympathetic nervous system
2. Sympathetic nervous system
3 . Enteric nervous system

3. ANS

4. FUNCTIONS

5. ENTERIC NERVOUS SYSTEM
• Parasympathetic control of the GI system is through
the craniospinal nerves (vagus and S2-S4 nerves) while
sympathetic control is through the thoracolumbar
region.
• The enteric nervous system itself is made up of a series
of ganglia that form a network of plexuses with
several hundred million cells (the equivalent of the
number of cells in the spinal cord).
• Meissner’s (submucosal) plexus, Auerbach’s
(myenteric), Cajal’s (deep muscular), mucosal and
submucosal plexuses comprise the majority of nerves
within the enteric nervous system.

6. SYMPTOMS ASSOCIATED WITH ANS
DYSFUNCTION
• Unexplained OH
• Syncope
• Sleep dysfunction
• Altered sweating (hyperhidrosis or hypohidrosis)
• Impotence
• Constipation or other GI symptoms (bloating, nausea,
vomiting of old food, diarrhea),
• Bladder disorders (urinary frequency, hesitancy, or
incontinence).

7. DISORDERS OF ANS
Can be classified broadly into three groups
I. Autonomic Disorders with Brain Involvement
II. Autonomic Disorders with Spinal Cord Involvement
III. Autonomic Neuropathies

10. Autonomic Disorders with Spinal Cord
Involvement
• Traumatic quadriplegia
• Syringomyelia
• Subacute combined degeneration
• Multiple sclerosis and neuromyelitis optica
• Amyotrophic lateral sclerosis
• Tetanus
• Stiff-person syndrome
• Spinal cord tumors

11. AUTONOMIC NEUROPATHIES
A. Acute/subacute autonomic neuropathies
a. Subacute autoimmune autonomic ganglionopathy
(AAG)
b. Subacute paraneoplastic autonomic neuropathy
c. Guillain-Barré syndrome
d. Botulism
e. Porphyria
f. Drug induced autonomic neuropathies-stimulants, drug
withdrawal, vasoconstrictor, vasodilators, beta-
receptor antagonists, beta-agonists
g. Toxin-induced

12. B. Chronic peripheral autonomic neuropathies
1. Distal small fiber neuropathy
2. Combined sympathetic and parasympathetic failure
a. Amyloid
b. Diabetic autonomic neuropathy
c. AAG (paraneoplastic and idiopathic)
d. Sensory neuronopathy with autonomic failure
e. Familial dysautonomia (Riley-Day syndrome)
f. uremic, or nutritional deficiency
g. Geriatric dysautonomia (age >80 years)
C. Disorders of orthostatic intolerance reflex syncope;
POTS; prolonged bed rest; space flight; chronic fatigue

13. NEUROGENIC ORTHOSTATIC
HYPOTENSION
• OH is defined as a sustained drop in systolic (≥20 mmHg)
or diastolic (≥10 mmHg) BP after 3 min of standing.
• OH due to dysfunction of the ANS it is referred to as
neurogenic OH .
• A clue that the patient has neurogenic OH is the
aggravation or precipitation of OH by autonomic
stressors (a meal, hot bath, or exercise) .
• In non-neurogenic causes of OH (such as hypovolemia),
the BP drop is accompanied by a compensatory increase
in heart rate of >15 beats/min.

14. Symptoms of Orthostatic Hypotension

15. DIAGNOSIS
• Orthostatic hypotension is diagnosed by comparing
blood pressure readings in the supine and standing
positions.
• Blood pressure is taken initially after a five-minute
period of supine rest then again after the patient has
been standing for two to five minutes.
• The threshold of change for orthostatic hypotension is:
A reduction of 20 mmHg or more in systolic pressure
A reduction of 10 mmHg or more in diastolic pressure

16. • The ratio between the increase in heart rate and the
fall in blood pressure provides the most sensitive and
specific bedside differentiator between neurogenic
(ie, due to baroreflex failure) and nonneurogenic
orthostatic hypotension (ie, due to volume depletion).
• An increase of ≤0.5 beats/minute for every 1 mmHg
drop in systolic blood pressure during tilt-table testing
or active standing may be useful to diagnose
neurogenic orthostatic hypotension.
• An increase in heart rate of >30 beats per minute in the
absence of orthostatic hypotension suggests postural
tachycardia syndrome (POTS), which usually does not
include orthostatic hypotension.

17. NONNEUROGENIC CAUSE OF
OH

19. POSTURAL ORTHOSTATIC
TACHYCARDIA SYNDROME (POTS)
• Symptomatic orthostatic intolerance without OH,
accompanied by either an increase in heart rate to >120
beats/min or an increase of 30 beats/min with standing
that subsides on sitting or lying down.
• Presyncopal symptoms (lightheadedness, weakness,
blurred vision) combined with symptoms of autonomic
overactivity (palpitations, tremulousness, nausea) are
common.
• Expansion of fluid volume with water, salt, and
fludrocortisone can be helpful as an initial intervention.
• Low-dose propranolol (20 mg) provides a modest
improvement in heart rate control and exercise capacity. If
these approaches are inadequate, then midodrine,
pyridostigmine, or clonidine can be considered.

20. AUTONOMIC TESTING
• Heart Rate Variation With Deep Breathing
• Valsalva Response
• Sudomotor Function
• Orthostatic BP Recordings
• Tilt Table Testing For Syncope

21. AUTONOMIC TESTING

22. VALSALVA MANEUVER

23. DIABETIC AUTONOMIC NEUROPATHY
(DAN)
• A wide spectrum of manifestations affecting many
different organ systems can occur, including the
cardiovascular, gastrointestinal, genitourinary,
pupillary, sudomotor, and neuroendocrine systems.
• Earliest clinical manifestation of cardiac autonomic
neuropathy may be a resting tachycardia.
• The increased resting heart rate is due to unopposed
cardiac sympathetic nerve activity.
• As the autonomic neuropathy progresses, the heart
rate gradually slows and in advanced cases will
manifest as a fixed heart rate

24. • The presence of orthostatic hypotension in
diabetes is associated with a significant increase in
10-year mortality.
• Peripheral autonomic nerve dysfunction may be
manifest as changes in the texture of the skin, itching,
edema, venous prominence, callus formation, loss of
nails, and sweating abnormalities of the feet. It is
contributing factor for the development of foot
ulceration, dry skin, pruritus, peripheral edema, and
the development of Charcot arthropathy.

25. • Gastrointestinal autonomic neuropathy results in
disorders of esophageal motility, gastric emptying
(gastroparesis), and intestinal function.
• Diabetic genitourinary autonomic neuropathy
causes bladder dysfunction, retrograde ejaculation,
erectile dysfunction, and dyspareunia.

26. Screening for DAN at the time of diagnosis of type 2
diabetes and five years after the diagnosis of type 1
diabetes.
• Screening should include a history and physical
examination for signs of autonomic dysfunction
• Tests of heart rate variability may be indicated,
including expiration-to-inspiration ratio, response to
the Valsalva maneuver, and response to standing.
• If initial screening is negative, a history and physical
examination for signs of autonomic dysfunction
should be repeated annually .

27. MULTIPLE SYSTEM ATROPHY
• is an entity that comprises autonomic failure (OH or a
neurogenic bladder) and either parkinsonism (MSA-p)
or a cerebellar syndrome (MSA-c).
• MSA-p is the more common form; the parkinsonism is
atypical in that there is more symmetric motor
involvement than in Parkinson’s disease (PD; Chap.
427), tremor is not as prominent, and there is a poor or
only transient response to levodopa.
• Symptomatic OH within 1 year of onset of
parkinsonism occurs.

28. • Brain magnetic resonance imaging (MRI) is a useful
diagnostic adjunct: in MSA-p, iron deposition in the
striatum may be evident as T2 hypointensity, and in
MSA-c, cerebellar atrophy is present with a
characteristic T2 hyperintense signal (“hot cross buns
sign”) in the pons

29. PERIPHERAL NERVE AND NMJ
DISORDERS
• Polyneuropathies that affect small myelinated and
unmyelinated fibers of the sympathetic and
parasympathetic nerves commonly occur in diabetes
mellitus, amyloidosis, chronic alcoholism, porphyria,
and Guillain-Barré syndrome.
• Neuromuscular junction disorders with autonomic
involvement include botulism and Lambert-Eaton
syndrome.

30. • Amyloidosis patients usually present with a distal
sensorimotor polyneuropathy accompanied by
autonomic insufficiency that can precede the
development of the polyneuropathy or occur in
isolation.
• Autonomic failure generally appear only when the
stocking-glove polyneuropathy is severe, and there is
usually coexisting Wernicke’s encephalopathy in
Alcoholic Neuropathy.
• BP fluctuations and arrhythmias from autonomic
instability can be severe in GBS. It is estimated that
between 2 and 10% of patients with severe Guillain-
Barré syndrome suffer fatal cardiovascular collapse.

31. DRUGS AFFECTING ANS

32. ACUTE SYMPATHETIC OVERACTIVITY
SYNDROMES
• Autonomic storm is an acute state of sustained
sympathetic surge that results in variable combinations
of alterations in BP and heart rate, body temperature,
respiration, and sweating.
• Causes of autonomic storm include brain and spinal cord
injury, toxins and drugs, autonomic neuropathy, and
chemodectomas (e.g., pheochromocytoma).
• Consistent setting is that of an acute intracranial
catastrophe of sufficient size and rapidity to produce a
massive catecholaminergic surge e.g hemorrhage,
cerebral infarction, rapidly expanding tumors,
subarachnoid hemorrhage, hydrocephalus,

33. • The surge can cause seizures, neurogenic pulmonary
edema, and myocardial injury.
• Manifestations include fever, tachycardia,
hypertension, tachypnea, hyperhidrosis, pupillary
dilatation, and flushing.
• Drugs and toxins can be a cause, including
sympathomimetics such as phenylpropanolamine,
cocaine, amphetamines, and tricyclic antidepressants;

34. Treatment of Orthostatic Hypotension

35. • If previous measures are not sufficient, additional
pharmacologic treatment may be necessary.
• Midodrine, a directly acting α1 -agonist that does not
cross the blood-brain barrier, is effective. It has a
duration of action of 2–4 h. The usual dose is 5–10 mg
orally tid, but some patients respond best to a
decremental dose.
• Droxidopa for treatment of neurogenic OH associated
with PAF, PD, or MSA is effective in decreasing
symptoms of OH.
• Fludrocortisone will reduce OH but aggravates supine
hypertension. At doses between 0.1 mg/d and 0.3 mg
bid orally, it enhances renal sodium conservation and
increases the sensitivity of arterioles to NE

36. • Postprandial OH may respond to frequent, small, low-
carbohydrate meals which may diminish splanchnic
shunting of blood after meals and reduce postprandial
OH.
• Prostaglandin inhibitors (ibuprofen or indomethacin)
taken with meals or midodrine (10 mg with the meal)
can be helpful.
• The somatostatin analogue octreotide can be useful in
the treatment of postprandial syncope by inhibiting the
release of GI peptides that have vasodilator and
hypotensive effects.

37. REFERENCES
• Harrison's Principles of Internal Medicine,
20th Edition
• Uptodate

38. THANK YOU