This document discusses disorders of the autonomic nervous system. It begins by describing the anatomy and neurotransmitters of the sympathetic and parasympathetic nervous systems. It then discusses various tests used to evaluate autonomic function, including heart rate variation with deep breathing, the Valsalva maneuver, sudomotor function tests, and orthostatic blood pressure recordings. The document concludes by describing specific autonomic disorders like Parkinson's disease, spinal cord lesions, autoimmune autonomic neuropathy, and postural orthostatic tachycardia syndrome.

1. Disorders of
Autonomic Nervous
System
Zubair Sarkar

2. Anatomic Organization
• Autonomic nervous system consists of
Parasympathetic nervous system
Sympathetic nervous system
• The activity of ANS is regulated by central neurons which
post integration of afferent information adjust the
autonomic outflow according to the need.

3. • The preganglionic neurons of the parasympathetic nervous
system leave CNS in the third, seventh, ninth, and tenth
cranial nerves as well as the second and third sacral nerves.
• The preganglionic neurons of the sympathetic nervous system
exit the spinal cord between the first thoracic and the second
lumbar segments.
• The preganglionic fibres are thinly myelinated

4. • The postganglionic neurons, located in ganglia outside the
CNS, give rise to the postganglionic unmyelinated autonomic
nerves that innervate organs and tissues throughout the
body.

6. • Acetylcholine (ACh) is the preganglionic neurotransmitter for
both divisions of the ANS as well as the postganglionic
neurotransmitter of the parasympathetic neurons
• Norepinephrine (NE) is the neurotransmitter of the
postganglionic sympathetic neurons, except for cholinergic
neurons innervating the eccrine sweat glands.
• Purinergic fibers may play a role in the control of vasomotor
tone and in the regulation of regional blood flow.

7. • Responses to sympathetic and parasympathetic stimulation
are frequently antagonistic reflecting highly coordinated
interactions within the CNS.

9. Autonomic control of BP and HR
• Arterial blood pressure is directly proportional to
both vascular resistance and cardiac output; it is
maintained within a narrow range by the baroreflex
mechanisms
• Vasomotor tone, which determines peripheral
resistance, is controlled by the sympathetic nervous
system through a group of neurons in the
ventrolateral medulla that project to the
intermediolateral column(ILC).

10. • The baroreceptors in the carotid sinus and aortic arch are
sensitive to transient blood pressure changes and
maintain the systemic blood pressure at a relatively
constant level.
• When the blood pressure falls, there is a reduction in the
frequency of impulses from the baroreceptors to the
nucleus tractus solitarius and other brainstem centers.
• The reflex increase in sympathetic activity causes an
increase in the vasomotor tone. The corresponding
decrease in vagal efferent activity to the heart causes an
increase in the heart rate.

12. • Sympathetic nerve fiber activity in muscles increases in
response to
a fall in blood pressure
to changes in posture from the lying to sitting and
standing positions and
to the application of negative pressure to the lower body,
which is thought to unload intra thoracic low-pressure
volume receptors.

13. • The splanchnic vascular bed plays an important part in
the regulation of blood pressure in humans. There is a
marked decrease in mesenteric blood flow
on assuming the upright posture or
on applying negative pressure to the lower body

14. Autonomic Control of Sweat Glands
and Skin Blood Vessels
• The sweat glands
postganglionic sympathetic cholinergic fibers and
vasoactive intestinal peptide (VIP)-containing fibers
• Skin blood vessels
postganglionic sympathetic noradrenergic fibers.

15. • The sudomotor fibers are faster conductors than the
vasomotor fibers.
• Muscle and skin sympathetic activity differ in their responses
to a range of stimuli.
• Skin sympathetic activity, in contrast to muscle sympathetic
activity, is increased by mental stress and emotional stimuli
and cooling, but not significantly by the Valsalva maneuver or
body posture.

16. Classification
I. Diseases affecting central nervous system
A. Progressive autonomic failure (PAF) (idiopathic
orthostatic hypotension)
1. Pure PAF
2. PAF with parkinsonian features(PAF-P)
3. PAF with multiple-system atrophy (Shy-Drager
syndrome)(PAF-MSA)
B. Parkinson’s disease
C. Spinal cord lesions
D. Wernicke’s encephalopathy

17. E. Miscellaneous diseases
1. Cerebrovascular disease
2. Brainstem tumors
3. Multiple sclerosis
4. Adie’s syndrome
5. Tabes dorsalis

18. II.Diseases affecting the peripheral autonomic
nervous system
A. Disorders with no associated peripheral neuropathy
1. Acute and subacute autonomic neuropathy
a. Pandysautonomia
b. Cholinergic dysautonomia
2. Botulism

19. B. Disorders associated with peripheral neuropathy
1. Autonomic dysfunction clinically important
a. Diabetes
b. Amyloidosis
c. Acute inflammatory neuropathy
d. Acute intermittent porphyria
e. Familial dysautonomia (Riley-Day syndrome)
f. Chronic sensory and autonomic neuropathy

20. 2. Autonomic dysfunction usually clinically not important
a. Alcohol-induced neuropathy
b. Toxic neuropathies
c. Malignancy
d. Vitamin B12 deficiency
e. Rheumatoid arthritis
f. Chronic renal failure
g. Systemic lupus eryrhematosus
h. Mixed connective tissue disease
i. Fabry’s disease
j. Chronic inflammatory neuropathy

21. Symptomsof Dysautonomia
• orthostatic hypotension
• syncope
• sleep dysfunction
• altered sweating (hyperhidrosis or hypohidrosis)
• constipation
• upper gastrointestinal symptoms (bloating, nausea, vomiting
of old food)
• impotence or
• bladder disorders (urinary frequency, hesitancy, or
incontinence)

22. Testsfor Dysautonomia
Heart Rate Variation with Deep Breathing
• parasympathetic component (vagus nerve) of cardiovascular
reflexes.
• Influenced by multiple factors
 subject’s position (recumbent, sitting or standing)
 rate and depth of respiration
 age
 medications
 weight and
 degree of hypocapnia

23. • Interpretation of results requires comparison of test data with
results from age-matched controls collected under identical
test conditions.
• For example, the lower limit of normal heart rate variation with
deep breathing in persons <20 years is 15–20 beats/min, but
for persons over age 60 it is 5–8 beats/min.
• Rate variation with deep breathing (respiratory sinus
arrhythmia) is abolished by the muscarinic acetylcholine (ACh)-
receptor antagonist atropine but is unaffected by sympathetic
postganglionic blockade (e.g., propranolol)

24. Valsalva Response
• Assesses integrity of the baroreflex control of heart rate
(parasympathetic) and BP (adrenergic).
• Tested in the supine position.
• The subject exhales against a closed glottis for 15s.
• Autonomic function during the Valsalva maneuver can be
measured using beat-to-beat blood pressure or heart rate
changes.

25.  Sudomotor Function
• Sweating is induced by release of Ach from sympathetic
postganglionic fiber.
• The quantitative sudomotor axon reflex test (QSART) is a
measure of regional autonomic function mediated by ACh-
induced sweating.
• A reduced or absent response indicates a lesion of the
postganglionic sudomotor axon. For example, sweating may be
reduced in the feet as a result of distal polyneuropathy (e.g.,
diabetes).

26. • The thermoregulatory sweat test (TST) is a qualitative measure
of regional sweat production in response to an elevation of
body temperature under controlled conditions.
• An indicator powder (alizarin red powder or iodine corn starch)
changes color with sweat production during temperature
elevation. The pattern of color change is a measure of regional
sweat secretion.

27. • A postganglionic lesion is present if both QSART and TST
show absent sweating.
• In a preganglionic lesion, QSART is normal but TST shows
anhidrosis.

28. Orthostatic BP Recordings
• Beat-to-beat BP measurements determined in supine, 70° tilt,
and tilt-back positions.
• The BP change combined with heart rate monitoring is useful
for the evaluation of patients with suspected OH or
unexplained syncope

29. Tilt Table Testing for Syncope
• The great majority of patients with syncope do not have
autonomic failure.
• Tilt table testing can be used to make the diagnosis of
vasovagal syncope with sensitivity, specificity, and
reproducibility.
• A standardized protocol is used that specifies the tilt
apparatus, angle and duration of tilt, and procedure for
provocation of vasodilation (e.g., sublingual or spray
nitroglycerin).

30. Treatment
• Management of autonomic failure is aimed at specific
treatment of the cause and alleviation of symptoms.
• Of particular importance is the removal of drugs or
amelioration of underlying conditions that cause or aggravate
the autonomic symptoms, especially in the elderly.

32. PATIENT EDUCATION
• Only a minority require drug treatment.
• All patients should be taught
the mechanisms of postural normotension
 volume status
resistance and capacitance bed
 autoregulation
the nature of orthostatic stressors
 time of day and
 the influence of meals, heat, standing, and exercise

33. Patients should learn to
• Recognize orthostatic symptoms early (especially subtle
cognitive symptoms, weakness, and fatigue) and to modify or
avoid activities that provoke episodes.
• Keep a BP log
• Dietary modification (salt/fluids).
• Learn physical counter maneuvers that reduce standing OH
• Practice postural and resistance training.

34. • SYMPTOMATIC TREATMENT
Non pharmacological:
Adequate intake of salt and fluids to produce a voiding volume
between 1.5 and 2.5 L of urine each 24 h is essential
Elevation of head end while sleeping.
Prolonged recumbency should be avoided when possible.

35.  Sitting with legs dangling over the edge of the bed for several
minutes before attempting to stand.
 Leg-crossing with maintained contraction of leg muscles for 30
seconds compresses leg veins and increases systemic
resistance.
 Compressive garments, such as compression stockings and
abdominal binders, are helpful occasionally but are
uncomfortable.

36. Anemia should be corrected with erythropoietin, administered
subcutaneously at doses of 25–75 U/kg three times per week.
The hematocrit increases after 2–6 weeks.
A weekly maintenance dose is usually necessary.
The increased intravascular volume that accompanies the rise
in hematocrit can exacerbate supine hypertension.

37. Pharmacological treatment
Midodrine
directly acting α 1 -agonist
does not cross the blood-brain barrier
duration of action 2–4 h.
The usual dose is 5–10 mg orally tid
Side effects include pruritus, uncomfortable piloerection, and
supine hypertension especially at higher doses.

38. Pyridostigmine
a parasympathomimetic and a reversible cholinesterase
inhibitor
enhances ganglionic transmission.
improves OH without aggravating supine hypertension

39. Fludrocortisone
enhances renal sodium conservation and increases the
sensitivity of arterioles to NE.
At doses between 0.1 mg/d and 0.3 mg bid orally, it reduces
OH, but it aggravates supine hypertension.
Susceptible patients may develop fluid overload, congestive
heart failure, supine hypertension, or hypokalemia.

40. Specific Syndromes
• Progressive Autonomic Failure
• Idiopathic orthostatic hypotension, or progressive autonomic
failure (PAF), is a primary degenerative disorder of the
central and peripheral autonomic nervous systems.
• The condition may be uncomplicated by other neurological
manifestations (PAF), or may be associated with
• Parkinsonian features (PAF-P)
• or multiple-system atrophy (PAF-MSA)

41. • In PAF there is a loss of cells in the ILC, loss of small
myelinated fibers in the ventral roots, and loss of neurons in
the dorsal vagal nuclei.
• Degeneration of sympathetic ganglia and the appearance of
Lewy bodies with hyaline structures in the sympathetic
ganglion cells.

42. • Clinical features include
postural hypotension (most important)
impairment of the sweating mechanism,
disturbances of heart rate and blood pressure control.
• Management is mostly non pharmacological. Drugs are
used for severe symptoms

43. Parkinson’s Disease
• Autonomic disturbances are common in advanced disease.
• Difficult to distinguish from PAF-P
• Management is symptomatic and that of underlying disease

44. Spinal Cord Lesions
• Spinal cord lesions from any cause may result in focal
autonomic deficits or autonomic hyper reflexia
• Autonomic dysreflexia describes a dramatic increase in blood
pressure in patients with traumatic spinal cord lesions above
the C6 level, often in response to stimulation of the bladder,
skin, or muscles.

45. • Potential complications include intracranial vasospasm or
hemorrhage, cardiac arrhythmia, and death.
• Awareness of the syndrome and monitoring of blood
pressure during procedures in patients with acute or chronic
spinal cord injury is essential.

46. Autoimmune Autonomic Neuropathy(AAN)
• Presents with the subacute development of autonomic
disturbances with
OH
enteric neuropathy (gastroparesis, ileus,
constipation/diarrhea), and
cholinergic failure(loss of sweating, sicca complex, and a tonic
pupil)

47. • Autoantibodies against the ganglionic ACh receptor (A3 AChR)
are present and are now considered to be diagnostic.
• Beneficial response to plasmapheresis or intravenous immune
globulin has been documented
• Symptomatic management of OH, gastroparesis, and sicca
symptoms is essential.

48. Postural Orthostatic Tachycardia Syndrome(POTS)
• Characterized by symptomatic orthostatic intolerance (not OH)
and 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.
• Syncopal symptoms (lightheadedness, weakness, blurred
vision) combined with symptoms of autonomic overactivity
(palpitations, tremulousness, nausea) are common.

49. • Expansion of fluid volume and postural training are initial
approaches to treatment.
• If these approaches are inadequate, then midodrine,
fludrocortisone, phenobarbital, beta blockers, or clonidine
may be used.

50. Inherited Disorders
• There are five known hereditary sensory and autonomic
neuropathies (HSAN I–V).
• The most important ones are HSAN I and HSAN III (Riley-Day
syndrome; familial dysautonomia).

51. • HSAN I is dominantly inherited and often presents as a distal
small-fiber neuropathy (burning feet syndrome).
• The responsible gene, on chromosome 9q, is designated
SPTLC1 . SPTLC is an important enzyme in the regulation of
ceramide.

52. • HSAN III, an autosomal recessive disorder of infants and
children that occurs among Ashkenazi Jews, is much less
prevalent than HSAN I.
• Decreased tearing, hyperhidrosis, reduced sensitivity to pain,
areflexia, absent fungiform papillae on the tongue, and labile
BP may be present . Episodic abdominal crises and fever are
common.
• The defective gene, named IKBKAP , is also located on the
long arm of chromosome 9.

53. Acute Autonomic Syndromes
• An autonomic storm is an acute state of sustained sympathetic
surge that results in variable combinations of alterations in
blood pressure and heart rate, body temperature, respiration,
and sweating.
• Causes of autonomic storm are
brain and spinal cord injury,
 toxins and drugs,
autonomic neuropathy, and
chemodectomas (e.g., pheochromocytoma).