DISORDERS OF AUTONOMIC

NERVOUS SYSTEM
By Dr.Girish .M.S.

CHAIR PERSONS :
Dr.K.V.Chandrashekhar.
Dr.
Karthik Sasalu.

INTRODUCTION
Autonomic Nervous System is an important part of
Nervous System involved in involuntary regulation of
certain homeostatic functions, like blood pressure,
heart rate, sleep, bowel and bladder functions which
are essential for survival of life.
ANATOMIC ORGANISATION:
Autonomic Nervous System is divided into two parts
1 Parasympathetic Nervous System
2 Sympathetic Nervous System
Functionally the two parts acts in a complementary
fashion in regulating activities of many visceral
organs.

FUNCTIONAL CONSEQUENCES OF NORMAL AUTONOMIC NERVOUS S

Sympathetic

Parasympathetic

Heart Rate

Increased

Decreased

Blood Pressure
Bladder

Increased
Increased sphincter
tone

mildly decreased
voiding(decreased
tone)

Bowel motility
Lung
Sweat glands
Pupils

Decreased
Bronchodilation
Sweating
Dilation

Increased
Bronchoconstriction
----Constriction

Adrenal gland

----

Sexual function

Catecholamine
release
Ejaculation, Orgasm

Lacrimal gland
Parotid gland

------------------------

Tearing
Salivation

Erection

DISORDERS OF AUTONOMIC NERVOUS

SYSTEM
Autonomic disorders with brain
involvement
Autonomic disorders with Spinal cord
involvement
Autonomic disorders with Peripheral
involvement

DISORDERS OF AUTONOMIC NERVOUS SYSTEM

Autonomic disorders with brain
involvement
MSA
Parkinson disease with autonomic failure
Brain tumors (posterior fossa, third ventricle, hypothalamus),
syringobulbia, MS, tetanus, Wernicke-Korsakoff syndrome,
Autonomic disorders with Spinal cord involvement
Transverse myelitis, trauma, mass lesion


involvement

Autonomic disorders with Peripheral

Immune mediated
Guillain-Barr syndrome, acute and subacute autonomic
neuropathy, SLE, rheumatoid arthritis
Metabolic
Diabetes, vitamin B12 and thiamine deficiency, uremia

Paraneoplastic

paraneoplastic syndromes with autonomic neuropathy, LambertEaton myasthenic syndrome [cholinergic])

Infectious
syphilis, leprosy, HIV, Lyme disease, diphtheria
Hereditary
Familial amyloidosis, hereditary sensory and autonomic
neuropathies, porphyria.
Toxins and medications
Botulism, alcohol, taxoids, amiodarone, heavy metals.
Drug and medication effects
Anticholinergics: tricyclic antidepressants, atropine,
-Adrenergic blockers: propranolol and others
2-Agonists: clonidine, prazosin, -methyl dopa, terazosin,
doxazosin
1-Antagonists: phentolamine, phenoxybenzamine,
Others: hydralazine, nitrates, diuretics, calcium channel blockers,
ACE inhibitors, antihistamines, antipsychotics,sildenafil, tadalafil.

SYMPTOMS AND SIGNS OF AUTONOMIC

DYSFUNCTION
1) CARDIOVASCULAR :
ORTHOSTATIC HYPOTENSION- Defined as drop in
systolic BP >20mmHg or diastolic BP >10mmHg within 3
mins of standing.
POSTURAL ORTHOSTATIC TACHYCARDIA
SYNDROME(POTS)-Defined as presence of symptoms of
orthostatic intolerance(not OH) associated with rise in
heart rate by 30b/min or 120 b/min with in 10mins of
standing or upright tilt.
AUTONOMIC DYSREFLEXIA-Rise BP in response to
stimulation of bladder , skin or muscles.
ORTOSTATIC SYMPTOMS- dizziness, tiredness, cognitive

2) G I SYMTOMS:
Dry mouth and dysphagia, Post-prandial
bloating, distension of abdomen, constipation
and intermittent diarrhoea.
3)BLADDER DISTURBANCES:
Daytime oliguria and nocturnal polyuria
Urinary retention or incontinence, difficulty in
initiation, incomplete emptying.
4) SEXUAL DYSFUNCTION:
Erectile failure, ejaculatory dysfunction,
retrograde ejaculation into bladder, priapism.

5) PSEUDOMOTOR SYMPTOMS:
Lack of sweating after hot bath or during
exercise or in a hot day.
6)VASOMOTOR SYMPTOMS:
Persistent cold extremities, heat intolerance.
7)EYE MANIFESTATIONS:
Dry eyes with irritation, Horners syndrome,
Holmes Adies Pupillary dilatation

APPROACH TO PATIENT WITH AUTONOMIC

DYSFUNCTION:
HISTORY; H/o Relationship of symptoms to meal,
standing, exercise
H/o Medications to find those which affect
ANS
H/o Any systemic disease DM,PD,CCF
which can cause
dysautonomia.
GENERAL PHYSICAL EXAMINATION:
BP and Heart rate measurement, in supine and standing
position
Eyes examination for dryness , pupils
Skin examination for Hypo or Hyperhidrosis
Temperature for hypo or hyperthermia
DETAILED SYSTEMIC EXAMINATION AND NEUROLOGICAL

Clinical Tests of Autonomic Function

Test

Normal Response

Main Part of Reflex Arc

Tested

Blood-pressure response to
standing or vertical tilt
[tilt table testing.]

Fall in BP 20/10 mm Hg

Afferent and sympathetic

efferent limbs

Heart rate response to

standing

Increase
30:15 ratio <1.04 is
abnormal
[R-R interval ratio]

Vagal afferent and

efferent limbs

Isometric exercise for 5 mins Increase in diastolic BP,

15 mm Hg

Sympathetic efferent limb

Heart rate variation with

respiration

Maximum-minimum heart Vagal afferent and

rate 15 b/min;[<10 is
efferent limbs
abnormal]
E:I ratio<1.2 is abnormal
[R-R interval ratio]

Sweat tests

Sweating over all body

and limbs

Sympathetic efferent limb

Test

Normal Response

Main Part of Reflex Arc

Tested

Valsalva maneuver (BP

response with indwelling
arterial catheter or
continuous noninvasive
BP measurement)

Phase I: Rise in BP

Afferent and sympathetic

efferent limbs

Phase II: Gradual

reduction of BP to plateau;
tachycardia
Phase III: Fall in BP
Phase IV: Overshoot of BP,
bradycardiaa

Immersion of hand in hot

water

Increased blood flow of

opposite hand

Sympathetic efferent limb

Tests of Pupillary Innervation

0.1% adrenaline

No response

Postganglionic
sympathetic innervation

4% cocaine

Pupil dilates

Sympathetic innervation

2.5% methacholine
0.125% pilocarpine

No response

Parasympathetic
innervation

0.5% apraclonidine

Pupil dilates and ptosis

resolves in Horner
syndrome

Parasympathetic
innervation

SPECIFIC SYNDROMES OF ANS

DYSFUNCTION:
1)Acute/ Subacute pandysautonomia:
Acute autonomic storm
Acute autonomic paralysis

2)Chronic autonomic Syndromes:

Primary autonomic dysfunction
syndromes
Secondary autonomic neuropathies

ACUTE AUTONOMIC STORM

CAUSES:
a) Brain and Spinal cord injury due to severe
head trauma,
hemorrhage, cerebral
infarction , hydrocephalus.
b)Drugs and Toxins: Cocaine, Amphetamine,
Tricyclic antidepressants, Tetanus , Botulism.
c)Pheochromocytoma
MECHANISM: Signs and symptoms are due to
massive catecholamine surge.

SIGNS AND SYMPTOMS:

Fever, Tachycardia, Seizures, Hypertension,
papillary dilatation, hyperhidrosis, anxiety,
palpitation.
MANAGEMENT: Patient to be managed in ICU
Morphine sulphate, 10mg 4th hourly
Labetolol, 100-200mg twice daily
Clonidine/propranolol in mild autonomic
storm

ACUTE AUTONOMIC
PARALYSIS
CAUSE:
Idiopathic, but roughly half of the cases are preceded
by viral infection similar to G B Syndrome.
Auto antibodies against ganglionic acetylcholine
receptors found in half of idiopathic cases.
SIGNS AND SYMPTOMS:
Develop over a period of week or few weeks.
Patient presents with orthostatic hypotension,
loss of lacrimation and salivation with dry eyes and
dry mouth
Bladder dysfunction-Urinary retention,
Bowel dysfunction-Post prandial bloating or
constipation,
Loss of vasomotor response in skin with heat

INVESTIGATIONS:
CSF Protein normal or slightly elevated.
Clinical tests indicate both PNS and SNS
involvement sparing somatosensory and motor
nerve fibres.
MANAGEMENT:
Symptom specific management of Orthostatic
Hypotension, Gastroparesis and Sicca
Symptoms.
Intravenous Gamma Globulin infusion and
plasma exchange have been used with benefit in

CHRONIC AUTONOMIC SYNDROMES:

MULTIPLE SYSTEM ATROPY
Chronic Degenerative disease characterized by
neuronal loss and gliosis in many CNS regions such as
Brain stem, cerebellum, and striatum
intermediolateral column of thoracolumbar spinal card.
MSA comprise autonomic failure and either
parkinsonism(MSA-p) or cerebellar syndrome (MSA- c)
MSA-P : SHY- DRAGGER SYNDROME
Parkinsonism is atypical, being unassociated with
significant tremor or response to levodopa.
Autonomic failure is more severe and generalized
compared to typical PD.
Symptomatic development of OH within one year of
onset of PD predicts eventual development of MSA P
in 75% of patients.
MRI brain shows T2 hypo intensity due to Iron

MULTIPLE SYSTEM ATROPHY ( CEREBELLAR

TYPE): MSA - C
Associated with degenerative changes in striatum,
cerebellum,pons and medulla.
Presents with OH, Urinary incontinence and
impotence.
MRI brain shows T2 hyperintense signal
( characteristically described as Hot cross buns sign)
MSA generally progress relentlessly to death in 7 10
years
Management Symptomatic for OH, Gastroparesis,
urinary incontinence.

PURE AUTONOMIC FAILURE:

Degenerative disease with severe reduction in
postganglionic sympathetic neurons.
The disorder begins in middle age, and more common
in women.
Parasympathetic Nervous System & Central Nervous
Systems are spared
Plasma levels of NE are subnormal
Symptoms- OH, impotance, bladder dysfunction and
defective sweating.
Symptoms can be disabling, but disease doesnot
shorten life.

POSTURAL ORTHOSTATIC TACHYCARDIA

SYNDROME (POTS):
Characterized by symptomatic orthostatic intolerance
and by either increase HR to > 120 bpm or increase HR
by 30 bpm on standing which subsides on sitting or
lying down.
Women are affected 5 times more commonly.
Approximately half of patients report antecedent viral
infection.
Pathogenesis not exactly clear, but impaired brain
stem regulation or beta receptor super sensitivity had
been proposed.
Symptoms: Syncopal symptoms (light headedness
weakness, blurring of vision) combined with symptoms
of autonomic over activity- Palpitation, tremulousness,
nausea.

PRIMARY HYPERHIDROSIS
Presents with excess sweating of palms and soles.
Affects 0.6 1.0 % population
Etiology unclear
Though not dangerous, but socially embarrassing or
disabling (soiling of paper while writing or
handshaking.)

MANAGEMENT:
Topical antiperspirants occasionally helpful
Anticholenergic drugs Glycopyrrolate, 1 -2 mg TID
Local injection with Botulinum toxin
T2 Ganglionectomy or sympathectomy is successful
in > 90 % of palmar hyperhydrosis.

RILEY DAY SYNDROME:

Hereditary sensory and autonomic neuropathy type
III (HSAN - III) which presents as familial
dysautonomia is known as Riley Day Syndrome.
Affects infants and children among Ashkenazi Jews
Autosomal recessive ,defective gene IKBKAP, is
located on long arm of chromosome 9.
Presents as decreased tearing, hyperhidrosis reduced
sensitivity to pain and labile BP.

ANS DYSFUNCTION IN SPINAL CARD

LEASIONS
Initial effect present as spinal shock which last for
several weeks with abolition of all autonomic functions,
and presents with hypotension, loss of sweating
paralytic ileus and gastric and bladder atony.
After spinal shock dissipates the autonomic function
returns but it may have OH or autonomic Dysreflexia.
Autonomic dysreflexia- seen in few cases of traumatic
lesions of
spinal card above C6 levels.
Characterized by increase on BP in response to
distention
of bladder, Suprapubic palpation, catheter
insertion, skin or
muscle stimuli.
Complication: Intracranial hemorrhage, cardiac
arrhythmias, death
may occur.

DIABETIC AUTONOMIC NEUROPATHY

Affects both type I and type II DM
Usually begins ~ 10 years after onset of DM
Can involve multiple systems- CVS, GIT, genitourinary
and metabolic systems.
Can cause-OH, abdominal bloating, nocturnal diarrhea
alternating with constipation, bladder dysfunction asfailure to void urine completely, urinary hesitancy or
incontinence, erectile dysfunction in men and loss of
libido in women.
Increases risk of hypoglycemia By decreasing ability to sense hypoglycemia.
By reducing counter regulatory hormone release.
Management: Glycemic control and symptomatic
treatment for autonomic dysfunction.

AMYLOIDOSIS AND ANS

DYSFUNCTION
AL type and ATTR familial type of Amyloidosis are
associated with autonomic dysfunction
Shows amyloid deposition in intraneural blood vessel
and in autonomic ganglia.
Diagnosis made by demonstration of Amyloid deposits
in AL type and by genetic testing for Transthyretin
mutation in familial cases.
Bone marrow, Stem cell transplantation are promising
evolving treatments

ALCOHOLIC AUTONOMIC
NEUROPATHY
Abnormalities of ANS functions are usually mild.
Symptoms of autonomic dysfunction appear usually
when polyneuropathy is severe , and there is usually
co-existing Wernickes encephalopathy.
orthostatic hypotension is usually due to brainstem
involvement ,
impotence is also a major problem.
Alcohol withdrawal symptoms and delirium tremens
may be associated with autonomic overactivity in the
form of increase in PR , BP, respiration and

ANS DYSFUNCTION IN
PORPHYRIA
Acute intermittent type of porphyria is more
commonly associated with autonomic dysfunction.
Symptoms are due to increased catecholamine
levels during the attacks and includes
tachycardia, hypertension(less commonly
hypotension) sweating, urinary retention, anxiety,
abdominal pain, nausea and vomiting .

ANS DYSFUNCTION IN GB
SYNDROME
Autonomic involvement is independent of severity of
motor and sensory neuropathy.
Demyelination has been described in vagus nerve and
sympathetic chains.
2-10% of suffer fatal cardiovascular collapse.
Other symptoms of autonomic dysfunction may also
appear as gastrointestinal and bladder disturbances,
abnormal sweating etc

BOTULINUM TOXIN AND ANS

DYSFUCTION
BT binds presynaptically to cholinergic nerve terminal
and blocks Ach release .
symptoms - blurring of vision, dry mouth, nausea,
unreactive pupil, constipation, and urinary retention.
LAMBERT EATON MYASTHENIC
SYNDROME [LEMS]
Caused by auto-antibodies against P/Q type of
calcium channels at nerve terminals, which causes
impaired release of Ach.

MANAGEMENT OF AUTONOMIC
FAILURE
Includes1] Specific treatment of primary causes if present-Eg:
withdrawal of affending drug, Alcohol, control of sugar
levels in DM etc.
2] Alleviation of symptoms of ANS dysfunction OH,
Eye care, Gastrointestinal and bladder disturbances.

MANAGEMENT OF ORTHOSTATIC
HYPOTENSION
Non-pharmacological measures;
1] Patient education- about orthostatic stressors and
to avoid factors which provoke symptoms, Eg..
prolonged standing, sudden postural change, hot bath,
severe exertion, large meals, alcohol.
2] High salt diet- 10 to 20 gm/day
3] High fluid intake [2L/day]
4] Frequent small low carbohydrate meals
5] Elevation of head of bed by 10cm

MANAGEMENT OF ORTHOSTATIC
HYPOTENSION
Pharmacological measures:
1] Medodrine [ Directly acting Alpha-1 agonist] Dose:
5-10mg, TID.
Side effects- pruritis, uncomfortable piloerection and
supine hypertension.
2] Fludrocortisone 0.1mg- 0.3 mg PO, BD
Side effects- CCF, Supine hypertension,hypokalemia.
3] Pyridostigmine- improves OH without causing
supine hypertension
4] Postprondial OH may respond to--Ibuprofen or
Indomethacin

MANAGEMENT OF SUPINE HYPERTENSION [BP>

180/110 mmHg]
Avoiding supine position or by decreasing dose of
Fludrocortisone.
A glass of wine shortly before bedtime [if requested by
patient]
Drugs used are-

1] Hydralazine 25mg qhs

2]Procardia 10mg qhs
3]Nitroglycerine patch.