The Autonomic Nervous System

The history in patients with autonomic insufficiency may
reveal symptoms related to orthostatic hypotension, abnormalities of
sweating, or dysfunction of the GI or genitourinary tracts. Symptoms of
orthostasis include dizziness or lightheadedness, feelings of
presyncope, syncope, palpitations, tremulousness, weakness, confusion,
or slurred speech, all worse with standing. Occasional patients
complain only of difficulty walking. The symptoms of orthostasis are
often worse postprandially,

after
a hot bath or ingestion of alcohol, or following exercise. Sweating
abnormalities may produce abnormal dryness of the skin, sometimes with
excessive sweating in uninvolved regions. Other symptoms include
constipation, dysphagia, early satiety, anorexia, diarrhea
(particularly at night), weight loss, erectile dysfunction, ejaculatory
failure, retrograde ejaculation, urinary retention, urinary urgency,
recurrent urinary tract infections, and urinary or fecal incontinence.

The general physical and neurologic examinations may
reveal a variety of abnormalities in patients with disorders of the
autonomic nervous system. Acromegaly, dwarfism, signs of endocrine
imbalance or sexual immaturity may indicate a hypothalamic abnormality.
Abnormal dryness of the skin may be a sign of sudomotor failure and
could occur in a localized distribution, as with a peripheral nerve
injury, or be generalized, as in diffuse dysautonomia. Lack of normal
moisture in the socks may indicate deficient sweating. A simple bedside
test to demonstrate the distribution of abnormal skin dryness related
to loss of sweating is to note the resistance to stroking of the skin
with a finger or an object such as the barrel of a pen or a spoon. When
a spoon is drawn over the skin, it pulls smoothly over dry
(sympathectomized) skin but irregularly and unevenly over moist,
perspiring skin. It is often possible to see the sweat droplets on the
skin, especially on the papillary ridges of the fingers, using the +20
ophthalmoscope lens. Other cutaneous signs of autonomic dysregulation
include changes in skin temperature or color, mottling, alopecia,
hypertrichosis, thickening or fragility of the nails, absent
piloerection, decreased hand wrinkling in water, and skin atrophy.
Acral vasomotor dysregulation may lead to pallor, acrocyanosis,
mottling, erythema, or livedo reticularis. Patients with dysautonomia
associated with a regional pain syndrome may have allodynia and
hyperalgesia in addition to the autonomic changes.

Assessment of orthostatic changes in blood pressure (BP)
and heart rate (HR) are basic tests of cardiovascular autonomic
function. At the bedside, BP and pulse are taken with the patient
supine and after standing for variable periods, typically the BP is
determined at 1, 3, and 5 minutes after standing. Tilt table testing is
more precise. Normally, systolic blood pressure (SBP) on standing does
not decrease by more than 20 mm Hg, and the diastolic blood pressure
(DBP) by not more than 10 mm Hg. There are more stringent diagnostic
criteria that permit a 30-point drop in SBP or a 15-point drop in DBP
in normals. When BP measurement is done with a standard
sphygmomanometer, the cuff should be kept at heart level to minimize
hydrostatic influence on the measurement. When routine measurements are
unrevealing, orthostatic blood pressure declines can sometimes be
detected by having the patient perform 5 to 10 squats and then
repeating the measurements.

The HR should not increase by more than 30 beats per
minute above baseline on standing. In hypovolemia, the most common
cause of orthostasis, a reflex tachycardia develops in response to the
fall in standing blood pressure. When autonomic cardiovascular reflexes
are impaired, the reflex tachycardia may not occur. Patients with the
postural tachycardia syndrome will develop a brisk tachycardia without
orthostatic hypotension (increased pulse rate more than 30 beats per
minute above baseline or more than 120 beats per minute). The sustained
hand grip, mental stress, and cold pressor tests all look for increases
in DBP of at least 15 mm Hg or an increase in HR of >10 beats per
minute in response to peripheral vasoconstriction induced respectively
by isometric hand exercise, mental arithmetic, or immersion of the hand
in cold water. The cold face test assesses the trigeminovagal (diving)
reflex. Resting tachycardia may be a sign of parasympathetic
dysfunction.

Clinical assessment of bladder function is done by
looking for evidence of distension by palpation and percussion, and by
checking the anal wink and bulbocavernous reflexes. The bulbocavernous
and superficial anal reflexes are somatic motor reflexes; the internal
anal and scrotal reflexes are autonomic reflexes. The internal anal
sphincter reflex is contraction of the internal sphincter on insertion
of a gloved finger into the anus. If the reflex is impaired there is
decreased sphincter tone and the anus does not close immediately after
withdrawal. Post void residual urine volume is determined by
catheterization after voiding.

Tear production by the lacrimal glands can be evaluated
in a number of ways by ophthalmologists. A convenient and simple
bedside assessment can be obtained with the Schirmer test, done by
placing a strip of sterile filter paper in the lower conjunctival sac
and measuring the degree of wetting over 5 minutes. Additional eye
findings include excessive dryness with redness and itching, and
ptosis. When autonomic failure occurs as part of a neurologic illness
(such as multisystem atrophy), there may be findings related to the
underlying condition such as extrapyramidal or cerebellar signs,
abnormal eye movements, weakness, sensory loss, or reflex abnormalities.

Autonomic disorders can be divided into those that
affect the central autonomic elements and are typically associated with
other evidence of CNS disease, and those that affect the peripheral
autonomic nervous system. Multiple system atrophy (MSA) is a
degenerative neurologic disorder, which is usually accompanied by
prominent dysautononia. The autonomic failure in MSA results from
involvement of preganglionic neurons in the brainstem and spinal cord
in the degenerative process. Autonomic dysfunction may also occur in
patients with Parkinson disease, but usually late in the illness and
not to the degree typical of MSA. Autonomic disturbances may accompany
seizures, including cardiovascular changes, flushing, pallor, sweating,
shivering, piloerection, vomiting, and respiratory abnormalities.
Seizure-induced cardiovascular abnormalities include sinus tachycardia,
bradyarrhythmia, sinus arrest, and ventricular tachyarrhythmias,
including ventricular fibrillation.

Hypothalamic disorders may cause many abnormalities of
autonomic function, including deficiencies in osmoregulation and
thermoregulation, as well as abnormalities of appetite, and body
weight; sleep disturbances; changes in carbohydrate, fat, and water
metabolism; and respiratory abnormalities; together with, in many
instances, behavioral abnormalities and personality changes.
Hypothalamic lesions may cause either hyperthermia or hypothermia.
Hyperthermia generally results from involvement of the tuberal region,
especially the supraoptic nuclei or the rostral portion of the anterior
hypothalamus. It is a common manifestation of third ventricular tumors,
and may occur after head trauma or cranial surgery; terminal
hyperthermia is a frequent manifestation of neurologic disease (central
fever). Hypothermia tends to occur with involvement of the posterior
hypothalamic area and mammillary bodies. Disorders of the anterior
hypothalamus tend to cause loss of the ability to regulate against
heat, and of the posterior hypothalamus with loss of the ability to
regulate against cold.

The hypothalamus is closely related anatomically and
physiologically to the pituitary gland. Since the hypothalamus controls
the release of many of the anterior pituitary hormones, abnormalities
of hypothalamic function may have a close relationship to some
endocrine disorders. Lesions of the supraoptic nuclei or the
supraopticohypophyseal tract cause diabetes insipidus. Diabetes
insipidus is a common manifestation of tumors in the parasellar region,
encephalitis, and meningitis, and it may develop after intracranial
surgery or head injury.

Abnormalities of respiration may be caused by
hypothalamic dysfunction. These include hyperpnea, apnea, Cheyne-Stokes
respirations, and Biot breathing. Disturbances of the sleep cycle may
occur with hypothalamic lesions, especially those involving its
posterior portions, including the mammillary bodies. There may be
hypersomnolence, inversion of the sleep cycle, or insomnia. Neurons in
the lateral hypothalamus synthesize hypocretin, a chemical involved in
the pathogenesis of narcolepsy. Disturbances of sexual function and
sexual development occur with hypothalamic lesions, including
precocious puberty and sexual infantilism.

The hypothalamus is involved with emotions. It is the
center that coordinates the neural and humoral mechanisms of emotional
expression. Hypothalamic lesions in animals may cause “sham rage,” with
pupillary dilatation, increased pulse rate and blood pressure,
piloerection, and other signs of sympathetic overactivity. These
physical manifestations suggest an intense emotional reaction is taking
place, but there is no change in affect.

Brainstem disorders commonly cause autonomic
dysfunction, including paroxysmal hypertension, profound bradycardia,
intractable vomiting, central hypoventilation, neurogenic pulmonary
edema, and Horner syndrome. The automatic and the voluntary breathing
pathways are separated in the brainstem and upper spinal cord.
Selective damage of the pathways subserving automatic breathing may
cause respiratory insufficiency during sleep, with preserved
respiration during wakefulness (Ondine curse). Myelopathy, particularly
spinal cord injury, is often associated with severe dysautonomia. The
Cushing reflex, or Cushing triad, is bradycardia, hypertension, and
slow, irregular respirations due to brainstem compromise, and has
ominous prognostic implications.

Peripheral autonomic failure results from disorders that
involve the autonomic ganglia or postganglionic nerve fibers. The
syndrome of pure autonomic failure is a slowly progressive,
degenerative disorder of the ANS in which dysautonomia occurs in
isolation, without other evidence of neurologic disease. Dysautonomia
occurs commonly in some peripheral nerve disorders. The most common
cause of autonomic neuropathy is diabetes mellitus. Patients typically
develop orthostatic hypotension, impotence, gastroparesis, constipation
alternating with diarrhea, nocturnal diarrhea, and difficulty voiding.

Dysautonomia may accompany disorders of neuromuscular
transmission, particularly Lambert-Eaton syndrome and botulism, in
which the defect is presynaptic and acetylcholine release is impaired
at autonomic synapses as well as at neuromuscular junctions. Some
autonomic disorders occur in a restricted distribution or involve a
particular organ system. Autonomic disorders of the pupil include
Argyll Robertson and Adie pupils, Horner syndrome, and third cranial
nerve palsy. Dysautonomia primarily involving the vascular system may
cause Raynaud phenomenon, acrocyanosis, erythromelalgia (Weir Mitchell
syndrome), and livedo reticularis. Autonomic dysfunction of the
genitalia causing erectile dysfunction and other abnormalities is
common, especially in diabetes mellitus. Abnormalities of sweating
occur frequently and are sometimes the only manifestation of the
autonomic disturbance. Autonomic dysregulation is a common component of
complex regional pain syndromes (reflex sympathetic dystrophy) and
occurs in the same distribution as the pain.