193 AUTONOMIC NERVOUS SYSTEM DISORDERS
Harrison’s Manual of Medicine
AUTONOMIC NERVOUS SYSTEM DISORDERS
Disorders of the ANS
The autonomic nervous system (ANS) regulates homeostatic functions critical to survival including blood pressure, blood flow, tissue perfusion, sweating, hunger, satiety, temperature, thirst, and circadian rhythms. The importance of this regulation is demonstrated by the severity of disability resulting from compromised ANS function.
Key features of the ANS are summarized in Table 193-1. Responses to sympathetic (S) or parasympathetic (P) activation often have opposite effects; partial activation of both systems allows for simultaneous integration of multiple body functions.
Table 193-1 ANS Overview
Catecholamines exert their effects on two types of receptors, a and b. The a1 receptor mediates vasoconstriction. The a2 receptor mediates presynaptic inhibition of norepinephrine (NE) release from adrenergic nerves, inhibits acetylcholine (ACh) release from cholinergic nerves, inhibits lipolysis in adipocytes, inhibits insulin secretion, and stimulates platelet aggregation. The b1 receptor responds to both NE and epinephrine (E) and mediates cardiac stimulation and lipolysis. The b2 receptor is more responsive to E than NE and mediates vasodilatation and bronchodilation.
DISORDERS OF THE ANS
The CNS, peripheral nervous system, or both may be affected; disorders may be generalized (with or without CNS signs) or focal (Table 193-2). Clinical signs and symptoms are due to interruption of the afferent limb, CNS processing centers, or efferent limb of the reflex arc controlling the autonomic responses. Clinical manifestations are influenced by the organ involved, normal balance of sympathetic-parasympathetic innervation, nature of the underlying illness, and severity/stage of disease. Orthostatic hypotension (OH) is defined as a postural decrease in BP from the supine to standing position of at least 20 mmHg systolic or 10 mmHg diastolic BP sustained for at least 2 min. OH is often disabling. Syncope or near syncope results when the drop in BP impairs cerebral perfusion. Presyncopal symptoms that may appear on standing include light-headedness, dimming of vision, nausea, diminished hearing, hyperhidrosis, hypohidrosis, pallor, and weakness.
Table 193-2 Classification of ANS Disorders
Approach to the Patient
The evaluation of symptomatic OH begins with the exclusion of treatable causes. Most causes of OH are not due to nervous system disease (Table 193-3). In nonneurogenic OH, the drop in blood pressure with standing is usually associated with an appropriate, compensatory rise in heart rate, in contrast to neurogenic OH in which a compensatory rise in heart rate does not occur. History should include a review of medications (e.g., diuretics) and medical problems (e.g., diabetes). Exaggerated medication responses may be the first sign of underlying autonomic disorder. The relationship of symptoms to meals (splanchnic shunting of blood) and awakening in the morning (relative intravascular volume depletion) should be sought. Examination of mental status (e.g., neurodegenerative disorders), cranial nerves (e.g., impaired downgaze with progressive supranuclear palsy), motor function (e.g., parkinsonian syndromes), and sensory function (e.g., polyneuropathy) is necessary. Disorders of autonomic function need to be considered in the differential diagnosis of pts with impotence, bladder dysfunction (urinary frequency, hesitancy, or incontinence), diarrhea, constipation, or altered sweating (hyperhidrosis or hypohidrosis).
Table 193-3 Nonneurogenic Causes of Orthostatic Hypotension
The most commonly used autonomic tests assess cardiovascular function; they are noninvasive, easy to administer, and provide quantitative information; normative data from healthy controls is essential. Heart rate variation with deep breathing is a measure of vagal function. The Valsalva maneuver measures changes in heart rate and blood pressure while a constant expiratory pressure of 40 mmHg for 15 s is maintained. The Valsalva ratio is calculated as the maximum heart rate during the maneuver divided by the minimum heart rate following the maneuver. The ratio reflects the integrity of the entire baroreceptor reflex arc and sympathetic efferents to blood vessels (Chap. 366, HPIM-15). Tilt-table beat-to-beat BP measurements in the supine, 80° tilt, and tilt-back positions can be used to evaluate orthostatic failure in BP control in pts with unexplained syncope.
Other tests of autonomic function include the quantitative sudomotor axon reflex test (QSART), the thermoregulatory sweat test (TST), and the cold pressor test. The QSART provides a quantitative, regional measure of sweating in response to iontophoresis of ACh. The TST provides a qualitative measure of regional sweating over the entire anterior surface of the body in response to a standardized elevation of body temperature. The cold pressor test is used to assess sympathetic efferent function. For a more complete discussion of autonomic function tests, see Chap. 366, HPIM-15.
SPECIFIC SYNDROMES OF ANS DYSFUNCTION Diseases of the CNS may cause ANS dysfunction at the level of the hypothalamus, brainstem, or spinal cord (Table 193-1). Multiple system atrophy (MSA) refers to several overlapping CNS syndromes with a variable combination of symptoms and signs including postural hypotension, impotence, bladder and bowel dysfunc tion, defective sweating, rigidity, tremor, loss of associative movements, upper motor neuron signs, cerebellar signs, or abnormal eye movements. Pts may present with only one symptom or sign and later develop the full clinical spec trum of MSA.
Spinal cord injury may be accompanied by autonomic hyperreflexia affecting bowel, bladder, sexual, temperature regulation, or cardiovascular functions. Dangerous increases or decreases in body temperature may result from the inability to experience the sensory accompaniments of heat or cold exposure below the level of the injury. Markedly increased autonomic discharge (autonomic dysreflexia) can be elicited by bladder pressure or stimulation of the skin or muscles. Bladder distention from palpation, catheter insertion, catheter obstruction, or urinary infection are common and correctable causes of autonomic dysreflexia.
Peripheral neuropathies are the most common cause of chronic autonomic insufficiency (Chap. 366, HPIM-15). Autonomic involvement in diabetes mellitus may begin at any stage in the disease. Diabetic enteric neuropathy may result in gastroparesis, nausea and vomiting, malnutrition, and bowel incontinence. Impotence, urinary incontinence, pupillary abnormalities, and postural hypotension may occur as well. Prolongation of the QT interval may occur and enhances the risk of sudden death. Autonomic neuropathy occurs in both sporadic and familial forms of amyloidosis. Pts may present with distal, painful polyneuropathy. Cardiac or renal disease is the usual cause of death. Alcoholic polyneuropathy produces clinical symptoms of autonomic failure only when the signs of peripheral neuropathy are severe. BP fluctuation and cardiac arrhythmias can be severe in Guillain-Barré syndrome. Attacks of acute intermittent porphyria (AIP) are associated with tachycardia, sweating, urinary retention, and hypertension. Botulism is associated with blurred vision, dry mouth, nausea, unreactive pupils, urinary retention, and constipation. Postural orthostatic tachycardia syndrome (POTS) consists of symptoms of orthostatic intolerance—including shortness of breath, light-headedness, and exercise intolerance—accompanied by an increase in heart rate but no drop in BP. The importance of postprandial hypotension in healthy elderly persons and hypertensive pts taking BP medications with meals is drawing increasing attention. Primary hyperhidrosis affects 0.6–1.0% of the population; the usual symptoms are excessive sweating of the palms and soles. Onset is in adolescence, and symptoms tend to improve with age. Although not dangerous, this condition is socially embarrassing.
REFLEX SYMPATHETIC DYSTROPHY (RSD) AND CAUSALGIA The role of the ANS in RSD and causalgia is controversial, and there is no generally accepted pathogenic mechanism to explain these disorders. The terms complex regional pain syndrome (CRPS) type I and CRPS type II have been proposed as substitutes for the terms RSD and causalgia, respectively.
In causalgia, spontaneous pain develops within the territory of an injured nerve and may spread outside, but contiguous to, the distribution of the affected nerve. Allodynia (the perception of a nonpainful stimulus as painful) and hyperpathia (an exaggerated pain response to a mildly painful stimulus) are common. RSD is a regional pain syndrome that develops after trauma. Unlike causalgia, limb symptoms are not confined to the distribution of a single peripheral nerve. Although pain is the primary feature of both causalgia and RSD, vasomotor, sudomotor, or edematous changes must be present to satisfy criteria for diagnosis. Treatment of both disorders is a difficult therapeutic challenge (Chap. 366 in HPIM-15).
Management of autonomic failure is limited typically to alleviating disability caused by symptoms. A review of medications, relationship of symptoms to meals, medical illnesses, and other symptoms of possible autonomic origin is mandatory. Orthostatic hypotension requires treatment only if it causes symptoms. In early stages, pts can maintain normal function by using simple measures. Alcohol use and exposure to elevated temperature should be avoided because vaosdilatation can suddenly lower BP. Drugs that affect BP should be used with great caution. Salt intake should be increased to the maximum tolerated. Sleeping in reverse Trendelenburg position (head-up tilt) minimizes supine hypertension. Frequent, small meals may improve postprandial hypotension. Most pts require drug therapy for the management of neurogenic OH. Fludrocortisone (0.1 mg/d–0.3 mg bid PO) is the initial drug of choice; potassium supplementation is necessary with chronic administration. Midodrine (5 mg tid–10 mg q4h PO) is an a1 agonist approved by the FDA for treatment of neurogenic OH. Other drugs may be effective for postprandial OH (indomethacin, caffeine), OH associated with diarrhea (clonidine), and OH associated with anemia (erythropoietin). Many agents can be used to elevate BP, but supine hypertension or a lack of symptomatic improvement often limits their value. Management during anesthesia poses unique problems since pts may have abnormal baroreceptor reflexes, sympathetic innervation of peripheral arterioles, abnormal fluid balance, and adrenal medullary insufficiency.
For a more detailed discussion, see Engstrom JW, Martin JB: Disorders of the Autonomic Nervous System, Chap. 366, p. 2416, in HPIM-15.