24-04: Dysautonomia

Dysautonomia may occur as a result of pathological processes in the central or peripheral nervous system. It is manifested by a variety of symptoms related to abnormalities of blood pressure regulation, thermoregulatory sweating, gastrointestinal function, sphincter control, sexual function, respiration, and ocular function. The differential diagnosis depends on the time course of autonomic dysfunction and whether dysautonomia is an isolated symptom or associated with central or peripheral neurologic symptoms and signs.

A. Causes in the Central Nervous System

Disease at certain sites, regardless of its nature, may lead to dysautonomic symptoms. Postural hypotension, which is usually the most troublesome and disabling symptom, may result from spinal cord transection and other myelopathies (eg, due to tumor or syringomyelia) above the T6 level or from brainstem lesions such as syringobulbia and posterior fossa tumors. Sphincter or sexual disturbances may result from cord lesions at any level. Certain primary degenerative disorders are responsible for dysautonomia occurring in isolation (pure autonomic failure) or in association with more widespread abnormalities (multisystem atrophy) that may include parkinsonism, pyramidal symptoms, and cerebellar deficits. Postural hypotension is also a prominent symptom of idiopathic Parkinson disease and dementia with Lewy bodies.

B. Causes in the Peripheral Nervous System

A pure autonomic neuropathy may occur acutely or subacutely after a viral infection or as a paraneoplastic disorder related usually to small cell lung cancer, particularly in association with certain antibodies, such as anti-Hu or those directed at neuronal nicotinic ganglionic acetylcholine receptors. Dysautonomia is often conspicuous in patients with Guillain-Barré syndrome, manifesting with marked hypotension or hypertension or cardiac arrhythmias that may have a fatal outcome. It may also occur with diabetic, uremic, amyloidotic, and various other metabolic or toxic neuropathies; in association with leprosy or Chagas disease; and as a feature of certain hereditary neuropathies with autosomal dominant or recessive inheritance or an X-linked pattern. Autonomic symptoms are prominent in the crises of hepatic porphyria. Small fiber neuropathies may underlie some cases of postural orthostatic tachycardia due to impaired contractility in denervated venules and resulting preload failure. Patients with botulism or the Lambert-Eaton myasthenic syndrome may have constipation, urinary retention, and a sicca syndrome as a result of impaired cholinergic function.

A. Symptoms and Signs

Dysautonomic symptoms include syncope, postural hypotension, paroxysmal hypertension, persistent tachycardia without other cause, facial flushing, hypohidrosis or hyperhidrosis, vomiting, constipation, diarrhea, dysphagia, abdominal distention, disturbances of micturition or defecation, erectile dysfunction, apneic episodes, and declining night vision. In syncope, prodromal malaise, nausea, headache, diaphoresis, pallor, visual disturbance, loss of postural tone, and a sense of weakness and impending loss of consciousness are followed by actual loss of consciousness. It is usually accompanied by hypotension and bradycardia and may occur in response to emotional stress, postural hypotension, vigorous exercise in a hot environment, obstructed venous return to the heart, acute pain or its anticipation, fluid loss, and a variety of other circumstances. Although the patient is usually flaccid, some motor activity is not uncommon, and urinary (and rarely fecal) incontinence may also occur, thereby simulating a seizure. Recovery is rapid once the patient becomes recumbent, but headache, nausea, and fatigue commonly persist.

B. Evaluation of the Patient

The extent and severity of autonomic dysfunction should be determined, and the presence of associated neurologic symptoms and signs ascertained. Bedside testing of autonomic function includes examination of pupillary reactivity, examination of the skin for areas of excessive or reduced sweating and of the hands and feet for color or temperature changes, as well as assessment of blood pressure and heart rate in the supine position and 2 minutes after standing. With dysautonomia, postural hypotension is not accompanied by a compensatory rise in heart rate. Specialized tests include the cardiovascular response to the Valsalva maneuver and deep respiration, tilt-table testing, the thermoregulatory sweat test, the quantitative sudomotor axon reflex test, and the quantitative direct and indirect axon reflex test. Tests of gastrointestinal motility and urodynamics may be helpful when symptoms of dysmotility, incontinence, or urinary retention are present.

The neurologic examination should focus on detecting signs of parkinsonism, cerebellar dysfunction, disorders of neuromuscular transmission, and peripheral neuropathy. All patients should be tested for vitamin B₁₂ deficiency and diabetes. Patients with acute or subacute isolated dysautonomia should undergo testing for ganglionic acetylcholine receptor, anti-Hu, voltage-gated potassium channel complex, and voltage-gated calcium channel antibodies. For those with evidence of peripheral neuropathy, nerve conduction studies; electromyography; and testing for HIV, amyloidosis, Sjögren syndrome, and Fabry disease are indicated. If there is evidence of central pathology, imaging studies will exclude a treatable structural cause. If the neurologic examination is normal, reversible, nonneurologic causes of symptoms must be considered. Isolated postural hypotension and syncope may relate to a reduced cardiac output, paroxysmal cardiac dysrhythmias, volume depletion, various medications, and endocrine and metabolic disorders such as Addison disease, hypothyroidism or hyperthyroidism, pheochromocytoma, and carcinoid syndrome.

The most disabling symptoms are usually postural hypotension and syncope. Abrupt postural change, prolonged recumbency, heavy meals, and other precipitants should be avoided. Medications associated with postural hypotension should be discontinued or reduced in dose. Treatment may include wearing waist-high elastic hosiery, salt supplementation, sleeping in a semierect position (which minimizes the natriuresis and diuresis that occur during recumbency), ingestion of 500 mL water 30 minutes before arising, and fludrocortisone (0.1–0.5 mg orally daily). Vasoconstrictor agents may be helpful and include midodrine (2.5–10 mg orally three times daily), droxidopa (100–600 mg orally three times daily), and ephedrine (15–30 mg orally three times daily). Other agents that have been used occasionally or experimentally are dihydroergotamine, yohimbine, pyridostigmine, and clonidine; refractory cases may respond to erythropoietin (epoetin alfa) or desmopressin. Patients must be monitored for recumbent hypertension. Postprandial hypotension is helped by caffeine. There is no satisfactory treatment for disturbances of sweating, but an air-conditioned environment is helpful in avoiding extreme swings in body temperature.

• When the diagnosis is uncertain.

• When symptoms persist despite conventional treatment.