Dysautonomia

Essentials of Diagnosis

• Postural hypotension or abnormal heart rate regulation

• Abnormalities of sweating, intestinal motility, sexual function, or sphincter control

• Syncope may occur

• Symptoms occur in isolation or any combination

General Considerations

• Primary neurodegenerative disorders with dysautonomia

  • Pure autonomic failure

  • Multisystem atrophy: constellation of parkinsonism, pyramidal signs, and cerebellar deficits

  • Parkinson disease

• CNS lesions that may exhibit features of dysautonomias (usually postural hypotension)

  • Spinal cord transection

  • Other myelopathies above the T6 level (eg, due to tumor or syringomyelia)

  • Brainstem lesions, such as syringobulbia and posterior fossa tumors

  • Sphincter or sexual disturbances may result from cord lesions at any level

• Peripheral causes

  • Guillain-Barré syndrome may have features of marked hypotension or hypertension or cardiac arrhythmias

  • Post-viral or paraneoplastic acute autonomic neuropathy

  • Diabetes mellitus

  • Uremia

  • Amyloidosis

  • Leprosy

  • Chagas disease

  • Hepatic porphyria

  • Small fiber neuropathies may underlie some cases of postural orthostatic tachycardia due to impaired contractility in denervated venules and resulting preload failure

  • Botulism

  • Lambert-Eaton myasthenic syndrome

Symptoms and Signs

• 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

• Declining night vision

• Impaired cholinergic function from botulism and the Lambert-Eaton myasthenic syndrome: constipation, urinary retention, and a sicca syndrome

Differential Diagnosis

• Hypovolemia

• Drugs, eg, β-blockers, calcium-channel blockers, vasodilators, diuretics

• Situational syncope, eg, micturition, defecation, cough, swallow

• Postural hypotension

  • Reduced cardiac output from volume depletion, aortic stenosis or cardiomyopathy, cardiac dysrhythmias, various medications

  • Endocrine disorders such as diabetes, Addison disease, hypothyroidism or hyperthyroidism, pheochromocytoma, and carcinoid syndrome

• The neurologic examination should focus on detecting signs of parkinsonism, cerebellar dysfunction, disorders of neuromuscular transmission, and peripheral neuropathy

• If the neurologic examination is normal,

  • Reversible, nonneurologic causes of symptoms must be considered

  • Isolated postural hypotension and syncope may relate to

    • Reduced cardiac output

    • Paroxysmal cardiac dysrhythmias

    • Volume depletion

    • Various medications

    • Endocrine and metabolic disorders, such as Addison disease, hypothyroidism or hyperthyroidism, pheochromocytoma, and carcinoid syndrome

• For those with evidence of peripheral neuropathy,

  • Nerve conduction studies and electromyography should be done

  • Testing for HIV, amyloidosis, Sjögren syndrome, and Fabry disease is indicated

Laboratory Tests

• Autonomic function tests

• 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

• Tests for vitamin B₁₂ deficiency and diabetes

Imaging Studies

• If there is evidence of central pathology, imaging studies will exclude a treatable structural cause

Diagnostic Procedures

• Specialized tests include

  • Cardiovascular response to the Valsalva maneuver and deep respiration

  • Tilt-table testing

  • Thermoregulatory sweat test

  • Quantitative sudomotor axon reflex test

  • 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

Medications

• 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

  • Fludrocortisone (0.1–0.5 mg orally once 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)

  • Ephedrine (15–30 mg orally three times daily)

• Less commonly used agents

  • Dihydroergotamine

  • Yohimbine

  • Pyridostigmine

  • Clonidine

• Refractory cases may respond to erythropoietin (epoetin alfa) or desmopressin

Therapeutic Procedures

• Avoid abrupt postural change, prolonged recumbency, heavy meals, and other precipitants (eg, straining with bowel movements)

• Medications associated with postural hypotension should be discontinued or reduced in dose

• There is no satisfactory treatment for disturbances of sweating, but an air-conditioned environment is helpful in avoiding extreme swings in body temperature

• Postprandial hypotension is helped by caffeine

When to Refer

• When the diagnosis is in question

• When symptoms do not respond to conventional therapy