Dysautonomia: Definition, Evaluation, and Management
What Dysautonomia Refers To
Dysautonomia refers to dysfunction of the autonomic nervous system that adversely affects health, encompassing a spectrum of disorders from transient neurally mediated hypotension to progressive neurodegenerative diseases affecting involuntary bodily functions including heart rate, blood pressure, temperature regulation, digestion, bladder function, and sexual function. 1, 2
The term bundles fundamentally different disorders including neurogenic orthostatic hypotension, reflex syncope, and postural orthostatic tachycardia syndrome (POTS), though when used specifically as "familial dysautonomia" (Riley-Day syndrome), it refers to a specific genetic disorder with abnormal sensory and autonomic nerve function. 1
Dysfunction can occur at multiple levels—peripheral nerves, autonomic ganglia, spinal cord, or brain—resulting in cardiac, respiratory, gastrointestinal, urinary, reproductive, ocular, and sudomotor defects. 3
Primary Clinical Presentations
Most Common Dysautonomia Types
Postural Orthostatic Tachycardia Syndrome (POTS) is the most prevalent form, defined by heart rate increase ≥30 bpm in adults (≥40 bpm in adolescents) within 10 minutes of upright posture WITHOUT orthostatic hypotension, often accompanied by lightheadedness, dizziness, nausea, dyspnea, palpitations, and exercise intolerance. 4, 5, 6
Neurogenic Orthostatic Hypotension (nOH) is characterized by systolic blood pressure drop ≥20 mmHg OR diastolic drop ≥10 mmHg within 3 minutes of quiet standing, representing more advanced autonomic failure. 4, 7
Chronic Fatigue Syndrome represents another dysautonomia form, now termed systemic exercise intolerance disease, requiring: (1) unexplained fatigue causing occupational disability >6 months, (2) post-exertional malaise, (3) non-restorative sleep, and (4) either cognitive impairment or orthostatic intolerance. 7
Cardinal Symptoms
Orthostatic intolerance symptoms—dizziness, lightheadedness, nausea, dyspnea, vision changes—occurring specifically when assuming or maintaining upright position and resolving when seated or supine should immediately trigger dysautonomia evaluation. 1, 4
Gastrointestinal manifestations include nausea, abdominal pain, vomiting, diarrhea, bloating, and severe constipation from enteric neuropathy. 1, 3
Autonomic neuropathy can present with urinary problems, sexual difficulties, sweating abnormalities, sluggish pupil reaction, and orthostatic hypertension. 1
Diagnostic Evaluation Algorithm
Step 1: Bedside Orthostatic Vital Sign Testing
Begin with bedside orthostatic vital signs as the primary screening tool: measure blood pressure and heart rate supine, then after 3 minutes of quiet standing. 4
This simple test identifies both orthostatic hypotension (BP drop ≥20/10 mmHg) and POTS (HR increase ≥30 bpm without hypotension). 4, 7
Step 2: Medication Review
Immediately review all medications, as tricyclic antidepressants, nitrates, antiparkinsonian medications, beta-blockers, calcium antagonists, ACE inhibitors, antipsychotics, phenothiazines, antihistamines, levodopa, MAO inhibitors, and narcotics can precipitate or unmask dysautonomia. 4, 1
Step 3: Laboratory Screening for Secondary Causes
Obtain comprehensive screening to exclude reversible causes: HbA1c, fasting glucose, TSH, AM cortisol, ACTH, vitamin B12, B6, folate, thiamine, HIV, hepatitis B/C, Lyme disease, serum protein electrophoresis, ANA, ESR, CRP, ANCA, anti-smooth muscle antibodies, SSA/SSB, RNP, anti-dsDNA, CPK, and ganglioside antibodies. 4
Diabetes is the most common cause of autonomic failure, with 38-44% of diabetics developing dysautonomia, particularly with poor glycemic control, hypertension, dyslipidemia, and obesity. 7, 6
Step 4: Cardiac Evaluation
Exclude cardiac causes first as they carry higher mortality risk: obtain 12-lead ECG, echocardiogram, and assess for ischemia, structural heart disease, cardiomyopathy, conduction abnormalities, long QT syndrome, and Wolff-Parkinson-White syndrome. 4
Step 5: Formal Autonomic Function Testing
When bedside testing is abnormal or clinical suspicion remains high despite normal bedside testing, proceed to comprehensive autonomic testing including tilt table testing, Valsalva maneuver, deep breathing test (cardiac response to respiration), and RR variability in time and frequency domains. 4, 7
The Valsalva, respiratory, and orthostatic (30:15) tests are gold standard methods for diagnosing cardiovascular autonomic neuropathy and can detect early subclinical abnormalities. 7
Tilt table testing should NOT be the initial test for early-stage dysautonomia as it only detects advanced cases; however, a dysautonomic pattern (gradual BP drop without HR increase) suggests cardiovascular autonomic neuropathy. 7
Sweat testing evaluates sudomotor function, which is often impaired. 4
Step 6: Neuroimaging (When Indicated)
Obtain MRI brain and/or spine when focal neurological signs are present, syncope occurs in supine position, cranial nerve involvement is suspected, or structural CNS pathology is a concern. 4
Routine neuroimaging is NOT recommended in the absence of focal neurological findings or head injury. 4
Step 7: Advanced Testing for Autoimmune Etiology
Consider lumbar puncture when autoimmune or inflammatory etiology is suspected, analyzing CSF for cell count and differential, protein, glucose, oligoclonal bands, IgG index, IgG synthesis rate, neuronal autoantibodies, and cytology. 4
Test for paraneoplastic autoimmune dysautonomia antibodies including anti-ganglionic acetylcholine receptor, ANNA-1, N-type voltage-gated calcium channel antibodies, NMDA receptor antibodies, and VGKC-complex antibodies in serum and CSF. 1, 4
Autoimmune autonomic ganglionopathy is associated with small cell lung cancer, requiring cancer screening. 3
Management Approach
Non-Pharmacologic Interventions (First-Line)
Implement postural care: sleep with head elevated 20-30 cm, avoid getting up at night, rise slowly from lying to sitting to standing. 7
Increase fluid intake to 2-3 liters daily and salt intake to 6-10 grams daily (unless contraindicated). 7
Use compression stockings (waist-high, 30-40 mmHg) and abdominal binders to reduce venous pooling. 7
Eat smaller, more frequent meals to prevent postprandial hypotension. 7
Engage in supervised physical activity, primarily sitting, lying down, or water-based exercise, as regular exercise prevents deleterious autonomic changes. 8, 7
Pharmacologic Therapy for Neurogenic Orthostatic Hypotension
For symptomatic nOH, use fludrocortisone (0.1-0.2 mg daily, titrate to 0.4 mg), midodrine (2.5-10 mg three times daily), or droxidopa (not available in all countries) as primary agents. 7, 5
Alternative agents include pyridostigmine, ivabradine, and stimulants depending on the specific dysautonomia subtype. 5
Beta-blockers can be used for POTS with excessive tachycardia. 5
Critical Management Pitfall: Supine Hypertension
More than 50% of nOH patients develop supine hypertension, representing a major therapeutic challenge; the immediate risk of orthostatic hypotension takes precedence over later risks of supine hypertension, and values up to 160/90 mmHg are tolerable. 7
For severe supine hypertension, use short-acting antihypertensives at bedtime: losartan, captopril, clonidine, or nitrate patches. 7
Inadequate blood pressure monitoring when initiating treatment is a common pitfall—monitor both supine and standing BP regularly. 3
Special Considerations for Diabetes
In diabetic patients, autonomic dysfunction initially involves the parasympathetic system, then sympathetic system, and finally presents as orthostatic hypotension in advanced stages; aggressive glucose control is essential to prevent progression. 7, 8
Age-Related Considerations
Aging significantly alters autonomic function with impaired adaptation to environmental stimuli; elderly patients often lack classic prodromal symptoms and may present with unexplained falls, requiring modified diagnostic approach. 4, 8
The degree of frailty correlates with autonomic dysfunction severity, and drugs inhibiting the renin-angiotensin system may reduce frailty scores and potentially improve autonomic function. 8
Prognosis and Long-Term Management
There is no cure for most types of dysautonomia at late stages; treatment focuses on improving quality of life and preventing complications. 7, 6
Cardiovascular autonomic neuropathy implies greater severity and worse prognosis with higher cardiovascular mortality. 7
The average time to diagnosis is 7.7 years, contributing to morbidity and psychological/economic burden; early recognition and treatment are critical. 9