Dysautonomia: Definition, Types, and Management

Dysautonomia is a condition characterized by severe imbalance in the autonomic nervous system, which controls involuntary bodily functions. 1

Definition and Pathophysiology

Dysautonomia refers to dysfunction of the autonomic nervous system, which can manifest in various forms with fundamentally different underlying mechanisms 1, 2
The autonomic nervous system consists of the parasympathetic and sympathetic nervous systems, which integrate control of heart rate, blood pressure, body temperature, and other involuntary functions 1
When dysfunction occurs, defects may appear at various levels from peripheral nerves, autonomic ganglia, the spinal cord, and/or the brain, resulting in cardiac, respiratory, alimentary, urinary, reproductive, ocular, and sudomotor defects 1

Familial dysautonomia (Riley-Day syndrome, hereditary sensory and autonomic neuropathy type III): A genetic disorder associated with abnormality of sensory and autonomic nerves, decreased sensation of pain, and decreased production of tears 1
Neurogenic orthostatic hypotension (multiple system atrophy, Shy-Drager syndrome): Characterized by neurologic degeneration, postural tachycardia, and muscular rigidity 1
Postural orthostatic tachycardia syndrome (POTS): Defined in adults as an increase in heart rate of ≥30 beats/min within 10 minutes of upright posture (≥40 beats/min in adolescents) with absence of orthostatic hypotension 1
Autoimmune autonomic ganglionopathy: Associated with small cell lung cancer, involving antibodies against neuronal acetylcholine receptors in autonomic ganglia 1

Cardiovascular autonomic neuropathy (CAN): Occurs secondary to systemic conditions such as diabetes mellitus, neurodegenerative diseases, Parkinson's disease, dementia syndromes, chronic renal failure, and amyloidosis 3
Age-related dysautonomia: Aging is associated with significant changes in autonomic function, resulting in impaired ability to adapt to environmental or intrinsic stimuli 2
Post-infectious dysautonomia: Up to 40% of POTS patients report a viral respiratory or GI infection as the precipitating event 1

Orthostatic intolerance: Presence of symptoms (dizziness, lightheadedness, nausea, dyspnea, vision changes) occurring specifically when assuming or maintaining upright position 1
Cardiovascular symptoms: Palpitations, orthostatic hypotension, syncope, and exercise intolerance 4
Gastrointestinal symptoms: Nausea, abdominal pain, vomiting, diarrhea, bloating, and severe constipation 1
Neurological symptoms: Cognitive dysfunction (brain fog), headache, and fatigue 4
Thermoregulatory dysfunction: Hyperthermia, hypothermia, and abnormal sweating patterns 5

The 10-minute stand test or tilt table test are primary diagnostic tools for orthostatic intolerance 4
Valsalva, respiratory, and orthostatic tests (30:15) are considered gold standard methods for diagnosing cardiovascular autonomic neuropathy 3
Heart rate variability tests in time and frequency domains can increase diagnostic sensitivity for detecting early or subclinical abnormalities 3
Monitoring heart rate and blood pressure with changes in position and respiration can demonstrate sympathetic withdrawal and cholinergic excess 6

Postural care: Sleeping with head elevated (20-30 cm) to minimize nighttime supine hypertension 3
Hydration: Maintaining good fluid intake throughout the day 3
Dietary modifications: Higher salt intake for those with orthostatic hypotension 3
Physical measures: Use of compression stockings and abdominal straps 3
Exercise: Supervised physical activity, mainly sitting, lying down, or exercising in water 3

Fludrocortisone: For neurogenic orthostatic hypotension, helps with sodium and fluid retention 3
Midodrine: An alpha1-agonist that increases vascular tone and elevates blood pressure; useful for orthostatic hypotension 7
- Caution: Can cause supine hypertension; last daily dose should be taken 3-4 hours before bedtime 7
Beta blockers, ivabradine, and pyridostigmine: May be useful for managing POTS 4
Droxidopa: For symptomatic neurogenic orthostatic hypotension (not available in all countries) 3

Supine hypertension occurs in >50% of neurogenic orthostatic hypotension patients, creating a therapeutic challenge 3
The immediate risks of orthostatic hypotension generally take precedence over the later risks of supine hypertension 3
Medication review is crucial as many drugs can exacerbate dysautonomic symptoms 3
Concomitant conditions such as Ehlers-Danlos syndrome or mast cell activation syndrome may complicate management 5

Delayed diagnosis due to nonspecific symptoms that cross multiple medical specialties 6
Misdiagnosis as psychiatric disorders, especially anxiety or panic disorder 4
Failure to recognize the association between dysautonomia and systemic diseases 4
Inappropriate use of vasoconstrictive medications in patients with supine hypertension 7
Inadequate monitoring of blood pressure when initiating treatment 8