Pure autonomic failure results from neuronal loss in autonomic ganglia, causing orthostatic hypotension and other autonomic symptoms.
(See also Overview of the Autonomic Nervous System.)
Pure autonomic failure, previously called idiopathic orthostatic hypotension or Bradbury-Eggleston syndrome, denotes generalized autonomic failure without central nervous system (CNS) involvement. This disorder differs from multiple system atrophy because it lacks central or preganglionic involvement. Pure autonomic failure affects women and men, tends to begin during a person’s 40s or 50s, and does not typically result in death.
Pure autonomic failure is a synucleinopathy (due to synuclein deposition); alpha-synuclein can also accumulate in patients with Parkinson disease, multiple system atrophy, or dementia with Lewy bodies . (Alpha-synuclein is a neuronal and glial cell protein that can aggregate into insoluble fibrils and form Lewy bodies.) Evidence that supports synucleinopathy as the cause is eventual development of motor or cognitive symptoms in patients. Some patients with pure autonomic failure eventually develop multiple system atrophy, Parkinson disease, or dementia with Lewy bodies.
Symptoms and Signs of Pure Autonomic Failure
The main symptom is
There may be other autonomic symptoms, such as decreased sweating, heat intolerance, urinary retention, bladder spasms (possibly causing urinary incontinence), erectile dysfunction, fecal incontinence or constipation, dry eyes and/or mouth, and pupillary abnormalities.
Diagnosis of Pure Autonomic Failure
Clinical evaluation
Diagnosis of pure autonomic failure is by exclusion. The norepinephrine level is usually < 100 pg/mL supine and does not increase with standing. Postural orthostatic tachycardia syndrome can be differentiated because with standing, it does not usually cause hypotension, the norepinephrine level increases, and heart rate increases by > 30 beats/minutes or to 120 beats/minutes within 10 minutes.
Treatment of Pure Autonomic Failure
Symptomatic treatment
Treatment of pure autonomic failure is symptomatic:
Orthostatic hypotension:Volume expansion, vasopressors, and support hose are used. Sometimes fludrocortisone and/or alpha-adrenoreceptor stimulation with midodrine is given, butmidodrinemay increase supine blood pressure more than is desirable. Raising the head of the bed about 10 cm reduces nocturnal polyuria and supine hypertension and may reduce morning orthostatic hypotension. Alternatively, droxidopa can be used. Droxidopa has a mechanism similar to that of midodrine but a longer duration of action.
Constipation: A high-fiber diet and stool softeners are recommended. Sometimes enemas are needed.
Bladder spasms:Oxybutynin chloride or tolterodine can be used to treat bladder spasms. For urinary urgency, tamsulosin or the beta-3 adrenergic agonist mirabegron (which does not increase orthostatic hypotension) may be given.
Urinary incontinence:If the cause is detrusor hyperreflexia, oxybutynin chloride or tolterodine may be used. Tamsulosin may be effective for urinary urgency. Alternatively, mirabegron can be used; unliketamsulosin, mirabegron does not worsen orthostatic hypotension.
Urinary retention:Self-catheterization of the bladder may be needed. Sometimes medications that induce bladder contraction (eg, bethanechol) are given.
Sweating abnormalities:Hot conditions should be avoided. For dry mouth, good dental care and regular dental check-ups are important. Artificial tears may help patients with dry eyes.
Erectile dysfunction:Medications such as sildenafil or tadalafil can be used, but these medications may worsen orthostatic hypotension.
Key Points
Pure autonomic failure, like Parkinson disease, multiple system atrophy, and dementia with Lewy bodies, is a synucleinopathy.
The main symptom is orthostatic hypotension.
Diagnose by excluding other disorders that cause similar symptoms.
Use treatments specific for the symptoms present.
