Continuing Education Activity
The autonomic nervous system (ANS) includes all regions implicated in the control of autonomic, unconscious, and involuntary functions in total body homeostasis. In general, the full range of physiologic functions are ultimately necessary for human survival and allow us to interact with the external environment in a wide range of conditions. Together with the slow-acting, long-lasting effects of the endocrine system, the ANS exerts its fast-acting, short-lived effects on the most diverse functions of the body, controlling visceral smooth muscle activation in vascular beds and other tubular organs and secretion of glands throughout. In this activity we will share a general overview of these different functions in health and how its malfunction affects daily life.
- Summarize the most common etiologic and risk factors for developing autonomic dysfunction.
- Outline the most common presentation and management considerations for patients with autonomic diseases.
- Identify how the levels where the ANS dysfunction can considered and evaluated.
- Explain the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care for patients with autonomic sphere symptoms and disorders.
The autonomic nervous system (ANS) includes all regions implicated in the control of “autonomic,” unconscious, and involuntary functions in total body homeostasis. In general, the full range of physiologic functions are ultimately necessary for human survival and allow us to interact with the external environment in a wide range of conditions. Together with the slow-acting, long-lasting effects of the endocrine system, the ANS exerts its fast-acting, short-lived effects on the following functions (among others):
- Perfusion of the whole body through regulation of heart rate and blood pressure
- Homoeothermic role through sweating control and shivering,
- Processing of nutrients through control and coordination of different parts of the gut and glands,
- Urinary motility, and
- Pupil movement, focusing, and lacrimation.
Dysfunction of one or more subdivisions of the ANS, when accompanying other diseases, is linked to a worse prognosis of the latter. In some circumstances or when severe, dysfunction of ANS itself results in symptoms and disability, which may, in turn, prompt treatment.
A myriad of the factors can cause autonomic dysfunction, and more than one can concur even in the same patient. The most common factors known to cause autonomic dysfunction include the following:
- Degenerative neurologic diseases, such as Parkinson’s disease, multiple-system atrophy, pure autonomic failure presenting or suffering from Orthostatic Hypotension (OH), fixed heart rate responses, etc.
- An immune-mediated attack, either idiopathic or paraneoplastic, can be a source of focal or generalized autonomic dysfunction, as in Guillain-Barre syndrome, or autoimmune autonomic ganglionopathy
- Metabolic and toxic damage, as in diabetes mellitus, amyloidosis and Fabry disease
- Genetic disorders, like in dopamine-beta-hydroxylase deficiency and familial dysautonomia
- Abnormal reflex responses in carotid sinus hypersensitivity, vasovagal syncope, and other neuro-meditated syncopes; and probably in Postural Tachycardia Syndrome (PoTS)
- Abnormal sweating responses, as in generalized or focal hyperhidrosis, related to an excessive activation
- Traumatic or tumoral spinal cord injuries at different levels and presenting with the so-called autonomic dysreflexia
- Pharmacologic effects of several drugs that interfere with normal autonomic function and provoke symptoms include alpha- and beta-blocker-triggered OH
Autonomic dysfunction, taken as a whole, is not infrequent. The most common autonomic dysfunction occurs in the cardiovascular control sphere and consists of an abnormal vasovagal response that leads to syncope. Other common manifestations are related to Postural Tachycardia Syndrome (POTS) or changes seen with Parkinson's disease and other parkinsonisms. Urinary incontinence, compared to other areas of autonomic control, as observed in multiple sclerosis and other nervous system disorders, is unspecific but not rare. Some symptoms of autonomic disturbance, such as the facial vasomotor and ocular symptoms in trigeminal autonomic headaches, are of secondary significance but help in diagnosis.
Pathophysiology in ANS depends upon the affected area. Both anatomically related, as well as isolated areas, can be affected. In the cardiovascular system, three pathophysiological syndromes are typically associated with chronic dysfunction of the ANS. These are Postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension with supine hypertension, and reflex cardiovascular syndromes. Hyperhidrosis and hypohidrosis are the main features in temperature control. Fixed mydriasis and myosis, also know as Adie’s pupil and Horner syndrome in the eye, are also seen.
History and Physical
A detailed account of symptoms in each area should guide us to a list of possible diseases with autonomic dysfunction. Emphasis should be placed on obtaining a good history and comprehensive examination of cardiovascular, urinary, neurological, and sudomotor manifestations. A key feature of autonomic dysfunction, either orthostatic syncope or presyncope, should guide us to suspicion of cardiovascular autonomic dysfunction. In this scenario, the usual symptoms are dizziness, giddiness, blurred or tunnel vision, headache, or neckache (coat-hanger pain), nausea, or fatigue. The alternating sweating intensity in different areas of the body, typically a length-dependent distal hypohidrosis with sparing of palms and soles, can raise suspicion for a sudomotor autonomic lesion. Urgency and incontinence tend to relate to a neurogenic bladder more than retention.
Testing the most disturbing or salient features of autonomic dysfunction is often necessary to confirm a diagnosis and give objective evidence supporting pharmacologic treatment.
Bedside tests such as orthostatic measurement of blood pressure and heart rate (while supine and after three minutes standing) are the most commonly used tests. When the bedside tests are not informative, but suspicion of an abnormal cardiovascular autonomic function is high, tilt table tests with natural cardiovascular stimuli such as Valsalva maneuver, hyperventilation, or cold pressor, are needed.
Sympathetic skin responses can add objective information, and thermoregulatory sweat test might be a good option if the symptoms of altered sweating predominate.
Vesical ultrasonography and urodynamic studies help diagnose and choose the best pharmacologic approach for urinary dysfunction in autonomic dysfunction.
Other tests are not as useful in changing the management but may play a role in supporting an explanation for the patient’s symptoms, or as adjunctive for syndromic diagnosis. Blocking eyedrop tests and pupillometry for pupillary abnormalities are examples of such tests.
Some tests do help in management. Positive testing for autoantibodies, for example, antibodies against alfa-3-acetylcholine receptors, helps support immunosuppressive therapy.
Treatment / Management
Treatment, when indicated, can be organized into three levels. Treatment strategies are aimed at etiology, physiopathology, and symptoms.
1. Symptom management is the most frequently used and must address first the most bothersome symptoms while keeping in mind the whole picture. Physical measures like exercise, tailored physiotherapy, pressure stockings can help in some cardiovascular autonomic dysfunctions. Sunglasses can be used for mydriatic pupils. Also, a wide range of measures, both non-pharmacologic and pharmacologic, are beneficial. Nonpharmacologic measures include supportive hydration, salt intake, and dietary changes. Commonly used drugs for orthostatic hypotension include the alfa-agonist midodrine and mineralocorticoid fludrocortisone. Octreotide is useful for postprandial hypotension. Powder desiccants are used in hyperhidrosis patients.
2. The pathophysiologic aspect can be addressed in the case of immune-mediated disorders. Immunotherapy, such as steroids and other immune suppressor drugs, intravenous immunoglobulins, and plasma exchange, are employed in management strategies in immune-mediated disorders.
3. Finally, etiology must always be addressed. In certain situations, it is essential to treat, such as the malignancy found in paraneoplastic and autoimmune autonomic neuropathy. However, in some other situations, it is imperative to taper or withdraw the drugs interfering with the ANS in drug-induced, symptomatic autonomic failure.
The various differentials depend on the symptom or condition
1. Symptoms such as orthostatic hypotension have broad differentials such as dehydration, syncope, hypoglycemia, bradycardia, arrhythmias
2. The neurodegenerative conditions causing the Autonomic failure also need to be identified. Parkinson's disease, Multisystem Atrophy, and Lewy Body Disease can all present similarly.
Pearls and Other Issues
Autonomic dysfunction is a prevalent health problem that remains underdiagnosed, undertreated, and underappreciated across healthcare systems. In most cases, patients tend to have a late diagnosis when their symptoms are chronic and long-standing. The lack of acknowledgment from the general population and the medical community, diagnostic testing set in the development, and a finite set of extensively tested and validated drugs to offer, among other causes, make the field one of the most promising for research.
Autonomic dysreflexia is a severe, potentially life-threatening condition affecting the cardiovascular system of patients exposed to various at-risk exposures and risk factors -- ranging from painful/noxious stimuli to more subtle conditions (e.g., bowel or bladder obstructions). Clinicians should remain cognizant, depending on the specific patient and clinical constellation of symptoms. The latter can lead to myocardial ischemia, brain hemorrhage, seizures, and even death.
Enhancing Healthcare Team Outcomes
The diagnosis and management of autonomic dysfunction is very complex and usually requires an interprofessional team compromising of various specialists such as a neurologist, endocrinologist, internist, urologist, and cardiologist. The treatment is symptomatic and usually requires medications, which also have adverse effects. The outcomes and quality of life with autonomic dysfunction are poor.