Autonomic Dysfunction


Article Author:
Juan Carlos Sánchez-Manso


Article Editor:
Matthew Varacallo


Editors In Chief:
Michael Labanowski


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/18/2019 9:54:23 PM

Introduction

The autonomic nervous system (ANS) includes all regions implicated in the control of “autonomic,” unconscious, and involuntary functions in the context of total body homeostasis.  In general, the wide 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-lived effects of the endocrine system, the ANS exerts its fast-acting, short-lived effects on the following functions, among other:

  • Perfusion of all the body with blood through heart rate and blood pressure control,
  • Homoeothermic function 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.[1][2][3][4][5]

Etiology

Autonomic dysfunction can be caused by a myriad of the following factors, and more than one can concur even in the same patient.

  • Degenerative neurologic diseases, such as Parkinson’s disease, multiple-system atrophy, and pure autonomic failure presenting or suffering from Orthostatic Hypotension (OH) and 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 in 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, for example, alpha- and beta-blocker-triggered OH

Epidemiology

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 disease and other parkinsonisms. Urinary incontinence, related to other areas of autonomic control, as observed in multiple sclerosis and other nervous system disorders, is unspecific but not rare. There are symptoms of autonomic disturbance in some situations where they are second in importance but help in diagnosis, for example, the facial vasomotor and ocular symptoms in trigeminal autonomic headaches.[6][7][8][9]

Pathophysiology

Depending on what the area of control of the ANS is affected, the pathophysiology will follow. It is not unlikely to find closely anatomically-related areas of the ANS malfunctioning, and neither it is to find anatomically remote isolated dysfunction. In the cardiovascular system, three pathophysiological syndromes are the most typically related to a chronic dysfunction of the ANS. These are Postural orthostatic tachycardia syndrome, orthostatic hypotension and 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.

History and Physical

A detailed history of symptoms in each area should guide us to a list of possible diseases with autonomic dysfunction. Place special emphasis on cardiovascular, urinary, and sudomotor symptoms, together with accompanying neurologic and non-neurologic manifestations, along with a thorough examination. A key feature of autonomic dysfunction, either orthostatic syncope or presyncope should guide us to a suspicion of cardiovascular autonomic dysfunction, the latter with 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, most typically a length dependent distal hypohidrosis with palms and soles preserved, may be a clue to a sudomotor autonomic lesion. Urgency and incontinence tend to relate to a neurogenic bladder more than retention, but the latter should be addressed in a general exam.

Evaluation

Testing of the most disturbing or salient features of autonomic dysfunction is often necessary to confirm a diagnosis and give objective evidence to support pharmacologic treatment.[10][11][12]

Tilt table test with usual cardiovascular stimuli, for example, Valsalva maneuver, hyperventilation, or cold pressor are among some of the more common types of techniques utilized. This is especially true in the case the bedside blood pressure and heart rate measurements (while supine and after three minutes standing, the orthostatic test) are not informative and the suspicion of an abnormal cardiovascular autonomic function is high. 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 figure out what the problem looks like and what the best pharmacologic approach is for urinary dysfunction. Other tests are not as useful in changing the management but may play a role in support of an explanation for the patient’s symptoms, or as adjunctive for syndromic diagnosis, as it is the case with blocking eyedrop tests and pupillometry for pupillary abnormalities. On the other hand, positive testing results for autoantibodies, for example, antibodies against alfa-3-acetylcholine receptor, help support immunosuppressive therapy.

Treatment / Management

Treatment, when indicated, can be organized into three levels. The physiopathologic, symptomatic level is the most frequently used and must address first the most bothersome symptoms while keeping in mind the whole picture. They consist of a wide range of measures from the non-pharmacologic, supportive hydration, salt intake, dietary changes to the alfa-agonist midodrine and mineralocorticoid fludrocortisone for orthostatic hypotension, octreotide for postprandial hypotension, powder desiccants for hyperhidrosis patients. Physical measures like exercise, tailored physiotherapy, pressure stockings can help in some cardiovascular autonomic dysfunctions, and sunglasses for mydriatic pupils. The pathophysiologic aspect can be addressed at least in the case of immune-mediated disorders through immunotherapy, for example, steroids and other immune suppressor drugs, intravenous immunoglobulins, and plasma exchange. Last but not least, etiology must always be addressed and can be as important to treat the malignancy found in paraneoplastic, autoimmune autonomic neuropathy as it is to taper or withdraw the drugs interfering with the ANS in drug-induced, symptomatic OH.

Pearls and Other Issues

Autonomic dysfunction is a very 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, a 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 a variety of 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 condition 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 best done with a multidisciplinary team that includes a neurologist, endocrinologist, internist, primary care provider, nurse practitioner, urologist and a 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.[13][14]


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Autonomic Dysfunction - Questions

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In evaluating a patient with complaints of recurrent syncope, which of the following would most likely suggest autonomic dysfunction related to diabetic neuropathy?



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What is the cardinal sign of idiopathic autonomic insufficiency?



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A 17-year-old, right-handed, college student presents after having her 4th episode of self-limited loss of consciousness. Her personal antecedents are non-remarkable. She suffered her first fit six months back, after a walking with her boyfriend, who described her falling to the ground suddenly while they were watching Cardinal on a tree branch, and jerking a few times. No tongue or cheek biting occurred, and she had urinary incontinence. After that, it took her the rest of the afternoon to fully recover. Her third episode occurred two months after the first fit, on her way back to her apartment from College. She waved her boyfriend hello, turned her head to her rucksack while she put her keys back in, felt epigastric discomfort that raised to her chest, dizziness and trembling; that lasted a few seconds before she fell on their welcome mat. Her boyfriend described her pale and that she shook while recovering, and she bit the tip of her tongue. No urinary incontinence occurred, and she got better after a few hours of resting. The second and fourth episodes occurred abruptly while in line at the supermarket, without tongue biting and urinary incontinence. Her mother was standing on her right and saw her turning her head towards her and dropping purse during one of the episodes, before falling like a dead body. She did not jerk and denied any recall from the events. In this case, what is the isolated most information obtained from the patient or witness that helps differentiate recurrent epileptic seizures from recurrent syncope?



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A 23-year-old left-handed cashier, with a history of episodic migraines controlled with naproxen, presents complaining of daily dizzy spells, blurred vision, trembling, occasional nausea, and fatigue, and often accompanied with a non-pulsating, bilateral headache, which is not like her usual migraine. The spells happen when on the upright position for a while so that she needs to sit down at work or she would faint. She has learned this after a couple of years of progressive worsening. A colleague told her that she may have sweated too much and might be dehydrated, but she started drinking 4 liters of water a day and her symptoms initially improved. Since then they have plateaued and persisted. She has already fainted a few times so far, usually standing. She recalls at least three episodes of loss of consciousness at work, near the time to close the market, while quickly standing from her seat; once she passed out while sitting in a dine-out with her boyfriend. They were celebrating his comeback from a long trip, and they could not finish their dinner in order to visit the emergency department. Her general physical examination of her pale skin shows two reddish, slightly elevated, old scars on her right flank and knee, and red cheeks. There are rhythmic, carotid and radial pulses without bruits. Complete cardiac, neurological, and rest of general exam are unremarkable. When testing her strength, she jokes about her being "extremely strong" of having over time trained her wrists, elbows, and knees to overextend, and she shows off on how she can force herself to touch her forearm with her thumb, with both hands. With your main suspicion in mind, what would you do to help figure out what this patient has?



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Which of the following patients is most likely to have symptomatic neurogenic orthostatic hypotension as the cause of episodes of falling?



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Autonomic Dysfunction - References

References

Ziemssen T,Siepmann T, The Investigation of the Cardiovascular and Sudomotor Autonomic Nervous System-A Review. Frontiers in neurology. 2019;     [PubMed]
Hong CT,Chan L,Wu D,Chen WT,Chien LN, Association Between Parkinson's Disease and Atrial Fibrillation: A Population-Based Study. Frontiers in neurology. 2019;     [PubMed]
James LA,Levin MA,Lin HM,Deiner SG, Association of Preoperative Frailty With Intraoperative Hemodynamic Instability and Postoperative Mortality. Anesthesia and analgesia. 2019 Feb 18;     [PubMed]
Chung SJ,Bae YJ,Jun S,Yoo HS,Kim SW,Lee YH,Sohn YH,Lee SK,Seong JK,Lee PH, Dysautonomia is associated with structural and functional alterations in Parkinson disease. Neurology. 2019 Feb 22;     [PubMed]
Spallone V, Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet. Diabetes     [PubMed]
Barboza CA,Fukushima AR,Carrozzi N,Machi JF,Dourado PMM,Mostarda CT,Irigoyen MC,Nathanson L,Morris M,Caperuto EC,Rodrigues B, Cholinergic Stimulation by Pyridostigmine Bromide Before Myocardial Infarction Prevent Cardiac and Autonomic Dysfunction. Scientific reports. 2019 Feb 21;     [PubMed]
Nattero-Chávez L,Redondo López S,Alonso Díaz S,Garnica Ureña M,Fernández-Durán E,Escobar-Morreale HF,Luque-Ramírez M, Association of cardiovascular autonomic dysfunction with peripheral arterial stiffness in patients with type 1 diabetes. The Journal of clinical endocrinology and metabolism. 2019 Feb 20;     [PubMed]
Traunmüller C,Stefitz R,Gaisbachgrabner K,Hofmann P,Roessler A,Schwerdtfeger AR, Psychophysiological concomitants of burnout: Evidence for different subtypes. Journal of psychosomatic research. 2019 Mar;     [PubMed]
Allen DR,Huang MU,Morris NB,Chaseling GK,Frohman EM,Jay O,Davis SL, Impaired Thermoregulatory Function during Dynamic Exercise in Multiple Sclerosis. Medicine and science in sports and exercise. 2019 Mar;     [PubMed]
Kadoya M,Koyama H, Sleep, Autonomic Nervous Function and Atherosclerosis. International journal of molecular sciences. 2019 Feb 13;     [PubMed]
Baschieri F,Cortelli P, Circadian rhythms of cardiovascular autonomic function: Physiology and clinical implications in neurodegenerative diseases. Autonomic neuroscience : basic     [PubMed]
Bellon G,Venturin A,Masiero S,Del Felice A, Intra-articular botulinum toxin injection in complex regional pain syndrome: Case report and review of the literature. Toxicon : official journal of the International Society on Toxinology. 2019 Mar 1;     [PubMed]
Magkas N,Tsioufis C,Thomopoulos C,Dilaveris P,Georgiopoulos G,Doumas M,Papadopoulos D,Tousoulis D, Orthostatic hypertension: From pathophysiology to clinical applications and therapeutic considerations. Journal of clinical hypertension (Greenwich, Conn.). 2019 Feb 6;     [PubMed]
Grisanti LA, Diabetes and Arrhythmias: Pathophysiology, Mechanisms and Therapeutic Outcomes. Frontiers in physiology. 2018;     [PubMed]

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