Diagnosis

The diagnostic journey for dysautonomia can be long, complicated, and frustrating.

For others, it can be quick with a medical professional picking up on the signs and symptoms and pointing the individual in the right direction for a diagnosis. The delay in diagnosis and misdiagnosis often occurs because symptoms overlap with other conditions that need to be ruled out first.

Oftentimes, individuals will see multiple doctors before they are able to get a diagnosis, sometimes receiving alternative or misdiagnoses along the way. Because of the range of signs and symptoms, patients may end up seeing a variety of specialists before finding a doctor that recognizes their autonomic dysfunction. For example, in a recent POTS survey, diagnosing providers were indicated as being cardiologists, cardiac electrophysiologists, neurologists, primary care physicians, rheumatologists, and other providers ¹.

Common tests used to diagnose dysautonomia include a tilt table test, autonomic function tests, cardiac tests, blood tests, and others. Providers will give specific instructions that need to be followed before some tests. This might include stopping some medications, not eating or drinking for a period of time, or not performing certain activities prior to the test. Discuss any specific requirements or concerns with your providers.

Typically, forms of dysautonomia are diagnosed after a detailed medical history, physical examination with orthostatic vitals, and a resting 12 lead electrocardiogram (ECG) ² ³. The medical history review should include: medications used, personal and family medical history, any relevant comorbidities, time since symptom onset, and a detailed description of symptoms the patient is experiencing ⁴. A physical exam might include various cardiovascular, neurologic, autonomic and other assessments and tests ⁵. Blood pressure and heart rate (orthostatic vitals) should be checked at varying intervals to assess the effects of standing on heart rate and blood pressure. A resting ECG will help rule out any cardiac conduction abnormalities that could be responsible for the high heart rate ⁶. A physician may also order a head-up tilt table test (HUTT) to assess heart rate and blood pressure at fixed intervals while the patient is passively moved ⁷ ⁸. Other autonomic testing and testing of other bodily systems can be performed based on physician recommendation ⁹ ¹⁰ ¹¹.

Below are tests that may be used to diagnose different forms of dysautonomia.

Not all tests are appropriate for all situations. Talk with your doctor to understand which tests may be right for you.

Autonomic Function Tests

Ambulatory Blood Pressure Monitoring- This test continuously monitors blood pressure. ¹²

Cold Pressor Test- During this test, hands are placed in ice-cold water for 1-2 minutes while vital signs are monitored to determine the functioning of the sympathetic nervous system. ¹³

Gastric Emptying Test- This test evaluates how long it takes for food containing traceable ingredients to move through the stomach. It is used for the evaluation of gastroparesis, which can be caused due to autonomic dysfunction. ¹⁴

Heart Rate Variability- This test measures fluctuations in the time intervals between adjacent heartbeats that can indicate autonomic dysfunction. ¹⁵

Orthostatic Vitals- This test assesses how heart rate and blood pressure respond to changes in position from lying down, sitting, and standing. ¹⁶ It can be done with minimal equipment. Heart rate and blood pressure are measured after laying down for a few minutes and then every few minutes while standing up to 10 minutes. Sources vary on recommended time increments.

Quantitative Sudomotor Axon Reflex Test (QSART)- This test helps determine the distribution of sweat loss within an individual that can indicate autonomic dysfunction by inserting a small capsule under the skin that picks up on changes in humidity from sweat during the test. ¹⁷

Thermoregulatory Sweat Test- This test assesses the ability of the individual to sweat, which can indicate autonomic dysfunction. This test can help determine small fiber neuropathy sympathetic cholinergic denervation in the hands or feet, or denervation in large areas of the body. ¹⁸

Tilt Table Test- This test assesses changes in heart rate and blood pressure in response to passive movement as the individual is tilted from lying down to upright. Sometimes blood samples will also be taken during the test to look at norepinephrine or adrenaline levels. ¹⁹

Valsalva Maneuver- This test evaluates cardiovagal functions and adrenergic functions within the autonomic nervous system by monitoring vital signs while performing breathing exercises and the Valsalva maneuver (blowing against resistance for several seconds then relaxing). ²⁰

Cardiac Tests

Echocardiogram (Echo)- This is a test that uses ultrasound to look at the heart's function. ²¹

Electrocardiogram (ECG/EKG)- This test records the electrical signals and conduction of the heart that can be used to determine if it is beating normally or if an arrhythmia (abnormal heart rhythm) is present. ²²

Holter/Cardiac Event Monitoring- These tests allow for the heart's electrical activity to be recorded for an extended period of time. Holter monitors are typically used for 24-48 hours, while event monitors can be in place for up to 30 days. ²³ ²⁴

Implantable Loop Recorder- This test is used to allow for more extended periods of monitoring the heart’s electrical activity. A device is implanted in the skin and allows for continuous recording. ²⁵

Blood Work

Acetylcholine Receptor Antibodies- This blood test measures the concentration of acetylcholine receptor (AChR) antibodies that can impact the parasympathetic nervous system and are sometimes high in autoimmune autonomic ganglionopathy. ²⁶ ²⁷

Autoimmune Panels- This blood test looks for the presence of autoimmune disorders. Oftentimes the anti-nuclear antibody (ANA) is run along with antibodies that have been identified for certain autoimmune conditions that might be responsible for symptom presentation. At times, antibodies can attack the autonomic nervous system resulting in symptoms of autonomic dysfunction and autonomic neuropathy. ²⁸ ²⁹ ³⁰

Blood Volume- Using a small amount of a radioactive isotope, this test can help determine the amount of blood in the body. This test is useful for determining hypovolemia in chronic orthostatic hypotension. ³¹ ³²

Catecholamine Tests- Catecholamines are hormones and neurotransmitters such as dopamine, epinephrine (adrenaline), and norepinephrine that impact the autonomic nervous system ³³. Plasma Norepinephrine (NE) is the chemical messenger of the noradrenergic system and is used as an index of sympathetic nervous system activity in the body. NE levels are often taken upon changing positions, as standing levels are usually double that of lying down. ³⁴ ³⁵

Complete blood cell count and iron studies – blood tests to rule out anemia and iron deficiency. ³⁶

Paraneoplastic Panels- This blood test looks for cancer cells that can produce antibodies to specific proteins expressed by the autonomic nervous system. ³⁷

Other Tests done by blood work - Often, other blood tests can be used to rule out other conditions or evaluate comorbid conditions that can occur.

Other Tests

Electromyography (EMG)- This is a test used to evaluate the electrical signals of the muscles at rest and when being used. It helps to determine if the muscles are responding correctly to the nerve signals from the body ³⁸. This test is used to diagnose peripheral neuropathy, myasthenia gravis, myopathy and other neuromuscular disorders.

Genetic Testing- Samples of genetic material are analyzed for abnormalities that can indicate certain forms of inherited dysautonomias or other co-occurring conditions ³⁹

Skin Biopsies/Punch Biopsies- This test is used in the evaluation of small fiber neuropathy ⁴⁰. Small sections of skin containing the epidermis, dermis, and superficial fat are analyzed to assess for any abnormalities ⁴¹

Sleep study – is used for evaluation of obstructive and central sleep apnea, narcolepsy, restless leg syndrome, and other sleep disorders ⁴²

Reviewed by Medical Content Experts, 2021

REFERENCES

American Heart Association. (2015). Holter monitor. {23}

American Heart Association. (2016). Cardiac event recorder. {24}

Arnold, A. C., Ng, J., & Raj, S. R. (2018). Postural tachycardia syndrome - diagnosis, physiology, and prognosis. Autonomic Neuroscience: Basic & Clinical, 215, 3–11. {2, 4, 9}

Cleveland Clinic. (2016). 24-hour ambulatory blood pressure monitoring. {12}

Cleveland Clinic. (2019). Echocardiogram. {21}

Cleveland Clinic. (2020). Blood volume testing. {3}

Freeman, K., Goldstein, D.S., & Thompson, C.R. (2015). The dysautonomia project: Understanding autonomic nervous system dysfunction for physicians and patients. Bardolf & Company. {28, 32, 34}

Goldstein, D.S. (n.d.). Principles of autonomic medicine 4.0. {29, 35, 39}

Goodman, B. P. (2018). Evaluation of postural tachycardia syndrome (POTS). Autonomic Neuroscience: Basic and Clinical, 215, 12–19. {5, 7,10}

Johns Hopkins Medicine. (2020a). Tilt table testing. {19}

Johns Hopkins Medicine. (2020b). Loop recorder implantation. {25}

Lanier, J. B., Mote, M.B., & Clay, E.C. (2011). Evaluation and management of orthostatic Hypotension. American Family Physician, 84(5), 527-536. {3, 6, 8, 16}

Levine, T. D., & Saperstein, D. S. (2015). Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients. Clinical Rheumatology, 34(3), 413–417. {40}

Low, P. A., Tomalia, V. A., & Park, K. J. (2013). Autonomic function tests: Some clinical applications. Journal of Clinical Neurology, 9(1), 1–8. {17, 18, 20}

Mayo Clinic. (2019). Skin biopsy. {41}

Mayo Clinic. (2020a). Paraneoplastic syndromes of the nervous system. {37}

Mayo Clinic. (2020b). Gastroparesis. {14}

Mayo Clinic. (2020c). Electrocardiogram (ECG or EKG). {22}

Mayo Clinic. (2020d). Polysomnography (sleep study). {42}

Medline Plus. (2020a). Autoimmune disorders. U.S. National Library of Medicine. {30}

Medline Plus. (2020b). Catecholamine blood test. U.S. National Library of Medicine. {33}

Medline Plus. (2020c). Complete blood count. U.S. National Library of Medicine. {36}

Shaffer, F., & Ginsberg, J. P. (2017). An overview of heart rate variability metrics and norms. Frontiers in Public Health, 5, 258. {38}

Shaw, B. H., Stiles, L. E., Bourne, K., Green, E. A., Shibao, C. A., Okamoto, L. E., Garland, E. M., Gamboa, A., Diedrich, A., Raj, V., Sheldon, R. S., Biaggioni, I., Robertson, D., & Raj, S. R. (2019). The face of postural tachycardia syndrome - Insights from a large cross-sectional online community-based survey. Journal of Internal Medicine, 286(4), 438–448. {15}

Sheldon, R. S., Grubb, B. P., Olshansky, B., Shen, W. K., Calkins, H., Brignole, M. Raj, S. R., Krahn, A.,D., Morillo, C.A., Stewart, J., M., Sutton, R., Sandroni, P., Friday, K.J., Hachul, D., T., Cohen, M., I., Lau, D. H., Mayuga, K. A., Moak. J. P., Sanhu, R., Kanjwal, K. (2015). 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm, 12(6), 41–63. {1}

University of Rochester Medical Center. (2020). Acetylcholine receptor antibody (Blood). {11}

Vanderbilt University Medical Center. (2020). Cold pressor test. {13}

Vernino, S. (2015). Autoimmune autonomic ganglionopathy: Bench to bedside. Autonomic Neuroscience: Basic and Clinical, 192, 14–14. {27}