Autonomic Neuropathy

Autonomic neuropathy is a symptom complex associated with the dysfunction of the autonomic nervous system that is responsible for the control of everyday body functions including blood pressure, heart rate, sweating, bowel and bladder function.

Autonomic Neuropathy results from the following process: endocrine.

Presentation

The most common presentation is orthostatic hypotension [9]. Symptoms may be mild, but can be disabling. Patients with POTS may develop true syncope. Sometimes, other autonomic symptoms may prevent prior to POTS. These may include anhidrosis, dry mouth or dry eyes. Also, bowel and bladder dysfunction are common in addition to impotence or ejaculatory dysfunction.

A detailed family history is important to help identify an inherited form of disease. Symptoms may be very subtle in family members and may require careful questioning to identify. In addition to careful history, physical examination is important. A drop in BP from sitting to standing more than 30 mm Hg is diagnostic of orthostatic hypotension. Motor examination is also important because a somatic peripheral neuropathy is frequently associated with an autonomic neuropathy.

Entire body system
  • Heat Intolerance Symptoms of Autonomic Neuropathy General symptoms of this condition may include: Inability to sweat properly, leading to heat intolerance Loss of bladder control, leading to infection or incontinence Dizziness, lightheadedness or fainting because of a [source] intolerance brought on with activity and exercise Sexual problems including erection problems in men and vaginal dryness and orgasm difficulties in women Small pupil in one eye Weight loss without trying Exams and Tests Signs of autonomic nerve damage [source] standing High blood pressure Shortness of breath with activity or exercise Bladder symptoms may include: Difficulty beginning to urinate Feeling of incomplete bladder emptying Leaking urine Other symptoms may include: Sweating too much or not enough Heat [source]
  • Hypothermia Changes in the body's ability to regulate temperature may make you more prone to body chilling ( hypothermia ) or heat-related illness, such as heatstroke or heat exhaustion . [source] Changes in the body's ability to regulate temperature may make you more prone to body chilling (hypothermia) or heat-related illness, such as heatstroke or heat exhaustion. [source] Temperature regulation Hypothermia and hyperpyrexia can result from disruption of the various temperature regulatory mechanisms. [source]
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neurologic
  • Dizziness Early symptoms of AN include dizziness or faintness when rising or standing, and vomiting or feeling nauseated when eating. [source] sleeping with your head elevated to reduce dizziness Abnormal sweating treatment includes: taking prescription medication to reduce excessive sweating Prevention How can I prevent autonomic neuropathy? [source] AN that affect your reproductive organs can include: erectile dysfunction premature ejaculation in women, difficulty achieving an orgasm vaginal dryness Heart and blood vessels The symptoms of AN that affect your heart and blood vessels can include: dizziness [source]
  • Dysautonomia He presented this lecture in 2011 at a dysautonomia symposium at St. [source] Lower levels of these antibodies are not believed to cause disease, but dysautonomia patients with low levels of these antibodies may want to have a careful examination for other autoimmune conditions that could be contributing to their dysautonomia symptoms [source] The g-AChR antibody is part of the Mayo Medical Laboratories Paraneoplastic Antibody Panel and the Autoimmune Dysautonomia Panel . [source]
  • Headache Currently my son has: Difficulty swallowing, erratic heart rate and blood pressure, dizziness, delayed gastric emptying, nausea, headaches, muscle weakness, heat and cold sensitivity, difficulty with his bowls, bladder issues. [source] Hypoglycemia is when blood sugar drops really low, causing shakiness, dizziness, headaches and even fainting. [source] This is, in part, the basis for the wide variety of symptoms (fatigue, headaches, heart burn, constipation and urinary difficulties) that often precede or are associated with many chronic diseases. [source]
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Skin
  • Night Sweats Night sweats or sweating while eating also may occur. [source] rising or standing fainting difficulty breathing during exercise rapid heart rate at rest heart attack without any warning signs Eyes The symptoms of AN that affect your eyes can include slow pupil adjustment from dark to light and difficulty driving at night [source] Sweat glands The symptoms of AN that affect your sweat glands can include dry skin on your feet and excessive sweating or lack of sweating. [source]
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respiratoric
gastrointestinal
  • Choking Accumulation of lipids inside blood vessels ( atherosclerosis ) can choke-off blood supply to certain peripheral nerves. [source]
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cardiovascular
  • Orthostatic Hypotension Orthostatic hypotension: see also the separate article on Hypotension . [source] Typically it manifests with genitourinary symptoms and orthostatic hypotension but without somatic symptoms. [source] Cardiovascular Orthostatic hypotension (often associated with or exacerbated by eating, exercise and raised temperature). [source]
  • Tachycardia Patients have an orthostatic intolerance characterized by hypotension and tachycardia[source] The most common form of autonomic neuropathy is postural orthostatic tachycardia syndrome (POTS). [source] Metoprolol (Lopressor, Toprol XL) is sometimes used to address the tachycardia associated with POTS. [source]
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urogenital
  • Bladder Distention They lost up to 10 percent of their body weight and developed marked bladder distention[source] A grossly overdistended bladder should be drained by catheter to improve contractility, and the patient should be instructed to void by the clock rather than waiting for the sensation of bladder distention[source]
  • Overflow Incontinence They may include: - A drop in blood pressure on standing (orthostatic hypotension), which can cause dizziness and fainting - Trouble with urination, including diminished sensation, overflow incontinence and inability to empty your bladder completely, [source] Finally, overflow incontinence occurs because of denervation of the external and internal sphincter ( 129 , 130 ). [source]
  • Urinary Incontinence incontinence Antibiotics may be prescribed to help treat bacterial infections and catheterization may be appropriate in people suffering from urinary incontinence[source] bladder and autonomic neuropathy If the nerves which control bladder function are affected by autonomic neuropathy, this can lead to problems including: Insufficient emptying of the bladder Bacteria developing in the bladder Loss of bladder control – urinary [source] Urinary incontinence : This may develop because a person may not be able to sense when the bladder is full. [source]
  • Urinary Retention The signs and symptoms of autonomic neuropathy include the following: Urinary bladder conditions: bladder incontinence or urinary retention Gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis [source] Symptoms Symptoms of AAG can include: -severe orthostatic hypotension (very low blood pressure upon standing) -fainting -constipation and GI dysmotility -urinary retention (neurogenic bladder) -fixed and dilated pupils (Adie's pupils) -dry mouth -dry [source] retention Exercise Intolerance Esophageal dysfunction : Heartburn, Dysphagia for solids Male Sexual Dysfunction : Erectile dysfunction, Decreased libido, Abnormal ejaculation Resting Tachycardia Diabetic Diarrhea: Profuse and watery diarrhea, Fecal incontinence [source]
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Eyes

Workup

  • Complete blood count (CBC), basic metabolic panel (BMP), liver function test
  • Immunoelectrophoresis
  • Glucose tolerance test to evaluate for DM.
  • SS-A and SS-B for Sjögren syndrome
  • AChR autoantibodies. Anti-ganglionic acetylcholine receptor
  • Genetic tests. Specific genetic testing can evaluate for some familial forms of autonomic neuropathies.
  • Testing for infections, non-specific inflammatory diseases, autoimmune diseases, or malignancies that could produce a paraneoplastic syndrome.
  • CSF. Elevation of CSF protein on lumbar tap can indicate pandysautonomia (along with elevation of CSF enolase that may indicate damage to the dorsal root ganglia). In HIV, there may be elevated CSF protein along with pleocytosis.
  • Nerve conduction studies. EMG, electromyography, may confirm a presynaptic neuromuscular defect.
  • Thermoregulatory sweat test (TST) and quantitative sudomotor axon reflex test (QSART) are used to evaluate the thermoregulatory pathways [13]. Using alizarin red powder, which changes from orange to purple with moisture, photography maps areas of anhidrosis where the color did not change [14].
  • Pupillometry is being investigated as a test for autonomic neuropathy [15].
  • Sympathetic skin responses (SSR). Using routine EMG, SSR identifies sweat production by looking for changes in skin conductance in response to electric stimuli.
  • Quantitative direct and indirect test (QDIRT). QDIRT tests sudomotor function. A silicone impression of the skin is made while the patient is sweating. Then, the water in the silicone cast can be quantified [16].
  • Vascular studies. Duplex imaging can evaluate the arterial and venous systems. In addition, percutaneous oxygen measurements can be informative.
  • Urologic studies. Urodynamics are used to assess the genitourinary system [17]. In particular, it is important to measure the post-void residual volume in the bladder. This can be done using ultrasonography.
  • GI studies. Gastric and esophageal motility can be examined. Video fluoroscopy or a barium swallow will evaluate for esophageal motility disorders. Gastric motility can be assessed with UGI or with radioisotope methods. Small bowel may be assessed with UGI follow through. Colon motility can be determined via measurement of transit time [18].

Imaging

X-ray

Treatment

The first goal of treatment is to identify possible underlying causes and begin their treatment. For example, with diabetic neuropathy it’s important to obtain careful control of glucose. In the setting of autoimmune disorders, use of immunomodulatory drugs is indicated. However, in many cases, there is no specific therapy to treat the disease.

In cases where underlying disease is not identified or not treatable, intervention is focused on addressing symptoms. For example with POTS, therapy is focused on increased fluid intake and taking care to avoid falling. By increasing fluid and salt intake, blood volume is increased. Alcohol is to be avoided as it can lead to dehydration. Then, patients should be instructed to slowly move from lying to sitting, and from sitting to standing positions. This allows time for body to equilibrate. Also, patients need to take care that when standing, they have support available to avoid falling and causing injury. When treatment is unsuccessful, pharmacological intervention may help with POTS.

Medications

  • Sympathomimetric agents. Midodrine (ProAmatine) may help in treatment of POTS.
  • Mineralocorticoids. Fludrocortisone (Florinef) is also used to treat POTS.
  • Beta-adrenergic blocker. Metoprolol (Lopressor, Toprol XL) is sometimes used to address the tachycardia associated with POTS. However, care must be taken because it will also lower the blood pressure.
  • Colony-stimulating factor. Epoetin alfa (Epogen, Procrit) causes an increase in red blood cell production. With increased hematocrit, symptoms of POTS may be lessened.
  • Acetylcholinesterase inhibitor. Pyridostigmine (Mestinon) will help with cases of POTS.
  • Anticholiinergic agents. Oxybutynin (Ditropan) and Tolterodine (Detrol) are used in the cases of difficult bladder emptying.
  • Vasopressin analogues. Desmopressin acetate (DDAVP) as a nasal spray will decrease nocturnal urinary production.
  • Cholinergic agents. Bethanechol hydrochloride (Duvoid, Urecholine) affect smooth muscle to help bladder emptying.
  • Phosphodiesterase inhibitors. Sildenafil (Viagra) is effective for treatment of erectile dysfunction by stimulating smooth muscle of corpora cavernosa.
  • Neuromusclar blocker. Botulinum toxin type A (Botox) helps in patients with hyperhidrosis.
  • Anticholinergic agent. Glycopyrrolate (Robinul) is also used to treat hyperhidrosis.
  • Immune globulin. IV immune globulin can be used for autoimmune causes of autonomic neuropathy.
  • Anti-inflammatory agent. Prednisone may be helpful in suppressing inflammatory response in a case with presumed autoimmune pathophysiology.

Prognosis

Most cases are idiopathic and demonstrate a very slow progression. For others, prognosis depends on the underlying disease process causing the neuropathy. In many cases, addressing the underlying problem, such as controlling diabetes, eliminating alcohol, or treating other diseases can improve symptoms. For those presenting with an acute idiopathic disease, such as pandysautonomia or Guillain-Barré syndrome, prognosis is excellent after resolution of the acute disease.

Complications

  • Constipation Gastrointestinal Symptoms of Autonomic Neuropathy Damage to the nerves of the digestive system can cause: Constipation (sometimes alternating with diarrhea) Difficulty swallowing Gastroparesis, a condition in which the stomach empties too slowly, causing [source] symptoms of this condition may include: Inability to sweat properly, leading to heat intolerance Loss of bladder control, leading to infection or incontinence Dizziness, lightheadedness or fainting because of a loss of control over blood pressure Diarrhea, constipation [source] Severe constipation may occur. [source]
  • Decreased Sweating Decreased sweating may be evident on examination. [source] For example, on a very warm day if the socks are very dry this likely represents decreased sweating. 4. [source] sweating Worsening night vision 3. [source]
  • Erectile Dysfunction Men may have difficulty initiating and maintaining an erection (erectile dysfunction). [source] People may feel light-headed when they stand and have urination problems, constipation, and vomiting, and men may have erectile dysfunction[source] Drugs to treat erectile dysfunction like sildenafil ( Viagra ), tadalafil ( Cialis ), and vardenafil ( Levitra ) may help some men with ED due to diabetic neuropathy. [source]
  • Hypotension Orthostatic hypotension: see also the separate article on Hypotension[source] Typically it manifests with genitourinary symptoms and orthostatic hypotension but without somatic symptoms. [source] Cardiovascular Orthostatic hypotension (often associated with or exacerbated by eating, exercise and raised temperature). [source]
  • Peripheral Neuropathy More discussions about peripheral neuropathy [source] There are hundreds of peripheral neuropathies[source] Patient discussion about peripheral neuropathy Q. [source]
  • Shy Drager Syndrome Primary causes of autonomic neuropathy include: Familial dysautonomia (Riley-Day syndrome) Idiopathic orthostatic hypotension (progressive autonomic failure) Multiple system atrophy with autonomic failure (Shy-Drager syndrome) Parkinson’s syndrome with [source] Congenital absence Respiratory disorders, Autonomic Multiple Systems Atrophy (Shy-Drager) Sporadic or Autosomal Dominant Nosology: Other similar or overlapping disorders Striatonigral degeneration Adult-onset sporadic olivopontocerebellar atrophy (OPCA) Shy-Drager [source] syndrome Genetic susceptibility COQ2 Clinical features Onset Age: Adult Parkinsonism: Early Bladder dysfunction Orthostatic hypotension 36 May initially present as: Pure autonomic failure Predictors of progression to MSA Cardiovagal impairment: Mild [source]
  • Syncope Patients with POTS may develop true syncope[source] In severe cases, patients may experience syncope[source] Sometimes, this may cause dizziness or even fainting (syncope). [source]
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Etiology

Autonomic neuropathy may be idiopathic, or may be part of a familial disease. In addition, secondary autonomic neuropathy may be the result of a number of different disorders, including diabetes mellitus, amyloidosis, autoimmune disorders, or viral infections. The most common neuropathy is that associated with diabetes. Infections can trigger an autoimmune reaction that results in the destruction of autonomic nerves. A similar problem occurs with Guillain-Barré syndrome. Other causes of autonomic neuropathies include cancer, drugs, alcohol, and toxins.

Epidemiology

Overall, there is not a significant age, sex, or ethnic predilection for autonomic neuropathies. However, one common presentation is with postural orthostatic tachycardia syndrome (POTS), which is primarily seen in women.

Sex distribution
Age distribution

Pathophysiology

The pathophysiology of autonomic neuropathies depends on the etiology of the disease. Although uncommon, there are a number of inherited autonomic neuropathies. Of the acquired autonomic neuropathies, there are both primary or idiopathic presentations and those that are secondary to other disease processes. Below, we outline some of these diseases.

Inherited autonomic neuropathies

  • Familial amyloid polyneuropathy. A genetic mutation causes amyloid deposition in the PNS and the ANS. Treatment is liver transplantation [2].
  • Hereditary sensory autonomic neuropathy (HSAN). Five distinct types of HSAN have been identified [3]. They differ in presentation and their inheritance patterns.
  • Fabry disease. Fabry disease is an X-linked recessive disorder that causes and accumulation of glycolipids.

Acquired autonomic neuropathies

Primary acquired autonomic neuropathies

  • Postural orthostatic tachycardia syndrome (POTS). POTS is the most common presentation of autonomic neuropathy. This is an idiopathic disorder seen in women. Patients have an orthostatic intolerance characterized by hypotension and tachycardia. In severe cases, patients may experience syncope.
  • Pandysautonomia. This presentation involved diffuse involvement of both the sympathetic and parasympathetic systems.
  • Idiopathic distal small-fiber neuropathy. This is a chronic distal neuropathy usually presenting with damage to sudomotor fibers (postganglionic sympathetic nerve fibers innervating the sweat glands).
  • Holmes-Adie syndrome and Ross syndrome. This most likely an autoimmune disease that presents with tonic pupils or pupils with tendon areflexia.
  • Chronic idiopathic anhidrosis. In this presentation, there is an idiopathic presentation with loss of sweating. Secondary acquired autonomic neuropathies (metabolic disorders)

Secondary Acquired Autonomic Neuropathies

  • Diabetes mellitus (DM). Neuropathy is the most common complication of DM and may have both somatic and autonomic components [4], [5], [6], [7].
  • Uremic neuropathy. Uremic neuropathy is primarily a somatic neuropathy but there may be autonomic components.
  • Liver disease. Biliary cirrhosis can be associated with autonomic neuropathy in 48% of patients.
  • Vitamin deficiency and nutrition-related neuropathy. Vitamin B-12 deficiency may cause an autonomic neuropathy [8].
  • Toxic and drug-induced autonomic neuropathy. A number of chemotherapy drugs may cause autonomic neuropathy. Other drugs include, acrylamide, pyridoxine, thallium, amiodarone, perhexiline, and gemcitabine [9].
  • Alcohol associated autonomic neuropathy. Alcohol use may have a direct effect on the autonomic nervous system or the damage may be mediated by a thiamine deficiency [10].
  • Infectious diseases. A number of diseases have been associated with autonomic neuropathy: Lyme disease, HIV, Chagas disease, Botulsim, Diptheria and Leprosy
  • Celiac disease. Patients with celiac disease may have autonomic neuropathies in 50% of cases.
  • Sjögren syndrome. It is thought that cause of neuropathy is via autoimmune mechanism [11].
  • Rheumatoid arthritis, systemic lupus erythematosis, and connective tissue disorders. These entities probably affect the ANS via an autoimmune mechanism.
  • Acute intermittent porphyria and variegate porphyria. Disease may be secondary to drug exposure. During episodes, presentation may mimic Guillain-Barré syndrome
  • Guillain-Barré syndrome. Antibodies are produced to gangliosides resulting in an autonomic neuropathy.
  • Lambert-Eaton myasthenic syndrome. In this syndrome, antibodies are produced against presynaptic voltage-gated P/Q-type Ca2+ channels.
  • Paraneoplastic autonomic neuropathy. With paraneoplastic syndrome, anti-Hu antibodies are produced in 23% of patietns resulting in autonomic neuropathy.
  • Amyloid neuropathy. Amyloid neuropathy can be associated with hematologic malignancies such as multiple myeloma.
  • Inflammatory bowel disease. Probably mediated by an autoimmune mechanism, IBD may have associated autonomic neuropathy involving the pupillary nerves [12].

Prevention

The most common symptom of autonomic neuropathy is postural hypotension. By increasing blood volume through fluid and salt intake, the symptoms of POTS can be minimized. In addition, patients need to be careful when changing postural position. When going from supine to sitting to standing, they need to move slowly and have something nearby to hold on to. As noted above, there are a number of drugs to help with some of the other symptoms of the disease, particularly with respect to bladder, bowel, or genitourinary systems.

Summary

The nervous system is divided into the central (CNS) and peripheral nervous systems (PNS) [1]. The PNS consists of the nerves that connect the CNS to the rest of the body, including not only the muscles, but also various receptors and glands. Within the PNS there are both afferent (sensory division) and efferent nerves (motor division), bringing information to the CNS and returning commands for action. The efferent system is divided into two components. There are somatic nerves that bring information to the skeletal muscles and there are autonomic nerves that transmit commands to the smooth muscle (heart) and glands. The autonomic nervous system (ANS) has two types of nerves, sympathetic and parasympathetic nerves. The parasympathetic system regulates resting body functions. Whereas, the sympathetic system allows the body to respond to need for increased activity, associated with stress or strenuous work. With autonomic neuropathy, symptoms may go unnoticed, or they may be disabling.

Patient Information

Neuropathy refers to a disorder of the nervous system. The autonomic nervous system is the part of the body that controls many basic functions, such as heart rate, blood pressure, sweating, bowel, and bladder function. Thus, autonomic neuropathy may present with symptoms of low blood pressure, fast heart rate, increased or decreased sweating, and problems with bowel/bladder emptying. Autonomic neuropathy can be from a familial disorder or may be secondary to another disease. Most times it is idiopathic, meaning that we will never know the cause. A careful family history and blood tests will help in determining the underlying diagnosis.

The most common form of autonomic neuropathy is postural orthostatic tachycardia syndrome (POTS). With POTS, when you suddenly stand up, you may have a drop in blood pressure (orthostatic hypotension) and your heart may beat too quickly (tachycardia). Sometimes, this may cause dizziness or even fainting (syncope). In most cases, a cause for the POTS is never identified. Usually, the problem is mild and can be controlled by increased fluid and salt intake to increase blood volume and limit alcohol to avoid dehydration. In addition, changing posture slowly allows the body time to adjust and reduces the symptoms. People with this disorder should also take care to have something/someone to hold on to as they go from sitting to standing. After standing, you should wait for a moment before beginning to walk. In more severe cases, medications can be prescribed.

Autonomic neuropathy can also prevent with increased/decreased sweating. If this is troublesome, there are medications that will diminish symptoms. Problems with bladder/bowel emptying can be treated with drug therapy and medicines for erectile dysfunction can be used when needed.

Many times autonomic neuropathy can be a symptom of another disease. The most common cause is diabetes and it is important to bring sugars under careful control to help manage the diabetic neuropathy. Autonomic neuropathy is also associated with some cancers and with autoimmune diseases. It is important to look for these other causes.

Self-assessment

References

  1. Seeley RR, Stephens TD, Tate P. Functional organization of nervous tissue. In: Anatomy & Physiology. 3rd ed. Philadelphia, PA : Mosby; 1995: 369-70.
  2. Delahaye N, Rouzet F, Sarda L, et al. Impact of liver transplantation on cardiac autonomic denervation in familial amyloid polyneuropathy. Medicine (Baltimore). 2006; 85(4):229-238.
  3. Davidson GL, Murphy SM, Polke JM, Laura M, Salih MA, Muntoni F, et al. Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort. J Neurol. 2012 Feb 1.
  4. Zochodne DW. Diabetic neuropathies: features and mechanisms. Brain Pathol. 1999 Apr; 9(2):369-91.
  5. Vinik AI, Freeman R, Erbas T. Diabetic autonomic neuropathy. Semin Neurol. 2003 Dec; 23(4):365-72.
  6. Clements RS Jr, Flint MA. Coping with autonomic neuropathy. J Diabet Complications. 1988 Jul-Sep; 2(3):130-2. 
  7. Supriya Simon A, Dinesh Roy D, Jayapal V, Vijayakumar T. Somatic DNA damages in cardiovascular autonomic neuropathy. Indian J Clin Biochem. 2011 Jan; 26(1):50-6. 
  8. Beitzke M, Pfister P, Fortin J, Skrabal F. Autonomic dysfunction and hemodynamics in vitamin B12 deficiency. Auton Neurosci. 2002 Apr 18; 97(1):45-54. 
  9. Low PA. Clinical autonomic disorders: evaluation and management. 2nd ed. New York: Lippincott Raven; 1997.
  10. Koike H, Sobue G. Alcoholic neuropathy. Curr Opin Neurol. 2006 Oct; 19(5):481-6. 
  11. Gemignani F, Marbini A, Pavesi G, Di Vittorio S, Manganelli P, Cenacchi G, et al. Peripheral neuropathy associated with primary Sjögren's syndrome. J Neurol Neurosurg Psychiatry. 1994 Aug; 57(8):983-6. 
  12. Straub RH, Antoniou E, Zeuner M, et al. Association of autonomic nervous hyperreflexia and systemic inflammation in patients with Crohn's disease and ulcerative colitis. J Neuroimmunol. 1997 Dec; 80(1-2):149-57.
  13. Low PA, Dyck PJ, Lambert EH, et al. Acute panautonomic neuropathy. Ann Neurol. 1983 Apr; 13(4):412-7.
  14. Fealey RD. Thermoregulatory sweat test. Low PA, ed. Clinical Autonomic Disorders: Evaluation and Management. 2nd ed. Philadelphia: Lippincott-Raven. 1997; 245-57.
  15. Davies DR, Smith SE. Pupil abnormality in amyloidosis with autonomic neuropathy. J Neurol Neurosurg Psychiatry. 1999 Dec; 67(6):819-22. 
  16. Gibbons CH, Illigens BM, Centi J, Freeman R. QDIRT: quantitative direct and indirect test of sudomotor function. Neurology. 2008 Jun 10; 70(24):2299-304. 
  17. Madersbacher HG. Neurogenic bladder dysfunction. Curr Opin Urol. 1999 Jul; 9(4):303-7.
  18. Bharucha AE, Camilleri M, Low PA, Zinsmeister AR. Autonomic dysfunction in gastrointestinal motility disorders. Gut. 1993 Mar; 34(3):397-401.

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