(Translated by https://www.hiragana.jp/)
Autonomic Neuropathy
The Wayback Machine - https://web.archive.org/web/20130419194448/http://emedicine.medscape.com/article/1173756-overview
 
 

Autonomic Neuropathy 

  • Author: Steven D Arbogast, DO; Chief Editor: Nicholas Lorenzo, MD, CPE   more...
 
Updated: Feb 6, 2012
 

Background

Autonomic neuropathies are a collection of syndromes and diseases affecting the autonomic neurons, either parasympathetic or sympathetic, or both. Autonomic neuropathies can be hereditary or acquired in nature. Most often, they occur in conjunction with a somatic neuropathy, but they can also occur in isolation.

The autonomic nervous system modulates numerous body functions; therefore, autonomic dysfunction may manifest with numerous clinical phenotypes and various laboratory and neurophysiologic abnormalities. Although a patient may present with symptoms related to a single portion of the autonomic system, the physician must be vigilant for other affected parts of the autonomic system.

In some forms, the degree and type of autonomic system involvement varies extensively. In some patients, the degree of autonomic dysfunction may be subclinical or clinically irrelevant; in others, symptoms may be disabling. Several clinically important features of autonomic neuropathies are treatable; therefore, the physician must be alert to these features.

Next

Pathophysiology

The pathophysiology of autonomic neuropathies is variable and depends upon the underlying medical conditions. We have chosen to classify the autonomic neuropathies into hereditary and acquired. The acquired autonomic neuropathies may then be subsequently subdivided into primary or secondary.

Previous
Next

Inherited Autonomic Neuropathies

All forms of inherited autonomic neuropathies are rare. Familial amyloid polyneuropathy, the hereditary sensory autonomic neuropathies, Fabry disease, and the porphyrias are genetic diseases in which autonomic neuropathy is a common feature.

Familial amyloid polyneuropathy

Familial amyloid polyneuropathy (FAP) is often caused by a genetic mutation of the transthyretin gene. Mutant transthyretin produced in the liver accumulates as amyloid deposits in the peripheral nervous system and autonomic nervous system. Rarely, a mutation in the gelsolin gene, which produces a protein important in cytoskeletal actin function, may also lead to amyloid deposition in autonomic nerves. Liver transplantation, currently the most effective treatment for FAP, may slow the development of autonomic neuropathy, but not in all cases.[1]

Hereditary sensory autonomic neuropathy

Currently, 5 types of hereditary sensory autonomic neuropathy (HSAN) have been defined (see Table 1). These types differ in their presentation, the portions of the autonomic nervous system affected, their associated genes, and inheritance pattern.[2]

HSAN I has an autosomal dominant inheritance, and the disease is characterized by distal limb involvement with marked sensory loss, including loss of pain sensation, making affected individuals more susceptible to injury. HSAN I has been associated with point mutations in serine palmitoyltransferase (SPT) at chromosome arm 9q22.1-q22.3.[3] SPT is the rate-limiting enzyme in synthesis of sphingolipids, including ceramide and sphingomyelin. Ceramide is necessary for regulation of programmed cell death in a number of tissues, including the differentiation of neuronal cells.

HSAN II is inherited as an autosomal recessive condition and is more severe with a congenital onset. HSAN II has a pansensory loss with early ulcers, and nerves demonstrate a marked loss of myelinated and unmyelinated fibers.

HSAN III (Riley-Day syndrome) is autosomal recessive in Ashkenazi Jews, with early childhood onset of autonomic crises. The genetic defect in HSAN III is in the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein (IKBKAP) at chromosome arm 9q31. HSAN III nerve pathology shows absence of unmyelinated fibers with essentially normal myelinated fibers.[4]

Patients with HSAN IV present with widespread anhidrosis and insensitivity to pain. The genetic defect in HSAN IV is in the tyrosine kinase receptor A or nerve growth factor receptor at chromosome arm 1q21-q22. This defect is autosomal recessive. Recently, 2 novel missense mutations in the tyrosine kinase domain were found in a 10-year-old patient with HSAN IV.[5] This finding may provide a better understanding of the neuropathophysiology of HSAN IV.

Patients with HSAN V present with pain insensitivity and preservation of other sensory modalities. Some patients with HSAN V have similar genetic abnormalities to those with HSAN IV. The genetic mutation has been isolated to the nerve growth factor beta gene.[6]

Table. Types of HSAN (Open Table in a new window)

HSANMode of InheritanceOnsetSymptomsSigns
Type IAutosomal dominant, point mutations in SPT, 9q22.1-9q22.3Second decade of lifeDistal lower-limb involvement, ulceration of the feet, particularly the solesLow sensory action potential amplitude
Type II, Morvan diseaseAutosomal recessiveCongenital onsetPansensory loss of upper and lower limbs, also trunk and forehead; early ulcersLoss of myelinated and unmyelinated fibers
Type III, Riley-Day syndrome or familial dysautonomia)Autosomal recessive, 9q31Childhood onset, predominantly Ashkenazi JewsPallor in infancy, irregularities in temperature and blood pressure; Difficulties in eating and swallowingAbsence of unmyelinated fibers
Type IVAutosomal recessive, 1q21-1q22Congenital onsetWidespread anhidrosis, lost sense of pain, mental retardationLoss of myelinated and small unmyelinated fibers
Type VAutosomal recessiveCongenital onsetPain insensitivity in extremitiesNot applicable

Fabry disease

Fabry disease is an X-linked recessive disorder with mutations in the gene for alpha-galactosidase. Somatic and autonomic neuropathy is due to accumulation of glycolipids. Attacks may be triggered by changes in temperature or exercise. Nerve pathology demonstrates loss of both small myelinated and unmyelinated fibers.[7]

Acute intermittent porphyria and variegate porphyria

Acute intermittent porphyria and variegate porphyria can both have forms of peripheral neuropathy. Attacks can be triggered by exposure to particular drugs. During episodes, affected individuals present with acute polyneuropathy that may mimic Guillain-Barré syndrome. Autonomic dysfunction, particularly cardiac and vascular in nature, can be prominent.

Previous
Next

Acquired Autonomic Neuropathies

The acquired autonomic neuropathies are much more prevalent than the inherited ones. Here, we subclassify the acquired autonomic neuropathies into primary and secondary disorders. Primary autonomic neuropathies are disorders that are idiopathic or that have autonomic neuropathy as a characteristic feature of the disease process itself. In the secondary autonomic neuropathies, an identifiable cause, such as a nutritional deficiency, may lead to autonomic neuropathy, but does not have autonomic neuropathy as a defining feature of the disease process. Subclassification can be somewhat artificial as the true mechanism of action is not clear in all cases, although it can be helpful when trying to develop an understanding of autonomic neuropathy.

Primary acquired autonomic neuropathies

  • Pandysautonomia: The syndrome of acute pandysautonomia includes both parasympathetic and sympathetic dysfunction.[8] An immunologic basis for acute pandysautonomia remains most likely, often with onset after a viral illness. Patients with what may have otherwise been called idiopathic autonomic neuropathy may test positive for an autonomic ganglionic acetylcholine receptor antibody supporting the autoimmune etiology of this condition.[9]
  • Idiopathic distal small-fiber neuropathy: Idiopathic distal small-fiber neuropathy is a chronic peripheral somatic neuropathy affecting sympathetic postganglionic sudomotor fibers. Clinical features may include allodynia, sympathetic vasomotor changes, pallor and rubor, cyanosis, and even mottling.[10]
  • Holmes-Adie syndrome and Ross syndrome: Holmes-Adie syndrome is probably autoimmune in nature and manifests as tonic pupil or pupils associated with tendon areflexia. In rare cases, it is associated with an autonomic neuropathy with prominent orthostatic hypotension.[11] Ross syndrome is a related condition where segmental anhidrosis occurs in conjunction with Adie pupil.[12]
  • Chronic idiopathic anhidrosis: Chronic idiopathic anhidrosis is an acquired generalized loss of sweating without other autonomic features. The lesions may be pre- or postganglionic.[13]
  • Amyloid neuropathy: Amyloid neuropathy can be inherited as noted above; however, it can also be associated with hematologic disease, such as multiple myeloma, leading to accumulation of immunoglobulins kappa or lambda light chains.[14] Another acquired amyloidosis occurs with dialysis, with βべーた2-microglobulin deposits in the nervous system. In syndromes of amyloidosis, the development of generalized autonomic failure significantly worsens the overall prognosis. Of all autonomic neuropathies, amyloidosis probably causes the most severe forms, with universal autonomic dysfunction common. A somatic neuropathy is often coexistent.[15]
  • Postural orthostatic tachycardia syndrome: Postural orthostatic tachycardia syndrome (POTS) is a syndrome most common in young females with orthostatic intolerance characterized by palpitations with excessive orthostatic sinus tachycardia, sensation of lightheadedness, and near-syncope. POTS may be associated with an infectious prodrome and thus may represent the chronic sequelae of a forme fruste of postviral pandysautonomia.[16] Antibodies against ganglionic receptors are found in 9% of patients with POTS.[17]

Secondary acquired autonomic neuropathies

Metabolic derangements that may have an associated autonomic neuropathy are as follows:

  • Diabetes mellitus
    • Diabetes mellitus is the most common cause of autonomic neuropathy. Neuropathy is the most common complication of diabetes mellitus and may have both somatic and autonomic features.[18, 19, 20, 21] See Medscape Reference's article on Diabetic Neuropathy. Parasympathetic abnormalities are thought to precede sympathetic abnormalities, but this has not been verified.
    • A disorder called acute diabetic autonomic neuropathy appears as an acute pandysautonomia and may be associated with ganglionic antibodies in some patients. Diabetic radiculoplexopathy is associated with prominent autonomic dysfunction, which may have an immunologic cause with destruction of both large and small nerve fibers.[18]
    • Diabetes affects autonomic neurons differently; sympathetic neurons from the celiac/superior mesenteric ganglia develop pathological changes, while sympathetic superior cervical ganglion neurons do not. This selectivity may be related to increased sensitivity to oxidative stress.[22]
  • Uremic neuropathy: Uremic neuropathy is a primarily somatic neuropathy commonly associated with coexistent autonomic neuropathy, either symptomatic or subclinical. The cause of uremic neuropathy remains unknown, although either accumulated toxins or lack of a neurotrophic factor may be responsible because renal transplantation reverses autonomic dysfunction while dialysis does not.[23]
  • Hepatic disease–related neuropathy: Neuropathies related to hepatic disease, such as primary biliary cirrhosis, can be associated with autonomic neuropathy in 48% of patients. The cause of autonomic neuropathy in hepatic disease remains unclear, but it may be associated with toxic metabolite accumulation or related immune-mediated mechanisms. It may be reversible following liver transplantation. Maheshwari et al hypothesized that patients with autonomic neuropathies are more likely to develop hepatic encephalopathy due to a decreased intestinal transit time.[24] Although this group's study did not show an independent effect of autonomic neuropathy on hepatic encephalopathy, their findings did demonstrate that patients with autonomic neuropathies were more likely to develop new-onset hepatic encephalopathy.

Vitamin deficiencies, toxins, and drugs that may have an associated autonomic neuropathy are as follows:

  • Vitamin deficiency and nutrition-related neuropathy: Deficiency of vitamin B12 neuropathy may also be associated with autonomic dysfunction.[25]
  • Toxic and drug-induced autonomic neuropathy: Toxic and drug-induced autonomic neuropathies may occur with a large variety of chemotherapeutic medications such as vincristine, cisplatin, carboplatin, vinorelbine, paclitaxel, and suramin. Other therapeutic agents associated with a toxic autonomic neuropathy include acrylamide, pyridoxine, thallium, amiodarone, perhexiline, and gemcitabine.[7]
  • Alcohol may be associated with an autonomic neuropathy, possibly related to directly toxic effects of alcohol, although thiamine deficiency may also play a role.[26]

Infectious diseases that may have an associated autonomic neuropathy are as follows:

  • Lyme disease: Patients with Lyme disease have shown lymphoplasmocellular infiltrates in the autonomic ganglia.[27]
  • HIV infection: HIV infection may lead to autonomic neuropathy, particularly in late-terminal stages of disease.[28] . Often, this occurs in conjunction with a somatic neuropathy related to HIV infection or complications of AIDS.[29]
  • Chagas disease: Chagas disease due to infection with Trypanosoma cruzi is occasionally associated with autonomic neuropathy during the chronic stage of infection.[30] Parasympathetic dysfunction tends to be greater than sympathetic dysfunction.[31] Autoimmune destruction of the peripheral nervous system and autonomic nervous system may occur, especially of autonomic nerves supplying the cardiovascular and gastrointestinal systems.
  • Botulism: Botulism produces neuromuscular paralysis by inhibiting the release of acetylcholine from the presynaptic terminus, as well as an acute cholinergic neuropathy.[32]
  • Diphtheria: Diphtheria has been associated with an autonomic neuropathy. Although the mechanism of action is not clear, the parasympathetic nervous system may be more affected than the sympathetic.[33]
  • Leprosy: Leprosy causes nerve injury by direct invasion of Mycobacterium leprae into the nerve and Schwann cells.[34] Leprosy has been shown to affect both the sympathetic and parasympathetic nervous system.[35]

Autoimmune conditions that may have an associated autonomic neuropathy are as follows:

  • Celiac disease: Autonomic neuropathy may occur in approximately 50% of adults with celiac disease, leading to clinical features of presyncope and postural nausea.[36] Autonomic denervation may be related to antineuronal antibodies; the neuropathy does not appear to respond to a gluten-free diet.[37]
  • Sj ö gren syndrome: Sj ö gren syndrome may lead to peripheral and autonomic neuropathy without characteristic systemic symptoms. A small-fiber neuropathy associated with Sj ö gren syndrome can be associated with widespread anhidrosis. Also, a sensory neuronopathy due to Sj ö gren syndrome can be associated with autonomic dysfunction. The cause of neuropathy in these patients is likely to be autoimmune, but this remains unclear.[38]
  • Rheumatoid arthritis, systemic lupus erythematosus, and connective tissue disorders: Abnormalities of sympathetic postganglionic function may be seen in rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders. Some of these patients may have autoantibodies to ganglionic acetylcholine receptors. Autoimmune thyroiditis, such as chronic thyroiditis and Hashimoto thyroiditis, can be associated with some features of Sj ö gren syndrome such as xerostomia. Patients with systemic sclerosis and mixed connective tissue disorder may have abnormalities of autonomic functioning of esophageal motor activity.[7]
  • Guillain-Barré syndrome: Guillain-Barré syndrome (GBS), or acute inflammatory demyelinating polyneuropathy (AIDP), is an acute autoimmune somatic neuropathy commonly associated with prominent autonomic dysfunction that can lead to both morbidity and mortality.[39, 40] Autoantibodies can be found against gangliosides, such as with anti-GM1 antibodies. Pathologic studies of the autonomic nervous system in GBS may demonstrate edema and inflammation of autonomic ganglia and destruction of peripheral ganglion cells. Chromatolysis, mononuclear cell infiltration, and nodules of Nageotte can be found within sympathetic ganglia.[39]
  • Lambert-Eaton myasthenic syndrome: Lambert-Eaton myasthenic syndrome (LEMS) is an acquired neuromuscular transmission disorder with antibodies present against presynaptic voltage-gated P/Q-type Ca2+ channels. LEMS is frequently associated with clinical and electrophysiologic evidence of dysautonomia, which can be severe in 20% of patients with LEMS.[41] In 50% of cases, LEMS is associated with a neoplasm, most commonly small cell carcinoma of the lung.
  • Paraneoplastic autonomic neuropathy
    • Paraneoplastic autonomic neuropathy may occur as a component of paraneoplastic neuronopathy with anti-Hu antibodies in 23% of patients. Autonomic dysfunction appears to result from autoimmune destruction of autonomic postganglionic and myenteric neurons.[42]
    • A variant of paraneoplastic autonomic neuropathy is an enteric neuronopathy that exists with antibodies directed against the myenteric plexus (anti-enteric neuronal antibodies).[43] Other paraneoplastic autonomic syndromes may have autoantibodies against neuronal cytoplasmic proteins of the collapsin response–mediator family (CRMP-5) and against Purkinje cell cytoplasm (PCA-2).[44]
  • Inflammatory bowel disease: Inflammatory bowel disease–related disorders may rarely have an associated autonomic neuropathy, particularly involving the pupillary nerves.[45]
Previous
Next

Epidemiology

Mortality/Morbidity

Falls and loss of consciousness are significant contributors to morbidity associated with autonomic neuropathies. They may lead to injury, particularly in the elderly. Often, an autonomic neuropathy manifests with orthostatic hypotension, which has been associated with increased mortality in the middle aged and elderly.[46] As the autonomic nervous system is involved in involuntary control of almost every organ system, patients may have many other complaints that are discussed below.

Many cases of autonomic neuropathy have a gradually progressive course, leading to a poor outcome. Patients with severe dysautonomia are at risk for sudden death secondary to cardiac dysrhythmia, as has been documented in GBS and diabetic neuropathy. Single-photon emission CT (SPECT) and positron emission tomography (PET) have demonstrated that cardiac sympathetic dysfunction is commonly present in both type I and type II diabetes mellitus. When associated with vascular complications, dysautonomia related to diabetic neuropathy is also associated with increased mortality. In other disorders, other forms of systemic dysfunction, such as with kidney failure in Fabry disease, may lead to mortality.

Race

Autonomic neuropathies may be seen in all races and ethnicities. Certain subtypes may demonstrate an increased incidence in specific ethnic groups. These subtypes are addressed individually above.

Sex

In general, no predilection for autonomic neuropathies exists with regard to sex. POTS and connective tissue diseases are more common among females. Fabry disease is inherited as an X-linked recessive disorder; therefore, it manifests predominantly in males.

Age

In general, no predilection for autonomic neuropathies exists with regard to age. Age of onset is highly dependent upon the underlying pathophysiology. Patients with most forms of HSAN (except HSAN I) present at birth or in childhood.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Steven D Arbogast, DO  Fellow, Neuromuscular Medicine, University Hospitals Case Medical Center, Cleveland

Steven D Arbogast, DO is a member of the following medical societies: American Academy of Neurology and American Osteopathic Association

Disclosure: Nothing to disclose.

Coauthor(s)

J Douglas Miles, MD, PhD  Assistant Professor of Neuroscience, Marshall University School of Medicine, and Clinical Instructor of Neurology, Case Western Reserve University School of Medicine

J Douglas Miles, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Medical Association, and Society for Neuroscience

Disclosure: Nothing to disclose.

Bashar Katirji, MD, FACP  Director, Neuromuscular Center and EMG Laboratory, The Neurological Institute, University Hospitals Case Medical Center; Professor of Neurology, Case Western Reserve University School of Medicine

Bashar Katirji, MD, FACP is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Physicians, and American Neurological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Paul E Barkhaus, MD  Professor, Department of Neurology, Medical College of Wisconsin; Director of Neuromuscular Diseases, Milwaukee Veterans Affairs Medical Center

Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Glenn Lopate, MD  Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa

Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting; Sunovion Consulting fee None

Chief Editor

Nicholas Lorenzo, MD, CPE  Chairman and CEO, Neurology Specialists and Consultants; Senior Vice President, Founding Executive Director, Continuing Medical Education, Gannett Education (Division Gannett Healthcare Group)

Nicholas Lorenzo, MD, CPE is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and American College of Physician Executives

Disclosure: Nothing to disclose.

References

  1. 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. [Medline].

  2. 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. Feb 1 2012;[Medline].

  3. Bejaoui K, Wu C, Scheffler MD, et al. SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet. Mar 2001;27(3):261-2. [Medline].

  4. Low PA, Vernino S, Suarez G. Autonomic dysfunction in peripheral nerve disease. Muscle Nerve. Jun 2003;27(6):646-61. [Medline].

  5. Ohto T, Iwasaki N, Fujiwara J, et al. The evaluation of autonomic nervous function in a patient with hereditary sensory and autonomic neuropathy type IV with novel mutations of the TRKA gene. Neuropediatrics. Oct 2004;35(5):274-8. [Medline].

  6. Einarsdottir E, Carlsson A, Minde J, et al. A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception. Hum Mol Genet. Apr 15 2004;13(8):799-805. [Medline].

  7. Low PA. Clinical autonomic disorders: evaluation and management. 2nd ed. New York: Lippincott Raven; 1997.

  8. Low PA, Dyck PJ, Lambert EH, et al. Acute panautonomic neuropathy. Ann Neurol. Apr 1983;13(4):412-7. [Medline].

  9. Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. Sep 21 2000;343(12):847-55. [Medline].

  10. Stewart JD, Low PA, Fealey RD. Distal small fiber neuropathy: results of tests of sweating and autonomic cardiovascular reflexes. Muscle Nerve. Jun 1992;15(6):661-5. [Medline].

  11. Emond D, Lebel M. Orthostatic hypotension and Holmes-Adie syndrome. Usefulness of the Valsalva ratio in the evaluation of baroreceptor dysfunction. J Hum Hypertens. Sep 2002;16(9):661-2. [Medline].

  12. Nolano M, Provitera V, Perretti A, Stancanelli A, Saltalamacchia AM, Donadio V, et al. Ross syndrome: a rare or a misknown disorder of thermoregulation? A skin innervation study on 12 subjects. Brain. Aug 2006;129:2119-31. [Medline].

  13. Low PA, Fealey RD, Sheps SG, Su WP, Trautmann JC, Kuntz NL. Chronic idiopathic anhidrosis. Ann Neurol. Sep 1985;18(3):344-8. [Medline].

  14. Benson MD, Kincaid JC. The molecular biology and clinical features of amyloid neuropathy. Muscle Nerve. Oct 2007;36(4):411-23. [Medline].

  15. Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. Oct 1983;58(10):665-83. [Medline].

  16. Low PA, Novak V, Spies JM, et al. Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS). Am J Med Sci. Feb 1999;317(2):124-33. [Medline].

  17. Novak V, Novak P, Opfer-Gehrking TL, et al. Clinical and laboratory indices that enhance the diagnosis of postural tachycardia syndrome. Mayo Clin Proc. Dec 1998;73(12):1141-50. [Medline].

  18. Zochodne DW. Diabetic neuropathies: features and mechanisms. Brain Pathol. Apr 1999;9(2):369-91. [Medline].

  19. Vinik AI, Freeman R, Erbas T. Diabetic autonomic neuropathy. Semin Neurol. Dec 2003;23(4):365-72. [Medline].

  20. Clements RS Jr, Flint MA. Coping with autonomic neuropathy. J Diabet Complications. Jul-Sep 1988;2(3):130-2. [Medline].

  21. Supriya Simon A, Dinesh Roy D, Jayapal V, Vijayakumar T. Somatic DNA damages in cardiovascular autonomic neuropathy. Indian J Clin Biochem. Jan 2011;26(1):50-6. [Medline]. [Full Text].

  22. Semra YK, Wang M, Peat NJ, et al. Selective susceptibility of different populations of sympathetic neurons to diabetic neuropathy in vivo is reflected by increased vulnerability to oxidative stress in vitro. Neurosci Lett. Oct 30 2006;407(3):199-204. [Medline].

  23. Zochodne DW. The autonomic nervous system in peripheral neuropathies. Handbook of Clinical Neurology. 2000;75(31):681-712.

  24. Maheshwari A, Thomas A, Thuluvath PJ. Patients with autonomic neuropathy are more likely to develop hepatic encephalopathy. Dig Dis Sci. Oct 2004;49(10):1584-8. [Medline].

  25. Beitzke M, Pfister P, Fortin J, Skrabal F. Autonomic dysfunction and hemodynamics in vitamin B12 deficiency. Auton Neurosci. Apr 18 2002;97(1):45-54. [Medline].

  26. Koike H, Sobue G. Alcoholic neuropathy. Curr Opin Neurol. Oct 2006;19(5):481-6. [Medline].

  27. Duray PH. Histopathology of clinical phases of human Lyme disease. Rheum Dis Clin North Am. Nov 1989;15(4):691-710. [Medline].

  28. Glück T, Degenhardt E, Schölmerich J, Lang B, Grossmann J, Straub RH. Autonomic neuropathy in patients with HIV: course, impact of disease stage, and medication. Clin Auton Res. Feb 2000;10(1):17-22. [Medline].

  29. Cohen JA, Laudenslager M. Autonomic nervous system involvement in patients with human immunodeficiency virus infection. Neurology. Aug 1989;39(8):1111-2. [Medline].

  30. Fernandez A, Hontebeyrie M, Said G. Autonomic neuropathy and immunological abnormalities in Chagas' disease. Clin Auton Res. Dec 1992;2(6):409-12. [Medline].

  31. Pentreath VW. Royal Society of Tropical Medicine and Hygiene Meeting at Manson House, London, 19 May 1994. Trypanosomiasis and the nervous system. Pathology and immunology. Trans R Soc Trop Med Hyg. Jan-Feb 1995;89(1):9-15. [Medline].

  32. Pickett JB 3rd. AAEE case report #16: Botulism. Muscle Nerve. Dec 1988;11(12):1201-5. [Medline].

  33. Idiaquez J. Autonomic dysfunction in diphtheritic neuropathy. J Neurol Neurosurg Psychiatry. Feb 1992;55(2):159-61. [Medline].

  34. Scollard DM. The biology of nerve injury in leprosy. Lepr Rev. Sep 2008;79(3):242-53. [Medline].

  35. Kyriakidis MK, Noutsis CG, Robinson-Kyriakidis CA, Venetsianos PJ, Vyssoulis GP, Toutouzas PC, et al. Autonomic neuropathy in leprosy. Int J Lepr Other Mycobact Dis. Sep 1983;51(3):331-5. [Medline].

  36. Gibbons CH, Freeman R. Autonomic neuropathy and coeliac disease. J Neurol Neurosurg Psychiatry. Apr 2005;76(4):579-81. [Medline].

  37. Tursi A, Giorgetti GM, Iani C. Peripheral Neurological Disturbances, Autonomic Dysfunction, and Antineuronal Antibodies in Adult Celiac Disease Before and After a Gluten-Free Diet. Dig Dis Sci. Sep 12; [Epub ahead of print] 2006;[Medline].

  38. 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. Aug 1994;57(8):983-6. [Medline].

  39. Zochodne DW. Autonomic involvement in Guillain-Barré syndrome: a review. Muscle Nerve. Oct 1994;17(10):1145-55. [Medline].

  40. Panegyres PK, Mastaglia FL. Guillain-Barre syndrome with involvement of the central and autonomic nervous systems. Med J Aust. Jun 5 1989;150(11):655-9. [Medline].

  41. O'Suilleabhain P, Low PA, Lennon VA. Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome: serologic and clinical correlates. Neurology. Jan 1998;50(1):88-93. [Medline].

  42. Sillevis Smitt P, Grefkens J, de Leeuw B, et al. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol. Jun 2002;249(6):745-53. [Medline].

  43. Zenone T. [Autoimmunity and cancer: paraneoplastic neurological syndromes associated with small cell cancer]. Bull Cancer. 1992;79(9):837-53. [Medline].

  44. Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. Feb 2001;49(2):146-54. [Medline].

  45. 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. Dec 1997;80(1-2):149-57. [Medline].

  46. Rose KM, Eigenbrodt ML, Biga RL, Couper DJ, Light KC, Sharrett AR, et al. Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study. Circulation. Aug 15 2006;114(7):630-6. [Medline].

  47. Suarez GA, Opfer-Gehrking TL, Offord KP, et al. The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms. Neurology. Feb 1999;52(3):523-8. [Medline].

  48. Watkins PJ. Diabetic diarrhea, gastroparesis, and gustatory sweating. In: Dyck PJ, Thomas PK, Asbury AK, et al, eds. Diabetic Neuropathy. Philadelphia: WB Saunders Co; 1987:199-200.

  49. Bharucha AE, Camilleri M, Low PA, Zinsmeister AR. Autonomic dysfunction in gastrointestinal motility disorders. Gut. Mar 1993;34(3):397-401. [Medline].

  50. England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology. Jan 13 2009;72(2):177-84. [Medline].

  51. Foss CH, Vestbo E, Frøland A, Gjessing HJ, Mogensen CE, Damsgaard EM. Autonomic neuropathy in nondiabetic offspring of type 2 diabetic subjects is associated with urinary albumin excretion rate and 24-h ambulatory blood pressure: the Fredericia Study. Diabetes. Mar 2001;50(3):630-6. [Medline].

  52. Fealey RD. Thermoregulatory sweat test. In: Low PA, ed. Clinical Autonomic Disorders: Evaluation and Management. 2nd ed. Philadelphia: Lippincott-Raven; 1997:245-57.

  53. Yarnitsky D, Sprecher E. Thermal testing: normative data and repeatability for various test algorithms. J Neurol Sci. Aug 1994;125(1):39-45. [Medline].

  54. Davies DR, Smith SE. Pupil abnormality in amyloidosis with autonomic neuropathy. J Neurol Neurosurg Psychiatry. Dec 1999;67(6):819-22. [Medline].

  55. Gibbons CH, Illigens BM, Centi J, Freeman R. QDIRT: quantitative direct and indirect test of sudomotor function. Neurology. Jun 10 2008;70(24):2299-304. [Medline].

  56. Madersbacher HG. Neurogenic bladder dysfunction. Curr Opin Urol. Jul 1999;9(4):303-7. [Medline].

  57. Ascaso JF, Herreros B, Sanchiz V, et al. Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy. Neurogastroenterol Motil. 2006;18(9):813-822. [Medline].

  58. Bissinger A, Grycewicz T, Grabowicz W, Lubinski A. The effect of diabetic autonomic neuropathy on P-wave duration, dispersion and atrial fibrillation. Arch Med Sci. Oct 2011;7(5):806-12. [Medline]. [Full Text].

  59. Pavy-Le Traon A, Fontaine S, Tap G, Guidolin B, Senard JM, Hanaire H. Cardiovascular autonomic neuropathy and other complications in type 1 diabetes. Clin Auton Res. Jun 2010;20(3):153-60. [Medline].

  60. Ohlsson B, Melander O, Thorsson O, et al. Oesophageal dysmotility, delayed gastric emptying and autonomic neuropathy correlate to disturbed glucose homeostasis. Diabetologia. Sep 2006;49(9):2010-4. [Medline].

  61. Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. Jul 2008;131:1912-25. [Medline].

  62. Singer W, Spies JM, McArthur J, et al. Prospective evaluation of somatic and autonomic small fibers in selected autonomic neuropathies. Neurology. Feb 24 2004;62(4):612-8. [Medline].

  63. Nolano M, Provitera V, Crisci C, et al. Quantification of myelinated endings and mechanoreceptors in human digital skin. Ann Neurol. Aug 2003;54(2):197-205. [Medline].

  64. Nolano M, Crisci C, Santoro L, et al. Absent innervation of skin and sweat glands in congenital insensitivity to pain with anhidrosis. Clin Neurophysiol. Sep 2000;111(9):1596-601. [Medline].

  65. Klein CM, Vernino S, Lennon VA, et al. The spectrum of autoimmune autonomic neuropathies. Ann Neurol. Jun 2003;53(6):752-8. [Medline].

  66. Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. Aug 1993;68(8):748-52. [Medline].

  67. Jordan J, Shannon JR, Black BK, et al. The pressor response to water drinking in humans : a sympathetic reflex?. Circulation. Feb 8 2000;101(5):504-9. [Medline].

  68. van Lieshout JJ, ten Harkel AD, Wieling W. Physical manoeuvres for combating orthostatic dizziness in autonomic failure. Lancet. Apr 11 1992;339(8798):897-8. [Medline].

  69. Thieben MJ, Sandroni P, Sletten DM, Benrud-Larson LM, Fealey RD, Vernino S, et al. Postural orthostatic tachycardia syndrome: the Mayo clinic experience. Mayo Clin Proc. Mar 2007;82(3):308-13. [Medline].

  70. Freeman R. Current pharmacologic treatment for orthostatic hypotension. Clin Auton Res. Mar 2008;18 Suppl 1:14-8. [Medline].

  71. Low PA. Autonomic neuropathies. Curr Opin Neurol. Oct 1998;11(5):531-7. [Medline].

  72. Singer W, Opfer-Gehrking TL, Nickander KK, Hines SM, Low PA. Acetylcholinesterase inhibition in patients with orthostatic intolerance. J Clin Neurophysiol. Oct 2006;23(5):476-81. [Medline].

  73. Grubb BP. Neurocardiogenic syncope and related disorders of orthostatic intolerance. Circulation. Jun 7 2005;111(22):2997-3006. [Medline].

  74. Gordon VM, Opfer-Gehrking TL, Novak V, Low PA. Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome. Clin Auton Res. Feb 2000;10(1):29-33. [Medline].

  75. Winkler AS, Landau S, Watkins PJ. Erythropoietin treatment of postural hypotension in anemic type 1 diabetic patients with autonomic neuropathy: a case study of four patients. Diabetes Care. Jun 2001;24(6):1121-3. [Medline].

  76. Mathias CJ, Fosbraey P, da Costa DF, Thornley A, Bannister R. The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure. Br Med J (Clin Res Ed). Aug 9 1986;293(6543):353-4. [Medline].

  77. Dalakas MC. The use of intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: evidence-based indications and safety profile. Pharmacol Ther. Jun 2004;102(3):177-93. [Medline].

  78. Schroeder C, Vernino S, Birkenfeld AL, Tank J, Heusser K, Lipp A, et al. Plasma exchange for primary autoimmune autonomic failure. N Engl J Med. Oct 13 2005;353(15):1585-90. [Medline].

  79. Modoni A, Mirabella M, Madia F, Sanna T, Lanza G, Tonali PA, et al. Chronic autoimmune autonomic neuropathy responsive to immunosuppressive therapy. Neurology. Jan 9 2007;68(2):161-2. [Medline].

  80. Shotton HR, Adams A, Lincoln J. Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric plexus of rat ileum. Auton Neurosci. Sep 18 [Epub ahead of print] 2006;[Medline].

  81. Klein CM. Evaluation and management of autonomic nervous system disorders. Semin Neurol. Apr 2008;28(2):195-204. [Medline].

  82. Grunfeld A, Murray CA, Solish N. Botulinum toxin for hyperhidrosis: a review. Am J Clin Dermatol. 2009;10(2):87-102. [Medline].

  83. Monteiro E, Perdigoto R, Furtado AL. Liver transplantation for familial amyloid polyneuropathy. Hepatogastroenterology. Sep-Oct 1998;45(23):1375-80. [Medline].

  84. Tashima K, Ando Y, Terazaki H, et al. Outcome of liver transplantation for transthyretin amyloidosis: follow-up of Japanese familial amyloidotic polyneuropathy patients. J Neurol Sci. Dec 1 1999;171(1):19-23. [Medline].

  85. Antonelli Incalzi R, Fuso L, Pitocco D, et al. Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal study. Diabetes Metab Res Rev. Oct 2 2006;[Medline].

  86. Dawkins JL, Hulme DJ, Brahmbhatt SB, et al. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet. Mar 2001;27(3):309-12. [Medline].

  87. El-Atat FA, McFarlane SI, Sowers JR, Bigger JT. Sudden cardiac death in patients with diabetes. Curr Diab Rep. Jun 2004;4(3):187-93. [Medline].

  88. Holland NR, Crawford TO, Hauer P, et al. Small-fiber sensory neuropathies: clinical course and neuropathology of idiopathic cases. Ann Neurol. Jul 1998;44(1):47-59. [Medline].

  89. Kamalakannan D, Baskar V, Singh BM. Severe and disabling diabetic autonomic neuropathy: a case report. J Diabetes Complications. Mar-Apr 2004;18(2):126-8. [Medline].

  90. Kudat H, Akkaya V, Sozen AB, et al. Heart rate variability in diabetes patients. J Int Med Res. May-Jun 2006;34(3):291-6. [Medline].

  91. Low PA, Caskey PE, Tuck RR, et al. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol. Nov 1983;14(5):573-80. [Medline].

  92. Lyu RK, Tang LM, Wu YR, Chen ST. Cardiovascular autonomic function and sympathetic skin response in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve. Nov 2002;26(5):669-72. [Medline].

  93. Toth C, Zochodne DW. Other autonomic neuropathies. Semin Neurol. Dec 2003;23(4):373-80. [Medline].

  94. Zochodne DW, Auer R, Fritzler MJ. Longstanding ataxic demyelinating polyneuronopathy with a novel autoantibody. Neurology. Jan 14 2003;60(1):127-9. [Medline].

 
Previous
Next
 
Table. Types of HSAN
HSANMode of InheritanceOnsetSymptomsSigns
Type IAutosomal dominant, point mutations in SPT, 9q22.1-9q22.3Second decade of lifeDistal lower-limb involvement, ulceration of the feet, particularly the solesLow sensory action potential amplitude
Type II, Morvan diseaseAutosomal recessiveCongenital onsetPansensory loss of upper and lower limbs, also trunk and forehead; early ulcersLoss of myelinated and unmyelinated fibers
Type III, Riley-Day syndrome or familial dysautonomia)Autosomal recessive, 9q31Childhood onset, predominantly Ashkenazi JewsPallor in infancy, irregularities in temperature and blood pressure; Difficulties in eating and swallowingAbsence of unmyelinated fibers
Type IVAutosomal recessive, 1q21-1q22Congenital onsetWidespread anhidrosis, lost sense of pain, mental retardationLoss of myelinated and small unmyelinated fibers
Type VAutosomal recessiveCongenital onsetPain insensitivity in extremitiesNot applicable
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2013 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.
Programs designed for you and your practice
 
Information from Industry