Autonomic Neuropathy Workup
- Author: Steven D Arbogast, DO; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE more...
Initial laboratory evaluation should include a complete blood count, basic metabolic panel, liver function testing, and immunoelectrophoresis. More specific testing should be based on the patient’s history of other medical conditions.
Based upon the findings of the initial evaluation and clinical situation, more specific tests may be considered.
Blood tests may be considered based upon the clinical history and findings on autonomic testing and may include the following:
Oral glucose tolerance test to evaluate for diabetes mellitus, if an initial serum glucose level is normal or nondiagnostic.
Testing for SS-A and SS-B if there is concerns for Sj ö gren syndrome (Sicca syndrome).
Anti-ganglionic acetylcholine receptor (AChR) autoantibodies if the onset was acute to subacute in nature.
Specific genetic tests for the familial forms of dysautonomia can be ordered.
Specific tests for infections, inflammatory, autoimmune, and paraneoplastic causes can be ordered based upon the history and physical examination.
Measurement of basal plasma norepinephrine levels can be useful in specific forms of autonomic neuropathy. In pandysautonomia, basal norepinephrine levels are low and do not rise on head-up tilt table testing. Following an overnight supine position, low norepinephrine levels can be found in patients with POTS.
A history of neuropathy, mental status changes, and abdominal pain should prompt the physician to evaluate the patient for acute intermittent porphyria. In cases of suspected porphyria, high levels of porphobilinogen and delta-aminolevulinic acid can be found in urine during acute episodes.
Evaluation of cerebrospinal fluid (CSF) via lumbar puncture can be useful in specific cases.
In pandysautonomia, CSF protein is elevated, as is CSF enolase, which may indicate damage to the dorsal root ganglia.
In HIV or AIDS, the CSF may demonstrate an elevated protein as well as pleocytosis.
Paraneoplastic varieties of autonomic neuropathies also tend to show an inflammatory picture in the CSF. However, abnormal CSF protein is not specific for autoimmune, inflammatory, or infectious causes of autonomic neuropathy.
See the list below:
SPECT and PET scanning may identify cardiac sympathetic dysfunction in both type I and type II diabetes mellitus.
The pattern of sympathetic disturbances tends to be heterogeneous, with denervation affecting mainly the posterior myocardial region, whereas focal hyperinnervation can be observed of the proximal segment.
Autonomic testing using the following methods should be performed to assess the severity and parts of the autonomic nervous system that are involved. These tests have also recently been recommended (Level B) by the American Academy of Neurology for evaluation of patients with distal symmetric polyneuropathy.
Tilt table testing to test adrenergic vasomotor function and cardiac sympathetic function.
Cardiac response to deep breathing and R-R interval to evaluate cardiovagal functions.
Cardiac response to Valsalva maneuvers to test parasympathetic innervation to the heart.
Quantitative Sudomotor Axon Reflex Testing (QSART) to evaluate the postganglionic segment of the thermoregulatory pathway. Four regions are tested: forearm, proximal leg, distal leg, and dorsum of the foot. Electrical stimulation (iontophoresis) is applied to the skin, and the volume of sweat produced can be measured.
Nerve conductions studies and electromyography
Findings on nerve conduction studies (NCS) and electromyography (EMG) can be normal in pure autonomic neuropathies because the involved fibers are small myelinated and unmyelinated fibers, which cannot be assessed with NCS or EMG.
In autonomic neuropathies with concomitant sensory neuropathy, absence of sensory potentials may occur.
In autonomic neuropathies with concomitant sensorimotor neuropathy, marked loss of motor and sensory potentials is noted.
In cases of suspected neuromuscular transmission defect, such as with botulism or LEMS, a typical electrophysiologic pattern of low-amplitude compound muscle action potentials increasing with high-frequency repetitive stimulation is characteristic of a presynaptic neuromuscular defect.
See the list below:
In Sj ö gren syndrome, results of the Schirmer test with a rose-Bengal eye stain, as well as lip biopsy to identify chronic sialoadenitis, can be diagnostic.
Postprandial blood pressures: An abnormal result would be to measure a drop in systolic blood pressure of >20 mm Hg approximately 15-20 minutes after a meal.
Other uncommon bedside stimuli that can be used to assess for a rise in blood pressure during continuous blood pressure monitoring include isometric exercise (sustained hand grip for 3 min), a cold pressor test (immersion of a hand in ice water for 90 s), and mental arithmetic (with serial-7 or serial-17 subtraction), all of which stimulate sympathetic outflow and elevate blood pressure in healthy patients.
Multiple daily blood pressures to examine for diurnal fluctuation: A difference of < 15 mm Hg with either systolic or diastolic blood pressure between daytime (awake) values and nighttime (sleeping) values could indicate presence of autonomic neuropathy (Foss, 2001). 
Skin or nerve biopsy (see histology findings) may be performed if clinically indicated.
Specific autonomic tests that are being performed at some institutions include the following:
- The thermoregulatory sweat test (TST) complements the quantitative sudomotor axon reflex test (QSART) and is used to assess thermoregulatory pathways. The patient is covered with alizarin red powder, which, when moist, changes from orange to purple. The patient's temperature is then raised above core temperature, and photography is performed to map for areas of color change, revealing areas of anhidrosis/hypohidrosis where color did not change. The TST and QSART can both be useful in idiopathic anhidrosis. A lack of color changes with the TST is essentially diagnostic for postganglionic sudomotor dysfunction.
- Sympathetic skin responses (SSR) can be assessed with routine EMG equipment. This test can be used to identify indirect evidence of sweat production via measurement of changes in skin conductance on the palm/sole in response to an electrical stimulus. The stimulation of an afferent somatic branch with SSRs gives an assessment of potential adrenergic sweat production. Brief electrical stimuli are administered at intermittent intervals and a response is measured from the hands or the feet, representing a change in skin resistance due to sweating.
- Quantitative sensory testing (QST) can be helpful in autonomic disorders with sensory neuropathy. QST permits comparison of sensory thresholds by using vibration and temperature perception to assess both large and small-fiber modalities. These patients typically have impaired thresholds for heat and pain , but vibration and cool sensitivity may be normal.
- Pupillometry measure changes in papillary response and is being investigated at some institutions as a potential marker for autonomic neuropathy.
- Quantitative direct and indirect test of sudomotor function (QDIRT) involves making a silicone impression of a patient's skin while sweating is induced by acetylcholine iontophoresis. The presence of sweat droplets can be quantified in the silicone cast , providing a marker of sudomotor function.
Vascular studies are occasionally useful in assessing autonomic neuropathy.
- Adrenergic function can be assessed by measuring skin blood flow, transcutaneous oxygenation, and skin temperature.
- Doppler probes can be used for blood flow measurements.
- Infrared thermometry and telethermography can be used to measure skin temperature.
- Assessment of skin temperature can be useful in patients with small-fiber neuropathy.
- Urodynamic studies may be used to examine the lower urinary tract function.
- Measurements include urine flow rate, residual volume, cystometry during filling and voiding, urethral pressure profile measurements, and pelvic floor neurophysiology.
- An important measure in assessment of a neurogenic bladder is the postmicturition residual volume; this can be measured invasively by urethral catheterization after voiding, but it can also be measured noninvasively with ultrasonography.
- Videofluoroscopy is useful in assessment of swallowing in the presence of oropharyngeal dysphagia.
- A barium swallow study, meal, and follow-through study are helpful in suspected upper gastrointestinal disorders, though endoscopic assessment provides the opportunity for biopsy in particular situations, as well as better visualization.
- Esophageal manometry may be of value in disorders of motility and esophagogastric function.
- Gastric motility may be assessed by using radioisotope methods and scintigraphic scanning.
- In cases of small-bowel disorders suspected to be neurologic in nature, manometry may be of value in discriminating myopathic from neuropathic disorders. Large-bowel dysfunction can be assessed via measurement of transit time.
- Esophageal manometry and gastric emptying scintigraphy can also be useful in patients with possible autonomic neuropathy and dysphagia.
- Diabetic patients with symptoms of esophageal dysmotility have insufficient lower esophageal sphincter relaxation and a higher percentage of simultaneous waves detected, while diabetic patients with cardiovascular autonomic neuropathy have greater pathological simultaneous contractions.[58, 59, 60]
- Esophageal dysmotility and delayed gastric emptying may occur in up to 50% of diabetic patients. In particular, reports of abdominal fullness predicted delayed gastric emptying.
Sural nerve biopsy is occasionally diagnostic for types of autonomic neuropathy. In inherited autonomic neuropathies, a selective loss of particular fiber types can indicate the diagnosis. In autoimmune or infectious mediated forms of autonomic neuropathy, small perivascular infiltrates may be visible. In amyloidosis, characteristic Congo red staining indicates the presence of eosinophilic, extracellular, amorphous material surrounding perineurial and endoneurial vessels and within sympathetic ganglia and vagal nerves.
Epidermal skin biopsy can be used in the diagnosis of small-fiber neuropathies. This technique is less invasive than nerve biopsy. In autonomic neuropathies, autonomic fibers are deeper than the epidermal level; therefore, deeper biopsy is required to assess the fibers innervating sweat glands and piloerector muscles. In general, autonomic neuropathies of greater severity are associated with reduced epidermal fiber densities.
As distal endings are primarily involved in distal axonopathy forms of neuropathy, skin biopsy may be more sensitive than sural nerve biopsy to detect early abnormalities. Skin biopsy is also useful in congenital causes of autonomic neuropathy, as in congenital insensitivity to pain with anhidrosis (CIPA), where a lack of nerve fibers in the epidermis and only a few hypotrophic and uninnervated sweat glands are found in the dermis.
Patients with autoimmune autonomic neuropathy can have antiganglionic acetylcholine receptor (AChR) autoantibodies. Patients with high antibody values (>1.00 nmol/L) tend to have a constellation of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light responses, upper gastrointestinal symptoms, and neurogenic bladder. Higher antibody titers correlate with greater autonomic dysfunction as well as increased frequency of cholinergic dysautonomia.
Patients with POTS may also demonstrate presence of ganglionic receptors.
In specific disorders, testing for the presence of autoantibodies can help determine a diagnosis. Antinuclear antibodies and antibodies to Sj ö gren syndrome antigens A and B (SSA and SSB) are seen in several connective tissue disorders. Antibodies against voltage-gated calcium channels (VGCC) are associated with LEMS.
The combination of tilt table testing, cardiac responses to deep breathing and the Valsalva maneuver, and QSART comprise the composite autonomic scoring scale (CASS), which may be used to assess the severity of autonomic dysfunction. The CASS is reliable and useful for monitoring clinical progression with an autonomic neuropathy. The CASS is a 10-point scale; 4 points are allotted for adrenergic and 3 points each for sudomotor and cardiovagal failure. Scores are normalized for age and sex. Patients with a score of less than 4 on the CASS have mild autonomic failure; a score of 4-6 suggests moderate autonomic failure; and a score of 7-10 implies severe failure.
The TST can be useful in monitoring progression of idiopathic anhidrosis and Sj ö gren syndrome where prominent anhidrosis/hypohidrosis occurs.
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].
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. [Medline].
Bejaoui K, Wu C, Scheffler MD, et al. SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet. 2001 Mar. 27(3):261-2. [Medline].
Low PA, Vernino S, Suarez G. Autonomic dysfunction in peripheral nerve disease. Muscle Nerve. 2003 Jun. 27(6):646-61. [Medline].
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. 2004 Oct. 35(5):274-8. [Medline].
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. 2004 Apr 15. 13(8):799-805. [Medline].
Low PA. Clinical autonomic disorders: evaluation and management. 2nd ed. New York: Lippincott Raven; 1997.
Low PA, Dyck PJ, Lambert EH, et al. Acute panautonomic neuropathy. Ann Neurol. 1983 Apr. 13(4):412-7. [Medline].
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. 2000 Sep 21. 343(12):847-55. [Medline].
Stewart JD, Low PA, Fealey RD. Distal small fiber neuropathy: results of tests of sweating and autonomic cardiovascular reflexes. Muscle Nerve. 1992 Jun. 15(6):661-5. [Medline].
Emond D, Lebel M. Orthostatic hypotension and Holmes-Adie syndrome. Usefulness of the Valsalva ratio in the evaluation of baroreceptor dysfunction. J Hum Hypertens. 2002 Sep. 16(9):661-2. [Medline].
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. 2006 Aug. 129:2119-31. [Medline].
Low PA, Fealey RD, Sheps SG, Su WP, Trautmann JC, Kuntz NL. Chronic idiopathic anhidrosis. Ann Neurol. 1985 Sep. 18(3):344-8. [Medline].
Benson MD, Kincaid JC. The molecular biology and clinical features of amyloid neuropathy. Muscle Nerve. 2007 Oct. 36(4):411-23. [Medline].
Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. 1983 Oct. 58(10):665-83. [Medline].
Low PA, Novak V, Spies JM, et al. Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS). Am J Med Sci. 1999 Feb. 317(2):124-33. [Medline].
Novak V, Novak P, Opfer-Gehrking TL, et al. Clinical and laboratory indices that enhance the diagnosis of postural tachycardia syndrome. Mayo Clin Proc. 1998 Dec. 73(12):1141-50. [Medline].
Zochodne DW. Diabetic neuropathies: features and mechanisms. Brain Pathol. 1999 Apr. 9(2):369-91. [Medline].
Vinik AI, Freeman R, Erbas T. Diabetic autonomic neuropathy. Semin Neurol. 2003 Dec. 23(4):365-72. [Medline].
Clements RS Jr, Flint MA. Coping with autonomic neuropathy. J Diabet Complications. 1988 Jul-Sep. 2(3):130-2. [Medline].
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. 2006 Oct 30. 407(3):199-204. [Medline].
Zochodne DW. The autonomic nervous system in peripheral neuropathies. Handbook of Clinical Neurology. 2000. 75(31):681-712.
Maheshwari A, Thomas A, Thuluvath PJ. Patients with autonomic neuropathy are more likely to develop hepatic encephalopathy. Dig Dis Sci. 2004 Oct. 49(10):1584-8. [Medline].
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. [Medline].
Koike H, Sobue G. Alcoholic neuropathy. Curr Opin Neurol. 2006 Oct. 19(5):481-6. [Medline].
Duray PH. Histopathology of clinical phases of human Lyme disease. Rheum Dis Clin North Am. 1989 Nov. 15(4):691-710. [Medline].
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. 2000 Feb. 10(1):17-22. [Medline].
Cohen JA, Laudenslager M. Autonomic nervous system involvement in patients with human immunodeficiency virus infection. Neurology. 1989 Aug. 39(8):1111-2. [Medline].
Fernandez A, Hontebeyrie M, Said G. Autonomic neuropathy and immunological abnormalities in Chagas' disease. Clin Auton Res. 1992 Dec. 2(6):409-12. [Medline].
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. 1995 Jan-Feb. 89(1):9-15. [Medline].
Pickett JB 3rd. AAEE case report #16: Botulism. Muscle Nerve. 1988 Dec. 11(12):1201-5. [Medline].
Idiaquez J. Autonomic dysfunction in diphtheritic neuropathy. J Neurol Neurosurg Psychiatry. 1992 Feb. 55(2):159-61. [Medline].
Scollard DM. The biology of nerve injury in leprosy. Lepr Rev. 2008 Sep. 79(3):242-53. [Medline].
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. 1983 Sep. 51(3):331-5. [Medline].
Gibbons CH, Freeman R. Autonomic neuropathy and coeliac disease. J Neurol Neurosurg Psychiatry. 2005 Apr. 76(4):579-81. [Medline].
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. 2006 Sep 12; [Epub ahead of print]. [Medline].
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. [Medline].
Zochodne DW. Autonomic involvement in Guillain-BarrÃ© syndrome: a review. Muscle Nerve. 1994 Oct. 17(10):1145-55. [Medline].
Panegyres PK, Mastaglia FL. Guillain-Barre syndrome with involvement of the central and autonomic nervous systems. Med J Aust. 1989 Jun 5. 150(11):655-9. [Medline].
O'Suilleabhain P, Low PA, Lennon VA. Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome: serologic and clinical correlates. Neurology. 1998 Jan. 50(1):88-93. [Medline].
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. 2002 Jun. 249(6):745-53. [Medline].
Zenone T. [Autoimmunity and cancer: paraneoplastic neurological syndromes associated with small cell cancer]. Bull Cancer. 1992. 79(9):837-53. [Medline].
Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001 Feb. 49(2):146-54. [Medline].
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. [Medline].
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. 2006 Aug 15. 114(7):630-6. [Medline].
Suarez GA, Opfer-Gehrking TL, Offord KP, et al. The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms. Neurology. 1999 Feb. 52(3):523-8. [Medline].
Watkins PJ. Diabetic diarrhea, gastroparesis, and gustatory sweating. Dyck PJ, Thomas PK, Asbury AK, et al, eds. Diabetic Neuropathy. Philadelphia: WB Saunders Co; 1987. 199-200.
Bharucha AE, Camilleri M, Low PA, Zinsmeister AR. Autonomic dysfunction in gastrointestinal motility disorders. Gut. 1993 Mar. 34(3):397-401. [Medline].
Törnblom H. Treatment of gastrointestinal autonomic neuropathy. Diabetologia. 2016 Mar. 59 (3):409-13. [Medline].
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. 2009 Jan 13. 72(2):177-84. [Medline].
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. 2001 Mar. 50(3):630-6. [Medline].
Fealey RD. Thermoregulatory sweat test. Low PA, ed. Clinical Autonomic Disorders: Evaluation and Management. 2nd ed. Philadelphia: Lippincott-Raven; 1997. 245-57.
Yarnitsky D, Sprecher E. Thermal testing: normative data and repeatability for various test algorithms. J Neurol Sci. 1994 Aug. 125(1):39-45. [Medline].
Davies DR, Smith SE. Pupil abnormality in amyloidosis with autonomic neuropathy. J Neurol Neurosurg Psychiatry. 1999 Dec. 67(6):819-22. [Medline].
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. [Medline].
Madersbacher HG. Neurogenic bladder dysfunction. Curr Opin Urol. 1999 Jul. 9(4):303-7. [Medline].
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].
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. 2011 Oct. 7(5):806-12. [Medline]. [Full Text].
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. 2010 Jun. 20(3):153-60. [Medline].
Ohlsson B, Melander O, Thorsson O, et al. Oesophageal dysmotility, delayed gastric emptying and autonomic neuropathy correlate to disturbed glucose homeostasis. Diabetologia. 2006 Sep. 49(9):2010-4. [Medline].
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. 2008 Jul. 131:1912-25. [Medline].
Singer W, Spies JM, McArthur J, et al. Prospective evaluation of somatic and autonomic small fibers in selected autonomic neuropathies. Neurology. 2004 Feb 24. 62(4):612-8. [Medline].
Nolano M, Provitera V, Crisci C, et al. Quantification of myelinated endings and mechanoreceptors in human digital skin. Ann Neurol. 2003 Aug. 54(2):197-205. [Medline].
Nolano M, Crisci C, Santoro L, et al. Absent innervation of skin and sweat glands in congenital insensitivity to pain with anhidrosis. Clin Neurophysiol. 2000 Sep. 111(9):1596-601. [Medline].
Klein CM, Vernino S, Lennon VA, et al. The spectrum of autoimmune autonomic neuropathies. Ann Neurol. 2003 Jun. 53(6):752-8. [Medline].
Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug. 68(8):748-52. [Medline].
Jordan J, Shannon JR, Black BK, et al. The pressor response to water drinking in humans : a sympathetic reflex?. Circulation. 2000 Feb 8. 101(5):504-9. [Medline].
van Lieshout JJ, ten Harkel AD, Wieling W. Physical manoeuvres for combating orthostatic dizziness in autonomic failure. Lancet. 1992 Apr 11. 339(8798):897-8. [Medline].
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. 2007 Mar. 82(3):308-13. [Medline].
Freeman R. Current pharmacologic treatment for orthostatic hypotension. Clin Auton Res. 2008 Mar. 18 Suppl 1:14-8. [Medline].
Low PA. Autonomic neuropathies. Curr Opin Neurol. 1998 Oct. 11(5):531-7. [Medline].
Singer W, Opfer-Gehrking TL, Nickander KK, Hines SM, Low PA. Acetylcholinesterase inhibition in patients with orthostatic intolerance. J Clin Neurophysiol. 2006 Oct. 23(5):476-81. [Medline].
Grubb BP. Neurocardiogenic syncope and related disorders of orthostatic intolerance. Circulation. 2005 Jun 7. 111(22):2997-3006. [Medline].
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. 2000 Feb. 10(1):29-33. [Medline].
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. 2001 Jun. 24(6):1121-3. [Medline].
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). 1986 Aug 9. 293(6543):353-4. [Medline].
Dalakas MC. The use of intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: evidence-based indications and safety profile. Pharmacol Ther. 2004 Jun. 102(3):177-93. [Medline].
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. 2005 Oct 13. 353(15):1585-90. [Medline].
Modoni A, Mirabella M, Madia F, Sanna T, Lanza G, Tonali PA, et al. Chronic autoimmune autonomic neuropathy responsive to immunosuppressive therapy. Neurology. 2007 Jan 9. 68(2):161-2. [Medline].
Shotton HR, Adams A, Lincoln J. Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric plexus of rat ileum. Auton Neurosci. 2006 Sep 18 [Epub ahead of print]. [Medline].
Klein CM. Evaluation and management of autonomic nervous system disorders. Semin Neurol. 2008 Apr. 28(2):195-204. [Medline].
Grunfeld A, Murray CA, Solish N. Botulinum toxin for hyperhidrosis: a review. Am J Clin Dermatol. 2009. 10(2):87-102. [Medline].
Monteiro E, Perdigoto R, Furtado AL. Liver transplantation for familial amyloid polyneuropathy. Hepatogastroenterology. 1998 Sep-Oct. 45(23):1375-80. [Medline].
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. 1999 Dec 1. 171(1):19-23. [Medline].
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. 2006 Oct 2. [Medline].
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. 2001 Mar. 27(3):309-12. [Medline].
El-Atat FA, McFarlane SI, Sowers JR, Bigger JT. Sudden cardiac death in patients with diabetes. Curr Diab Rep. 2004 Jun. 4(3):187-93. [Medline].
Holland NR, Crawford TO, Hauer P, et al. Small-fiber sensory neuropathies: clinical course and neuropathology of idiopathic cases. Ann Neurol. 1998 Jul. 44(1):47-59. [Medline].
Kamalakannan D, Baskar V, Singh BM. Severe and disabling diabetic autonomic neuropathy: a case report. J Diabetes Complications. 2004 Mar-Apr. 18(2):126-8. [Medline].
Kudat H, Akkaya V, Sozen AB, et al. Heart rate variability in diabetes patients. J Int Med Res. 2006 May-Jun. 34(3):291-6. [Medline].
Low PA, Caskey PE, Tuck RR, et al. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol. 1983 Nov. 14(5):573-80. [Medline].
Lyu RK, Tang LM, Wu YR, Chen ST. Cardiovascular autonomic function and sympathetic skin response in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve. 2002 Nov. 26(5):669-72. [Medline].
Toth C, Zochodne DW. Other autonomic neuropathies. Semin Neurol. 2003 Dec. 23(4):373-80. [Medline].
Zochodne DW, Auer R, Fritzler MJ. Longstanding ataxic demyelinating polyneuronopathy with a novel autoantibody. Neurology. 2003 Jan 14. 60(1):127-9. [Medline].
|HSAN||Mode of Inheritance||Onset||Symptoms||Signs|
|Type I||Autosomal dominant, point mutations in SPT, 9q22.1-9q22.3||Second decade of life||Distal lower-limb involvement, ulceration of the feet, particularly the soles||Low sensory action potential amplitude|
|Type II, Morvan disease||Autosomal recessive||Congenital onset||Pansensory loss of upper and lower limbs, also trunk and forehead; early ulcers||Loss of myelinated and unmyelinated fibers|
|Type III, Riley-Day syndrome or familial dysautonomia)||Autosomal recessive, 9q31||Childhood onset, predominantly Ashkenazi Jews||Pallor in infancy, irregularities in temperature and blood pressure; Difficulties in eating and swallowing||Absence of unmyelinated fibers|
|Type IV||Autosomal recessive, 1q21-1q22||Congenital onset||Widespread anhidrosis, lost sense of pain, mental retardation||Loss of myelinated and small unmyelinated fibers|
|Type V||Autosomal recessive||Congenital onset||Pain insensitivity in extremities||Not applicable|