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Immune-mediated autonomic neuropathies

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Abstract

Improved recognition and availability of noninvasive testing of autonomic disorders has prompted a better understanding of disease mechanisms of some disease forms, especially potentially treatable immune-mediated autonomic neuropathies. Development is acute, subacute, or less commonly chronic. Autonomic involvement is common and an important cause of morbidity and mortality in Guillain-Barré syndrome. Acute autonomic neuropathy can affect parasympathetic, sympathetic, and enteric nerves or neurons and is associated with antibodies to ganglionic nicotinic acetylcholine receptors. These antibodies appear to be causative based on a rabbit immunization model and serum transfer studies from patients and animals. Other important immune autonomic disorders discussed include Lambert-Eaton myasthenic syndrome, some forms of orthostatic intolerance, chronic autonomic neuropathy, and Sjögren syndrome. Paraneoplastic autonomic disorders are clinically indistinguishable and associated with various overlapping antibody associations, including anti-Hu (ANNA-1), ganglionic acetylcholine receptors, CRMP-5, and PCA-2.

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References and Recommended Reading

  1. Low PA: Testing the autonomic nervous system. Semin Neurol 2003, 23:407–421.

    Article  PubMed  Google Scholar 

  2. Novak V, Freimer ML, Kissel JT, et al.: Autonomic impairment in painful neuropathy. Neurology 2001, 56:861–868.

    PubMed  CAS  Google Scholar 

  3. Periquet MI, Novak V, Collins MP, et al.: Painful sensory neuropathy: prospective evaluation using skin biopsy. Neurology 1999, 53:1641–1647.

    PubMed  CAS  Google Scholar 

  4. Hilz MJ, Dutsch M: Quantitative studies of autonomic function. Muscle Nerve 2005, In press.

  5. Low PA, Vernino S, Suarez G: Autonomic dysfunction in peripheral nerve disease. Muscle Nerve 2003, 27:646–661.

    Article  PubMed  Google Scholar 

  6. Osler LD, Sidell AD: The Guillain-Barré syndrome, the need for exact diagnostic criteria. N Engl J Med 1960, 262:964–969.

    Article  PubMed  CAS  Google Scholar 

  7. Winer JB, Hughes RA: Identification of patients at risk of arrhythmia in the Guillain-Barre syndrome. Q J Med 1988, 68:735–739.

    PubMed  CAS  Google Scholar 

  8. Guillain-Barré study group: Plasmapheresis and acute Guillain-Barre syndrome. Neurology 1985, 35:1096–1104.

    Google Scholar 

  9. Fagius J, Wallin BG: Microneurographic evidence of excessive sympathetic outflow in the Guillain-Barré syndrome. Brain 1983, 106:589–600.

    Article  PubMed  Google Scholar 

  10. Flachenecker P, Wermuth P, Hartung HP, Reiners K: Quantitative assessment of cardiovascular autonomic function in Guillain-Barré syndrome. Ann Neurol 1997, 42:171–179.

    Article  PubMed  CAS  Google Scholar 

  11. Truax BT: Autonomic disturbances in Guillain-Barre syndrome. Semin Neurol 1984, 4:462–468.

    Google Scholar 

  12. Wheeler JS Jr, Siroky MB, Pavlakis A, Krane RJ: The urodynamic aspects of the Guillain-Barre syndrome. J Urol 1984, 131:917–919.

    PubMed  Google Scholar 

  13. Toth C, Zochodne DW: Other autonomic neuropathies. Semin Neurol 2003, 23:373–380.

    Article  PubMed  Google Scholar 

  14. Tuck RR, McLeod JG: Autonomic dysfunction in Guillain-Barre syndrome. J Neurol Neurosurg Psychiatry 1981, 44:983–990.

    PubMed  CAS  Google Scholar 

  15. Wang N, Chapman J, Rabinowitz R, et al.: Autonomic dysfunction in experimental autoimmune neuritis: heart rate. J Neurol Sci 2001, 184:183–188.

    Article  PubMed  CAS  Google Scholar 

  16. Dornonville de la Cour C, Jakobsen J: Residual neuropathy in long-term population-based follow-up of Guillain-Barré syndrome. Neurology 2005, 64:246–253.

    PubMed  Google Scholar 

  17. Stamboulis E, Katsaros N, Koutsis G, et al.: Clinical and subclinical autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 2005, In press.

  18. Suarez GA, Fealey RD, Camilleri M, et al.: Idiopathic autonomic neuropathy: clinical, neurophysiologic, and follow-up studies on 27 patients. Neurology 1994, 44:1675–1682.

    PubMed  CAS  Google Scholar 

  19. Young RR, Asbury AK, Corbett JL, et al.: Pure pan-dysautonomia with recovery. Description and discussion of diagnostic criteria. Brain 1975, 98:613–636.

    Article  PubMed  CAS  Google Scholar 

  20. Vernino S, Lennon VA: Neuronal ganglionic acetylcholine receptor autoimmunity. Ann N Y Acad Sci 1998:211–214.

  21. Klein CM, Vernino S, Lennon VA, et al.: The spectrum of autoimmune autonomic neuropathies. Ann Neurol 2003, 53:752–758. Excellent overview and characterization of forms of autoimmune autonomic neuropathy.

    Article  PubMed  Google Scholar 

  22. Vernino S, Low PA, Fealey RD, et al.: Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathy. N Engl J Med 2000, 343:847–855.

    Article  PubMed  CAS  Google Scholar 

  23. Vernino S, Low PA, Lennon VA: Experimental autoimmune autonomic neuropathy. J Neurophysiol 2003, 90:2053–2059.

    Article  PubMed  CAS  Google Scholar 

  24. Vernino S, Ermilov LG, Sha L, et al.: Passive transfer of autoimmune autonomic neuropathy to mice. J Neurosci 2004, 24:7037–7042. This is the best evidence that AChR antibodies are pathogenic in AAN. The article also supports current treatment recommendations and contains a review and citation of an earlier EAAN model that led to this point.

    Article  PubMed  CAS  Google Scholar 

  25. Xu W, Gelber S, Orr-Urtreger A, et al.: Megacystis, mydriasis, and ion channel defect in mice lacking the alpha 3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A 1999, 96:5746–5751.

    Article  PubMed  CAS  Google Scholar 

  26. Sandroni P, Vernino S, Klein C, et al.: Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody. Arch Neurol 2004, 61:44–48.

    Article  PubMed  Google Scholar 

  27. Schondorf R, Low PA: Idiopathic postural orthostatic tachycardia syndrome. An attenuated form of acute pandysautonomia? Neurology 1993, 43:132–137.

    PubMed  CAS  Google Scholar 

  28. Freeman R: Autonomic peripheral neuropathy. Lancet 2005, 365:1259–1270. Excellent recent review of pathogenesis, diagnosis, and management of autonomic neuropathies.

    Article  PubMed  CAS  Google Scholar 

  29. Schroeder C, Vernino S, Birkenfeld AL, et al.: Plasma exchange for primary autoimmune autonomic failure. N Engl J Med 2005, 353:1585–1590. This is a review of studies in 20-year progressive disease. It demonstrated reversal of long-standing fixed symptoms correlating with drops in Ab titer. It also reported in vitro antibody effects on receptor function and Ca influx.

    Article  PubMed  CAS  Google Scholar 

  30. Heafield MT, Gammage MD, Nightingale S, Williams AC: Idiopathic dysautonomia treated with intravenous gammaglobulin. Lancet 1996, 347:28–29.

    Article  PubMed  CAS  Google Scholar 

  31. Smit AA, Vermeulen M, Koelman JH, Wieling W: Unusual recovery from acute panautonomic neuropathy after immunoglobulin therapy. Mayo Clin Proc 1997, 72:333–335.

    PubMed  CAS  Google Scholar 

  32. Vernino S, Cheshire WP, Lennon VA: Myasthenia gravis with autoimmune autonomic neuropathy. Auton Neurosci 2001, 88:187–192.

    Article  PubMed  CAS  Google Scholar 

  33. Gibbons CH, Vernino SA, Kaufmann H, et al.: L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy. Neurology 2005, 65:1104–1106.

    Article  PubMed  Google Scholar 

  34. Lennon VA, Kryzer TJ, Griesmann GE, et al.: Calciumchannel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 1995, 332:1467–1474.

    Article  PubMed  CAS  Google Scholar 

  35. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear auto-antibodies. Neurology 1998, 50:652–657.

    PubMed  CAS  Google Scholar 

  36. Oh SJ, Gurtekin Y, Dropcho EJ, et al.: Anti-Hu antibody neuropathy: a clinical, electrophysiological, and pathological study. Clin Neurophysiol 2005, 116:28–34.

    Article  PubMed  Google Scholar 

  37. Camdessanche JP, Antoine JC, Honnorat J, et al.: Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. A clinical and electrophysiological study of 20 patients. Brain 2002, 125:166–175.

    Article  PubMed  Google Scholar 

  38. Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004, 56:715–719.

    Article  PubMed  CAS  Google Scholar 

  39. De Giorgio R, Guerrini S, Barbara G, et al.: Inflammatory neuropathies of the enteric nervous system. Gastroenterology 2004, 126:1872–1883. This is an excellent review of etiology of immune-mediated enteric neuronopathy, with the most recent pathology and probable mechanisms

    Article  PubMed  Google Scholar 

  40. Van Voorhis WC, Schlekewy L, Trong HL: Molecular mimicry by Trypanosoma cruzi: the F1-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide. Proc Natl Acad Sci U S A 1991, 88:5993–5997.

    Article  PubMed  Google Scholar 

  41. Lennon VA, Sas DF, Busk MF, et al.: Enteric neuronal autoantibodies in pseudo-obstruction with small-cell lung carcinoma. Gastroenterology 1991, 100:137–142.

    PubMed  CAS  Google Scholar 

  42. Chinn JS, Schuffler MD: Paraneoplastic visceral neuropathy as a cause of severe gastrointestinal motor dysfunction. Gastroenterology 1988, 95:1279–1286.

    PubMed  CAS  Google Scholar 

  43. Colombel JF, Parent M, Lescut D, et al.: Paraneoplastic intestinal pseudo-obstruction as the presenting feature of small-cell lung cancer. Gastroenterol Clin Biol 1988, 12:394–396.

    PubMed  CAS  Google Scholar 

  44. Gamez-Nava JI, Gonzalez-Lopez L, Ramos-Remus C, et al.: Autonomic dysfunction in patients with systemic lupus erythematosus. J Rheumatol 1998, 25:1092–1096.

    PubMed  CAS  Google Scholar 

  45. Sorajja P, Poirier MK, Bundrick JB, et al.: Autonomic failure and proximal skeletal myopathy in a patient with primary Sjögren syndrome. Mayo Clin Proc 1999, 74:695–697.

    Article  PubMed  CAS  Google Scholar 

  46. Sakakibara R, Hirano S, Asahina M, et al.: Primary Sjögren’s syndrome presenting with generalized autonomic failure. Eur J Neurol 2004, 11:635–638.

    Article  PubMed  CAS  Google Scholar 

  47. Mori K, Iijima M, Koike H, et al.: The wide spectrum of clinical manifestations in Sjögren’s syndrome-associated neuropathy. Brain 2005, 128:2518–2534. Detailed description of somatic and autonomic clinical and laboratory neuropathy findings in a large cohort of Sjögren’s syndrome patients.

    Article  PubMed  Google Scholar 

  48. Magaro M, Mirone L, Altmonte L, et al.: Lack of correlation between anticardiolipin antibodies and peripheral autonomic nerve involvement in systemic lupus erythematosus. Clin Rheumatol 1992, 11:231–234.

    Article  PubMed  CAS  Google Scholar 

  49. Jacob G, Biaggioni I: Idiopathic orthostatic intolerance and postural tachycardia syndromes. Am J Med Sci 1999, 317:88–101.

    Article  PubMed  CAS  Google Scholar 

  50. Weimer LH, Williams O: Syncope and orthostatic intolerance. Med Clin North Am 2003, 87:835–865.

    Article  PubMed  Google Scholar 

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  1. Neurological Institute of New York, 710 West 168th Street, Unit 55, 10032, New York, NY, USA

    Louis H. Weimer MD

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  1. Mill Etienne MD
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Correspondence to Louis H. Weimer MD.

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Etienne, M., Weimer, L.H. Immune-mediated autonomic neuropathies. Curr Neurol Neurosci Rep 6, 57–64 (2006). https://doi.org/10.1007/s11910-996-0010-2

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  • DOI: https://doi.org/10.1007/s11910-996-0010-2

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