Clinical Autonomic Research

, 19:13 | Cite as

Antibody testing as a diagnostic tool in autonomic disorders

REVIEW ARTICLE

Abstract

Some forms of peripheral autonomic dysfunction (especially enteric neuropathy and subacute panautonomic failure) occur as autoimmune phenomena either in isolation or in the context of cancer. Autoimmune autonomic ganglionopathy is an example of a severe, but potentially treatable, antibody-mediated form of autonomic failure. Diagnostic evaluation of autonomic disorders can be supplemented by testing for paraneoplastic antibodies and antibodies against membrane receptors. The diagnostic antibodies most commonly associated with dysautonomia are paraneoplastic antibodies (anti-Hu and CRMP-5) and ganglionic acetylcholine receptor antibodies.

Keywords

paraneoplastic autonomic ganglia 

References

  1. 1.
    Candler PM, Hart PE, Barnett M, Weil R, Rees JH (2004) A follow up study of patients with paraneoplastic neurological disease in the United Kingdom. J Neurol Neurosurg Psychiatry 75:1411–1415 PubMedCrossRefGoogle Scholar
  2. 2.
    Chinn JS, Schuffler MD (1988) Paraneoplastic visceral neuropathy as a cause of severe gastrointestinal motor dysfunction. Gastroenterology 95:1279–1286 PubMedGoogle Scholar
  3. 3.
    Darnell RB (2004) Paraneoplastic neurologic disorders: windows into neuronal function and tumor immunity. Arch Neurol 61:30–32 PubMedCrossRefGoogle Scholar
  4. 4.
    Font J, Ramos-Casals M, de la Red G, Pou A, Casanova A, Garcia-Carrasco M, Cervera R, Molina JA, Valls J, Bove A, Ingelmo M, Graus F (2003) Pure sensory neuropathy in primary Sjogren’s syndrome. Longterm prospective followup and review of the literature. J Rheumatol 30:1552–1557 PubMedGoogle Scholar
  5. 5.
    Goldstein D, Holmes C, Dendi R, Li S-T, Brentzel S, Vernino S (2002) Pandysautonomia associated with impaired ganglionic neurotransmission and circulating antibody to the neuronal nicotinic receptor. Clin Auton Res 12:281–285 PubMedCrossRefGoogle Scholar
  6. 6.
    Graus F, Lang B, Pozo-Rosich P, Saiz A, Casamitjana R, Vincent A (2002) P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 59:764–766 PubMedGoogle Scholar
  7. 7.
    Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR (2002) Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 125:1887–1895 PubMedCrossRefGoogle Scholar
  8. 8.
    Hart RG, Kanter MC (1990) Acute autonomic neuropathy. Two cases and a clinical review. Arch Intern Med 150:2373–2376 PubMedCrossRefGoogle Scholar
  9. 9.
    Honnorat J, Byk T, Kusters I, Aguera M, Ricard D, Rogemond V, Quach T, Aunis D, Sobel A, Mattei MG, Kolattukudy P, Belin MF, Antoine JC (1999) Ulip/CRMP proteins are recognized by autoantibodies in paraneoplastic neurological syndromes. Eur J Neurosci 11:4226–4232 PubMedCrossRefGoogle Scholar
  10. 10.
    Josephs KA, Silber MH, Fealey RD, Nippoldt TB, Auger RG, Vernino S (2004) Neurophysiologic studies in Morvan syndrome. J Clin Neurophysiol 21:440–445 PubMedCrossRefGoogle Scholar
  11. 11.
    Jun S, Dimyan M, Jones KD, Ladabaum U (2005) Obstipation as a paraneoplastic presentation of small cell lung cancer: case report and literature review. Neurogastroenterol Motil 17:16–22 PubMedCrossRefGoogle Scholar
  12. 12.
    Klein CM, Vernino S, Lennon VA, Sandroni P, Fealey RD, Benrud-Larson L, Sletten D, Low PA (2003) The spectrum of autoimmune autonomic neuropathies. Ann Neurol 53:752–758 PubMedCrossRefGoogle Scholar
  13. 13.
    Knowles CH, Lang B, Clover L, Scott SM, Gotti C, Vincent A, Martin JE (2002) A role for autoantibodies in some cases of acquired non-paraneoplastic gut dysmotility. Scand J Gastroenterol 37:166–170 PubMedCrossRefGoogle Scholar
  14. 14.
    Lambert EH, Lennon VA (1988) Selected IgG rapidly induces Lambert-Eaton myasthenic syndrome in mice: complement independence and EMG abnormalities. Muscle Nerve 11:1133–1145 PubMedCrossRefGoogle Scholar
  15. 15.
    Lawn ND, Westmoreland BF, Kiely MJ, Lennon VA, Vernino S (2003) Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. Mayo Clin Proc 78:1363–1368 PubMedCrossRefGoogle Scholar
  16. 16.
    Lee EK, Maselli RA, Ellis WG, Agius MA (1998) Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma. J Neurol Neurosurg Psychiatry 65:857–862 PubMedCrossRefGoogle Scholar
  17. 17.
    Liguori R, Vincent A, Clover L, Avoni P, Plazzi G, Cortelli P, Baruzzi A, Carey T, Gambetti P, Lugaresi E, Montagna P (2001) Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 124:2417–2426 PubMedCrossRefGoogle Scholar
  18. 18.
    Liu W, Fackler W, Rice TW, Richter JE, Achkar E, Goldblum JR (2002) The pathogenesis of pseudoachalasia: a clinicopathologic study of 13 cases of a rare entity. Am J Surg Pathol 26:784–788 PubMedCrossRefGoogle Scholar
  19. 19.
    Lucchinetti CF, Camilleri M, Lennon VA (1994) Gastrointestinal dysmotility spectrum in patients seropositive for paraneoplastic type 1 anti-neuronal nuclear autoantibodies. Clin Auton Res 4:206 Google Scholar
  20. 20.
    Lucchinetti CF, Kimmel DW, Lennon VA (1998) Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 50:652–657 PubMedGoogle Scholar
  21. 21.
    Naito Y, Matsumoto I, Wakamatsu E, Goto D, Sugiyama T, Matsumura R, Ito S, Tsutsumi A, Sumida T (2005) Muscarinic acetylcholine receptor autoantibodies in patients with Sjogren’s syndrome. Ann Rheum Dis 64:510–511 PubMedCrossRefGoogle Scholar
  22. 22.
    Newsom-Davis J, Mills KR (1993) Immunological associations of acquired neuromyotonia (Isaacs’ syndrome) Report of five cases and literature review. Brain 116:453–469 PubMedCrossRefGoogle Scholar
  23. 23.
    O’Neill JH, Murray NM, Newsom-Davis J (1988) The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain 111:577–596 PubMedCrossRefGoogle Scholar
  24. 24.
    Pittock SJ, Kryzer TJ, Lennon VA (2004) Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 56:715–719 PubMedCrossRefGoogle Scholar
  25. 25.
    Rakocevic G, Barohn R, McVey AL, Damjanov I, Vernino S, Lennon V (2003) Myasthenia gravis, thymoma, and intestinal pseudo-obstruction: a case report and review. J Clin Neuromusc Dis 5:93–95 CrossRefGoogle Scholar
  26. 26.
    Shillito P, Molenaar PC, Vincent A, Leys K, Zheng W, Berg RJvd, Plomp JJ, Kempen GTHV, Chauplannaz G, Wintzen AR, Dijk JGv, Newsom-Davis J (1995) Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves. Ann Neurol 38:714–722 PubMedCrossRefGoogle Scholar
  27. 27.
    Sillevis Smitt PA, Manley GT, Posner JB (1995) Immunization with the paraneoplastic encephalomyelitis antigen HuD does not cause neurologic disease in mice. Neurology 45:1873–1878 PubMedGoogle Scholar
  28. 28.
    Suarez GA, Fealey RD, Camilleri M, Low PA (1994) Idiopathic autonomic neuropathy: clinical, neurophysiologic, and follow-up studies on 27 patients. Neurology 44:1675–1682 PubMedGoogle Scholar
  29. 29.
    Thieben M, Sandroni P, Benrud-Larson L, Fealey R, Vernino S, Lennon V, Low P (2007) Postural Orthostatic Tachycardia Syndrome—Mayo Clinic Experience. Mayo Clin Proc Google Scholar
  30. 30.
    Vernino S, Adamski J, Kryzer TJ, Fealey RD, Lennon VA (1998) Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. Neurology 50:1806–1813 PubMedGoogle Scholar
  31. 31.
    Vernino S, Ermilov LG, Sha L, Szurszewski JH, Low PA, Lennon VA (2004) Passive transfer of autoimmune autonomic neuropathy to mice. J Neurosci 24:7037–7042 PubMedCrossRefGoogle Scholar
  32. 32.
    Vernino S, Kryzer T, Lennon V (2002) Autoantibodies in autoimmune autonomic neuropathies and neuromuscular hyperexcitability disorders. In: Rose N, Hamilton R, Detrick B (eds) Manual of clinical laboratory immunology. ASM Press, Washington, DC, pp 1013–1017 Google Scholar
  33. 33.
    Vernino S, Lennon VA (2004) Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res 10:7270–7275 PubMedCrossRefGoogle Scholar
  34. 34.
    Vernino S, Lennon VA (2002) Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve 26:702–707 PubMedCrossRefGoogle Scholar
  35. 35.
    Vernino S, Lindstrom J, Hopkins S, Wang Z, Low PA (2008) Characterization of ganglionic acetylcholine receptor autoantibodies. J Neuroimmunol 197:63–69 PubMedCrossRefGoogle Scholar
  36. 36.
    Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA (2000) Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med 343:847–855 PubMedCrossRefGoogle Scholar
  37. 37.
    Vernino S, Wolfe GI (2007) Antibody testing in peripheral neuropathies. Neurol Clin 25:29–46 PubMedCrossRefGoogle Scholar
  38. 38.
    Viallard J-F, Vincent A, Moreau J-F, Parrens M, Pellegrin J-L, Ellie E (2005) Thymoma-associated neuromyotonia with antibodies against voltage-gated potassium channels presenting as chronic intestinal pseudo-obstruction. Eur Neurol 53:60–63 PubMedCrossRefGoogle Scholar
  39. 39.
    Vincent A (2002) Unravelling the pathogenesis of myasthenia gravis. Nature Rev Immunol 2:797–804 CrossRefGoogle Scholar
  40. 40.
    Vincent A, Lang B, Newsom-Davis J (1989) Autoimmunity to the voltage-gated calcium channel underlies the Lambert-Eaton myasthenic syndrome, a paraneoplastic disorder. Trends Neurosci 12:496–502 PubMedCrossRefGoogle Scholar
  41. 41.
    Voltz R, Carpentier AF, Rosenfeld MR, Posner JB, Dalmau J (1999) P/Q-type voltage-gated calcium channel antibodies in paraneoplastic disorders of the central nervous system. Muscle Nerve 22:119–122 PubMedCrossRefGoogle Scholar
  42. 42.
    Wang Z, Low PA, Jordan J, Freeman R, Gibbons CH, Schroeder C, Sandroni P, Vernino S (2007) Autoimmune autonomic ganglionopathy: IgG effects on ganglionic acetylcholine receptor current. Neurology 68:1917–1921 PubMedCrossRefGoogle Scholar
  43. 43.
    Younes-Mhenni S, Janier MF, Cinotti L, Antoine JC, Tronc F, Cottin V, Ternamian PJ, Trouillas P, Honnorat J (2004) FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes. Brain 127:2331–2338 PubMedCrossRefGoogle Scholar
  44. 44.
    Young R, Asbury A, Adams R, Corbett J (1969) Pure pandysautonomia with recovery. Trans Am Neurol Assoc 94:355–357 PubMedGoogle Scholar
  45. 45.
    Young RR, Asbury AK, Corbett JL, Adams RD (1975) Pure pan-dysautonomia with recovery. Brain 98:613–636 PubMedCrossRefGoogle Scholar
  46. 46.
    Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA (2001) CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 49:146–154 PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2008

Authors and Affiliations

  1. 1.Dept. of NeurologyUniversity of Texas, Southwestern Medical CenterDallasUSA

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