Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course. 1. Introduction Among the peripheral neuropathies, there is a group in which autonomic fibers are prominently or selectively targeted. Disorders of autonomic function are present when small, lightly myelinated and unmyelinated nerve fibers are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Autonomic dysfunction may occur in association with various diseases such as diabetes mellitus, chronic alcoholism, amyloidosis, infections, paraneoplastic syndrome, and Sjogren syndrome (secondary autonomic neuropathies) or without any underlying disease (idiopathic or primary autonomic neuropathies) [1]. Sensitive and reproducible noninvasive measures of autonomic function together with laboratory and electrophysiological testing can help to establish diagnosis, allowing to recognize potentially treatable immune-mediated disorders. Tests of cardiovagal (parasympathetic), adrenergic vasoconstriction (sympathetic) are now available in most laboratories and commonly performed [2]. This paper will focus on autonomic involvement in immune-mediated neuropathies with a subacute or chronic course. 2. Subacute and Chronic Neuropathies with Immune-Mediated Mechanisms and Autonomic Involvement 2.1. Immune-Mediated Idiopathic (Primary) Autonomic Neuropathies 2.1.1. Autoimmune Autonomic Ganglionopathy (AAG) AAG includes a wide spectrum of acquired disorders characterized by diffuse autonomic dysfunction with an immune-mediated pathophysiology and positivity of ganglionic nicotinic α3-acetylcholine receptors (α3-AChR) autoantibodies. Viral upper respiratory tract infections and gastrointestinal infections have been described as antecedent infections. AAG may also be associated with vaccination, surgery, or interferon therapy. Classical AAG is a subacute disorder with a
References
[1]
H. Koike, H. Watanabe, and G. Sobue, “The spectrum of immune-mediated autonomic neuropathies: insights from the clinicopathological features,” Journal of Neurology, Psychiatry and Neurosurgery, vol. 84, pp. 98–106, 2013.
[2]
R. Di Leo, O. Musumeci, C. de Gregorio et al., “Evidence of cardiovascular autonomic impairment in mitochondrial disorders,” Journal of Neurology, vol. 254, no. 11, pp. 1498–1503, 2007.
[3]
P. Sandroni and P. A. Low, “Other autonomic neuropathies associated with ganglionic antibody,” Autonomic Neuroscience, vol. 146, no. 1-2, pp. 13–17, 2009.
[4]
S. Vernino, P. Sandroni, W. Singer, and P. A. Low, “Invited article: autonomic ganglia: target and novel therapeutic tool,” Neurology, vol. 70, no. 20, pp. 1926–1932, 2008.
[5]
N. Winston and S. Vernino, “Recent advances in autoimmune autonomic ganglionopathy,” Current Opinion in Neurology, vol. 23, no. 5, pp. 514–518, 2010.
[6]
S. Vernino, S. Hopkins, and Z. Wang, “Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy,” Autonomic Neuroscience, vol. 146, no. 1-2, pp. 3–7, 2009.
[7]
S. Vernino, P. A. Low, R. D. Fealey, J. D. Stewart, G. Farrugia, and V. A. Lennon, “Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neukopathies,” New England Journal of Medicine, vol. 343, no. 12, pp. 847–855, 2000.
[8]
C. H. Gibbons and R. Freeman, “Antibody titers predict clinical features of autoimmune autonomic ganglionopathy,” Autonomic Neuroscience, vol. 146, no. 1-2, pp. 8–12, 2009.
[9]
V. Iodice, K. Kimpinski, S. Vernino, P. Sandroni, R. D. Fealey, and P. A. Low, “Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy,” Neurology, vol. 72, no. 23, pp. 2002–2008, 2009.
[10]
H. Koike, R. Hashimoto, M. Tomita, et al., “The spectrum of clinicopathological features in pure autonomic neuropathy,” Journal of Neurology, vol. 259, no. 10, pp. 2067–2075, 2012.
[11]
H. Koike, S. Koyano, S. Morozumi et al., “Slowly progressive autonomic neuropathy with antiganglionic acetylcholine receptor antibody,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 81, no. 5, pp. 586–587, 2010.
[12]
E. Tajzoy, S. Mukherjee, and S. Vernino, “Autonomic ganglia neuronal density and synaptic structure in chronic experimental autoimmune autonomic ganglionopathy,” Archives of Neurology, vol. 68, no. 4, pp. 540–541, 2011.
[13]
R. de Giorgio and M. Camilleri, “Human enteric neuropathies: morphology and molecular pathology,” Neurogastroenterology and Motility, vol. 16, no. 5, pp. 515–531, 2004.
[14]
J. D. Wood, “Neuropathy in the brain-in-the-gut,” European Journal of Gastroenterology and Hepatology, vol. 12, no. 6, pp. 597–600, 2000.
[15]
M. D. Schuffler, H. W. Baird, and C. R. Fleming, “Intestinal pseudo-obstruction as the presenting manifestation of small-cell carcinoma of the lung. A paraneoplastic neuropathy of the gastrointestinal tract,” Annals of Internal Medicine, vol. 98, no. 2, pp. 129–134, 1983.
[16]
A. Gerl, M. Storck, A. Schalhorn et al., “Paraneoplastic chronic intestinal pseudoobstruction as a rare complication of bronchial carcinoid,” Gut, vol. 33, no. 7, pp. 1000–1003, 1992.
[17]
D. S. Horoupian and Y. Kim, “Encephalomyeloneuropathy with ganglionitis of the myenteric plexuses in the absence of cancer,” Annals of Neurology, vol. 11, no. 6, pp. 628–632, 1982.
[18]
G. B. McDonald, M. D. Schuffler, M. E. Kadin, and G. N. J. Tytgat, “Intestinal pseudoobstruction caused by diffuse lymphoid infiltration of the small intestine,” Gastroenterology, vol. 89, no. 4, pp. 882–889, 1985.
[19]
S. B. Clark, T. W. Rice, R. R. Tubbs, J. E. Richter, and J. R. Goldblum, “The nature of the myenteric infiltrate in achalasia: an immunohistochemical analysis,” American Journal of Surgical Pathology, vol. 24, no. 8, pp. 1153–1158, 2000.
[20]
B. Bogers, M. Moreels, D. M. de Man et al., “Schistosoma mansoni infection causing diffuse enteric inflammation and damage of the enteric nervous system in the mouse small intestine,” Neurogastroenterology and Motility, vol. 12, no. 5, pp. 431–440, 2000.
[21]
M. G. Sch？ppi, V. V. Smith, P. J. Milla, and K. J. Lindley, “Eosinophilic myenteric ganglionitis is associated with functional intestinal obstruction,” Gut, vol. 52, no. 5, pp. 752–755, 2003.
[22]
H. R. Lee, V. A. Lennon, M. Camilleri, and C. M. Prather, “Paraneoplastic gastrointestinal motor dysfunction: clinical and laboratory characteristics,” American Journal of Gastroenterology, vol. 96, no. 2, pp. 373–379, 2001.
[23]
R. de Giorgio, M. Bovara, G. Barbara et al., “Anti-HuD-induced neuronal apoptosis underlying paraneoplastic gut dysmotility,” Gastroenterology, vol. 125, no. 1, pp. 70–79, 2003.
[24]
R. de Giorgio, G. Barbara, V. Stanghellini et al., “Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases,” American Journal of Gastroenterology, vol. 97, no. 9, pp. 2454–2459, 2002.
[25]
F. Graus, J. Y. Delattre, J. C. Antoine et al., “Recommended diagnostic criteria for paraneoplastic neurological syndromes,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 75, no. 8, pp. 1135–1140, 2004.
[26]
B. Giometto, W. Grisold, R. Vitaliani, F. Graus, J. Honnorat, and G. Bertolini, “Paraneoplastic neurologic syndrome in the PNS euronetwork database: a European study from 20 centers,” Archives of Neurology, vol. 67, no. 3, pp. 330–335, 2010.
[27]
H. Koike, F. Tanaka, and G. Sobue, “Paraneoplastic neuropathy: wide-ranging clinicopathological manifestations,” Current Opinion in Neurology, vol. 24, no. 5, pp. 504–510, 2011.
[28]
Y. Oki, H. Koike, M. Iijima et al., “Ataxic vs painful form of paraneoplastic neuropathy,” Neurology, vol. 69, no. 6, pp. 564–572, 2007.
[29]
H. Koike and G. Sobue, “Small neurons may be preferentially affected in ganglionopathy,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 79, no. 2, p. 113, 2008.
[30]
M. Etienne and L. H. Weimer, “Immune-mediated autonomic neuropathies,” Current Neurology and Neuroscience Reports, vol. 6, no. 1, pp. 57–64, 2006.
[31]
C. F. Lucchinetti, D. W. Kimmel, and V. A. Lennon, “Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies,” Neurology, vol. 50, no. 3, pp. 652–657, 1998.
[32]
Z. Yu, T. J. Kryzer, G. E. Griesmann, et al., “CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity,” Annals of Neurology, vol. 49, no. 2, pp. 146–154, 2001.
[33]
A. McKeon, V. A. Lennon, D. H. Lachance, R. D. Fealey, and S. J. Pittock, “Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments,” Archives of Neurology, vol. 66, no. 6, pp. 735–741, 2009.
[34]
S. Vernino, P. Sandroni, W. Singer, and P. A. Low, “Invited Article: autonomic ganglia: target and novel therapeutic tool,” Neurology, vol. 70, no. 20, pp. 1926–1932, 2008.
[35]
B. Giometto, R. Vitaliani, E. Lindeck-Pozza, W. Grisold, and C. Vedeler, “Treatment for paraneoplastic neuropathies,” Cochrane Database of Systematic Reviews, vol. 2012, Article ID CD007625, 2012.
[36]
H. Goto, H. Matsuo, T. Fuiudome, N. Shibuya, A. Ohnishi, and H. Nakamura, “Chronic autonomic neuropathy in a patient with primary Sjogren's syndrome,” Journal of Neurology Neurosurgery and Psychiatry, vol. 69, no. 1, p. 135, 2000.
[37]
R. Sakakibara, S. Hirano, M. Asahina et al., “Primary Sjogren's syndrome presenting with generalized autonomic failure,” European Journal of Neurology, vol. 11, no. 9, pp. 635–638, 2004.
[38]
K. Mori, M. Iijima, H. Koike et al., “The wide spectrum of clinical manifestations in Sj？gren's syndrome-associated neuropathy,” Brain, vol. 128, no. 11, pp. 2518–2534, 2005.
[39]
J. W. Griffin, D. R. Cornblath, E. Alexander et al., “Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjogren's syndrome,” Annals of Neurology, vol. 27, no. 3, pp. 304–315, 1990.
[40]
Y. Takahashi, T. Takata, M. Hoshino, M. Sakurai, and I. Kanazawa, “Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sj？gren's syndrome,” Neurology, vol. 60, no. 3, pp. 503–505, 2003.
[41]
A. Ammendola, S. Sampaolo, S. Migliaresi et al., “Autonomic neuropathy in mixed cryoglobulinemia,” Journal of Neurology, vol. 254, no. 2, pp. 215–219, 2007.
[42]
Y. Kawagashira, H. Koike, Y. Fujioka, et al., “Differential, size-dependent sensory neuron involvement in the painful and ataxic forms of primary Sj？gren's syndrome-associated neuropathy,” Journal of the Neurological Sciences, vol. 319, no. 1, pp. 139–146, 2012.
[43]
S. C. Shin and J. Robinson-Papp, “Amyloid neuropathies,” Mount Sinai Journal of Medicine, vol. 79, no. 6, pp. 733–748, 2012.
[44]
M. Matsuda, T. Gono, H. Morita, N. Katoh, M. Kodaira, and S. Ikeda, “Peripheral nerve involvement in primary systemic AL amyloidosis: a clinical and electrophysiological study,” European Journal of Neurology, vol. 18, no. 4, pp. 604–610, 2011.
[45]
H. Koike, K. Misu, S. Ikeda et al., “Type I (transthyretin Met30) familial amyloid polyneuropathy in Japan: early- vs late-onset form,” Archives of Neurology, vol. 59, no. 11, pp. 1771–1776, 2002.
[46]
H. Koike, F. Tanaka, R. Hashimoto et al., “Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 83, no. 2, pp. 152–158, 2012.
[47]
D. M. Benson, “Liver transplantation and transthyretin amyloidosis,” Muscle Nerve, vol. 47, no. 2, pp. 157–162, 2013.
[48]
V. Planté-Bordeneuve, A. Ferreira, T. Lalu et al., “Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP),” Neurology, vol. 69, no. 7, pp. 693–698, 2007.
[49]
H. Koike, R. Hashimoto, M. Tomita et al., “Diagnosis of sporadic transthyretin Val30Met familial amyloid polyneuropathy: a practical analysis,” Amyloid, vol. 18, no. 2, pp. 53–62, 2011.
[50]
S. Mathis, L. Magy, L. Diallo, S. Boukhris, and J. Vallat, “Amyloid neuropathy mimicking chronic inflammatory demyelinating polyneuropathy,” Muscle and Nerve, vol. 45, no. 1, pp. 26–31, 2012.
[51]
G. Vita, A. Mazzeo, R. Di Leo, and A. Ferlini, “Recurrent syncope as persistently isolated feature of transthyretin amyloidotic polyneuropathy,” Neuromuscular Disorders, vol. 15, no. 3, pp. 259–261, 2005.
[52]
M. Russo, A. Mazzeo, C. Stancanelli, et al., “Transthyretin-related familial amyloidotic polyneuropathy: description of a cohort of patients with Leu64 mutation and late onset,” Journal of Peripheral Nervous System, vol. 17, no. 4, pp. 385–390, 2012.
[53]
R. J. Barohn, J. T. Kissel, J. R. Warmolts, and J. R. Mendell, “Chronic inflammatory demyelinating polyradiculoneuropathy. Clinical characteristics, course, and recommendations for diagnostic criteria,” Archives of Neurology, vol. 46, no. 8, pp. 878–884, 1989.
[54]
K. C. Gorson, G. Allam, and A. H. Ropper, “Chronic inflammatory demyelinating polyneuropathy: clinical features and response to treatment in 67 consecutive patients with and without a monoclonal gammopathy,” Neurology, vol. 48, no. 2, pp. 321–328, 1997.
[55]
P. A. McCombe, J. D. Pollard, and J. G. McLeod, “Chronic inflammatory demyelinating polyradiculoneuropathy. A clinical and electrophysiological study of 92 cases,” Brain, vol. 110, no. 6, pp. 1617–1630, 1987.
[56]
Z. Simmons, J. W. Albers, M. B. Bromberg, and E. L. Feldman, “Presentation and initial clinical course in patients with chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients without and with monoclonal gammopathy,” Neurology, vol. 43, no. 11, pp. 2202–2209, 1993.
[57]
R. K. Lyu, L. M. Tang, Y. R. Wu, and S. T. Chen, “Cardiovascular autonomic function and sympathetic skin response in chronic inflammatory demyelinating polyradiculoneuropathy,” Muscle and Nerve, vol. 26, no. 5, pp. 669–672, 2002.
[58]
P. J. Dyck, A. C. Lais, and M. Ohta, “Chronic inflammatory polyradiculoneuropathy,” Mayo Clinic Proceedings, vol. 50, no. 11, pp. 622–637, 1975.
[59]
J. W. Prineas and J. G. McLeod, “Chronic relapsing polyneuritis,” Journal of the Neurological Sciences, vol. 27, no. 4, pp. 427–458, 1976.
[60]
T. J. Ingall, J. G. McLeod, and N. Tamura, “Autonomic function and unmyelinated fibers in chronic inflammatory demyelinating polyradiculoneuropathy,” Muscle and Nerve, vol. 13, no. 1, pp. 70–76, 1990.
[61]
K. Yamamoto, M. Watarai, T. Hashimoto, and S. Ikeda, “Chronic inflammatory demyelinating polyradiculoneuropathy with autonomic involvement,” Muscle and Nerve, vol. 31, no. 1, pp. 108–112, 2005.
[62]
G. Cavaletti, P. Santoro, E. Agostoni et al., “Chronic axonal sensory and autonomic polyneuropathy without motor involvement: a new ‘chronic inflammatory neuropathy?’,” European Journal of Neurology, vol. 6, no. 2, pp. 249–253, 1999.
[63]
E. Stamboulis, N. Katsaros, G. Koutsis, H. Iakovidou, A. Giannakopoulou, and I. Simintzi, “Clinical and subclinical autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy,” Muscle and Nerve, vol. 33, no. 1, pp. 78–84, 2006.
[64]
J. J. Figueroa, P. J. B. Dyck, R. S. Laughlin et al., “Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy,” Neurology, vol. 78, no. 10, pp. 702–708, 2012.
[65]
S. J. Oh, K. Kurokawa, D. F. de Almeida, H. F. Ryan Jr., and G. C. Claussen, “Subacute inflammatory demyelinating polyneuropathy,” Neurology, vol. 61, no. 11, pp. 1507–1512, 2003.
[66]
R. Hughes, E. Sanders, S. Hall, P. Atkinson, A. Colchester, and P. Payan, “Subacute idiopathic demyelinating polyradiculoneuropathy,” Archives of Neurology, vol. 49, no. 6, pp. 612–616, 1992.
