Further Outpatient Care

Custodial nursing home care may be needed if the autonomic failure is severe, and patients are bedridden and completely disabled.

Further Inpatient Care

Typically, the disorder is progressive, although stabilization with antineoplastic therapy has been reported. Subsequent follow-up is devoted to assessing adequacy of blood pressure support and bowel and bladder management.

Inpatient & Outpatient Medications

Medications are the same as those used in inpatient care, except doses are adjusted with time and disease progression. See article Idiopathic Orthostatic Hypotension and Other Autonomic Failure Syndromes for specific suggestions.

Deterrence/Prevention

No known method is effective in deterring or preventing occurrence of autonomic paraneoplastic failure, except to prevent exposure to known carcinogens such as tobacco smoke.

Complications

Sudden death, often due to cardiac causes, can occur. Intestinal pseudo-obstruction and urinary tract infections from incomplete bladder emptying are possible. Overheating due to reduced sweat function can occur in hot temperatures or with physical exertion.

Prognosis

Prognosis is generally poor. Prompt and effective treatment of the underlying malignancy may arrest progression of autonomic dysfunction, but in many cases, no improvement occurs. Survival is dependent on underlying cancer, patient age, and extent of nervous system involvement. The median survival of all patients with paraneoplastic syndromes has been estimated to be 1 to 3 years.^[7]The two major exceptions are LEMS and NMDA receptor antibody disease. In Lambert-Eaton myasthenic syndrome, effective treatment often results in remission of the mild autonomic symptoms and better than expected survival.^{[45, 46, 47]}In NMDA receptor antibody disease, treatment results in recovery 75% of the time; however, this disease is still poorly characterized and likely underdiagnosed, so these numbers may change as more data become available.^[22]

Questions

Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004 Aug. 75(8):1135-40. [QxMD MEDLINE Link].
Anderson NE, Rosenblum MK, Graus F. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology. 1988 Sep. 38(9):1391-8. [QxMD MEDLINE Link].
Elrington GM, Murray NM, Spiro SG. Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective survey of 150 patients. J Neurol Neurosurg Psychiatry. 1991 Sep. 54(9):764-7. [QxMD MEDLINE Link].
Veilleux M, Bernier JP, Lamarche JB. Paraneoplastic encephalomyelitis and subacute dysautonomia due to an occult atypical carcinoid tumour of the lung. Can J Neurol Sci. 1990 Aug. 17(3):324-8. [QxMD MEDLINE Link].
Blaes F, Strittmatter M, Schwamborn J, et al. Antineuronal antibody-associated paraneoplastic neuropathy in Hodgkin's disease. Eur J Neurol. 1998 Jan. 5(1):109-112. [QxMD MEDLINE Link].
Ficker DM, Hammack JE. Primary central nervous system lymphoma presenting as autonomic dysfunction. J Neurooncol. 1995. 23(3):245-8. [QxMD MEDLINE Link].
Candler PM, Hart PE, Barnett M, et al. A follow up study of patients with paraneoplastic neurological disease in the United Kingdom. J Neurol Neurosurg Psychiatry. 2004 Oct. 75(10):1411-5. [QxMD MEDLINE Link].
Altermatt HJ, Rodriguez M, Scheithauer BW, Lennon VA. Paraneoplastic anti-Purkinje and type I anti-neuronal nuclear autoantibodies bind selectively to central, peripheral, and autonomic nervous system cells. Lab Invest. 1991 Oct. 65(4):412-20. [QxMD MEDLINE Link].
Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004 Nov. 56(5):715-9. [QxMD MEDLINE Link].
Panegyres PK, Reading MC, Esiri MM. The inflammatory reaction of paraneoplastic ganglionitis and encephalitis: an immunohistochemical study. J Neurol. 1993 Feb. 240(2):93-7. [QxMD MEDLINE Link].
Vernino S, Adamski J, Kryzer TJ. Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. Neurology. 1998 Jun. 50(6):1806-13. [QxMD MEDLINE Link].
Vernino S, Low PA, Fealey RD. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. 2000 Sep 21. 343(12):847-55. [QxMD MEDLINE Link].
Freeman R. Autonomic peripheral neuropathy. Lancet. 2005 Apr 2-8. 365(9466):1259-70. [QxMD MEDLINE Link].
Peltier AC, Black BK, Raj SR, Donofrio P, Robertson D, Biaggioni I. Coexistent autoimmune autonomic ganglionopathy and myasthenia gravis associated with non-small-cell lung cancer. Muscle Nerve. 2010 Mar. 41(3):416-9. [QxMD MEDLINE Link].
Lorusso L, Hart IK, Ferrari D, Ngonga GK, Gasparetto C, Ricevuti G. Autonomic paraneoplastic neurological syndromes. Autoimmun Rev. 2007 Jan. 6(3):162-8. [QxMD MEDLINE Link].
de Beukelaar JW, Sillevis Smitt PA. Managing paraneoplastic neurological disorders. Oncologist. 2006 Mar. 11(3):292-305. [QxMD MEDLINE Link].
Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998 Mar. 50(3):652-7. [QxMD MEDLINE Link].
Camdessanche JP, Antoine JC, Honnorat J. Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. A clinical and electrophysiological study of 20 patients. Brain. 2002 Jan. 125(Pt 1):166-75. [QxMD MEDLINE Link].
Vernino S. Antibody testing as a diagnostic tool in autonomic disorders. Clin Auton Res. 2009 Feb. 19(1):13-9. [QxMD MEDLINE Link].
Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010 Dec. 10(12):835-44. [QxMD MEDLINE Link].
Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011 Jul 12. 77(2):179-89. [QxMD MEDLINE Link]. [Full Text].
Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008 Dec. 7(12):1091-8. [QxMD MEDLINE Link].
Nazif TM, Vázquez J, Honig LS, Dizon JM. Anti-N-methyl-D-aspartate receptor encephalitis: an emerging cause of centrally mediated sinus node dysfunction. Europace. 2012 Feb 15. [QxMD MEDLINE Link].
Millichap JJ, Goldstein JL, Laux LC, Nordli DR Jr, Stack CV, Wainwright MS. Ictal asystole and anti-N-methyl-D-aspartate receptor antibody encephalitis. Pediatrics. 2011 Mar. 127(3):e781-6. [QxMD MEDLINE Link].
Mahadeva B, Phillips LH 2nd, Juel VC. Autoimmune disorders of neuromuscular transmission. Semin Neurol. 2008 Apr. 28(2):212-27. [QxMD MEDLINE Link].
Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol. 2000 Mar. 47(3):297-305. [QxMD MEDLINE Link].
Tschernatsch M, Klotz M, Probst C, Hosch J, Valtorta F, Diener M, et al. Synaptophysin is an autoantigen in paraneoplastic neuropathy. J Neuroimmunol. 2008 Jun 15. 197(1):81-6. [QxMD MEDLINE Link].
Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology. 2008 May 13. 70(20):1883-90. [QxMD MEDLINE Link].
Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology. 2008 May 13. 70(20):1883-90. [QxMD MEDLINE Link].
Vincent A, Bien CG, Irani SR, Waters P. Autoantibodies associated with diseases of the CNS: new developments and future challenges. Lancet Neurol. 2011 Aug. 10(8):759-72. [QxMD MEDLINE Link].
Dhamija R, Tan KM, Pittock SJ, Foxx-Orenstein A, Benarroch E, Lennon VA. Serologic profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility. Clin Gastroenterol Hepatol. 2008 Sep. 6(9):988-92. [QxMD MEDLINE Link].
Malhotra K, Georgiades IB, Davies J. Functional colonic obstruction in an adult as a presenting feature of thymoma. Ann R Coll Surg Engl. 2011 Sep. 93(6):e61-3. [QxMD MEDLINE Link].
Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009. 26:147-65. [QxMD MEDLINE Link].
Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol. 2010 Apr. 257(4):509-17. [QxMD MEDLINE Link].
Tschernatsch M, Klotz M, Probst C, Hosch J, Valtorta F, Diener M. Synaptophysin is an autoantigen in paraneoplastic neuropathy. J Neuroimmunol. 2008 Jun 15. 197(1):81-6. [QxMD MEDLINE Link].
Sven Jarius, Marius Ringelstein, Jurgen Hass, Irina I. Serysheva, Lars Komorowski, Kai Fechner, et al. Inositol 1,4,5-trisphosphate receptor type 1 autoantibodies in paraneoplastic and non-paraneoplastic peripheral neuropathy. Journal of Neuroinflammation. Oct 24, 2016. 13:278. [QxMD MEDLINE Link].
William Oliver Tobin, Vanda A. Lennon, Lars Komorowski, Christian Probst, Stacey Lynn Clardy, Allen J. Aksamit, et al. DPPX potassium channel antibody; frequency, clinical accompaniments, and outcomes in 20 patients. Neurology. Nov. 11, 2014. 83:1797-1803. [QxMD MEDLINE Link].
Byrne T, Mason WP, Posner JB, et al. Spontaneous neurological improvement in anti-Hu associated encephalomyelitis. J Neurol Neurosurg Psychiatry. 1997 Mar. 62(3):276-8. [QxMD MEDLINE Link].
Chalk CH, Windebank AJ, Kimmel DW, McManis PG. The distinctive clinical features of paraneoplastic sensory neuronopathy. Can J Neurol Sci. 1992 Aug. 19(3):346-51. [QxMD MEDLINE Link].
Chinn JS, Schuffler MD. Paraneoplastic visceral neuropathy as a cause of severe gastrointestinal motor dysfunction. Gastroenterology. 1988 Nov. 95(5):1279-86. [QxMD MEDLINE Link].
Dalmau J, Graus F, Rosenblum MK. Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore). 1992 Mar. 71(2):59-72. [QxMD MEDLINE Link].
Titulaer MJ, Soffietti R, Dalmau J, Gilhus NE, Giometto B, Graus F, et al. Screening for tumours in paraneoplastic syndromes: report of an EFNS Task Force. Eur J Neurol. 2010 Sep 29. [QxMD MEDLINE Link].
Oh SJ, Dropcho EJ, Claussen GC. Anti-Hu-associated paraneoplastic sensory neuropathy responding to early aggressive immunotherapy: report of two cases and review of literature. Muscle Nerve. 1997 Dec. 20(12):1576-82. [QxMD MEDLINE Link].
Dhamija R, Tan KM, Pittock SJ, Foxx-Orenstein A, Benarroch E, Lennon VA. Serologic profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility. Clin Gastroenterol Hepatol. 2008 Sep. 6(9):988-92. [QxMD MEDLINE Link].
Khurana RK, Koski CL, Mayer RF. Autonomic dysfunction in Lambert-Eaton myasthenic syndrome. J Neurol Sci. 1988 May. 85(1):77-86. [QxMD MEDLINE Link].
Maddison P, Lang B. Paraneoplastic neurological autoimmunity and survival in small-cell lung cancer. J Neuroimmunol. 2008 Sep 15. 201-202:159-62. [QxMD MEDLINE Link].
Mamdani MB, Walsh RL, Rubino FA. Autonomic dysfunction and Eaton Lambert syndrome. J Auton Nerv Syst. 1985 Apr. 12(4):315-20. [QxMD MEDLINE Link].
Block MS, Vassallo R. Lack of FDG uptake in small cell carcinoma associated with ANNA-1 positive paraneoplastic autonomic neuropathy. J Thorac Oncol. 2008 May. 3(5):542-4. [QxMD MEDLINE Link].

Media Gallery

Paraneoplastic autonomic neuropathy. Histopathology of peripheral nerve and sympathetic ganglion from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive anti-HU antibody titer. (a) Peripheral nerve in longitudinal section stained with Luxol fast blue-periodic acid-Schiff (PAS) showing scattered wallerian degeneration (arrowheads). (b) Low-power view of a paravertebral sympathetic ganglion stained with hematoxylin and eosin (H&E). Arrowhead indicates perivascular mononuclear infiltrates. (c) High-power view of the same sympathetic ganglion showing degenerating neurons (single arrowheads) and mononuclear infiltrates (double arrowhead). Magnification bars in a and b indicate 100 mm; c is 50 mm.
Paraneoplastic autonomic neuropathy. Hematoxylin and eosin (H&E)–stained sections from dorsal root ganglion showing the hallmark histopathology of anti-HU disease; a and c are from a healthy patient; b and d are from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive titer of anti-HU antibodies. The arrowheads in b and d indicate degenerating sensory neurons. Also note the interstitial hypercellularity and decreased numbers of neurons in b and d. Magnification bar in b indicates 100 mm and applies also to a. Similarly, the magnification bar in d indicates 50 mm, which also applies to c.
Paraneoplastic autonomic neuropathy. Central nervous system sections from a patient with autonomic failure, oat-cell carcinoma of the lung, and positive titer of anti-HU antibodies stained with hematoxylin and eosin (H&E). (a) Inferior olive showing a cluster of mononuclear cells (arrowhead); (b) hippocampus showing perivascular mononuclear infiltrate (arrowhead); (c) midbrain section showing a vessel encased in a mononuclear infiltrate; (d) ventral horn of the thoracic spinal cord showing clusters of mononuclear cells around degenerating motor neurons (arrowheads). Magnification bars indicate 100 mm. The bar in b applies also to a and the bar in d also applies to c.

of 3

Author

Stacy E Dixon, MD, PhD Assistant Professor of Neurology, University of Colorado School of Medicine

Stacy E Dixon, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Colorado Society of Clinical Neurologists

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Biogen; Genetech.

Coauthor(s)

Dianna Quan, MD Professor of Neurology, Director of Electromyography Laboratory, University of Colorado School of Medicine

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Association of Neuromuscular and Electrodiagnostic Medicine; American Neuromuscular Foundation<br/>Serve(d) as a speaker or a member of a speakers bureau for: Alnylam<br/>Received research grant from: Alnylam; Pfizer; Ionis; Cytokinetics; Momenta/Janssen; Viela Bio; Avidity bioscience.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS † Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, American College of International Physicians, American College of Physicians, American Heart Association, American Stroke Association, National Association of Managed Care Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Ronald G Wiley, MD, PhD Professor of Neurology and Pharmacology, Vanderbilt University, Chief of the Neurology Service, Veterans Affairs Tennessee Valley Healthcare System

Ronald G Wiley, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association for the Advancement of Science, New York Academy of Sciences, Society for Neuroscience

Disclosure: Nothing to disclose.

Bjorn E Oskarsson, MD Assistant Professor, Department of Neurology, University of California, Davis, School of Medicine

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Flex Pharma<br/>Serve(d) as a speaker or a member of a speakers bureau for: Grifols<br/>Received research grant from: Neuraltus, Glaxo, Eisai, Cytokinetics, Genentech,.

Daniel Mordechai Goldenholz, MD, PhD Resident Physician, Department of Neurology, University of California Davis Medical Center

Daniel Mordechai Goldenholz, MD, PhD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.