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Paraneoplastic Encephalomyelitis Clinical Presentation

  • Author: David S Liebeskind, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
 
Updated: Apr 07, 2014
 

History

The neurologic manifestations of PEM precede the diagnosis of cancer in 80% of cases. Typically, a subacute onset of neurologic symptoms is followed by progression over weeks to months, finally reaching a plateau of neurologic impairment. The clinical presentation reflects the distribution of this multifocal inflammatory condition. Specific clinical syndromes have been described, although considerable overlap exists.

  • Paraneoplastic limbic encephalitis presents with memory loss, personality changes, anxiety or depression, neuropsychiatric disturbances, partial or generalized seizures including status epilepticus, olfactory and gustatory hallucinations, sleep disturbances, and abnormalities in other homeostatic functions.[11]
  • Focal encephalitis may affect nonlimbic cortical regions, presenting with seizures or epilepsia partialis continua and focal neurologic disturbances such as aphasia, weakness, or numbness.
  • Brainstem encephalitis is present in one third of patients, presenting with oscillopsia, diplopia, facial numbness, dysarthria, hearing loss, and dysphagia.
  • Motor neuron dysfunction occurs in 20% of cases, presenting with asymmetric proximal weakness and neck weakness. Subsequent symptoms may include distal limb weakness and fasciculations.
  • Subacute sensory neuronopathy accompanies most cases of PEM, with absence of clinical manifestations in only 20-30% of cases. Symptoms include asymmetric focal numbness or paresthesias, typically involving the face, trunk, and proximal extremities. Burning or lancinating dysesthesias of all extremities may be noted at later stages.
  • Autonomic dysfunction is noted in one fourth of cases, presenting with postural hypotension, gastrointestinal disturbances, sweating abnormalities, urinary difficulties, impotence, sluggish pupils, and cardiovascular instability.
  • Lambert-Eaton myasthenic syndrome occurs in 10-16% of cases.[12]
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Physical

Physical examination findings assist in the localization of clinical symptoms and anatomical classification of specific paraneoplastic syndromes.

  • Paraneoplastic limbic encephalitis: Anterograde or retrograde amnesia and neuropsychiatric disturbances predominate, with altered levels of consciousness at later stages. Focal neurologic deficits also may be noted.
  • Focal encephalitis: Focal neurologic deficits occur and include aphasia and motor or sensory abnormalities. Epilepsia partialis continua or seizures may be evident.[13]
  • Brainstem encephalitis: Patients experience oscillopsia, diplopia, vertical and horizontal gaze abnormalities, facial numbness, dysarthria, hearing loss, and dysphagia.
  • Motor neuron dysfunction: Patients have neck flexor/extensor weakness, asymmetric limb weakness, fasciculations, atrophy, and a combination of upper and lower motor neuron signs.
  • Subacute sensory neuronopathy: Asymmetric focal sensory loss occurs on the face, trunk, and proximal extremities. Prominent sensory ataxia with vibratory and proprioceptive loss, pseudoathetosis, diminished reflexes, and gait abnormalities are noted.
  • Autonomic neuropathy: Patients have abnormal pupillary responses, postural hypotension, sweating abnormalities, neurogenic bladder, and respiratory or cardiovascular disturbances.
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Causes

See the list below:

  • Smoking is a potential risk factor, as most cases are associated with small-cell lung cancer.
  • Family history of cancer is another risk factor.
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Contributor Information and Disclosures
Author

David S Liebeskind, MD Professor of Neurology, Program Director, Vascular Neurology Residency Program, University of California, Los Angeles, David Geffen School of Medicine; Neurology Director, Stroke Imaging Program, Co-Medical Director, Cerebral Blood Flow Laboratory, Associate Neurology Director, UCLA Stroke Center

David S Liebeskind, MD is a member of the following medical societies: American Academy of Neurology, Stroke Council of the American Heart Association, American Heart Association, American Medical Association, American Society of Neuroimaging, American Society of Neuroradiology, National Stroke Association

Disclosure: Nothing to disclose.

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

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Frederick M Vincent, Sr, MD Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University Colleges of Human and Osteopathic Medicine

Frederick M Vincent, Sr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Forensic Examiners Institute, American College of Legal Medicine, American College of Physicians

Disclosure: Nothing to disclose.

References
  1. Blaes F. Paraneoplastic neurological syndromes--diagnosis and management. Curr Pharm Des. 2012. 18(29):4518-25. [Medline].

  2. Shirafuji T, Kanda F, Sekiguchi K, Higuchi M, Yokozaki H, Tanaka K, et al. Anti-Hu-associated paraneoplastic encephalomyelitis with esophageal small cell carcinoma. Intern Med. 2012. 51(17):2423-7. [Medline].

  3. Graus F, Saiz A, Lai M, Bruna J, López F, Sabater L, et al. Neuronal surface antigen antibodies in limbic encephalitis: clinical-immunologic associations. Neurology. 2008 Sep 16. 71(12):930-6. [Medline].

  4. Benyahia B, Liblau R, Merle-Beral H, et al. Cell-mediated autoimmunity in paraneoplastic neurological syndromes with anti-Hu antibodies. Ann Neurol. 1999 Feb. 45(2):162-7. [Medline].

  5. D'Alessandro V, Muscarella LA, Copetti M, Zelante L, Carella M, Vendemiale G. Molecular detection of neuron-specific ELAV-like-positive cells in the peripheral blood of patients with small-cell lung cancer. Cell Oncol. 2008. 30(4):291-7. [Medline].

  6. Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010 Aug. 9(8):776-85. [Medline].

  7. Aguirre-Cruz L, Charuel JL, Carpentier AF, et al. Clinical relevance of non-neuronal auto-antibodies in patients with anti-Hu or anti-Yo paraneoplastic diseases. J Neurooncol. 2005 Jan. 71(1):39-41. [Medline].

  8. Saiz A, Graus F, Dalmau J. Detection of 14-3-3 brain protein in the cerebrospinal fluid of patients with paraneoplastic neurological disorders. Ann Neurol. 1999 Nov. 46(5):774-7. [Medline].

  9. Sharshar T, Auriant I, Dorandeu A, et al. Association of herpes simplex virus encephalitis and paraneoplastic encephalitis - a clinico-pathological study. Ann Pathol. 2000 May. 20(3):249-52. [Medline].

  10. Foster AR, Caplan JP. Paraneoplastic limbic encephalitis. Psychosomatics. 2009 Mar-Apr. 50(2):108-13. [Medline].

  11. Adam VN, Marin D, Budincevic H, Mrsic V, Goranovic T, Tonkovic D. [Paraneoplastic limbic encephalitis]. Acta Med Croatica. 2012 Mar. 66(1):29-32. [Medline].

  12. Maddison P, Lang B. Paraneoplastic neurological autoimmunity and survival in small-cell lung cancer. J Neuroimmunol. 2008 Sep 15. 201-202:159-62. [Medline].

  13. Shavit YB, Graus F, Probst A, et al. Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis. Ann Neurol. 1999 Feb. 45(2):255-8. [Medline].

  14. Saiz A, Blanco Y, Sabater L, González F, Bataller L, Casamitjana R, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008 Oct. 131:2553-63. [Medline].

  15. Mihara M, Sugase S, Konaka K, et al. The "pulvinar sign" in a case of paraneoplastic limbic encephalitis associated with non-Hodgkin's lymphoma. J Neurol Neurosurg Psychiatry. 2005 Jun. 76(6):882-4. [Medline].

  16. Wingerchuk DM, Noseworthy JH, Kimmel DW. Paraneoplastic encephalomyelitis and seminoma: importance of testicular ultrasonography. Neurology. 1998 Nov. 51(5):1504-7. [Medline].

  17. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007 May 4. 2:22. [Medline].

  18. Dropcho EJ. Paraneoplastic Diseases of the Nervous System. Curr Treat Options Neurol. 1999 Nov. 1(5):417-427. [Medline].

  19. Keime-Guibert F, Graus F, Broet P, et al. Clinical outcome of patients with anti-Hu-associated encephalomyelitis after treatment of the tumor. Neurology. 1999 Nov 10. 53(8):1719-23. [Medline].

  20. Keime-Guibert F, Graus F, Fleury A, et al. Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry. 2000 Apr. 68(4):479-82. [Medline].

  21. Shams'ili S, de Beukelaar J, Gratama JW, Hooijkaas H, van den Bent M, van 't Veer M, et al. An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes. J Neurol. 2006 Jan. 253(1):16-20. [Medline].

  22. Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 2005 Aug. 128(Pt 8):1764-77. [Medline].

  23. Bakheit AM, Kennedy PG, Behan PO. Paraneoplastic limbic encephalitis: clinico-pathological correlations. J Neurol Neurosurg Psychiatry. 1990 Dec. 53(12):1084-8. [Medline].

  24. Compta Y, Valldeoriola F, Urra X, Gómez-Ansón B, Rami L, Tolosa E, et al. Isolated frontal disequilibrium as presenting form of anti-Hu paraneoplastic encephalomyelitis. Mov Disord. 2007 Apr 15. 22(5):736-8. [Medline].

  25. Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004 Aug. 127(Pt 8):1831-44. [Medline].

  26. de Beukelaar JW, Sillevis Smitt PA. Managing paraneoplastic neurological disorders. Oncologist. 2006 Mar. 11(3):292-305.

  27. de Beukelaar JW, Sillevis Smitt PA, Hop WC, Kraan J, Hooijkaas H, Verjans GM, et al. Imbalances in circulating lymphocyte subsets in Hu antibody associated paraneoplastic neurological syndromes. Eur J Neurol. 2007 Dec. 14(12):1383-91. [Medline].

  28. de Graaf M, de Beukelaar J, Bergsma J, Kraan J, van den Bent M, Klimek M, et al. B and T cell imbalances in CSF of patients with Hu-antibody associated PNS. J Neuroimmunol. 2008 Mar. 195(1-2):164-70. [Medline].

  29. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000 Jul. 123 ( Pt 7):1481-94. [Medline].

  30. Inuzuka T. Autoantibodies in paraneoplastic neurological syndrome. Am J Med Sci. 2000 Apr. 319(4):217-26. [Medline].

  31. Provenzale JM, Barboriak DP, Coleman RE. Limbic encephalitis: comparison of FDG PET and MR imaging findings. AJR Am J Roentgenol. 1998 Jun. 170(6):1659-60. [Medline].

  32. Sabater L, Gomez-Choco M, Saiz A, Graus F. BR serine/threonine kinase 2: a new autoantigen in paraneoplastic limbic encephalitis. J Neuroimmunol. 2005 Dec 30. 170(1-2):186-90. [Medline].

  33. Scaravilli F, An SF, Groves M, Thom M. The neuropathology of paraneoplastic syndromes. Brain Pathol. 1999 Apr. 9(2):251-60. [Medline].

  34. Tani T, Tanaka K, Idezuka J, Nishizawa M. Regulatory T cells in paraneoplastic neurological syndromes. J Neuroimmunol. 2008 May 30. 196(1-2):166-9. [Medline].

  35. Vincent A. Antibodies associated with paraneoplastic neurological disorders. Neurol Sci. 2005 May. 26 Suppl 1:S3-4. [Medline].

  36. Vincent A, Buckley C, Schott JM, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. 2004 Mar. 127(Pt 3):701-12. [Medline].

  37. Voltz R, Gultekin SH, Rosenfeld MR, et al. A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N Engl J Med. 1999 Jun 10. 340(23):1788-95. [Medline].

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Paraneoplastic encephalomyelitis.
Paraneoplastic encephalomyelitis.
Mesial temporal hyperintensity demonstrated on T2-weighted (left) and fluid-attenuated inversion recovery (FLAIR, right) MRI.
 
 
 
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