Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Paraneoplastic Encephalomyelitis Workup

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

Laboratory Studies

See the list below:

  • Serum and CSF paraneoplastic antibody panel - Identify paraneoplastic etiology and detect autoimmune markers (eg, high levels of autoantibodies to glutamic acid decarboxylase [GAD-ab][14] ).
  • Cerebrospinal fluid
    • Cell count, protein, glucose, oligoclonal bands, IgG synthesis rate, cytology, and PCR for herpes simplex virus and varicella zoster virus.
    • Assess for differential diagnoses involving the central nervous system.
  • Serum tumor markers
    • Carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), prostate-specific antigen (PSA).
    • Evaluate for an underlying malignancy.
  • Complete blood cell count with platelets - Monitor for infection, immunosuppression, anemia, or thrombocytopenia.
  • Prothrombin time (PT)/activated partial thromboplastin time (aPTT) - Identify coagulopathies.
  • Serum chemistries, including electrolytes and osmolarity - Monitor for associated electrolyte abnormalities or metabolic derangements.
  • Toxicology screen - Identify a toxic etiology.
  • Vitamin B 12 level - Rule out vitamin deficiency.
  • Liver function tests - Evaluate hepatic causes of encephalopathy.
  • Screening for infectious or hematologic etiologies - Selective evaluation of possible infectious or hematologic etiologies.
Next

Imaging Studies

See the list below:

  • Head CT provides limited information regarding PEM but allows for preliminary evaluation of differential diagnoses such as herpes simplex encephalitis or intracranial metastatic disease. Hypodensity on CT scan may be seen in chronic stages of paraneoplastic encephalomyelitis (PEM).
  • Brain MRI may help to rule out the differential diagnoses. Usually, MRI in a patient with PEM is unremarkable, although T2-weighted hyperintensity may be noted in mesial temporal lobes and associated limbic structures (see following image). Posterior thalamic T2 hyperintensity, or the "pulvinar sign[15] ," may be present. Contrast enhancement may be demonstrated with subsequent development of atrophy and gliosis, reflecting the dynamic evolution of inflammatory injury. MR spectroscopy of the brain may add further information.
    Mesial temporal hyperintensity demonstrated on T2-Mesial temporal hyperintensity demonstrated on T2-weighted (left) and fluid-attenuated inversion recovery (FLAIR, right) MRI.
  • Positron emission tomography (PET) may illustrate hypermetabolism of limbic regions during the active phase of disease, supplanted by hypometabolism in the chronic phase. Whole body PET may also identify the primary lesion.
  • Myelography may demonstrate an enlarged spinal cord associated with inflammation.
  • The following studies may be done to identify an underlying malignancy:
    • CT/MRI of the chest, abdomen, and pelvis
    • Testicular ultrasonography[16]
    • Mammography
Previous
Next

Other Tests

See the list below:

  • Electroencephalography (EEG) may reveal focal temporal or diffuse paroxysmal sharp waves and spikes, and/or slowing.
  • Electromyography/nerve conduction studies of subacute sensory neuronopathy may reveal selective damage of sensory pathways with limited detection of H waves and preservation of motor nerve velocities and F waves. Studies of myelitis may exhibit motor denervation.
Previous
Next

Procedures

See the list below:

  • Lumbar puncture is essential for determination of the CSF profile and detection of intrathecal paraneoplastic antibodies.
  • Diagnostic imaging modalities may help avoid the need for brain biopsy in some cases.
Previous
Next

Histologic Findings

The neuropathologic findings are typically more extensive than the degree of neurologic manifestations. Gross examination of the brain is usually unremarkable. Neuronal degeneration, gliosis, and an inflammatory infiltrate may be demonstrated throughout the brain. Perivascular and interstitial infiltrates are composed of B lymphocytes and cluster of differentiation 4 (CD4+) and CD8+ T lymphocytes, with microglial proliferation and neuronophagia. Limbic structures are particularly vulnerable, with prominent involvement of the hippocampus, amygdala, parahippocampus, cingulate cortex, insular cortex, and basal frontal lobes. Similar changes may be noted in the diencephalon, brain stem, deep cerebellar nuclei, spinal cord, dorsal root ganglia, sympathetic ganglia, and myenteric plexus.

Previous
 
 
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].

Previous
Next
 
Paraneoplastic encephalomyelitis.
Paraneoplastic encephalomyelitis.
Mesial temporal hyperintensity demonstrated on T2-weighted (left) and fluid-attenuated inversion recovery (FLAIR, right) MRI.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.