eMedicine Specialties > Neurology > Neuro-oncology
Paraneoplastic Encephalomyelitis: Differential Diagnoses & Workup
Updated: Jun 11, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Sensory nerve conduction disorders
Electroencephalogram in coma
Workup
Laboratory Studies
- Serum and CSF paraneoplastic antibody panel - Identify paraneoplastic etiology and detect autoimmune markers (eg, high levels of autoantibodies to glutamic acid decarboxylase [GAD-ab]10 ).
- 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.
Imaging Studies
- 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 Media file 1). Posterior thalamic T2 hyperintensity, or the "pulvinar sign11 ," 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-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 ultrasonography12
- Mammography
Other Tests
- 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.
Procedures
- 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.
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.
More on Paraneoplastic Encephalomyelitis |
| Overview: Paraneoplastic Encephalomyelitis |
 Differential Diagnoses & Workup: Paraneoplastic Encephalomyelitis |
| Treatment & Medication: Paraneoplastic Encephalomyelitis |
| Follow-up: Paraneoplastic Encephalomyelitis |
| Multimedia: Paraneoplastic Encephalomyelitis |
| References |
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References
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. Sep 16 2008;71(12):930-6. [Medline].
Benyahia B, Liblau R, Merle-Beral H, et al. Cell-mediated autoimmunity in paraneoplastic neurological syndromes with anti-Hu antibodies. Ann Neurol. Feb 1999;45(2):162-7. [Medline].
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].
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. Jan 2005;71(1):39-41. [Medline].
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. Nov 1999;46(5):774-7. [Medline].
Sharshar T, Auriant I, Dorandeu A, et al. Association of herpes simplex virus encephalitis and paraneoplastic encephalitis - a clinico-pathological study. Ann Pathol. May 2000;20(3):249-52. [Medline].
Foster AR, Caplan JP. Paraneoplastic limbic encephalitis. Psychosomatics. Mar-Apr 2009;50(2):108-13. [Medline].
Maddison P, Lang B. Paraneoplastic neurological autoimmunity and survival in small-cell lung cancer. J Neuroimmunol. Sep 15 2008;201-202:159-62. [Medline].
Shavit YB, Graus F, Probst A, et al. Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis. Ann Neurol. Feb 1999;45(2):255-8. [Medline].
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. Oct 2008;131:2553-63. [Medline].
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. Jun 2005;76(6):882-4. [Medline].
Wingerchuk DM, Noseworthy JH, Kimmel DW. Paraneoplastic encephalomyelitis and seminoma: importance of testicular ultrasonography. Neurology. Nov 1998;51(5):1504-7. [Medline].
Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. May 4 2007;2:22. [Medline].
Dropcho EJ. Paraneoplastic Diseases of the Nervous System. Curr Treat Options Neurol. Nov 1999;1(5):417-427. [Medline].
Keime-Guibert F, Graus F, Broet P, et al. Clinical outcome of patients with anti-Hu-associated encephalomyelitis after treatment of the tumor. Neurology. Nov 10 1999;53(8):1719-23. [Medline].
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. Apr 2000;68(4):479-82. [Medline].
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. Jan 2006;253(1):16-20. [Medline].
Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. Aug 2005;128(Pt 8):1764-77. [Medline].
Bakheit AM, Kennedy PG, Behan PO. Paraneoplastic limbic encephalitis: clinico-pathological correlations. J Neurol Neurosurg Psychiatry. Dec 1990;53(12):1084-8. [Medline].
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. Apr 15 2007;22(5):736-8. [Medline].
Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain. Aug 2004;127(Pt 8):1831-44. [Medline].
de Beukelaar JW, Sillevis Smitt PA. Managing paraneoplastic neurological disorders. Oncologist. Mar 2006;11(3):292-305.
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. Dec 2007;14(12):1383-91. [Medline].
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. Mar 2008;195(1-2):164-70. [Medline].
Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. Jul 2000;123 ( Pt 7):1481-94. [Medline].
Inuzuka T. Autoantibodies in paraneoplastic neurological syndrome. Am J Med Sci. Apr 2000;319(4):217-26. [Medline].
Provenzale JM, Barboriak DP, Coleman RE. Limbic encephalitis: comparison of FDG PET and MR imaging findings. AJR Am J Roentgenol. Jun 1998;170(6):1659-60. [Medline].
Sabater L, Gomez-Choco M, Saiz A, Graus F. BR serine/threonine kinase 2: a new autoantigen in paraneoplastic limbic encephalitis. J Neuroimmunol. Dec 30 2005;170(1-2):186-90. [Medline].
Scaravilli F, An SF, Groves M, Thom M. The neuropathology of paraneoplastic syndromes. Brain Pathol. Apr 1999;9(2):251-60. [Medline].
Tani T, Tanaka K, Idezuka J, Nishizawa M. Regulatory T cells in paraneoplastic neurological syndromes. J Neuroimmunol. May 30 2008;196(1-2):166-9. [Medline].
Vincent A. Antibodies associated with paraneoplastic neurological disorders. Neurol Sci. May 2005;26 Suppl 1:S3-4. [Medline].
Vincent A, Buckley C, Schott JM, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. Mar 2004;127(Pt 3):701-12. [Medline].
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. Jun 10 1999;340(23):1788-95. [Medline].
Further Reading
Keywords
anti-Hu syndrome, anti-Hu–associated paraneoplastic encephalomyelitis, paraneoplastic limbic encephalitis, paraneoplastic limbic encephalopathy, paraneoplastic brainstem encephalopathy, paraneoplastic myelopathy, subacute sensory neuronopathy, SSN, paraneoplastic ganglioradiculoneuritis, paraneoplastic sensory neuropathy, paraneoplastic encephalomyelitis, PEM, multifocal inflammatory CNS disorder
