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Table of Contents    
Year : 2011  |  Volume : 59  |  Issue : 6  |  Page : 912-913

Anti-Ma2-positive paraneoplastic brainstem encephalitis associated with prostatic adenocarcinoma

Department of Neurology, Faculty of Neurology, Lund University Hospital, Lund, Sweden

Date of Submission30-Sep-2011
Date of Decision01-Oct-2011
Date of Acceptance10-Oct-2011
Date of Web Publication2-Jan-2012

Correspondence Address:
Bengt Edvardsson
Department of Neurology, Faculty of Neurology, Lund University Hospital, Lund
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.91381

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How to cite this article:
Edvardsson B. Anti-Ma2-positive paraneoplastic brainstem encephalitis associated with prostatic adenocarcinoma. Neurol India 2011;59:912-3

How to cite this URL:
Edvardsson B. Anti-Ma2-positive paraneoplastic brainstem encephalitis associated with prostatic adenocarcinoma. Neurol India [serial online] 2011 [cited 2020 Aug 11];59:912-3. Available from:


Paraneoplastic neurological syndromes (PNS) are considered to be autoimmune-mediated disorders of the nervous system. In 1999, Voltz [1] detected an antibody against the Ma2 protein in tumors as well as in normal brain tissue of patients with paraneoplastic limbic/brainstem encephalitis and germ cell cancer. PNS are seldom associated with prostate cancer, and paraneoplastic brainstem encephalitis due to prostate cancer is very uncommon. Brainstem, diencephalic and limbic encephalopathy are associated with Ma2 antibodies. Prostate cancer alone has not been associated with anti-Ma2 antibodies.

A 62-year-old man, a diagnosed case of local adenocarcinoma of prostate, presented with diplopia and dysarthria of three weeks' duration. Neurologic examination revealed left sixth nerve palsy, right fourth nerve palsy, bilateral ptosis, vertical gaze palsy, facial diplegia, hoarseness of voice, dysarthria and dysphagia. Cerebrospinal fluid (CSF) examination was normal and no oligoclonal bands were found. Laboratory evaluation for sarcoidosis, borrelia, Wegener's granulomatosis, HIV types 1 and 2, varicella-zoster and HHV-6 was negative. Electrophysiological investigations were normal. An initial contrast brain magnetic resonance imaging (MRI) and a repeat contrast MRI after one month were normal. A whole-body computed tomography (CT) scan revealed no abnormality. Recombinant immunoblotting was negative against Hu/Yo/Ri/CV2/amphiphysin/Ma1/Tr antibodies but was positive against Ma2 in serum and CSF. The positive antibody test result was confirmed in an independent laboratory. His prostate-specific antigen (PSA) was 2.0 (normal <4 μg/L). Carcinoembryonic antigen (CEA), beta human chorionic gonadotropin (ί-HCG) and alpha-fetoprotein (AFP) were normal. Testicular ultrasound was normal. MRI of the testicles/pelvis and abdomen/chest displayed normality. Positron-emission tomography (PET) CT, whole-body 18- fluorodeoxyglucose-PET/CT revealed no evidence of testicular tumor or disseminated prostate cancer or other tumors. A bone scan and a spinal MRI were normal. Corticosteroids and plasmapheresis improved his symptoms. He remains symptom-free.

The case study highlights a patient with brainstem encephalitis and prostate cancer where evaluations revealed Ma2 antibodies. Paraneoplastic brainstem encephalitis associated with prostate cancer is very rare. In 1993, Baloh [2] reported two patients with unusual brainstem syndromes associated with prostate cancer, and CSF in both the patients showed mild pleocytosis and elevated immunoglobulin G. No paraneoplastic antibodies were detected. Berger [3] described a patient with a paraneoplastic brainstem syndrome associated with prostate cancer. The authors for the first time demonstrated an antibody in both serum and CSF directed against intraneuronal antigens, but the target antigen was not identified. Clinically, Ma2 antibodies have been correlated with symptoms associated with limbic, diencephalic, or brainstem encephalopathy. [4] Dalmau [5] studied the clinical findings of cancer patients with anti-Ma2-associated encephalitis. The majority of the patients developed symptoms of limbic, diencephalic or brainstem dysfunction. In the study by Gultekin [6] patients with anti-Ma2 antibodies were young men with testicular germ-cell tumors (100%) and with frequent hypothalamic involvement and a poor neurological outcome. Thus testicular carcinoma should be ruled out in younger men displaying a Ma2 paraneoplastic syndrome. In men over 50 years old and in women other tumors such as lung cancer and breast cancer should be excluded. [7] The presence of prostate cancer and of Ma2 antibodies proves paraneoplastic etiology as the cause of the brainstem encephalitis. [8]

In conclusion, this case study strongly suggests an association between the patient's Ma2 antibodies and the prostate cancer. However, it cannot be proved, based on this case, whether the anti-Ma2 reactivity in this patient is specific for prostate cancer or not. The detection of anti-Ma2 reactivity in an older male with unexplained subacute predominant upper brainstem dysfunction should exclude adenocarcinoma of the prostate as a diagnostic consideration.

 » References Top

1.Voltz R. Paraneoplastic neurological syndromes: an update on diagnosis, pathogenesis, and therapy. Lancet Neurol 2002; 1:294-305.  Back to cited text no. 1
2.Baloh RW, DeRossett SE, Cloughesy TF, Kuncl RW, Miller NR, Merrill J, et al. Novel brainstem syndrome associated with prostate carcinoma. Neurology 1993; 43:2591-6.  Back to cited text no. 2
3.Berger JR, Bensalem M, Dalmau J. A brainstem paraneoplastic syndrome associated with prostate cancer. J Neurol Neurosurg Psychiatry 2009; 80:934-5.  Back to cited text no. 3
4.Schüller M, Jenne D, Voltz R. The human PNMA family: Novel neuronal proteins implicated in paraneoplastic neurological disease. J Neuroimmunol 2005; 169:172-6.  Back to cited text no. 4
5.Dalmau J, Graus F, Villarejo A, Posner JB, Blumenthal D, Thiessen B. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127:1831-44.  Back to cited text no. 5
6.Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000; 123:1481-94.  Back to cited text no. 6
7.Sutton I, Winer J, Rowlands D, Dalmau J. Limbic encephalitis and antibodies to Ma2: A paraneoplastic presentation of breast cancer. J Neurol Neurosurg Psychiatry 2000; 69:266-8.  Back to cited text no. 7
8.Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 2004; 75:1135-40.  Back to cited text no. 8

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