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Anti-Ma2 Antibody Paraneoplastic Cerebellar Degeneration Associated with Renal Cell Carcinoma: A Case Report.

K. Zahra, N. Ahmed, D. Sivakumar, E. Urrea-Mendoza, V. Veerappan (Greenville, USA)

Meeting: 2022 International Congress

Abstract Number: 434

Keywords: Ataxia: Clinical features, Cerebellum

Category: Ataxia

Objective: To highlight a unique case of Anti-Ma2 antibody paraneoplastic cerebellar degeneration (PCD) associated with renal cell carcinoma (RCC).

Background: Paraneoplastic neurologic syndromes are a group of immune mediated disorders that can have a multitude of presentations including limbic encephalitis, PCD, and polyneuropathy. PCD is a rare presentation of a rapidly progressive ataxia associated with variety of antibodies. In 0.5-1% of patients, anti-Ma2 antibody has been known to cause PCD in the setting of neoplasms (1).

Method: Case report.

Results: A 70-year-old male presented with three-month history of progressive gait difficulty, poor balance and recurrent falls. Past medical history pertinent for metastatic RCC, for which he underwent a total left nephrectomy, radiation therapy and chemotherapy with nivolumab and axitinib. During initial neurologic evaluation, he was noted to have end-gaze nystagmus, limb dysmetria, truncal ataxia and wide based ataxic gait. Nivolumab and axitinib were discontinued at the onset of symptoms. Work-up demonstrated cerebellar atrophy and cerebrospinal fluid (CSF) studies revealed mildly elevated protein and oligoclonal bands. He was hospitalized one month after initial neurology evaluation for rapidly worsening ataxia. Repeat serum and CSF studies were positive for anti-Ma2 antibodies. He underwent 5 sessions of plasmapheresis with minimal improvement. Despite treatment, disease continued to progress with patient becoming wheelchair bound. Further treatment with immunotherapies were discussed, but patient elected to pursue palliative care.

Conclusion: Anti-Ma2 antibodies have been well characterized in PCD in the setting of neoplasms (1). Immune checkpoint inhibitors (ICI) have also been associated with anti-Ma2 antibodies, causing immune related adverse events including encephalitis and cranial neuropathies (2-4). Nivolumab has been reported with cerebellar ataxia in the absence of anti-Ma2 antibodies with symptoms starting shortly after the initiation of therapy. However, symptoms improved after discontinuation of nivolumab and treatment with steroids (5). In our case, symptoms started almost one year after the initiation of ICI and patient continued to decline even after discontinuation of ICI. This presentation demonstrates a unique case of anti-Ma2 antibody PCD associated with RCC.

References: 1. Sadeghian H, Vernino S. Progress in the management of paraneoplastic neurological disorders. Ther Adv Neurol Disord. 2010 Jan;3(1):43-52. doi: 10.1177/1756285609349521. PMID: 21180635; PMCID: PMC3002612.
2. Vogrig A, Fouret M, Joubert B, Picard G, Rogemond V, Pinto AL, Muñiz-Castrillo S, Roger M, Raimbourg J, Dayen C, Grignou L, Pallix-Guyot M, Lannoy J, Ducray F, Desestret V, Psimaras D, Honnorat J. Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors. Neurol Neuroimmunol Neuroinflamm. 2019 Aug 7;6(6):e604. doi: 10.1212/NXI.0000000000000604. PMID: 31454760; PMCID: PMC6705619.
3. Dalmau J, Graus F, Villarejo A, Posner JB, Blumenthal D, Thiessen B, Saiz A, Meneses P, Rosenfeld MR. Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004 Aug;127(Pt 8):1831-44. doi: 10.1093/brain/awh203. Epub 2004 Jun 23. PMID: 15215214.
4. Ortega Suero G, Sola-Valls N, Escudero D, Saiz A, Graus F. Anti-Ma and anti-Ma2-associated paraneoplastic neurological syndromes. Neurologia (Engl Ed). 2018 Jan-Feb;33(1):18-27. English, Spanish. doi: 10.1016/j.nrl.2016.05.010. Epub 2016 Jul 25. PMID: 27460184.
5. Kawamura R, Nagata E, Mukai M, Ohnuki Y, Matsuzaki T, Ohiwa K, Nakagawa T, Kohno M, Masuda R, Iwazaki M, Takizawa S. Acute Cerebellar Ataxia Induced by Nivolumab. Intern Med. 2017;56(24):3357-3359. doi: 10.2169/internalmedicine.8895-17. Epub 2017 Dec 15. PMID: 29249765; PMCID: PMC5790727.

To cite this abstract in AMA style:

K. Zahra, N. Ahmed, D. Sivakumar, E. Urrea-Mendoza, V. Veerappan. Anti-Ma2 Antibody Paraneoplastic Cerebellar Degeneration Associated with Renal Cell Carcinoma: A Case Report. [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/anti-ma2-antibody-paraneoplastic-cerebellar-degeneration-associated-with-renal-cell-carcinoma-a-case-report/. Accessed May 21, 2025.
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