Case Presentation: An 89 year-old female with hyperlipidemia presented with diplopia, vertigo, and dysarthria. Seven weeks prior to presentation, she developed horizontal diplopia. Four weeks prior, she noted vertigo with no hearing loss, tinnitus, or aural fullness. Two weeks prior, her speech became slurred. She presented to an outside hospital where MRI with contrast was normal and acetylcholine receptor antibody binding was normal. She was started on pyridostigmine with no noted improvements. On physical exam, the patient was dysarthric with difficulty stating “baba” and “mama” but retained ability to repeat “lala” and “tata.” Nystagmus with slow phase to right exacerbated on left, right, and upward gaze, was noted. She also exhibited dysdiadochokinesia, worse on the right, and struggled with tandem gait with falls to the right on regular gait testing. Three brain MRIs, chest radiograph, and 2 lumbar punctures were within normal limits. Flow cytometry showed a mixed lymphoid population with CD4 predominant T cell population. Paraneoplastic panel was drawn but did not result prior to treatment initiation. CT and PET showed enlarged left supraclavicular lymph node, internal mammary lymph nodes, anterior diaphragmatic lymph nodes, and retroperitoneal lymph nodes, but no primary source of malignancy. Lymph node biopsy revealed cells positive for CK7, PAX8, and p53. Tumor markers were then obtained which showed CA-125 elevated to 3214, consistent with ovarian cancer. After her hospitalization, anti-Yo antibodies were found to be elevated at 1:1024. The patient has since received chemotherapy with carboplatin/paclitaxel with reduction of CA-125 to 12, but neurologic symptoms have persisted.

Discussion: Paraneoplastic cerebellar degeneration is typically associated with lung cancer, gynecologic and breast cancer, and lymphoma. The presence of anti-Yo antibodies is typically associated with ovarian malignancy. Anti-Yo IgG binds to an intracellular Purkinje cell protein. On biopsy, there is marked degeneration of Purkinje cells with minimal involvement of molecular or granular layers. 60-70% of patients do not have a cancer diagnosis at their initial presentation, so they often may not present to an oncology or general medicine service. As in this patient, symptoms worsen for weeks to months. Earlier diagnosis can prevent progression of the underlying malignancy. 75-80% of patients become non-ambulatory even with treatment of the underlying malignancy.

Conclusions: Paraneoplastic cerebellar degeneration due to anti-Yo antibodies is frequently related to ovarian cancer. However, the paraneoplastic panel can take weeks to result and diagnosis should not be delayed. If an underlying malignancy cannot be found on CT scan, other methods of diagnosis such as lymph node biopsy and tumor markers should be pursued. Despite treatment, it is unlikely that neurologic symptoms will resolve.