Anti-Yo paraneoplastic cerebellar degeneration (PCD) typically occurs in patients with breast or gynecologic malignancies. Supportive Oligonucleotide Therapy (SOT) is an unapproved alternative cancer treatment marketed as a gene-targeted therapy, for which no peer-reviewed  safety data are available. We report the case of a patient who developed rapidly neurologic decline shortly after SOT exposure.

Case Report: 

 A 70-year-old woman with HER2-positive breast carcinoma underwent partial mastectomy followed by adjuvant chemotherapy, achieving remission. Ten days after receiving an experimental SOT infusion, she developed blurred vision, diplopia, dizziness, and progressive gait instability. Neurological examination revealed vertical nystagmus, dysmetria, and dysarthria, although brain MRI with contrast was unrevealing. CSF analysis demonstrated a mild lymphocytic pleocytosis and elevated protein levels, as well as increased IgG index, and the presence of thirteen oligoclonal bands. The CSF paraneoplastic antibody panel was positive for high-titers of anti-Yo (PCA-1 1:1024) and anti-GFAP (1:128), while whole-body PET/CT showed no evidence of tumor recurrence. The patient was treated with intravenous methylprednisolone, immunoglobulin, and five plasma exchange sessions, resulting in partial stabilization. At two-month follow-up, her neurological condition remained largely unchanged.

Discussion: 

 Although causality cannot be definitively established, the close temporal association between SOT infusion and symptom onset, the presence of dual intrathecal antibody positivity, and the absence of tumor recurrence suggest that immune activation may have been triggered or unmasked by SOT. Anti-Yo-associated PCD carries a poor prognosis despite aggressive immunotherapy, as cytotoxic T-cell-mediated injury leads to irreversible Purkinje cell loss. Early recognition and immunotherapy may stabilize progression but rarely result in full neurologic recovery.

Conclusion: 

 Experimental cancer therapies may carry unforeseen risks, warranting neuroimmunologic evaluation for paraneoplastic or autoimmune syndromes when new neurologic symptoms arise. Stronger regulatory oversight and mechanistic studies are needed to clarify the immune effects of experimental oligonucleotide therapies.