To present a rare case of TRIM9 antibody-mediated paraneoplastic cerebellar degeneration (PCD), highlighting the diagnostic journey, treatment response, and imaging findings.

Tripartite motif-containing (TRIM) protein 9 and 67 are recently characterized autoantibody targets identified in fewer than 15 PCD cases. Associated cancers include lung adenocarcinoma, melanoma, breast cancer, and small-cell lung cancer, frequently with metastatic disease at PCD onset. Cases are generally treatment-resistant. MRI findings are highly variable. Although the predominant phenotype is a pan-cerebellar syndrome, limbic encephalitis has also been reported.

A 66-year-old man with stage IV lung adenocarcinoma, diagnosed two years prior, presented with subacute pancerebellar syndrome. CSF showed mild lymphocytic pleocytosis. Initial serum paraneoplastic testing returned positive GABA-B titers (1:15360), though CSF titers were significantly lower (<1:240). Co-existing Calmodulin Kinase-like Vesicle-Associated (CAMKV) and TRIM9 antibodies were identified on a research basis. Treatment with IVIg, corticosteroids, plasma exchange, and rituximab produced no meaningful neurological improvement. Serial MRIs demonstrated progressive diffuse cerebellar atrophy without enhancing lesions. The patient remains alive 2 years after symptom onset, although severely debilitated with a Modified Rankin Scale of 4.

This case adds to the limited clinical characterization of TRIM9 antibody-mediated PCD. Consistent with prior reports, our patient had metastatic lung adenocarcinoma at diagnosis, reinforcing the association between tumor burden and type with this antibody. The treatment-resistant course underscores the poor prognosis. Notably, the co-occurrence of CAMKV and GABA-B antibodies with TRIM9 has not been previously described. Furthermore, neither CAMKV nor GABA-B have been associated with an isolated PCD phenotype, reinforcing the pathogenic role of TRIM9 in this presentation. The initial reported GABA-B titers highlights the importance of critically evaluating antibody panel results when clinical presentation and antibody phenotype are discordant.