To highlight a rare case of CASPR2 associated paraneoplastic encephalitis presenting as chronic chorea in the setting of an underlying testicular germ cell tumor.

A 55-year-old man with a history of biopsy-confirmed sarcoidosis and diabetes mellitus presented with a two-year history of involuntary movements that initially involved his left leg, before spreading to his other limbs and torso. Additional symptoms included stuttering speech, paraphasic errors, cognitive and executive dysfunction, irritability, and inattention. Neurological examination demonstrated mild dysarthria, motor impersistence with tongue protrusion, and choreiform movements in all extremities. He was adopted and had no prior exposure to dopamine receptor blocking agents. While undergoing initial diagnostic workup, empirical treatment with Deutetrabenazine was initiated with partial benefit. 

He underwent an extensive workup, including serologic testing with ceruloplasmin levels, Anti-phospholipid syndrome antibodies, and smear testing for acanthocytosis, all of which were unremarkable. His MRI did not reveal any structural abnormalities or areas of enhancement. His Huntington's disease and DRPLA gene panel returned negative. Eventually, his serum paraneoplastic panel returned with positive for Contactin associated protein like -2 (CASPR2),1:40. He was initiated on IVIG and underwent a PET scan that showed avid uptake in the right testicle. The patient underwent orchiectomy with biopsy consistent with germ cell tumor. On follow-up post chemotherapy, his chorea drastically improved.

CASPR2 is part of the VGKC protein complex and is ubiquitously present in the central and peripheral nervous system. CASPR2 antibody-associated disease typically manifests as limbic encephalitis, and neuromyotonia. It is most frequently associated with thymoma and lung adenocarcinoma. This case further demonstrates the male predominance and prolonged disease course observed with CASPR2 antibodies compared to other antibody-mediated disorders. It also highlights an uncommon association between CASPR2 antibody, chorea, and an underlying testicular germ cell tumor.