Among Abs carrying a high risk for paraneoplastic neurological syndromes (PNS), anti-Yo-Abs are mostly detected in women with gynecological malignancies who develop a paraneoplastic cerebellar degeneration (PCD). 

Yo-Abs were initially detected in serum and cerebrospinal fluid (CSF) samples by commercial line dots (RAVO diagnostika and Euroimmun) and further confirmed with in-house techniques: immunohistochemistry on rat brain sections, cell-based assay and Western blot for cerebellar degeneration-related 2 (CDR2) and CDR2-like (CDR2L) proteins.

Three patients were referred to the French national reference center for PNS: 59-year-old woman and 60-year-old man with lung adenocarcinoma, and 63-year-old woman with ovarian adenocarcinoma, all developing the first neurological symptoms within 3 months of ICI (pembrolizumab) first dose. The woman with ovarian cancer and the man with lung adenocarcinoma had a PCD, while the woman with lung cancer had a myelitis. In all patients, CSF analysis disclosed pleocytosis and brain magnetic resonance imaging was normal. Yo-Abs were retrospectively detected in pre-ICI serum samples in the patient with ovarian cancer. Management consisted of permanent ICI discontinuation (3/3) and immunomodulation, including corticosteroids (3/3), immunoglobulins (2/3), rituximab (1/3), or cyclophosphamide (1/3). No patient substantially improved (modified Rankin Score pre- and post-treatment 4). In all cases, cancer progressed after ICI discontinuation and at last follow-up (4-16 months after neurological onset) the two patients with PCD were dead and the one with myelitis was in palliative care.