Fulminant paraneoplastic Ma2 (PNMA2) and zinc finger protein of the cerebellum 4 (ZIC4) antibody-positive encephalitis in triple-negative breast cancer treated with pembrolizumab.

Paraneoplastic neurological syndromes (PNS) associated with triple-negative breast carcinoma (TNBC) are exceptionally rare. We report a case of fulminant encephalitis in a middle-aged woman with TNBC presenting with concurrent PNMA2 (Ma2/Ta), ZIC4 and recoverin antibody positivity. The patient initially developed a subacute cerebellar syndrome characterised by downbeat nystagmus, gait ataxia and diplopia. Comprehensive evaluation revealed FDG-avid left axillary lymphadenopathy and biopsy confirmed high-grade TNBC with PD-L1 CPS of 77. She received neoadjuvant chemo-immunotherapy as per standard institutional protocol (paclitaxel, carboplatin, epirubicin, cyclophosphamide and pembrolizumab). Following the sixth cycle, she developed refractory focal seizures progressing to status epilepticus with MRI findings consistent with cortical encephalitis. Despite aggressive immunosuppression including corticosteroids, intravenous immunoglobulin and rituximab, her condition proved refractory. She ultimately succumbed despite maximal supportive care. This case illustrates a rare paraneoplastic overlap syndrome combining PNMA2-associated encephalitis and ZIC4-associated cerebellar degeneration in TNBC, highlights diagnostic challenges when immune checkpoint inhibitors may amplify pre-existing onconeural immunity and underscores the dismal prognosis of intracellular antibody-mediated neurological syndromes despite aggressive immunotherapy.