Paraneoplastic neurological syndromes: an update on incidence, antibody discovery, and testing

This review aims to provide a summary of the latest novelties in the field of paraneoplastic neurological syndromes (PNS), emphasizing relevant clinical updates on epidemiology, antibody discovery, and testing.

Population-based studies have provided estimates of PNS incidence in the United States and Europe. A wider availability of commercial and in-house antibody testing, together with the discovery of novel antibodies, was pinpointed as a possible reason for the progressive increase in PNS incidence observed in recent years. Updated diagnostic criteria for PNS diagnosis published in 2021 were validated in cohorts of adults and children, showing improved sensitivity and similar specificity compared to the 2004 criteria. Laboratory studies have highlighted the pitfalls of commercial and in-house assays for antibody detection, underscoring the importance of sample referral to reference centers for additional analyses in selected cases. Novel antibodies to intracellular and cell-surface antigens associated with paraneoplastic encephalitis (NIF, ZSCAN1, septin-7, PDE10A, CAMKV), cerebellar syndrome (e.g. TRIM46, TRIM9/67, SEZ6L2, RGS8, mGluR2), and brainstem encephalitis (KELCH11, LUZP4) were described and related to recurring cancer types, expanding the PNS spectrum.

The present review provides an update on PNS, including novel antibodies and phenotypes.