Paraneoplastic Neurologic Syndromes

A paraneoplastic neurologic syndrome (PNS) is an immune-mediated injury to the nervous system that occurs because tumour cells display antigens resembling proteins in neurons or synapses. The anti-tumour response then cross-reacts with neural tissue. The neurologic disorder is not caused by tumour invasion, metastasis, a metabolic derangement, infection, stroke, chemotherapy, radiation or another treatment toxicity. The neurologic syndrome may be the first sign of cancer. A patient can develop rapidly progressive neurologic symptoms months before the tumour becomes visible, so an unexplained subacute decline over days to weeks deserves both neurologic assessment and a search for malignancy. The type of neural antigen helps predict reversibility: - Intracellular-antigen antibodies include Hu, Yo, CV2/CRMP5, Ma2, amphiphysin and SOX1. They are usually markers of cytotoxic T-cell injury. Neurons may be permanently lost, so neurologic deficits often stabilize rather than reverse, and immunotherapy response is limited. - Cell-surface or synaptic antibodies include NMDAR, LGI1, CASPR2, AMPAR and GABA-B receptor antibodies. These antibodies can directly disrupt neuronal signalling and are more likely to respond to immunotherapy. This distinction changes the clinical conversation. A patient with...