Central neurological paraneoplastic syndromes. Part 1. Clinical features, pathophysiology and immunopharmacology

Neurological paraneoplastic syndromes, sometimes called remote effects of cancer on the nervous system, are rare but important and often devastating complications of cancer. The immunological theory of causation is supported by many different lines of evidence and reasoning which implicate abnormalities of both humoral and cellular immunity. The targets of immunologically mediated injury, although remote from the tumor, may be hard hit and irreversibly damaged, giving rise to discrete syndromes of motor or cognitive impairment. In the CNS, they are neuronal nuclei, cerebellar Purkinjie cells and cell surface glutamate receptors. Although central paraneoplastic neurological syndromes may occur in children or adults, the clinical syndromes and response to treatment differ substantially between the two groups. The current therapeutic armamentarium provides a broad spectrum of nonselective immunotherapies including noncytotoxic and cytotoxic drugs, intravenous immunoglobulins and plasma exchange, some selected for induction and others for maintenance. Combination immunotherapies allow steroid sparing and targeting of more than one immunologic effector pathway, and deploy an advantageous mixture of early- and late-acting drugs. More selective and efficacious immunotherapies are needed.