Paraneoplastic syndromes: an unsolved murder

With neuroimmunology playing an ever greater role in child neurology, paraneoplastic syndromes--uncommon but often devastating complications of cancer--are in the forefront. Abnormalities of both humoral and cellular immunity support the immunological theory of causation. Through co-complicity of host and tumor factors, targets of immunologically mediated injury remote from the tumor may be damaged or destroyed, giving rise to discrete neurological deficits. In the nervous system, the main targets are neuronal nuclei or cell bodies, structural constituents, surface receptors, synapses, and ion channels. The clinical syndromes and response to treatment differ substantially between children and adults. Current pharmacological and biological therapies, which are nonselective, include noncytotoxic and cytotoxic drugs, intravenous immunoglobulins, plasma exchange, and immunoadsorption, some chosen for induction and others for maintenance. Tumor resection and thymectomy are surgical treatments. Combination immunotherapies allow steroid sparing, 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.