Paraneoplastic Diseases of the Nervous System

Several neurologic paraneoplastic disorders are believed to be caused by an autoimmune reaction against an antigen or antigens coexpressed by tumor cells and neurons. Of the paraneoplastic syndromes, the Lambert-Eaton myasthenic syndrome (LEMS)--in which autoantibodies downregulate voltage-gated calcium channels at the presynaptic nerve terminal--is associated with the strongest evidence of an autoimmune cause. For the other syndromes, including cerebellar degeneration, multifocal encephalomyelitis, sensory neuronopathy, limbic encephalitis, opsoclonus-myoclonus, and retinal degeneration, an autoimmune cause is indicated by the presence of specific anti-neuronal antibodies. These antibodies serve as a useful diagnostic tool, but their actual role in causing neuronal injury and clinical disease remains unclear. A small percentage of patients with paraneoplastic disorders shows major neurologic improvement after successful treatment of the associated tumor. Of patients who require further therapy for the neurologic disorder, those with LEMS have the best outcome. The response to immunosuppression among patients with paraneoplastic central nervous system (CNS) dysfunction is much less favorable. Although exceptions clearly exist, most patients with CNS paraneoplastic disorders do not improve despite tumor treatment and immunosuppressive therapy. It is likely that many patients already have irreversible neuronal injury at the time of diagnosis. The decision to attempt immunosuppressive treatment must be made on an individual basis.