Clinical and pathological advances on central nervous system paraneoplastic syndromes

In the last decade, several features have improved our knowledge of CNS paraneoplastic syndromes. Patients with paraneoplastic cerebellar degeneration (PCD) and breast or ovarian cancer, but not with other tumors, harbor an antibody against Purkinje cells (called anti-Yo). Clinical features of anti-Yo positive and negative PCD are similar but the latter may have a less progressive clinical course with occasional remissions. In addition to the association of opsoclonus with neuroblastoma, this syndrome has been identified in patients with breast or small-cell lung cancer (SCLC). Patients with opsoclonus and breast cancer have an antineuronal antibody (called anti-Ri) not present if opsoclonus is associated with SCLC or neuroblastoma. Paraneoplastic encephalomyelitis (PEM) is almost always associated with SCLC. Most patients present with sensory neuronopathy, limbic or brainstem encephalitis but involvement of multiple levels is usual. An antibody (called anti-Hu) against neuronal nuclear antigens is present in patients with PEM and SCLC. Autopsy studies demonstrate deposits of anti-Hu specific IgG in the neurons and a predominance of T cells in the inflammatory infiltrates. Treatment of the tumor and immunosuppressors are effective in opsoclonus whereas patients with PCD or PEM with circulating antibodies do not improve.