SUBACUTE CEREBELLAR DEGENERATION WITH ANTI-YO AUTOANTIBODIES - IMMUNOHISTOCHEMICAL ANALYSIS OF THE IMMUNE-REACTION IN THE CENTRAL-NERVOUS-SYSTEM

We report the pathological findings of a woman with a sub-acute cerebe llar syndrome who had undergone surgery 3 years before for endometrial carcinoma. Both serum and cerebrospinal fluid contained high titres o f autoantibodies against the cytoplasm of Purkinje cells that recogniz ed a band of 62 kDa on immunoblotting of neuronal extracted proteins ( pattern anti-Yo). No tumour was found despite a full range of gynaecol ogical investigations; the neoplastic marker CA125 was slightly elevat ed and oligoclonal bands were detected in the cerebrospinal fluid. The patient died from acute myocardial infarction 4 months after developi ng this syndrome. At autopsy, no macroscopic evidence of tumour was ob tained and the brain showed no abnormalities. On microscopic examinati on of the central nervous system diffuse degeneration of Purkinje cell s could be seen throughout the cerebellum. Immunohistochemical analysi s showed a CD8 lymphocyte infiltration in the cerebellum and cerebral cortex and diffuse microglial activation throughout the brain, These c ells expressed high levels of MHC-II antigens on their cell membranes. The serum autoantibodies reacted with the cytoplasm of the remaining Purkinje cells. The short interval between the onset of symptoms and d eath of the patient could explain the difference between our findings and those reported in the literature in which no inflammatory infiltra tes were detected. The immunohistochemical findings as well as the inf lammatory cerebrospinal fluid profile seen in our case seem to support the concept that in paraneoplastic cerebellar degeneration with anti- Yo antibodies, an immune mediated mechanism is responsible for the dam age to the cerebellum.