In 1988 and 1991, Budde-Steffen at al [5
] and Luque et al [6
] described a subpopulation of patients with opsoclonus and a history of breast cancer in whose serum and CSF were identified an antibody that reacted against 55 kD and 80 kD proteins that were designated Anti-Ri (also known as ANNA-2). It has since been shown that these antigens are highly conserved but widely distributed central nervous system neuronal proteins which are encoded by the Nova-1
genes and which may play a role in neuronal maturation and homeostasis [7
]. As those seminal reports indicate, Anti-Ri was initially associated with opsoclonus/myoclonus and cerebellar ataxia symptomatology in patients with breast and gynecologic cancers. They have however subsequently been associated with a wide variety of malignancies that have included lung, gastric and bladder carcinomas [10
]. Indeed, in one study, 32% and 36% of cancers associated with anti-Ri in patients with suspected PNS were breast and lung carcinomas respectively [10
]. The spectrum of associated neurologic symptoms has also expanded considerably and now includes vertigo, muscle weakness, dysarthria, dysphagia, dementia, deafness, myelopathy, opthalmoplegia, encephalomyelitis, rigidity, nausea, myelopathy, sensorimotor neuropathy [10
]. What these cases illustrate is that with a few exceptions [4
], the vast majority of tumors associated with PNS-neurological disorders are malignant. Our case thus highlights the potential association between a benign neoplasm and the presence of these antibodies and neuronal symptomatology.
Is it possible that the presence of the autoantibody and the ovarian tumor are completely fortuitous?. Given the temporal relationship between the resolution of her symptoms and the sharp decrease in her anti-Ri titer following her surgery, we believe this is unlikely. However, the precise mechanistic basis for this association as well as potential influence of outside factors remains to be elucidated. It should also be noted that high titers of Anti-Ri have been identified in patients with a history of ovarian cancer but without any evidence of a PNS, suggesting caution in assessing the specificity of this auto-antibody for PNS.
In summary, we describe in this report an association of a common anti-neuronal antibody (anti-Ri) in a patient with a benign neoplasm, mature cystic teratoma of the ovary, and whose neurologic symptoms, short-term memory deficits, was apparently associated with her tumor. Although, Anti-Ri antibodies are typically associated with malignancies, this case illustrates the potential association between benign tumors and this autoantibody.