Pearls & Oy-sters: Gait Instability, Jaw Dystonia, and Horizontal Diplopia in a Woman with Anti-Ri Antibodies and Breast Cancer

A 40-year-old woman was admitted for 6 months of progressive gait disturbance, lower limb-predominant weakness, stiffness, falls, jaw dystonia, horizontal diplopia, and weight loss. Neurologic examination revealed horizontal gaze paresis, limited jaw opening with palpable masseter hypertrophy, and spastic paraparesis with sustained clonus and upgoing plantar responses. MRI revealed T2-hyperintense signal abnormalities in the dorsal pons, medulla, and upper cervical cord central gray matter extending to C3, without gadolinium enhancement. CSF showed mildly elevated protein and immunoglobulin (IgG) index with CSF-specific oligoclonal bands. Neural autoantibody testing was positive for anti-Ri in CSF and serum by mouse brain indirect immunofluorescence and immunoblot. Testing for aquaporin-4 (AQP4)-IgG and myelin oligodendrocyte glycoprotein (MOG)-IgG by cell-based assay was negative. The patient received methylprednisolone 1 g for 5 days and IV immunoglobulin 2 g/kg over 2 days with prednisone taper and botulinum toxin injections for jaw dystonia. PET-CT revealed an enlarged left axillary lymph node with high FDG uptake. Left axillary lymph node biopsy confirmed high-grade, locally invasive breast adenocarcinoma. Neurologic stabilization was documented at 2-week follow-up after hospital discharge before modified radical mastectomy. Our case demonstrates a clinical triad highly suggestive of anti-Ri-associated paraneoplastic neurologic syndrome (Ri-PNS): gait instability, jaw dystonia, and horizontal gaze paresis. The more slowly progressive course and poor response to immunotherapy help distinguish it from AQP4-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD) and MOG-IgG-associated disease (MOGAD) that share similar radiographic features. Early diagnosis, prompt immunotherapy, and cancer treatment are paramount for disease stabilization

Autoimmune-associated seizure disorders

With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA-receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T-cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune-associated seizure disorders