Dawit, Sara

Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by “dancing” eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.

Abstract INTRODUCTION Opsoclonus–myoclonus syndrome (OMS) is a rare neurological disorder characterized by spontaneous multidirectional saccadic eye movements, myoclonus, and ataxia. It is suspected to be an autoimmune mediated process precipitated by a paraneoplastic or infectious trigger. Among the pediatric population, OMS is often associated with neuroblastoma and anti-Hu antibody. Paraneoplastic syndromes in adults manifesting as OMS are most commonly described in breast, gynecological and small cell lung cancer with associated anti-neuronal antibodies (ANNA-2; anti-Ri). We describe the first case of OMS associated with lung adenocarcinoma and Contactin-associated protein-like 2 (Caspr2) antibody. CASE REPORT: A 46-year-old-woman with history of limited small cell lung cancer (SCLC) status-post chemotherapy with cisplatin and etoposide and prophylactic whole brain radiation, presented with new onset gait instability, nausea, vomiting, vertigo, and opsoclonus. Two months prior to her presentation, a chest computed topography (CT) revealed no evidence of recurrent disease. Brain MRI revealed T2 hyperintensities in the white matter and central pons presumably related to chronic small vessel ischemic changes, unchanged from prior imaging. CSF studies revealed normal cell count, glucose, and protein. Gram stain, culture and meningoencephalitis panel were negative. Her paraneoplastic panel revealed a positive Caspr2 antibody. A repeat CT chest for cancer surveillance revealed a new lung mass. Immunotherapy treatment included plasmapheresis, corticosteroids, and intravenous immunoglobulin therapy. She underwent a biopsy of the new pulmonary lesion and the pathology was consistent with non-small cell lung carcinoma. Her symptoms slowly improved after treatment. Unfortunately, her disease progressed on repeat PET scan despite surgical resection of the lung mass. She ultimately elected for hospice. CONCLUSION We report a novel antibody, Caspr2, occurring in association with paraneoplastic OMS. While SCLC is the most common neoplasm associated with OMS among adults, non-small cell lung carcinoma should be considered. Prompt immunotherapy and neoplasm treatment may result in improvement.

Background: Brain-derived neurotrophic factor (BDNF) is associated with body weight and other health conditions but remains understudied in the Latino population. The aim of this study was to examine the associations of BDNF serum levels with body mass index (BMI), physical activity, and the rs6265 nonconservative polymorphism among 349 Latinos aged ≥18 years enrolled in the Arizona Insulin Resistance Registry. Materials and Methods: Data on physical activity were acquired using a self-reported questionnaire. BDNF serum levels were measured utilizing a modified ELISA method, and the rs6265 polymorphism was genotyped by the Assay-by-Design service. Two sample t -tests or chi-squared tests were employed to compare demographics and outcomes between physically active and nonactive groups as well as between rs6265 CC and CT+TT groups. Results: BDNF levels and rs6265 polymorphism did not differ significantly between the physically active ( N = 195) and nonactive group ( N = 154). Participants with the rs6265 polymorphism did not show any significant difference in BDNF levels or BMI when compared with those with the normal functional variant. Higher BDNF levels were significantly associated with higher age ( r = 0.11, P = 0.04) and higher 2-hr glucose level ( r = 0.11, P = 0.04). Conclusions: In this cross-sectional study, the rs6265 polymorphism was not associated with a higher risk of obesity, or lower circulating levels of BDNF. Thus, the rs6265 polymorphism may have a different impact in Latinos as compared with other previously studied populations.