RT Journal Article SR Electronic T1 Cerebellar Ataxia With Anti-DNER Antibodies JF Neurology - Neuroimmunology Neuroinflammation JO Neurol Neuroimmunol Neuroinflamm FD Lippincott Williams & Wilkins SP e200018 DO 10.1212/NXI.0000000000200018 VO 9 IS 5 A1 Peter, Elise A1 Do, Le Duy A1 Hannoun, Salem A1 Muñiz-Castrillo, Sergio A1 Vogrig, Alberto A1 Wucher, Valentin A1 Pinto, Anne-Laurie A1 Chounlamountri, Naura A1 Zakaria, Walaa A1 Rogemond, Veronique A1 Picard, Geraldine A1 Hedou, Julien-Jacques A1 Ambati, Aditya A1 Alentorn, Agusti A1 Traverse-Glehen, Alexandra A1 Manto, Mario A1 Psimaras, Dimitri A1 Mignot, Emmanuel A1 Cotton, Francois A1 Desestret, Virginie A1 Honnorat, Jérôme A1 Joubert, Bastien YR 2022 UL http://nn.neurology.org/content/9/5/e200018.abstract AB Background and Objectives There is no report on the long-term outcomes of ataxia with antibodies against Delta and Notch-like epidermal growth factor–related (DNER). We aimed to describe the clinical-immunologic features and long-term outcomes of patients with anti-DNER antibodies.Methods Patients tested positive for anti-DNER antibodies between 2000 and 2020 were identified retrospectively. In those with available samples, immunoglobulin G (IgG) subclass analysis, longitudinal cerebellum volumetry, human leukocyte antigen isotyping, and CSF proteomic analysis were performed. Rodent brain membrane fractionation and organotypic cerebellar slices were used to study DNER cell-surface expression and human IgG binding to the Purkinje cell surface.Results Twenty-eight patients were included (median age, 52 years, range 19–81): 23 of 28 (82.1%) were male and 23 of 28 (82.1%) had a hematologic malignancy. Most patients (27/28, 96.4%) had cerebellar ataxia; 16 of 28 (57.1%) had noncerebellar symptoms (cognitive impairment, neuropathy, and/or seizures), and 27 of 28 (96.4%) became moderately to severely disabled. Half of the patients (50%) improved, and 32.1% (9/28) had no or slight disability at the last visit (median, 26 months; range, 3–238). Good outcome significantly associated with younger age, milder clinical presentations, and less decrease of cerebellar gray matter volumes at follow-up. No human leukocyte antigen association was identified. Inflammation-related proteins were overexpressed in the patients' CSF. In the rodent brain, DNER was enriched in plasma membrane fractions. Patients' anti-DNER antibodies were predominantly IgG1/3 and bound live Purkinje cells in vitro.Discussion DNER ataxia is a treatable condition in which nearly a third of patients have a favorable outcome. DNER antibodies bind to the surface of Purkinje cells and are therefore potentially pathogenic, supporting the use of B-cell–targeting treatments.DNER=Delta and Notch-like epidermal growth factor–related; HLA=human leukocyte antigen; IgG=immunoglobulin G; mRS=modified Rankin Scale; PCA=paraneoplastic cerebellar ataxia