PT  - JOURNAL ARTICLE
AU  - Elise Peter
AU  - Le Duy Do
AU  - Salem Hannoun
AU  - Sergio Muñiz-Castrillo
AU  - Alberto Vogrig
AU  - Valentin Wucher
AU  - Anne-Laurie Pinto
AU  - Naura Chounlamountri
AU  - Walaa Zakaria
AU  - Veronique Rogemond
AU  - Geraldine Picard
AU  - Julien-Jacques Hedou
AU  - Aditya Ambati
AU  - Agusti Alentorn
AU  - Alexandra Traverse-Glehen
AU  - Mario Manto
AU  - Dimitri Psimaras
AU  - Emmanuel Mignot
AU  - Francois Cotton
AU  - Virginie Desestret
AU  - Jérôme Honnorat
AU  - Bastien Joubert
TI  - Cerebellar Ataxia With Anti-DNER Antibodies
AID  - 10.1212/NXI.0000000000200018
DP  - 2022 Sep 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e200018
VI  - 9
IP  - 5
4099  - http://nn.neurology.org/content/9/5/e200018.short
4100  - http://nn.neurology.org/content/9/5/e200018.full
SO  - Neurol Neuroimmunol Neuroinflamm2022 Sep 01; 9
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