Early Neuroaxonal Damage in Neurologic Disorders Associated With GAD65 Antibodies

  • Katharina Eisenhut
  • Jennifer Faber
  • Daniel Engels
  • Ramona Gerhards
  • Jan Lewerenz
  • Kathrin Doppler
  • Claudia Sommer
  • Robert Markewitz
  • Kim K Falk
  • Rosa Rössling
  • Harald Pruess
  • Carsten Finke
  • Jonathan Wickel
  • Christian Geis
  • Dominica Ratuszny
  • Lena K Pfeffer
  • Stefan Bittner
  • Johannes Piepgras
  • Andrea Kraft
  • Jaqueline Klausewitz
  • Brigitte Nuscher
  • Tania Kümpfel
  • Franziska S Thaler
  • German Network for Research on Autoimmune Encephalitis (GENERATE)

Abstract

OBJECTIVES: Neurodegeneration is considered a relevant pathophysiologic feature in neurologic disorders associated with antibodies against glutamic acid decarboxylase 65 (GAD65). In this study, we investigate surrogates of neuroaxonal damage in relation to disease duration and clinical presentation.

METHODS: In a multicentric cohort of 50 patients, we measured serum neurofilament light chain (sNfL) in relation to disease duration and disease phenotypes, applied automated MRI volumetry, and analyzed clinical characteristics.

RESULTS: In patients with neurologic disorders associated with GAD65 antibodies, we detected elevated sNfL levels early in the disease course. By contrast, this elevation of sNfL levels was less pronounced in patients with long-standing disease. Increased sNfL levels were observed in patients presenting with cerebellar ataxia and limbic encephalitis, but not in those with stiff person syndrome. Using MRI volumetry, we identified atrophy predominantly of the cerebellar cortex, cerebellar superior posterior lobe, and cerebral cortex with similar atrophy patterns throughout all clinical phenotypes.

DISCUSSION: Together, our data provide evidence for early neuroaxonal damage and support the need for timely therapeutic interventions in GAD65 antibody-associated neurologic disorders.

Bibliographical data

Original languageEnglish
ISSN2332-7812
DOIs
Publication statusPublished - 01.2024

Comment Deanary

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PubMed 37914416