Eisenhut, Katharina; Faber, Jennifer; Engels, Daniel; Gerhards, Ramona; Lewerenz, Jan; Doppler, Kathrin; Sommer, Claudia; Markewitz, Robert; Falk, Kim K.; Rössling, Rosa; Pruess, Harald; Finke, Carsten; Wickel, Jonathan; Geis, Christian; Ratuszny, Dominica; Pfeffer, Lena K.; Bittner, Stefan; Piepgras, Johannes; Kraft, Andrea; Klausewitz, Jaqueline; Nuscher, Brigitte; Kümpfel, Tania; Thaler, Franziska S. (2024): Early Neuroaxonal Damage in Neurologic Disorders Associated With GAD65 Antibodies. Neurology - Neuroimmunology Neuroinflammation, 11 (1): e200176. ISSN 2332-7812
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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.
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.
11 01 2023 01 2024 e200176 /nnn/11/1/e200176.atom 10.1212/NXI.0000000000200176 2.0 10.1212/crossmarkpolicy neurology.org true 10.1212/NXI.0000000000200176 2023110115050678000 http://nn.neurology.org/lookup/doi/10.1212/NXI.0000000000200176 https://syndication.highwire.org/content/doi/10.1212/NXI.0000000000200176 10.1136/jnnp-2020-325275 10.1093/brain/awac404 10.1212/NXI.0000000000200090 10.1001/jamaneurol.2014.1011 10.1038/nrneurol.2016.127 10.1212/WNL.0000000000207221 10.1212/WNL.0000000000011937 10.1212/WNL.0000000000007032 10.1002/mds.28610 10.1016/j.neuroimage.2004.06.018 10.1016/j.neuroimage.2022.119703 10.1056/NEJMoa01167 10.1212/NXI.0000000000001088 10.1016/j.nicl.2021.102826 10.1212/NXI.0000000000200125
Doc-Type: | Article (LMU Hospital) |
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Organisational unit (Faculties): | 07 Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute |
DFG subject classification of scientific disciplines: | Life sciences |
Date Deposited: | 30. Jan 2024 07:14 |
Last Modified: | 30. Jan 2024 07:14 |
URI: | https://oa-fund.ub.uni-muenchen.de/id/eprint/1004 |
DFG: | Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892 |