Early Neuroaxonal Damage in Neurologic Disorders Associated With GAD65 Antibodies

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

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.
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• Dokumententyp: Artikel (Klinikum der LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Klinikum der LMU München > Neurologische Klinik und Poliklinik mit Friedrich-Baur-Institut
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892