Early Neuroaxonal Damage in Neurologic Disorders Associated With GAD65 Antibodies

TY - JOUR

T1 - Early Neuroaxonal Damage in Neurologic Disorders Associated With GAD65 Antibodies

AU - Eisenhut, Katharina

AU - Faber, Jennifer

AU - Engels, Daniel

AU - Gerhards, Ramona

AU - Lewerenz, Jan

AU - Doppler, Kathrin

AU - Sommer, Claudia

AU - Markewitz, Robert

AU - Falk, Kim K

AU - Rössling, Rosa

AU - Pruess, Harald

AU - Finke, Carsten

AU - Wickel, Jonathan

AU - Geis, Christian

AU - Ratuszny, Dominica

AU - Pfeffer, Lena K

AU - Bittner, Stefan

AU - Piepgras, Johannes

AU - Kraft, Andrea

AU - Klausewitz, Jaqueline

AU - Nuscher, Brigitte

AU - Kümpfel, Tania

AU - Thaler, Franziska S

AU - German Network for Research on Autoimmune Encephalitis (GENERATE)

N1 - Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - Humans

KW - Atrophy

KW - Autoantibodies

KW - Cerebellar Ataxia

KW - Nervous System Diseases

KW - Stiff-Person Syndrome

U2 - 10.1212/NXI.0000000000200176

DO - 10.1212/NXI.0000000000200176

M3 - Short publication

C2 - 37914416

VL - 11

JO - NEUROL-NEUROIMMUNOL

JF - NEUROL-NEUROIMMUNOL

SN - 2332-7812

IS - 1

ER -