Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis

TY - JOUR

T1 - Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis

AU - Finke, Carsten

AU - Kopp, Ute A

AU - Scheel, Michael

AU - Pech, Luisa-Maria

AU - Soemmer, Carina

AU - Schlichting, Jeremias

AU - Leypoldt, Frank

AU - Brandt, Alexander U

AU - Wuerfel, Jens

AU - Probst, Christian

AU - Ploner, Christoph J

AU - Prüss, Harald

AU - Paul, Friedemann

N1 - © 2013 American Neurological Association.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - OBJECTIVE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis.METHODS: Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry.RESULTS: Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls.INTERPRETATION: Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.

AB - OBJECTIVE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis.METHODS: Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry.RESULTS: Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls.INTERPRETATION: Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.

KW - Adult

KW - Anti-N-Methyl-D-Aspartate Receptor Encephalitis

KW - Female

KW - Functional Neuroimaging

KW - Hippocampus

KW - Humans

KW - Leukoencephalopathies

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Nerve Net

KW - Neuropsychological Tests

KW - Severity of Illness Index

KW - Young Adult

U2 - 10.1002/ana.23932

DO - 10.1002/ana.23932

M3 - SCORING: Journal article

C2 - 23686722

VL - 74

SP - 284

EP - 296

JO - ANN NEUROL

JF - ANN NEUROL

SN - 0364-5134

IS - 2

ER -