Progressive cortical and sub-cortical alterations in patients with anti-N-methyl-d-aspartate receptor encephalitis

Xu, Jinping; Guo, Yuanyuan; Lv, Xinyi; Zhang, Juanjuan; Zhang, Jinhuan; Hu, Qingmao; Wang, Kai; Tian, Yanghua

doi:10.1007/s00415-021-10643-1

Cited by 11 publications

(7 citation statements)

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“…The precuneus is an important DMN node, which is closely related to self-cognition, monitoring the surrounding environment, introspection, and modulating the interaction between cognition and emotion (43). A previous study assessing cortical thickness reported DMN gray matter atrophy in patients with anti NMDAR encephalitis (44). The above results were not corrected for multiple comparisons, although a recent meta-analysis based of resting state fMRI data showed that strict multiple comparison correction could not increase the reliability of the results in a single study with small samples (45).…”

Section: Discussionmentioning

confidence: 99%

Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study

Long

Zhao

et al. 2022

Front. Neurol.

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Background:Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease with typical clinical features. Whether and how cerebral gray matter structural damage inherent to the disorder affects cognitive function in patients is still unclear. Therefore, this study aimed to explore the changes in cerebral gray matter volume and whether these alterations contribute to cognitive impairment and mood disorders.MethodsForty patients with anti-NMDAR encephalitis and forty healthy controls (HCs) matched for gender, age, and education were recruited. All participants underwent attention network tests (ANT), neuropsychological tests and magnetic resonance imaging (MRI). Voxel-based morphological analysis (VBM) and correlation analysis was performed on all participants. Finally, according to the course of disease, patients were divided into two groups: NMDARE_SD (short duration; course ≤ 2 years since diagnosis) and NMDARE_LD (long duration; course >2 years since diagnosis), to evaluate gray matter volume changes that differ as a function of disease course.ResultsCompared to HCs, patients with anti-NMDAR encephalitis showed decreased executive control ability and lower MoCA score, while increased anxiety and depression as reflected by HAMA and HAMD24 scores (all P < 0.05). In VBM analysis, patients showed decreased gray matter volume in bilateral thalamus, left medial prefrontal cortex (mPFC_L), left superior temporal gyrus (STG_L), and left rectus gyrus. In the analysis stratified by disease course, the NMDARE_LD group exhibited decreased gray matter volume in the left precuneus and right posterior cerebellar lobe compared to the NMDARE_SD group.ConclusionsPatients with anti-NMDAR encephalitis have cognitive, executive, and emotional dysfunction, and the sites of gray matter atrophy are concentrated in the thalamus, frontal lobe, and temporal lobe. These abnormalities may be involved in the process of cognitive and affective dysfunction.Patients with different courses of anti-NMDAR encephalitis have different brain atrophy sites. These results may help to clarify the contradiction between clinical and imaging manifestations of anti NMDAR encephalitis, which is worthy of further longitudinal studies.

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Section: Discussionmentioning

confidence: 99%

Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study

Long

Zhao

et al. 2022

Front. Neurol.

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“…The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative of receptor hypofunction and topographical distribution of antigenic receptors. The most specific pattern was observed in anti‐NMDA encephalitis showing frontotemporal hypermetabolism and occipito‐parietal hypometabolism 7,9,50 . The mechanism of the decrease of glucose metabolism in autoimmune encephalitis could be cortical dysfunction mediated by antibodies; anti‐NMDAR antibodies cause receptor internalization 51 .…”

Section: Discussionmentioning

confidence: 99%

“…The most specific pattern was observed in anti-NMDA encephalitis showing frontotemporal hypermetabolism and occipito-parietal hypometabolism. 7,9,50 The mechanism of the decrease of glucose metabolism in autoimmune encephalitis could be cortical dysfunction mediated by antibodies; anti-NMDAR antibodies cause receptor internalization. 51 Conversely, anti-AMPAR encephalitis showed frontal hypometabolism instead.…”

Section: Discussionmentioning

confidence: 99%

Positron emission tomography in autoimmune encephalitis: Clinical implications and future directions

Liu

et al. 2022

Acta Neuro Scandinavica

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Autoimmune encephalitis is an immune-mediated inflammatory disease of the central nervous system caused by abnormal immune response against surface or intracellular antigens. 1 In addition to the previously discovered classical paraneoplastic encephalitisassociated antibodies, a variety of autoimmune encephalitis-related antibodies have been reported in recent years, including antibodies targeting N-methyld-aspartate receptor (NMDAR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), leucine-rich glioma inactivated 1 (LGI1), contactin-associated proteinlike 2 (CASPR2), gamma-aminobutyric acid receptor (GABAR) A/B, dipeptidyl-peptidase-like protein-6 (DPPX), glycine receptor (GlyR), glutamic acid decarboxylase 65 (GAD65), dipeptidyl-peptidase-like protein-6 (DPPX), IgLON5 et al. 2 The clinical manifestations, severity, and prognosis with specific antibodies are different, but in general, early detection and early treatment are the principles to handle this disease. However, it has to be admitted that there are still difficulties in the early diagnosis of autoimmune encephalitis, although we have made improvements and revision in the diagnostic criteria based on the clinical criteria defined by Graus et al. 3 in 2016 to avoid excessive reliance on the detection of autoimmune antibodies from serum or cerebrospinal fluid (CSF). The problems focus on the heterogeneity of clinical manifestations, low positive rate of imaging evidence, and lack of specificity of EEG. For example, autoimmune encephalitis may involve

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“…However, brain structural and functional abnormalities in NMDAR encephalitis seems to extend beyond hippocampus. A number of recent works using different MR techniques as DTI, diffusion kurtosis imaging, voxel-based morphometry (VBM) and surface-based morphometry disclosed diffuse structural changes in hemispheric WM and cortical and subcortical GM, with correlation with cognitive scores ( Table 3 ) [ 117 , 118 , 119 , 120 , 121 ]. Accordingly, network analysis of resting-state fMRI data in patients with post-acute NMDAR encephalitis revealed alterations in whole-brain functional connectivity including impairment of the connectivity between the hippocampus and the medial temporal lobe (MTL) and the DMN, and significant reductions in intranetwork connectivity within the MTL, sensorimotor, lateral-temporal, and visual networks [ 122 ].…”

Section: Secondary Neurodegeneration In Patients With Autoimmune Ence...mentioning

confidence: 99%

Neural Surface Antibodies and Neurodegeneration: Clinical Commonalities and Pathophysiological Relationships

et al. 2023

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Autoimmune encephalitis and neurodegenerative disorders share several clinical features, including behavioural and psychiatric manifestations, cognitive impairment, sleep and movement disorders. Therefore, it is not surprising that autoimmune encephalitis is one of the main differential diagnoses of rapidly progressive dementia. However, more chronic presentations of autoimmune disorders have been reported and can lead to the misdiagnosis of a neurodegenerative disease. On the other hand, antibodies against neuronal proteins, such as those directed against NMDAR, can occur during established neurogenerative disorders, and their role in this context is still unclear. They might be simple bystanders or modify the disease course and phenotype. Indeed, autoimmune encephalitis can leave long-term cognitive sequelae and specific antibodies to neuronal surface antigens are associated with clinical and pathological neurodegenerative features. Here we review the link between these antibodies and neurodegeneration. In particular we discuss: (a) the possibility that autoimmune encephalitis presents as a neurodegenerative disease, identifying the red flags that can help in the differential diagnosis between antibody-mediated and neurodegenerative disorders; (b) the occurrence of antibodies against neuronal surface antigens in patients with neurodegenerative disorders and their possible role in the disease course; and (c) the long-term cognitive and neuroradiological changes associated with autoimmune encephalitis, as well as the biomarkers that can help to predict the cognitive outcome. Finally, we review the clinical and pathological features of IgLON5 antibodies-related encephalitis, a unique model of the relationship between antibodies and neurodegeneration.

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Progressive cortical and sub-cortical alterations in patients with anti-N-methyl-d-aspartate receptor encephalitis

Cited by 11 publications

References 50 publications

Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study

Cerebral gray matter volume changes in patients with anti-N-methyl-D-aspartate receptor encephalitis: A voxel-based morphometry study

Positron emission tomography in autoimmune encephalitis: Clinical implications and future directions

Neural Surface Antibodies and Neurodegeneration: Clinical Commonalities and Pathophysiological Relationships

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