Abnormal global and local connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis: A resting-state functional MRI study.

OBJECTIVE: We decided to investigate the changes of global and local connectivity in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients based on eigenvector centrality (EC) and regional homogeneity (ReHo). We sought new biomarkers to identify the patients based on multivariate pattern analysis (MVPA). METHODS: Functional MRI (fMRI) was performed on all participants. EC, ReHo and MVPA were used to analyze the fMRI images. The correlation between the global or local connectivity and neuropsychology tests was detected. RESULTS: The MoCA scores of the patients were lower than those of the healthy controls (HCs), while the HAMD24 and HAMA scores of the patients were higher than those of the HCs. Increased EC values in the right calcarine (CAL.R) and decreased EC values in the right putamen (PUT.R) distinguished these subjects with anti-NMDAR encephalitis from HCs. The higher ReHo values in the left postcentral gyrus (PoCG.L) were detected in the patients. The correlation analysis showed that the EC values in the PUT.R were negatively correlated with HAMD24 and HAMA scores, while the ReHo values in the PoCG.L were negatively correlated with MoCA scores. Better classification performance was reached in the EC-based classifier (AUC = 0.80), while weaker classification performance was achieved in the ReHo-based classifier (AUC = 0.74) or the classifier based on EC and ReHo (AUC = 0.74). The brain areas with large weights were located in the frontal lobe, parietal lobe, cerebellum and basal ganglia. CONCLUSION: Our findings suggest that abnormal global and local connectivity may play an important part in the pathophysiological mechanism of neuropsychiatric symptoms in the anti-NMDAR encephalitis patients. The EC-based classifier may be better than the ReHo-based classifier in identifying anti-NMDAR encephalitis patients.

Abnormalities of regional brain activity and executive function in patients with temporal lobe epilepsy: A cross-sectional and longitudinal resting-state functional MRI study.

PURPOSE: We decided to track changes in regional brain activity and executive function in temporal lobe epilepsy (TLE) patients based on cross-sectional and longitudinal designs and sought potential imaging features for follow-up observation. METHODS: Thirty-two TLE patients and thirty-three healthy controls (HCs) were recruited to detect changes in fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to evaluate executive function both at baseline and at two-year (23.3 ± 8.3 months) follow-up. Moreover, multivariate pattern analysis (MVPA) was used for follow-up observation. RESULTS: TLE patients displayed lower fALFF values in the right superior frontal gyrus (SFG) and higher ReHo values in the left putamen (PUT) relative to the HCs. Longitudinal analysis revealed that TLE patients at follow-up exhibited higher fALFF values in the left postcentral gyrus (PoCG), higher ReHo values in the left PoCG and the right middle frontal gyrus (MFG), lower ReHo values in the bilateral PUT and the right fusiform gyrus (FFG) compared with these patients at baseline. The executive function was impaired in TLE patients but didn't deteriorate over time. No correlations were discovered between regional brain activity and executive function. The MVPA based on ReHo performed well in differentiating the follow-up group from the baseline group. CONCLUSION: We revealed the abnormalities in regional brain activity and executive function as well as their longitudinal trends in TLE patients. The ReHo might be a good imaging feature for follow-up observation.

The role of the thalamus in modular functional networks in temporal lobe epilepsy with cognitive impairment.

OBJECTIVE: Cognitive deficit is common in patients with temporal lobe epilepsy (TLE). Here, we aimed to investigate the modular architecture of functional networks associated with distinct cognitive states in TLE patients together with the role of the thalamus in modular networks. METHODS: Resting-state functional magnetic resonance imaging scans were acquired from 53 TLE patients and 37 matched healthy controls. All patients received the Montreal Cognitive Assessment test and accordingly were divided into TLE patients with normal cognition (TLE-CN, n = 35) and TLE patients with cognitive impairment (TLE-CI, n = 18) groups. The modular properties of functional networks were calculated and compared including global modularity Q, modular segregation index, intramodular connections, and intermodular connections. Thalamic subdivisions corresponding to the modular networks were generated by applying a 'winner-take-all' strategy before analyzing the modular properties (participation coefficient and within-module degree z-score) of each thalamic subdivision to assess the contribution of the thalamus to modular functional networks. Relationships between network properties and cognitive performance were then further explored. RESULTS: Both TLE-CN and TLE-CI patients showed lower global modularity, as well as lower modular segregation index values for the ventral attention network and the default mode network. However, different patterns of intramodular and intermodular connections existed for different cognitive states. In addition, both TLE-CN and TLE-CI patients exhibited anomalous modular properties of functional thalamic subdivisions, with TLE-CI patients presenting a broader range of abnormalities. Cognitive performance in TLE-CI patients was not related to the modular properties of functional network but rather to the modular properties of functional thalamic subdivisions. CONCLUSIONS: The thalamus plays a prominent role in modular networks and potentially represents a key neural mechanism underlying cognitive impairment in TLE.

Impaired interhemispheric synchrony and effective connectivity in right temporal lobe epilepsy.

BACKGROUND: The brain functional network plays a crucial role in cognitive impairment in temporal lobe epilepsy (TLE). Based on voxel-mirrored homotopic connectivity (VMHC), this study explored how directed functional connectivity changes and is associated with impaired cognition in right TLE (rTLE). METHODS: Twenty-seven patients with rTLE and twenty-seven healthy controls were included to perform VMHC and Granger causality analysis (GCA). Correlation analysis was performed based on GCA and cognitive function. RESULTS: Bilateral middle frontal gyrus (MFG), middle temporal gyrus, dorsolateral superior frontal gyrus (SFGdor), and supramarginal gyrus (SMG) exhibited decreased VMHC values in the rTLE group. Brain regions with altered VMHC had abnormal directed functional connectivity with multiple brain regions, mainly belonging to the default mode network, sensorimotor network, and visual network. Besides, the Montreal Cognitive Assessment (MoCA) score was positively correlated with the connectivity from the left SFGdor to the right cerebellum crus2 and was negatively correlated with the connectivity from the left SMG to the right supplementary motor area (SMA) before correction. Before correction, both phasic and intrinsic alertness reaction time were positively correlated with the connectivity from the left MFG to the left precentral gyrus (PreCG), connectivity from the left SMG to the right PreCG, and the connectivity from the left SMG to the right SMA. The executive control effect reaction time was positively correlated with the connectivity from the left MFG to the left calcarine fissure surrounding cortex before correction. CONCLUSION: The disordered functional network tended to be correlated with cognition impairment in rTLE.

Abnormalities in modular connectivity of functional brain networks and cognitive changes in patients with anti -N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: To explore potential mechanisms of cognitive changes in patients with anti-NMDAR encephalitis (ANMDARE) from intramodule and intermodule effects of brain functional networks. METHODS: Resting-state functional MRI(rs-fMRI) imaging data was collected from 30 ANMDARE and 30 healthy controls (HCs). A brain functional matrix was constructed, and sparsity was established by module similarity. For both groups, changes in functional connectivity (FC) within and between modules was calculated, and whole-brain functional topology was analyzed. Finally, the association of brain functional with cognitive function in ANMDARE was further analyzed. RESULTS: Compared to HCs, ANMDARE had enhanced connectivity within the modules that included the occipito-parietal-temporal and parahippocampal gyri. ANMDARE had significantly higher participation coefficients (PC) in the right inferior frontal gyrus than HCs and significantly lower PC in the left superior parietal lobule, left caudate nucleus, and right putamen. No statistically significant differences in global topological properties were found between the two groups. No correlations were found between functional and structural brain indicators and the Cognitive Assessment Scale and the Emotional Deficit Scale. CONCLUSIONS: Patients with ANMDARE are manifested by enhanced intramodular FC and intermodular connectivity changes in the brain. This may help to understand the pathophysiological mechanisms of the disease from a global perspective.

The alterations of spontaneous neural activities and white matter microstructures in anti-N-methyl-D-aspartate receptor encephalitis: a resting-state fMRI and DTI study.

BACKGROUND AND PURPOSE: Limited studies had jointly excavated the structural and functional changes in cognitive deficit in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients. We aimed to explore these changes in anti-NMDAR patients and their effect on cognitive function. METHODS: Twenty-three patients and 25 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, diffusion tensor imaging scanning, and neuroethology tests. The significantly differentiated brain regions via the fractional amplitude of low-frequency fluctuation (fALFF) were defined as regions of interest (ROIs). Granger causal, functional connectivity, and tract-based spatial statistical analyses were applied to explore the functional changes in ROIs and assess the structural changes. RESULTS: HCs outperformed patients in Montreal Cognitive Assessment. The fALFF values of right gyrus rectus (RGR) in patients were significantly reduced. The fractional anisotropy (FA) values of WM in the genu of corpus callosum and right superior corona radiata were significantly decreased and positively associated with neuroethology testing scores. The Granger causal connectivity (GCC) from the left inferior parietal lobule to RGR was significantly decreased and positively associated with inherent vigilance. Indicated by the multiple linear regression result, decreased FA value of the right superior corona radiata might be a reliable marker that reflects the cognitive impairment. CONCLUSIONS: Significant changes in spontaneous neural activities, GCC, and WM structures in anti-NMDAR encephalitis were reported. These findings promote the understanding of underlying relationships between cerebral function, structural network alterations, and cognitive dysfunction.

A meta-analysis to investigate the role of magnetic resonance spectroscopy in the detection of temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is a complex neuropsychiatric illness that alters patient's behavior and social well-being. Early and accurate diagnosis of TLE is a key factor in its treatment. Currently, magnetic resonance spectroscopy (MRS) is recommended due to its high sensitivity and specificity in the detection of seizures. However, some studies have reported on its limited role in lesion detection. OBJECTIVES: The present meta-analysis aims to analyze different studies thoroughly and investigate the role of MRS in the detection of TLE. MATERIAL AND METHODS: A systematic literature review was conducted using Medline (via PubMed), Cinahl (via EBSCO), Scopus, and Web of Sciences databases for case-control, retrospective and prospective studies regarding the use of MRS in detecting TLE. Studies were included using the Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria and relevant event data were extracted. The risk of publication bias was analyzed using the Begg and Mazumdar test. A risk of bias assessment was conducted using RevMan software. The Mantel-Haenszel method was used to calculate the sensitivity, pooled odds ratio (OR), and risk ratio (RR), also using RevMan software. RESULTS: A total of 16 studies published between 2000 and 2022 were included, which encompassed a total of 645 patients. We obtained a high sensitivity of 84.8%, which shows a high efficiency of MRS, and a pooled OR value of 0.37 (95% confidence interval (95% CI): 0.14-0.97) with a tau2 value of 2.63, χ2 value of 84.99, degrees of freedom (df) value of 15, I2 value of 82%, Z-value of 2.03, and p < 0.05. The pooled RR was 0.82 (95% CI: 0.69-0.97) with a tau2 value of 0.10, χ2 value of 122.11, df of 15, I2 value of 88%, Z-value of 2.25, and p < 0.05. These results were statistically significant for a low risk of publication bias. CONCLUSION: The current meta-analysis highly recommends the use of MRS in the accurate detection of alterations seen in the brain in patients with TLE.

Identification and effective connections of core networks in patients with temporal lobe epilepsy and cognitive impairment: Granger causality analysis and multivariate pattern analysis.

OBJECTIVE: This study aimed to explore effective connectivity (EC) of the core networks in cognition impairment associated with temporal lobe epilepsy (CI-TLE) by applying resting state and Granger causality analysis (REST-GCA). The specific brain regions that played a critical role in classification were assessed using multivariate pattern analysis (MVPA). METHODS: Thirty-two patients with CI-TLE and 29 healthy controls who were matched based on age and gender underwent functional magnetic resonance imaging (fMRI). RESULTS: REST-GCA revealed that patients with CI-TLE displayed decreased GC values in the following brain areas: from the posterior cingulate cortex (PCC) to the left fusiform gyrus (lFFG) and the right parahippocampal gyrus (rPPG); from the right dorsal prefrontal cortex (rDPFC) to the left superior parietal lobule (lSPL); from the left amygdala (lAG) to the PCC. Inhibitory EC was observed from the rDPFC to the PCC compared to HCs. The GC values increased from the right dorsal prefrontal cingulate cortex (rdACC) to the PCC and from the right dorsal forebrain insula (rDAI) to the right middle temporal gyrus (rMTG) in the CI-TLE patients. MVPA showed that the classification yielded an accuracy of 81.91% (78.12%, specificity =85.71%). CONCLUSION: Our observations indicated that the abnormal EC between the frontal and parietal regions might be associated with the pathophysiological mechanism of CI-TLE. These results also indicated that EC might be play a role as a potential discriminative pattern to detect CI-TLE in patients.

Longitudinal alterations of cortical structural-functional coupling in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: To investigate the longitudinal alterations of cortical structural-functional coupling (SF coupling) in patients with temporal lobe epilepsy (TLE) over a 2-year follow-up, thereby exploring the neuropathophysiological mechanisms of TLE. METHODS: Twenty-eight TLE patients and 42 age- and gender-matched healthy controls (HCs) were recruited. We used resting-state functional MRI and diffusion-weighted imaging to estimate and compare SF coupling at the multiscale network level (whole-brain, modular, and regional levels). Then, we analyzed the relationships between the spatial patterns of SF coupling, the principal functional connectivity (FC) gradient, and the functional participation coefficient (PC). Finally, we related regional SF coupling changes between baseline and follow-up to the expression of regional TLE-specific genes. RESULTS: Compared with HCs, TLE patients showed higher baseline SF couplings within the whole-brain, limbic, and default-mode modules. SF couplings within visual and dorsal attention modules were increased at follow-up compared to baseline. In all three groups, the spatial patterns of SF coupling aligned with the principal FC gradient and the functional PC. The longitudinal change in regional SF coupling in TLE patients was significantly positively correlated with the expression of the CUX2 gene. CONCLUSIONS: Aberrant SF coupling was revealed in TLE and related to macroscale cortical hierarchies, functional segregation, and TLE-specific gene expression; these data help increase our understanding of the neuropathophysiological mechanisms underlying TLE.

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

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. Methods: Forty 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. Results: Compared 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. Conclusions: Patients 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.

Disruption of Cerebellar-Cerebral Functional Connectivity in Temporal Lobe Epilepsy and the Connection to Language and Cognitive Functions.

Objective: To investigate the changes in the cerebellar-cerebral language network in temporal lobe epilepsy (TLE) patients from the cerebellar perspective, the research analyzes the changes of language and cognitive network in terms of functional connectivity (FC), as well as their efficiency of the reorganization were evaluated basing on relationship between the network metrics and neuropsychological scale scores. Methods: 30 TLE patients and 30 healthy controls were recruited. Brain activity was evaluated by voxel-mirrored homotopic connectivity analysis (VMHC). Two groups were analyzed and compared in terms of language FC using the following methods: Seed-to-Voxel analysis, pairwise correlations [region of interest(ROI)-to-ROI] and graph theory. Correlation analysis was performed between network properties and neuropsychological score. Results: Compared with healthy participants, VMHC values in the Cerebellum Anterior Lobe, Frontal Lobe, Frontal_Sup_R/L, Cingulum_Ant_R/L, and Cingulum_Mid_R/L were decreased in TLE patients. Decreased FC was observed from the Cerebelum_10_R to the left inferior frontal gyrus, from the Cerebelum_6_R to the left Lingual Gyrus, from the Cerebelum_4_5_R to left Lingual Gyrus, left Cuneal Cortex and Precuneous Cortex, from the Cerebelum_3_R to Brain-Stem, and from the Cerebelum_Crus1_L to Cerebelum_6_R in TLE patients. The FC was enhanced between bilateral Cingulum_Mid and angular gyrus and frontoparietal insular cranium, between Frontal_Sup_Med L and left/right superior temporal gyrus (pSTG l/r), while it was decreased between left middle temporal gyrus and pSTG l/r. Compared with controls, the Betweenness Centrality (BC) of the right superior marginal gyrus (SMG), Temporal_Pole_Mid_R and Temporal_Mid_L as well as the Degree Centrality (DC) and Nodal Efficiency (NE) of the right SMG were lower in TLE patients. Further analysis showed that decreased VMHC in bilateral Cerebellum Anterior Lobe was positively correlated with the Boston Naming Test score in TLE patients, but it was negatively correlated with the Verbal Fluency Test score. The NE and DC of SMG_R were both negatively correlated with visual perception score in Montreal Cognitive Assessment. Conclusion: Our results suggest that presence of abnormalities in the static functional connectivity and the language and cognitive network of TLE patients. Cerebellum potentially represents an intervention target for delaying or improving language and cognitive deficits in patients with TLE.

The Degree Centrality and Functional Connectivity in Patients With Temporal Lobe Epilepsy Presenting as Ictal Panic: A Resting State fMRI Study.

Objectives: Ictal panic (IP) can be observed occasionally in patients with temporal lobe epilepsy (TLE). Such descriptions can be found in previous studies, but the mechanism is still not clear and often confused with panic attacks in patients with panic disorder (PD). We try to use imaging methods (resting-state functional magnetic resonance imaging, rs-fMRI) to study the mechanism of this psychiatric comorbidity in patients with TLE. Methods: Forty right-onset TLE patients were observed, including 28 patients with TLE but without IP and 12 patients with TLEIP along with 30 gender-age matched healthy controls were included. We collected clinical/physiological/neuropsychological and rs-fMRI data. Degree centrality (DC) and functional connectivity (FC) were calculated. For the DC and FC values, analysis of covariance (ANCOVA) was used to find different areas and t-tests were used to compare differences between the TLEIP, TLE without IP, and healthy control(HC)groups. The relationship between brain abnormalities and patient characteristics was explored by correlation analyses. Results: No significant differences in gender and age were found among the three groups, and no significant differences in education level, Montreal Cognitive Assessment (MOCA), Hamilton Depressive Scale (HAMD), Hamilton Anxiety Scale (HAMA), and epilepsy duration (years) between the TLEIP and TLE without IP groups. In addition to fear, other symptoms were observed, including nausea, palpitations, rising epigastric sensation, and dyspnea. There was no correlation between the duration of IP and HAMA. Moreover, all IP durations were <2 min. Compared to the HCs and TLE without IP group, the DC value of the TLEIP group in the left middle temporal gyrus (LMTG) was significantly increased. Compared to the HCs, FC could be found between the LMTG and left inferior temporal gyrus (LITG) in the TLEIP group. In addition, there was FC between the LMTG and cerebellum in the TLEIP group. The difference in the magnitude of FC between the TLEIP vs. HC group was greater than the difference between the TLE vs. HC group. Conclusions: This study describes brain abnormalities in patients with TLEIP. These results will help to preliminarily understand the mechanism of ictal panic and abnormal functional connection in patients with TLE, and further explore the neuroimaging mechanism of ictal panic in patients with TLE.

Correlation Between the Functional Connectivity of Basal Forebrain Subregions and Vigilance Dysfunction in Temporal Lobe Epilepsy With and Without Focal to Bilateral Tonic-Clonic Seizure.

Purpose: Previous research has shown that subcortical brain regions are related to vigilance in temporal lobe epilepsy (TLE). However, it is unknown whether alterations in the function and structure of basal forebrain (BF) subregions are associated with vigilance impairment in distinct kinds of TLE. We aimed to investigate changes in the structure and function BF subregions in TLE patients with and without focal to bilateral tonic-clonic seizures (FBTCS) and associated clinical features. Methods: A total of 50 TLE patients (25 without and 25 with FBTCS) and 25 healthy controls (HCs) were enrolled in this study. The structural and functional alterations of BF subregions in TLE were investigated using voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC) analysis. Correlation analyses were utilized to investigate correlations between substantially altered imaging characteristics and clinical data from patients. Results: FBTCS patients had a lower rsFC between Ch1-3 and the bilateral striatum as well as the left cerebellum posterior lobe than non-FBTCS patients. In comparison to non-FBTCS patients, the rsFC between Ch4 and the bilateral amygdala was also lower in FBTCS patients. Compared to HCs, the TLE patients had reduced rsFC between the BF subregions and the cerebellum, striatum, default mode network, frontal lobe, and occipital lobes. In the FBTCS group, the rsFC between the left Ch1-3 and striatum was positive correlated with the vigilance measures. In the non-FBTCS group, the rsFC between the left Ch4 and striatum was significantly negative correlated with the alertness measure. Conclusion: These results extend current understanding of the pathophysiology of impaired vigilance in TLE and imply that the BF subregions may serve as critical nodes for developing and categorizing TLE biomarkers.

Aberrant resting-state interhemispheric functional connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis.

PURPOSE: Previous studies have discovered different neuroimaging features in anti-NMDAR encephalitis associated with cognitive dysfunction. However, it is unknown whether there is a correlation between abnormal homotopic connectivity and cognitive impairment in anti-NMDAR encephalitis. We aim to explore the homotopic connectivity patterns of patients with anti-NMDAR encephalitis and their associations with clinical characteristics. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs). Voxel-mirrored homotopic connectivity (VMHC) and multivariate pattern analysis (MVPA) were applied to analyze the imaging data. A correlation was also performed between aberrant brain regions and clinical parameters. RESULTS: Compared to HCs, the performance of alertness in the patient group was typically worse (p < 0.05). A significant decrease in VMHC was observed in many regions of the patients in comparison to HCs, including the cerebellar 6, para-hippocampal gyrus, insula, precuneus, and middle frontal gyrus (p < 0.001). The insula and middle frontal gyrus were found to show positive correlations with alertness. The MVPA method achieved a classification accuracy of 74.55% with a sensitivity of 82.76% and a specificity of 65.38% in discriminating patients from HCs. CONCLUSION: Our findings indicate that interhemispheric functional imbalance may play a significant role in the pathophysiology of cognitive dysfunction in anti-NMDAR encephalitis. The MVPA results suggest that abnormal VMHC may play a crucial role in the identification of patients with anti-NMDAR encephalitis from HCs.

Factors Influencing the Withdrawal of Antiepileptic Drugs in Adult Patients with Symptomatic Seizures Secondary to Neuronal Surface Antibodies-Associated Autoimmune Encephalitis.

PURPOSE: This retrospective study aimed to investigate the relationship between clinical characteristics, seizure outcomes, and the potential factors influencing the withdrawal of antiepileptic drugs (AEDs) in adult patients with symptomatic seizures secondary to neuronal surface antibody (NSAb)-associated autoimmune encephalitis (AE). PATIENTS AND METHODS: Eighty-one patients (age ≥18 years) diagnosed with NSAb-associated AE were included in this retrospective study. After at least 1 year of follow-up, clinical details, magnetic resonance imaging (MRI) findings, electroencephalography (EEG) data, cerebrospinal fluid parameters, and the therapeutic outcomes were analyzed. Patients who needed long-term AEDs to control seizures were divided into two groups (withdrawal ≤1 year and withdrawal >1 year). Multivariable logistic regression analysis was performed to identify the risk factors affecting the AEDs' withdrawal in patients with seizures secondary to NSAb-associated AE. RESULTS: During the 12-month follow-up after AEDs' withdrawal, 28 (44.4%) patients among the 63 patients who needed long-term AEDs stopped AEDs within 1 year, while 35 (55.6%) patients continued AEDs treatment. Multivariable logistic regression analysis showed that delayed immunotherapy, status epilepticus (SE), and elevated intrathecal Immunoglobulin G synthesis rate of 24 hours (24-h intrathecal IgG) were independent risk factors for delayed withdrawal in patients with seizure secondary to NSAb-associated AE (odds ratios: 1.129, 6.497, 3.415, P<0.05). The receiver operating characteristics (ROC) curve analysis showed that the area under the curve (AUC) of delayed immunotherapy, SE, and elevated 24-h intrathecal IgG was 0.816 (95% CI=0.711-0.921, P<0.001). CONCLUSION: Delayed immunotherapy, status epilepticus and elevated 24-hour intrathecal IgG synthesis rate are the factors that may influence the decision to delay AEDs' withdrawal.

The local neural markers of MRI in patients with temporal lobe epilepsy presenting ictal panic: A resting resting-state postictal fMRI study.

OBJECTIVES: Temporal lobe epilepsy (TLE) is one of the most common focal epilepsies. Some patients with TLE have ictal panic (IP), which is often confused with panic attack (PA) in panic disorder (PD). Previous studies have described temporal lobe epilepsy with ictal panic (TLEIP), but the specific mechanisms remain unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate local brain abnormalities in patients with TLEIP and tried to find neural markers to explore the mechanism of IP in patients with TLE. METHODS: A total of 40 patients with TLE, including 28 patients with TLE and 12 patients with TLEIP along with 30 age- and gender-matched healthy controls were included. We collected clinical/physiological/neuropsychological and rs-fMRI data. Fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated. ANOVA was used to find different areas and t-tests used to compare differences among fALFF, ReHo, and DC. Correlation analyses explored the relationship between local brain abnormalities and patient characteristics. RESULTS: No significant differences in age and gender were found among the three groups, nor were there differences in education level, Montreal Cognitive Assessment (MOCA) and Hamilton Anxiety Scale (HAMA) between the TLEIP and TLE groups. All the onset sites of patients with TLEIP were on the right. In addition to fear, other symptoms observed included nausea, palpitations, rising epigastric sensation, and dyspnea. There were no correlations between duration of IP and HAMA (p = 0.659). Moreover, all IP durations were <2 min and most <1 min. Compared to the HCs group, the ReHo value of the TLEIP group in the right middle frontal gyrus was significantly decreased (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). Compared to the HCs and TLE groups, the DC value of the TLEIP group in the left middle temporal gyrus (MTG) was significantly increased (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). No regions showed any significant fALFF difference between HCs and TLE groups (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). CONCLUSIONS: This research describes local brain abnormalities in patients with TLE presenting as IP. These results will be preliminarily conducive to understand the seizure mechanism of IP in patients with TLE, find out the MRI neural markers, and to further explore the neurophysiological mechanisms of IP in patients with TLE.

A study of brain functional network and alertness changes in temporal lobe epilepsy with and without focal to bilateral tonic-clonic seizures.

BACKGROUND: Temporal lobe epilepsy (TLE) is commonly refractory. Epilepsy surgery is an effective treatment strategy for refractory epilepsy, but patients with a history of focal to bilateral tonic-clonic seizures (FBTCS) have poor outcomes. Previous network studies on epilepsy have found that TLE and idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTCS) showed altered global and nodal topological properties. Alertness deficits also were found in TLE. However, FBTCS is a common type of seizure in TLE, and the implications for alertness as well as the topological rearrangements associated with this seizure type are not well understood. METHODS: We obtained rs-fMRI data and collected the neuropsychological assessment data from 21 TLE patients with FBTCS (TLE- FBTCS), 18 TLE patients without FBTCS (TLE-non- FBTCS) and 22 controls, and constructed their respective functional brain networks. The topological properties were analyzed using the graph theoretical approach and correlations between altered topological properties and alertness were analyzed. RESULTS: We found that TLE-FBTCS patients showed more serious impairment in alertness effect, intrinsic alertness and phasic alertness than the patients with TLE-non-FBTCS. They also showed significantly higher small-worldness, normalized clustering coefficient (γ) and a trend of higher global network efficiency (gE) compared to TLE-non-FBTCS patients. The gE showed a significant negative correlation with intrinsic alertness for TLE-non-FBTCS patients. CONCLUSION: Our findings show different impairments in brain network information integration, segregation and alertness between the patients with TLE-FBTCS and TLE-non-FBTCS, demonstrating that impairments of the brain network may underlie the disruptions in alertness functions.

Correlation analysis between regional homogeneity and executive dysfunction in anti-N-methyl-D-aspartate receptor encephalitis patients.

BACKGROUND AND PURPOSE: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti-NMDAR encephalitis patients and its relationship with the executive function. METHODS: Forty patients and 42 healthy volunteers undertook an Attention Network Test and a resting-state functional magnetic resonance imaging scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups. RESULTS: Compared to controls, the patients had higher executive control scores (p < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule and the left middle frontal gyrus. The ReHo values of the bilateral inferior parietal lobule in patients were found to be negatively associated with executive control scores. The classification of patients and controls using MVPA had an accuracy of 76.83%, a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve was 0.83. CONCLUSIONS: Our study provides evidence of abnormal cerebral function in anti-NMDAR encephalitis patients, which may contribute to unveiling the neuropathological mechanisms of anti-NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti-NMDAR encephalitis patients from healthy controls.

Deep Cerebellar Nuclei Functional Connectivity with Cerebral Cortex in Temporal Lobe Epilepsy With and Without Focal to Bilateral Tonic-Clonic Seizures: a Resting-State fMRI Study.

We aimed to explore the altered functional connectivity patterns within cerebello-cerebral circuits in temporal lobe epilepsy (TLE) patients with and without focal to bilateral tonic-clonic seizures (FBTCS). Forty-two patients with unilateral TLE (21 with and 21 without FBTCS) and 22 healthy controls were recruited. We chose deep cerebellar nuclei as seed regions, calculated static and dynamic functional connectivity (sFC and dFC) in the patients with and without FBTCS and healthy controls, and compared sFC and dFC among the three groups. Correlation analyses were used to assess relationships between the significantly altered imaging features and patient clinical parameters. Compared to the group without FBTCS, the FBTCS group showed decreased sFC between the right dentate nuclei and left hemisphere regions including the middle frontal gyrus, superior temporal gyrus, superior medial frontal gyrus and posterior cingulate gyrus, and significantly increased dFC between the right interposed nuclei and contralateral precuneus. Relative to HCs, the FBTCS group demonstrated prominently decreased sFC between the right dentate nuclei and left middle frontal gyrus. No significant correlations between the altered imaging features and patient clinical parameters were observed. Our results suggest that the disrupted cerebello-cerebral FC might be related to cognitive impairment, epileptogenesis, and propagation of epileptic activities in patients with FBTCS.