Contribution of cerebrospinal fluid antibody titers and sex to acute cerebral blood flow in patients with anti-NMDAR autoimmune encephalitis.

Objective: The objective of this study was to elucidate the contribution of cerebrospinal fluid (CSF) antibody titers (AT) and sex to acute cerebral blood flow (CBF) in patients diagnosed with anti-N-methyl-d-aspartate receptor autoimmune encephalitis (NMDAR AE). Methods: Forty-five patients diagnosed with NMDAR AE were recruited from December 2016 to January 2023. The acute CBF in patients with NMDAR AE at the early stage of the disease was analyzed using arterial spin labeling. The groups were compared based on CSF AT and sex. The connectivity of the CBF in the region of interest was also compared between groups. Results: The patients with different CSF AT exhibited varied brain regions with CBF abnormalities compared to the healthy subjects (p = 0.001, cluster-level FWE corrected). High antibody titers (HAT) in CSF contributed to more brain regions with CBF alterations in female patients than in female patients with low antibody titers (LAT) in CSF (p = 0.001, cluster-level FWE corrected). Female patients with HAT in CSF displayed more decreased CBF in the left post cingulum gyrus, left precuneus, left calcarine, and left middle cingulum gyrus than the male patients with the same AT in CSF (p = 0.001, cluster-level FWE corrected). All patients with NMDAR AE showed increased CBF in the left putamen (Putamen_L) and left amygdala (Amygdala_L) and decreased CBF in the right precuneus (Precuneus_R), which suggests that these are diagnostic CBF markers for NMDAR AE. Conclusion: CSF AT and sex contributed to CBF abnormalities in the patients diagnosed with NMDAR AE. Altered CBF might potentially serve as the diagnostic marker for NMDAR AE.

Topological properties and connectivity patterns in brain networks of patients with refractory epilepsy combined with intracranial electrical stimulation.

Objective: Although intracranial electrical stimulation has emerged as a treatment option for various diseases, its impact on the properties of brain networks remains challenging due to its invasive nature. The combination of intracranial electrical stimulation and whole-brain functional magnetic resonance imaging (fMRI) in patients with refractory epilepsy (RE) makes it possible to study the network properties associated with electrical stimulation. Thus, our study aimed to investigate the brain network characteristics of RE patients with concurrent electrical stimulation and obtain possible clinical biomarkers. Methods: Our study used the GRETNA toolbox, a graph theoretical network analysis toolbox for imaging connectomics, to calculate and analyze the network topological attributes including global measures (small-world parameters and network efficiency) and nodal characteristics. The resting-state fMRI (rs-fMRI) and the fMRI concurrent electrical stimulation (es-fMRI) of RE patients were utilized to make group comparisons with healthy controls to identify the differences in network topology properties. Network properties comparisons before and after electrode implantation in the same patient were used to further analyze stimulus-related changes in network properties. Modular analysis was used to examine connectivity and distribution characteristics in the brain networks of all participants in study. Results: Compared to healthy controls, the rs-fMRI and the es-fMRI of RE patients exhibited impaired small-world property and reduced network efficiency. Nodal properties, such as nodal clustering coefficient (NCp), betweenness centrality (Bc), and degree centrality (Dc), exhibited differences between RE patients (including rs-fMRI and es-fMRI) and healthy controls. The network connectivity of RE patients (including rs-fMRI and es-fMRI) showed reduced intra-modular connections in subcortical areas and the occipital lobe, as well as decreased inter-modular connections between frontal and subcortical regions, and parieto-occipital regions compared to healthy controls. The brain networks of es-fMRI showed a relatively weaker small-world structure compared to rs-fMRI. Conclusion: The brain networks of RE patients exhibited a reduced small-world property, with a tendency toward random networks. The network connectivity patterns in RE patients exhibited reduced connections between cortical and subcortical regions and enhanced connections among parieto-occipital regions. Electrical stimulation can modulate brain network activity, leading to changes in network connectivity patterns and properties.

Acute Cerebellitis Associated With Anti-homer 3 Antibodies: A Rare Case Report and Literature Review.

Acute cerebellitis associated with Homer-3 antibodies is very rare. Here we present a 20-year-old woman who suffered from uncontrollable head shaking quickly from side to side and an unsteady gait for 2 days after the cold. Antibodies were screened by cell-based assays. The indirect immunofluorescence technique results revealed anti-Homer-3 antibody titers of 1:3.2 in the CSF and 1:100 in the serum. The woman was obviously improved after antiviral and immunosuppression (immunoglobin, methylprednisolone and mycophenolate mofetil) treatment. Our report indicated immune-mediated causes should be considered in the acute cerebellitis. Immunotherapy can contribute to the improvement of cerebellar syndrome.

Frequency-Dependent Dynamics of Functional Connectivity Networks During Seizure Termination in Childhood Absence Epilepsy: A Magnetoencephalography Study.

Objective: Our aim was to investigate the dynamics of functional connectivity (FC) networks during seizure termination in patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and graph theory (GT) analysis. Methods: MEG data were recorded from 22 drug-naïve patients diagnosed with CAE. FC analysis was performed to evaluate the FC networks in seven frequency bands of the MEG data. GT analysis was used to assess the topological properties of FC networks in different frequency bands. Results: The patterns of FC networks involving the frontal cortex were altered significantly during seizure termination compared with those during the ictal period. Changes in the topological parameters of FC networks were observed in specific frequency bands during seizure termination compared with those in the ictal period. In addition, the connectivity strength at 250-500 Hz during the ictal period was negatively correlated with seizure frequency. Conclusions: FC networks associated with the frontal cortex were involved in the termination of absence seizures. The topological properties of FC networks in different frequency bands could be used as new biomarkers to characterize the dynamics of FC networks related to seizure termination.

Using EEG and MEG to characterize extreme delta brush in a patient with anti-NMDA receptor encephalitis.

BACKGROUND: Extreme delta brush (EDB) is considered a potential marker for anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. The brain regions involved in EDB are unclear. CASE PRESENTATION: A 16-year-old woman with anti-NMDAR encephalitis who was experiencing psychosis was admitted. Electroencephalography (EEG) and magnetoencephalography (MEG) were used to analyze EDB in the patient. EDB on EEG could be disturbed by opening and closing the eyes, by occipital alpha rhythms and by sleep-wake cycles. The MEG results showed beta activity originating from bilateral superior parietal lobes. However, the delta wave originated from bilateral superior temporal gyri, the right middle temporal gyrus, the right inferior frontal gyrus, and the left inferior parietal lobe. CONCLUSIONS: Delta wave and beta activity might originate from different brain regions. Beta activity might be transmitted forward to the frontotemporal lobe and superimposed with delta activity to form EDB on EEG.

Clinical Features and Prognosis in Chinese Patients With Dipeptidyl-Peptidase-Like Protein 6 Antibody-Associated Encephalitis.

OBJECTIVES: Anti-dipeptidyl-peptidase-like protein 6 (anti-DPPX) encephalitis an extremely rare type of immune-mediated encephalitis. This study aimed to analyze the electroclinical characteristics and prognosis of anti-DPPX encephalitis. METHODS: Five patients (all male) with anti-DPPX encephalitis in East China from January 2016 to October 2021 was retrospective analyzed. Electroclinical features and outcomes were reviewed. RESULTS: All five patients were male. The media age at disease onset was 32 years old with a range of 14-56 years. The main symptoms included psychiatric disturbances (2/5), amnesia (4/5), confusion (3/5), and seizures (3/5). Migrating myoclonus were identified in patient 4 with positive DPPX and contactin-associated protein-like 2 antibodies in blood. All of the patients had positive DPPX antibodies in serum. Only one of them had positive antibody in the cerebrospinal fluid. EEG showed diffuse slowing in two patients, but no epileptiform discharges were observed. Eighty percent (4/5) of the patients showed normal brain magnetic resonance imaging. After immunotherapy, improvement of neuropsychiatric symptoms from all of the patients was observed. Over a mean follow-up of 30.8 weeks, all of the patients had marked improvement in the modified Rankin Scale. To date, no tumors were not observed in any patients. CONCLUSIONS: Anti-DPPX encephalitis mainly presents as neuropsychiatric symptoms. Cooperation of DPPX antibodies and CASPR2 antibodies might have contributed to the migration of myoclonus in the patient 4. Prompt immunotherapy often results in improvement.

Frequency-Dependent Interictal Neuromagnetic Activities in Children With Benign Epilepsy With Centrotemporal Spikes: A Magnetoencephalography (MEG) Study.

Objective: This study aimed to investigate interictal neuromagnetic activities in the low- to high-frequency ranges in patients with benign epilepsy with centrotemporal spikes (BECTS), especially those without interictal epileptiform discharges (IEDs). Methods: We studied 21 clinically-diagnosed BECTS patients and 11 age-matched healthy controls (HC) using high-sampling magnetoencephalography (MEG). Neuromagnetic sources were assessed with accumulated source imaging (ASI). The MEG data were analyzed in seven frequency bands. The MEG recordings distinguished BECTS without IEDs (n = 10) from those with IEDs (n = 11) and HC (n = 11). Results: At 1-4 Hz, the neuromagnetic activities in healthy subjects tended to locate at the precuneus/posterior cingulate, while those of the BECTS patients without IEDs tended to locate at the medial frontal cortex (MFC) compared to BECTS patients with IEDs. The MEG source imaging at 30-80 Hz revealed that BECTS patients without IEDs had higher occurrences of interictal brain activity in the medial temporal lobe (MTL) compared to controls and the brain activity strength seemed to be weaker. There was a significant correlation between the source strength of the interictal gamma oscillations of BECTS patients without IEDs and the duration of epilepsy. Conclusions: IEDs might disrupt the default mode network (DMN). Aberrant brain activities in BECTS patients without IEDs were associated with cognitive areas of the brain. The strength of gamma oscillations in the chronic epilepsy state reflected the duration of BECTS. Significance: MEG could reveal the aberrant neural activities in BECTS patients during the interictal period, and such abnormality is frequency-dependent. Gamma oscillations could be used to identify BECTS patients without IEDs.

Influencing electroclinical features and prognostic factors in patients with anti-NMDAR encephalitis: a cohort follow-up study in Chinese patients.

The clinical manifestations of patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in East China and factors associated with prognosis were analyzed. A retrospective study of 106 patients (58 females; 48 males) with anti-NMDAR encephalitis in East China was carried out from June 2015 to February 2019. Clinical features and factors influencing outcomes were reviewed. Behavioral changes were observed in 74.5% (79/106) of patients, and comprised the initial symptoms in 61.3% (65/106). Seizures were observed in 67% (71/106) of patients, and served as initial symptoms in 31.1% (33/106). A total of 54.9% (39/71) of seizures were focal seizures. More clinical symptoms were observed in female patients than in male patients (P = 0.000). Similarly, background activity (BA) with high cerebrospinal fluid (CSF) antibody titers at the peak stage was more severe in female patients than in male patients (P = 0.000). The Binary logistic regression and receiver operating characteristic (ROC) curve analyses revealed the factors associated with poor outcomes included consciousness disturbance (OR 4.907, 95% CI 1.653-14.562, P = 0.004; area: 65.4%, sensitivity: 44.2%, specificity: 86.5%, P = 0.014), EEG BA (OR 3.743, 95% CI 1.766-7.932, P = 0.001; area: 76.6%, sensitivity: 73%, specificity: 75%, P = 0.000), number of symptoms (OR 2.911, 95% CI 1.811-4.679, P = 0.000; area: 77.1%, sensitivity: 59.5%, specificity: 78.6%, P = 0.000) and CSF antibody titer (OR 31.778, 95% CI 8.891-113.57, P = 0.000; area: 83.9%, sensitivity: 89.2%, specificity: 78.6%, P = 0.000). EEG BA and number of symptoms were associated with CSF antibody titers. Consciousness disturbances, EEG BA, number of symptoms and CSF antibody titers served as predictors of poor outcomes.

Multifrequency Dynamics of Cortical Neuromagnetic Activity Underlying Seizure Termination in Absence Epilepsy.

PURPOSE: This study aimed to investigate the spectral and spatial signatures of neuromagnetic activity underlying the termination of absence seizures. METHODS: Magnetoencephalography (MEG) data were recorded from 18 drug-naive patients with childhood absence epilepsy (CAE). Accumulated source imaging (ASI) was used to analyze MEG data at the source level in seven frequency ranges: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), gamma (30-80 Hz), ripple (80-250 Hz), and fast ripple (250-500 Hz). RESULT: In the 1-4, 4-8, and 8-12 Hz ranges, the magnetic source during seizure termination appeared to be consistent over the ictal period and was mainly localized in the frontal cortex (FC) and parieto-occipito-temporal junction (POT). In the 12-30 and 30-80 Hz ranges, a significant reduction in source activity was observed in the frontal lobe during seizure termination as well as a decrease in peak source strength. The ictal peak source strength in the 1-4 Hz range was negatively correlated with the ictal duration of the seizure, whereas in the 30-80 Hz range, it was positively correlated with the course of epilepsy. CONCLUSION: The termination of absence seizures is associated with a dynamic neuromagnetic process. Frequency-dependent changes in the FC were observed during seizure termination, which may be involved in the process of neural network interaction. Neuromagnetic activity in different frequency bands may play different roles in the pathophysiological mechanism during absence seizures.

Altered cerebral blood flow in patients with anti-NMDAR encephalitis.

OBJECTIVE: This study aimed to identify to resting-state cerebral blood flow (CBF) connectivity alterations in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. METHODS: Three-dimensional pseudo-continuous arterial spin labeling (pcASL) imaging was performed to measure the resting-state CBF in 23 patients with anti-NMDAR encephalitis at the peak stage of the disease and 32 healthy subjects. CBF was normalized to reduce variations among subjects. CBF was compared between the groups, and the correlations between the CBF alterations and clinical parameters were assessed. Differences in CBF connectivity in specific brain regions were also compared between groups. RESULTS: Compared with the healthy subjects, the patients with anti-NMDAR encephalitis exhibited increased CBF in the left insula (L_insula), left superior temporal lobe (L_STL), L_hippocampus, L_pallidum, bilateral putamen (Bi_putamen), and Bi_caudate, and decreased CBF in the bilateral precuneus (Bi_Pc) and bilateral occipital lobe (Bi_OL) (P < 0.05, FEW corrected). Compared with healthy subjects, the patients with anti-NMDAR encephalitis exhibited increased negative CBF connectivity between the Bi_Pc, Bi_OL and L_TL, L_insula (P < 0.05, FEW corrected). Anti-NMDAR encephalitis patients with behavioral changes exhibited higher CBF in the L_insula and lower CBF in the R_Pc, Bi_calcarine, Bi_cuneus, and Bi_lingual than patients without behavioral changes and health controls. The ROC curve shows changed CBF in the L_insula, and R_Pc, Bi_calcarine, Bi_cuneus, and Bi_lingual served as a predictor of behavioral changes in patients with anti-NMDAR encephalitis. CONCLUSIONS: Our results suggest that patients with anti-NMDAR encephalitis may exhibit both regional CBF abnormalities and deficits in CBF connectivity, which may underlie the clinical symptoms of anti-NMDAR encephalitis.

Brain astrocytoma misdiagnosed as anti-NMDAR encephalitis: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, which is the most common type of autoimmune encephalitis, is caused by the production of autoantibodies against NMDA receptor. Anti-NMDAR encephalitis patients present with various non-specific symptoms, such as abnormal psychiatric or behaviour, speech dysfunction, cognitive dysfunction, seizures, movement disorders, decreased level of consciousness, and central hypoventilation or autonomic dysfunction. CASE PRESENTATION: A 67-year-old man presented with new-onset focal seizures. The brain magnetic resonance imaging (MRI) plain scan and enhanced scan showed abnormal signal on the proximal midline frontoparietal junction region. Anti-NMDAR antibody was detected in cerebrospinal fluid (CSF) and serum using a commercial kit (Euroimmune, Germany) by indirect immunofluorescence testing (IIFT) according to the manufacturer's instructions for twice. Both of the test results were positive in CSF and serum. The patient was diagnosed as anti-NMDAR encephalitis and then was treated repeatedly with large dose of intravenous corticosteroids and gamma globulin. Accordingly, the refractory nature of seizures in this case may be attributed to NMDAR autoantibodies. When the patient presented at the hospital for the third time, the brain MRI revealed an increase in the size of the frontal parietal lesion and one new lesion in the left basal ganglia. The patient underwent a surgical biopsy and astrocytoma was confirmed by histopathology. CONCLUSIONS: Although the sensitivity and specificity of anti-NMDAR-IgG antibodies in CSF to diagnose anti-NMDAR encephalitis are close to 100%, it is not absolute. Anti-NMDAR antibodies were positive, which might make the diagnosis more complex. The diagnosis of atypical presentation of anti-NMDAR encephalitis requires reasonable exclusion of other disorders.

Dynamic Neuromagnetic Network Changes of Seizure Termination in Absence Epilepsy: A Magnetoencephalography Study.

Objective: With increasing efforts devoted to investigating the generation and propagation mechanisms of spontaneous spike and wave discharges (SWDs), little attention has been paid to network mechanisms associated with termination patterns of SWDs to date. In the current study, we aimed to identify the frequency-dependent neural network dynamics during the offset of absence seizures. Methods: Fifteen drug-naïve patients with childhood absence epilepsy (CAE) were assessed with a 275-Channel Magnetoencephalography (MEG) system. MEG data were recorded during and between seizures at a sampling rate of 6,000 Hz and analyzed in seven frequency bands. Source localization was performed with accumulated source imaging. Granger causality analysis was used to evaluate effective connectivity networks of the entire brain at the source level. Results: At the low-frequency (1-80 Hz) bands, activities were predominantly distributed in the frontal cortical and parieto-occipito-temporal junction at the offset transition periods. The high-frequency oscillations (HFOs, 80-500 Hz) analysis indicated significant source localization in the medial frontal cortex and deep brain areas (mainly thalamus) during both the termination transition and interictal periods. Furthermore, an enhanced positive cortico-thalamic effective connectivity was observed around the discharge offset at all of the seven analyzed bands, the direction of which was primarily from various cortical regions to the thalamus. Conclusions: Seizure termination is a gradual process that involves both the cortices and the thalamus in CAE. Cortico-thalamic coupling is observed at the termination transition periods, and the cerebral cortex acts as the driving force.

Ictal Source Locations and Cortico-Thalamic Connectivity in Childhood Absence Epilepsy: Associations with Treatment Response.

Childhood absence epilepsy (CAE), the most common pediatric epilepsy syndrome, is usually treated with valproic acid (VPA) and lamotrigine (LTG) in China. This study aimed to investigate the ictal source locations and functional connectivity (FC) networks between the cortices and thalamus that are related to treatment response. Magnetoencephalography (MEG) data from 25 patients with CAE were recorded at 300 Hz and analyzed in 1-30 Hz frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. The FC networks between the cortices and thalamus were evaluated at the source level through a connectivity analysis. Treatment outcome was assessed after 36-66 months following MEG recording. The children with CAE were divided into LTG responder, LTG non-responder, VPA responder and VPA non-responder groups. The ictal source locations and cortico-thalamic FC networks were compared to the treatment response. The ictal source locations in the post-dorsal medial frontal cortex (post-DMFC, including the medial primary motor cortex and the supplementary sensorimotor area) were observed in all LTG non-responders but in all LTG responders. At 1-7 Hz, patients with fronto-thalamo-parietal/occipital (F-T-P/O) networks were older than those with fronto-thalamic (F-T) networks or other cortico-thalamic networks (p = 0.000). The duration of seizures in patients with F-T-P/O networks at 1-7 Hz was longer than that in patients with F-T networks or other cortico-thalamic networks (p = 0.001). The ictal post-DMFC source localizations suggest that children with CAE might experience initial LTG monotherapy failure. Moreover, the cortico-thalamo-cortical network is associated with age. Finally, the cortico-thalamo-cortical network consists of anterior and posterior cortices and might contribute to the maintenance of discharges.

Analysis of Relation Between Electroclinical Features and Cerebrospinal Fluid Antibody Titers in Patients With anti-NMDAR Encephalitis.

PURPOSE: This study aimed to determine the relation between electroclinical features and cerebrospinal fluid (CSF) antibody titers in patients with anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. METHOD: Clinical symptoms and electroencephalography (EEG) at different stages were analyzed in 51 hospitalized patients with anti-NMDAR encephalitis. RESULTS: Behavioral changes were the initial symptoms in 90.9% (20/22) of female patients with high (1:10 or 1:32) CSF antibody titers. A greater number of clinical symptoms were observed in the patients with high CSF antibody titers than in those with low (1:1 or 1:3.2) CSF antibody titers (mean 3.11 ± 1.06 vs 1.62 ± 0.65, P = .000). The number of clinical symptoms was greater in the female patients than in the male patients (mean 3.52 ± 0.98 vs 2.69 ± 1.09, P = .000). At the peak stage, worse background activity (BA) in EEG recordings was observed in patients with high CSF antibody titers than in those with low CSF antibody titers (Mann-Whitney U test, P = .001). The peak-stage BA in EEG was worse in female patients than in male patients (Mann-Whitney U test, P = .000). Modified Rankin scale scores were higher in patients with high CSF antibody titers than in those with low CSF antibody titers (mean 2.62 ± 1.42 vs 0.75 ± 0.97, P = .000). Brush patterns and constant chewing were observed primarily in female patients with high CSF antibody titers. Epileptic discharges were located predominately in the frontal regions and were noted to vary. CONCLUSION: The electroclinical features of patients with anti-NMDAR encephalitis were associated with gender and CSF antibody titers.

Differences Between Interictal and Ictal Generalized Spike-Wave Discharges in Childhood Absence Epilepsy: A MEG Study.

Purpose: To investigate the differences between interictal and ictal generalized spike-wave discharges (GSWDs) for insights on how epileptic activity propagates and the physiopathological mechanisms underlying childhood absence epilepsy (CAE). Methods: Twenty-five patients with CAE were studied using magnetoencephalography (MEG). MEG data were digitized at 6,000 Hz during the interictal and ictal GSWDs. GSWDs were analyzed at both neural magnetic source levels and functional connectivity (FC) in multifrequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), gamma (30-80 Hz), ripple (80-250 Hz), and fast ripple (250-500 Hz). Brain FC was studied with the posterior cingulate cortex/precuneus (PCC/pC) as the seed region. Results: The magnetic source of interictal GSWDs mainly locates in the PCC/pC region at 4-8 and 8-12 Hz, while that of ictal GSWDs mainly locates in the medial frontal cortex (MFC) at 80-250 Hz. There were statistically significant differences between interictal and ictal GSWDs (p < 0.05). The FC network involving the PCC/pC showed strong connections in the anterior-posterior pathways (mainly with the frontal cortex) at 80-250 Hz during ictal GSWDs, while the interictal GSWDs FC were mostly limited to the posterior cortex region. There was no significant difference in the magnetic source strength among interictal and ictal GSWDs at all bandwidths. Conclusions: There are significant disparities in the source localization and FC between interictal and ictal GSWDs. Low-frequency activation in the PCC/pC during inhibition of seizures possibly relates to the maintenance of consciousness during interictal GSWDs. High-frequency oscillations (HFOs) of the MFC during CAE may associate with the inducing or occurrence of GSWDs. Weakened network connections may be in favor of preventing overexcitability and relates to the termination of GSWDs.

Ictal Rhythmic Alpha Sinusoidal Waves in 3 Cases of Anti-NMDAR Encephalitis.

Previous studies have shown that extreme delta brush and high beta/delta power ratio on electroencephalogram are suggestive of anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Here we report 3 anti-NMDAR encephalitis patients with ictal rhythmic alpha sinusoidal waves in temporal regions, which suggested electrographic seizures in anti-NMDAR encephalitis and indicated potential for seizure occurrence in the future. Rhythmic alpha sinusoidal waves may be an electrographic feature and helpful in distinguishing anti-NMDAR encephalitis. In addition, extreme delta brush was also observed at 47-50 days after morbidity in 2 of 3 patients.

Disrupted topological organization of structural brain networks in childhood absence epilepsy.

Childhood absence epilepsy (CAE) is the most common paediatric epilepsy syndrome and is characterized by frequent and transient impairment of consciousness. In this study, we explored structural brain network alterations in CAE and their association with clinical characteristics. A whole-brain structural network was constructed for each participant based on diffusion-weighted MRI and probabilistic tractography. The topological metrics were then evaluated. For the first time, we uncovered modular topology in CAE patients that was similar to healthy controls. However, the strength, efficiency and small-world properties of the structural network in CAE were seriously damaged. At the whole brain level, decreased strength, global efficiency, local efficiency, clustering coefficient, normalized clustering coefficient and small-worldness values of the network were detected in CAE, while the values of characteristic path length and normalized characteristic path length were abnormally increased. At the regional level, especially the prominent regions of the bilateral precuneus showed reduced nodal efficiency, and the reduction of efficiency was significantly correlated with disease duration. The current results demonstrate significant alterations of structural networks in CAE patients, and the impairments tend to grow worse over time. Our findings may provide a new way to understand the pathophysiological mechanism of CAE.

Quantify neuromagnetic network changes from pre-ictal to ictal activities in absence seizures.

OBJECTIVE: The cortico-thalamo-cortical network plays a key role in childhood absence epilepsy (CAE). However, the exact interaction between the cortex and the thalamus remains incompletely understood. This study aimed to investigate the dynamic changes of frequency-dependent neural networks during the initialization of absence seizures. METHODS: Magnetoencephalography data from 14 patients with CAE were recorded during and between seizures at a sampling rate of 6000Hz and analyzed in seven frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. Effective connectivity networks of the entire brain, including the cortico-thalamo-cortical network, were evaluated at the source level through Granger causality analysis. RESULTS: The low-frequency (1-80Hz) activities showed significant frontal cortical and parieto-occipito-temporal junction source localization around seizures. The high-frequency (80-250Hz) oscillations showed predominant activities consistently localized in deep brain areas and medial frontal cortex. The increased cortico-thalamic effective connectivity was observed around seizures in both low- and high-frequency ranges. The direction was predominantly from the cortex to the thalamus at the early time, although the cortex that drove connectivity varied among subjects. CONCLUSIONS: The cerebral cortex plays a key role in driving the cortico-thalamic connections at the early portion of the initialization of absence seizures. The oscillatory activities in the thalamus could be triggered by networks from various regions in the cortex. SIGNIFICANCE: The dynamic changes of neural network provide evidences that absence seizures are probably resulted from cortical initialized cortico-thalamic network.