Dataset Information

Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures.

ABSTRACT: The aim of this study was to better understand the imaging features of drug-resistant epilepsy (DRE), especially in idiopathic generalized tonic-clonic seizure (GTCS), as well as to discover the associated mechanisms and functional connectivity (FC). A total of 31 idiopathic generalized epilepsy-GTCS patients and 17 healthy controls were enrolled. For each patient, resting-state functional MRI was performed. After a 12-month follow-up observation, patients were further divided into either drug-resistant (DR) or drug-sensitive (DS) groups. Compared to the DS group, DR patients had previously received more types of antiepileptic drugs and had taken more types of failed antiepileptic drugs. There were distinct FC changes toward the left thalamus, left putamen, left precuneus, and right precentral gyrus in the left hippocampus between DR and DS patients. FCs in the DR group largely decreased or remained unchanged, while DS patients exhibited compensatory enhancement. Disease duration was negatively correlated with FC between the left hippocampus and the left thalamus-putamen in patients with DRE. Further, DRE patients had an extremely high area under the curve (0.978) and a cut-off FC between the left hippocampus and thalamus-putamen of 0.282. Together, hippocampal FCs in patients with DR GTCS were impaired and time-dependently correlated with disease duration. Hippocampal FCs in DS patients showed overall compensatory enhancement, which could be used as a sensitive and specific marker to identify and predict DR GTCS.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6571184 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures.

Wang Zhengge Z Wang Xiaoyun X Rong Rong R Xu Yun Y Zhang Bing B Wang Zhongyuan Z

Neuroreport 20190701 10

The aim of this study was to better understand the imaging features of drug-resistant epilepsy (DRE), especially in idiopathic generalized tonic-clonic seizure (GTCS), as well as to discover the associated mechanisms and functional connectivity (FC). A total of 31 idiopathic generalized epilepsy-GTCS patients and 17 healthy controls were enrolled. For each patient, resting-state functional MRI was performed. After a 12-month follow-up observation, patients were further divided into either drug-r ...[more]

PMID: 31116131

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Project description:IntroductionGeneralized tonic-clonic seizures (GTCS) are a subtype of generalized seizures exhibiting bursts of bilaterally synchronous generalized spike-wave discharges. Numerous neuroimaging studies have reported aberrant functional activity and topological organization of brain network in epilepsy patients with GTCS, but most studies have focused on adults. However, the effect of GTCS on the spatial and temporal properties of brain function in children remains unclear. The present study aimed to explore whole-brain static (sFC) and dynamic functional connectivity (dFC) in children with GTCS.MethodsTwenty-three children with GTCS and 32 matched healthy controls (HCs) were recruited for the present study. Resting-state functional magnetic resonance imaging (MRI) data were collected for each subject. The group independent component analysis method was used to obtain independent components (ICs). Then, sFC and dFC methods were applied and the differences in functional connectivity (FC) were compared between the children with GTCS and the HCs. Additionally, we investigated the correlations between the dFC indicators and epilepsy duration.ResultsCompared to HCs, GTCS patients exhibited a significant decrease in sFC strengths among most networks. The K-means clustering method was implemented for dFC analysis, and the optimal number of clusters was estimated: two discrete connectivity configurations, State 1 (strong connection) and State 2 (weak connection). The decreased dFC mainly occurred in State 1, especially the dFC between the visual network (VIS) and somatomotor network (SMN); but the increased dFC mainly occurred in State 2 among most networks in GTCS children. In addition, GTCS children showed significantly shorter mean dwell time and lower fractional windows in stronger connected State 1, while GTCS children showed significantly longer mean dwell time in weaker connected State 2. In addition, the dFC properties, including mean dwell time and fractional windows, were significantly correlated with epilepsy duration.ConclusionOur results indicated that GTCS epilepsy not only alters the connectivity strength but also changes the temporal properties of connectivity in networks in the whole brain. These findings also emphasized the differences in sFC and dFC in children with GTCS. Combining sFC and dFC methods may provide more comprehensive understanding of the abnormal changes in brain architecture in children with GTCS.

Project description:Partial seizures produce increased cerebral blood flow in the region of seizure onset. These regional cerebral blood flow increases can be detected by single photon emission computed tomography (ictal SPECT), providing a useful clinical tool for seizure localization. However, when partial seizures secondarily generalize, there are often questions of interpretation since propagation of seizures could produce ambiguous results. Ictal SPECT from secondarily generalized seizures has not been thoroughly investigated. We analysed ictal SPECT from 59 secondarily generalized tonic-clonic seizures obtained during epilepsy surgery evaluation in 53 patients. Ictal versus baseline interictal SPECT difference analysis was performed using ISAS (http://spect.yale.edu). SPECT injection times were classified based on video/EEG review as either pre-generalization, during generalization or in the immediate post-ictal period. We found that in the pre-generalization and generalization phases, ictal SPECT showed significantly more regions of cerebral blood flow increases than in partial seizures without secondary generalization. This made identification of a single unambiguous region of seizure onset impossible 50% of the time with ictal SPECT in secondarily generalized seizures. However, cerebral blood flow increases on ictal SPECT correctly identified the hemisphere (left versus right) of seizure onset in 84% of cases. In addition, when a single unambiguous region of cerebral blood flow increase was seen on ictal SPECT, this was the correct localization 80% of the time. In agreement with findings from partial seizures without secondary generalization, cerebral blood flow increases in the post-ictal period and cerebral blood flow decreases during or following seizures were not useful for localizing seizure onset. Interestingly, however, cerebral blood flow hypoperfusion during the generalization phase (but not pre-generalization) was greater on the side opposite to seizure onset in 90% of patients. These findings suggest that, with appropriate cautious interpretation, ictal SPECT in secondarily generalized seizures can help localize the region of seizure onset.

Project description:Generalized tonic-clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analysed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: (i) during the partial seizure phase prior to generalization; (ii) during the generalization period; and (iii) post-ictally. We found that in the pre-generalization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients had focal CBF increases in variable regions of the cerebral cortex. Group analysis during generalization revealed that the most consistent increase occurred in the superior medial cerebellum, thalamus and basal ganglia. Post-ictally, there was a marked progressive CBF increase in the cerebellum which spread to involve the bilateral lateral cerebellar hemispheres, as well as CBF increases in the midbrain and basal ganglia. CBF decreases were seen in the fronto-parietal association cortex, precuneus and cingulate gyrus during and following seizures, similar to the 'default mode' regions reported previously to show decreased activity in seizures and in normal behavioural tasks. Analysis of patient behaviour during and following seizures showed impaired consciousness at the time of SPECT tracer injections. Correlation analysis across patients demonstrated that cerebellar CBF increases were related to increases in the upper brainstem and thalamus, and to decreases in the fronto-parietal association cortex. These results reveal a network of cortical and subcortical structures that are most consistently involved in secondarily generalized tonic-clonic seizures. Abnormal increased activity in subcortical structures (cerebellum, basal ganglia, brainstem and thalamus), along with decreased activity in the association cortex may be crucial for motor manifestations and for impaired consciousness in tonic-clonic seizures. Understanding the networks involved in generalized tonic-clonic seizures can provide insights into mechanisms of behavioural changes, and may elucidate targets for improved therapies.

Dataset Information

Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures.

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Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures.

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