White matter alterations in focal to bilateral tonic-clonic seizures.
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ABSTRACT:
SUBMITTER: Maher C
PROVIDER: S-EPMC9515421 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
White matter alterations in focal to bilateral tonic-clonic seizures.
Maher Christina C D'Souza Arkiev A Zeng Rui R Barnett Michael M Kavehei Omid O Nikpour Armin A Wang Chenyu C
Frontiers in neurology 20220914
We examined the white matter of patients with and without focal to bilateral tonic-clonic seizures (FBTCS), and control participants. A neural network based tract segmentation model (Tractseg) was used to isolate tract-specific, track-weighted tensor-based measurements from the tracts of interest. We compared the group differences in the track-weighted tensor-based measurements derived from whole and hemispheric tracts. We identified several regions that displayed significantly altered white mat ...[more]
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Project description:Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia-thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia-thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.
| S-EPMC7954388 | biostudies-literature
Project description:ObjectivesThis study aims to investigate whether alterations in white matter topological networks are associated with focal to bilateral tonic-clonic seizures (FBTCS) in temporal lobe epilepsy (TLE). Additionally, we investigated the variables contributing to memory impairment in TLE.MethodsThis cross-sectional study included 88 unilateral people with TLE (45 left/43 right), and 42 healthy controls. Graph theory analysis was employed to compare the FBTCS (+) group (n = 51) with the FBTCS (-) group (n = 37). The FBTCS (+) group was subcategorized into current-FBTCS (n = 31) and remote-FBTCS (n = 20), based on the history of FBTCS within 1 year or longer than 1 year before scanning, respectively. We evaluated the discriminatory power of topological network properties by receiver operating characteristic (ROC) analysis. Generalized linear models (GLMs) were employed to investigate variables associated with memory impairment in TLE.ResultsGlobal efficiency (Eg) was significantly reduced in the FBTCS (+) group, especially in the current-FBTCS subgroup. Greater disruption of regional properties in the ipsilateral occipital and temporal association cortices was observed in the FBTCS (+) group. ROC analysis revealed that Eg, normalized characteristic shortest path length, and nodal efficiency of the ipsilateral middle temporal gyrus could distinguish between FBTCS (+) and FBTCS (-) groups. Additionally, GLMs linked the occurrence of current FBTCS with poorer verbal memory outcomes in TLE.InterpretationOur study suggests that abnormal networks could be the structural basis of seizure propagation in FBTCS. Strategies aimed at reducing the occurrence of FBTCS could potentially improve the memory outcomes in people with TLE.
| S-EPMC11537139 | biostudies-literature
Project description:ObjectiveOur objective was to identify whether the whole-brain structural network alterations in patients with temporal lobe epilepsy (TLE) and focal to bilateral tonic-clonic seizures (FBTCS) differ from alterations in patients without FBTCS.MethodsWe dichotomized a cohort of 83 drug-resistant patients with TLE into those with and without FBTCS and compared each group to 29 healthy controls. For each subject, we used diffusion-weighted magnetic resonance imaging to construct whole-brain structural networks. First, we measured the extent of alterations by performing FBTCS-negative (FBTCS-) versus control and FBTCS-positive (FBTCS+) versus control comparisons, thereby delineating altered subnetworks of the whole-brain structural network. Second, by standardizing each patient's networks using control networks, we measured the subject-specific abnormality at every brain region in the network, thereby quantifying the spatial localization and the amount of abnormality in every patient.ResultsBoth FBTCS+ and FBTCS- patient groups had altered subnetworks with reduced fractional anisotropy and increased mean diffusivity compared to controls. The altered subnetwork in FBTCS+ patients was more widespread than in FBTCS- patients (441 connections altered at t > 3, p < .001 in FBTCS+ compared to 21 connections altered at t > 3, p = .01 in FBTCS-). Significantly greater abnormalities-aggregated over the entire brain network as well as assessed at the resolution of individual brain areas-were present in FBTCS+ patients (p < .001, d = .82, 95% confidence interval = .32-1.3). In contrast, the fewer abnormalities present in FBTCS- patients were mainly localized to the temporal and frontal areas.SignificanceThe whole-brain structural network is altered to a greater and more widespread extent in patients with TLE and FBTCS. We suggest that these abnormal networks may serve as an underlying structural basis or consequence of the greater seizure spread observed in FBTCS.
| S-EPMC8600951 | biostudies-literature
Project description: Not available
| S-EPMC10663961 | biostudies-literature
Project description:Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG), these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABA(A) receptor antagonist, was injected systemically and seizure activity was observed on EEG as high-amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high-resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which "generalized" tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans.
| S-EPMC2830359 | biostudies-literature
Project description:ObjectivesTo evaluate the effects of nonadherence to antiseizure medications (ASMs) and clinical characteristics on seizure control, we employed a prospective cohort cross-sectional study using self-reports and medical records of patients with epilepsy (PWEs).MethodsEight hundred and fifty-five PWEs taking ASMs were enrolled from fourteen collaborative outpatient clinics from January 2018 to March 2019. Questions from the Morisky Medication Adherence Scale were used as adherence self-reports. If a PWE's questionnaire indicated that they had missed doses of their ASMs, outpatient physicians asked them directly about the details of their compliance, including the timing of intentionally or unintentionally missed doses. The association between lack of seizure control and utilization outcomes, such as missed doses, demographics, and clinical characteristics of the PWEs, were assessed by univariate and multivariate analyses.ResultsMultivariate analysis revealed that forgetting to take ASMs was associated with lack of seizure control and the existence of focal to bilateral tonic-clonic seizures. Dementia, younger age, use of three or more antiepileptic agents, and living in a one-person household were associated with the risk of forgetting to take ASMs.SignificanceFor PWEs with poor drug management or a high incidence of missed doses of ASMs, efforts to improve adherence could facilitate better seizure control and decrease focal to bilateral tonic-clonic propagation.
| S-EPMC7529199 | biostudies-literature
Project description:ObjectivesElectroencephalograms (EEGs) or multi-unit activities (MUAs) of tonic-clonic seizures typically exhibit a distinct structure. After a preliminary phase (DC shift, spikes), the tonic phase is characterized by synchronized activity of numerous neurons, followed by the clonic phase, marked by a periodic sequence of spikes. However, the mechanisms underlying the transition from tonic to clonic phases remain poorly understood.MethodsWe employ a simple two-dimensional cellular automaton model to simulate seizure activity, specifically focusing on replicating the tonic-clonic transition. This model effectively illustrates the physical processes during the ictal phase and, more importantly, differentiates the roles of neurons' activity, identifying their origin as either synaptic or ephaptic.ResultsOur model reveals an intriguing interaction between the synaptic and ephaptic modes of action potential wave conduction. By replicating the EEG and multi-unit activity (MUA) structure of a tonic-clonic seizure and comparing it with real MUA data, we validate the model's underlying assumption: the transition from tonic to clonic phases is driven by a shift in dominance from synaptic to ephaptic conduction. During synaptic-mode control, neural conduction occurs through synaptic transmission involving chemical substances, while in the ephaptic mode, information transfer occurs through direct Ohmic conduction.SignificanceGaining a deeper understanding of the neuronal electrical conduction transitions during tonic-clonic seizures is crucial for improving the treatment of this debilitating condition.
| S-EPMC11638044 | biostudies-literature
Project description:Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.
| S-EPMC10582624 | biostudies-literature
Project description:BackgroundTemporal 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.
| S-EPMC8740350 | biostudies-literature
Project description:ObjectiveTonic-clonic seizures (TCS) lead to metabolic stress and changes in related blood markers. Such markers may indicate harmful conditions but can also help to identify TCS as a cause of transient loss of consciousness. In this study, we hypothesized that the alterations of circulating markers of metabolic stress depend on the clinical features of TCS.MethodsNinety-one adults undergoing video-EEG monitoring participated in this prospective study. Electrolytes, renal parameters, creatine kinase (CK), prolactin (PRL), lactate, ammonia, glucose, and other parameters were measured at inclusion and different time points after TCS.ResultsA total of 39 TCS were recorded in 32 patients (six generalized onset tonic-clonic seizures in 6 and 33 focal to bilateral tonic-clonic seizures in 26 patients). Shortly after TCS, mean lactate, ammonia, and PRL levels were significantly increased 8.7-fold, 2.6-fold, and 5.1-fold, respectively, with levels of more than twofold above the upper limits of the normal (ULN) in 90%, 71%, and 70% of the TCS and returned to baseline levels within 2 hours. Only postictal lactate levels were significantly correlated with the total duration of the tonic-clonic phase. In contrast, CK elevations above the ULN were found in three TCS (~10%) only with a peak after 48 hours. Immediately after the TCS, hyperphosphatemia occurred in one third of the patients, whereas hypophosphatemia was observed in one third 2 hours later. TCS led to subtle but significant alterations of other electrolytes, creatinine, and uric acid, whereas glucose levels were moderately increased.SignificanceLactate is a robust metabolic marker of TCS with elevations found in ~90% of cases within 30 minutes after seizure termination, whereas ammonia rises in ~ 70%, similarly to PRL. Phosphate levels show an early increase and a decrease 2 hours after TCS in a third of patients. CK elevations are rare after video-EEG-documented TCS, challenging its value as a diagnostic marker.
| S-EPMC6885665 | biostudies-literature