Forgetting to take antiseizure medications is associated with focal to bilateral tonic-clonic seizures, as revealed by a cross-sectional study.
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ABSTRACT:
SUBMITTER: Suzuki H
PROVIDER: S-EPMC7529199 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Forgetting to take antiseizure medications is associated with focal to bilateral tonic-clonic seizures, as revealed by a cross-sectional study.
Suzuki Hime H Mikuni Nobuhiro N Ohnishi Hirofumi H Yokoyama Rintaro R Enatsu Rei R Ochi Satoko S
PloS one 20201001 10
<h4>Objectives</h4>To 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).<h4>Methods</h4>Eight 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 adherenc ...[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.
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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.
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Project description:ObjectiveThe purpose of this study was to assess the differences of topological characteristic and rich club organization between temporal lobe epilepsy (TLE) patients with focal seizure (FS) only and those with focal to bilateral tonic-clonic seizures (FBTCS).MethodsWe recruited 130 unilateral TLE patients, of which 57 patients with FS only and 73 patients with both FS and FBTCS, and 68 age- and gender-matched healthy controls (HC). Whole-brain networks were constructed based on diffusion weighted imaging data. Graph theory was applied to quantify the topological network metrics and rich club organization. Network-based statistic (NBS) analysis was administered to investigate the difference in edge-wise connectivity strength. The non-parametric permutation test was applied to evaluate the differences between groups. Benjamini-Hochberg FDR at the alpha of 5% was carried out for multiple comparations.ResultsIn comparison with HC, both the FS and FBTCS group displayed a significant reduction in whole-brain connectivity strength and global efficiency. The FBTCS group showed lower connectivity strength both in the rich club and feeder connections compared to HC. The FS group had lower connectivity strength in the feeder and local connections compared to HC. NBS analysis revealed a wider range of decreased connectivity strength in the FBTCS group, involving 90% of the rich club regions, mainly affecting temporal-subcortical, frontal-parietal, and frontal-temporal lobe, the majority decreasing connections were between temporal lobe and stratum. While the decreased connectivity strength in the FS group were relatively local, involving 50% of rich club regions, mainly concentrated on the temporal-subcortical lobe.ConclusionsNetwork integration was reduced in TLE. TLE with FBTCS selectively disrupted the rich club regions, while TLE with FS only were more likely to affect the non-rich club regions, emphasizing the contribution of rich club organization to seizure generalization.
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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.
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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.
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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.
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