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Atrophy in the Left Amygdala Predicted Drug Responses in Idiopathic Generalized Epilepsy Patients With Tonic-Clonic Seizures.

ABSTRACT: We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-GTCS) via MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D T₁WI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs (p = 0.004, false discovery rate corrected) and SF patients (p = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC (p < 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency (r = -0.324, p = 0.030) and between shape (r = -0.438, p = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency (r = -0.689, p = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.

SUBMITTER: Li X

PROVIDER: S-EPMC8044327 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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Atrophy in the Left Amygdala Predicted Drug Responses in Idiopathic Generalized Epilepsy Patients With Tonic-Clonic Seizures.

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