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Objective Postictal generalized electroencephalographic suppression (PGES) is a pattern of low-voltage scalp electroencephalographic (EEG) activity following termination of generalized seizures. PGES has been associated with both sudden unexplained death in patients with epilepsy and therapeutic efficacy of electroconvulsive therapy (ECT). Automated detection of PGES epochs may aid in reliable quantification of this phenomenon. Methods We developed a voltage-based algorithm for detecting PGES. This algorithm applies existing criteria to simulate expert epileptologist readings. Validation relied on postictal EEG recording from patients undergoing ECT (NCT02761330), assessing concordance among the algorithm and four clinical epileptologists. Results We observed low-to-moderate concordance among epileptologist ratings of PGES. Despite this, the algorithm displayed high discriminability in comparison to individual epileptologists (c-statistic range: 0.86-0.92). The algorithm displayed high discrimination (c-statistic: 0.91) and substantial peak agreement (Cohen’s Kappa: 0.65) in comparison to a consensus of clinical ratings. Interrater agreement between the algorithm and individual epileptologists was on par with that among expert epileptologists. Conclusions An automated voltage-based algorithm can be used to detect PGES following ECT, with discriminability nearing that of experts. Significance Algorithmic detection may support clinical readings of PGES and improve precision when correlating this marker with clinical outcomes following generalized seizures.

SummaryObjectives Specific changes in the functional connectivity of brain networks occur in patients with epilepsy. Yet whether such changes reflect a stable disease effect or one that is a function of active seizure burden remains unclear. Here, we longitudinally assessed the connectivity of canonical cognitive functional networks in patients with intractable temporal lobe epilepsy (TLE), both before and after patients underwent epilepsy surgery and achieved seizure freedom. Methods Seventeen patients with intractable TLE who underwent epilepsy surgery with Engel class I outcome and 17 matched healthy controls took part in the study. The functional connectivity of a set of cognitive functional networks derived from typical cognitive tasks was assessed in patients, preoperatively and postoperatively, as well as in controls, using stringent methods of artifact reduction. Results Preoperatively, functional networks in TLE patients differed significantly from healthy controls, with differences that largely, but not exclusively, involved the default mode and temporal/auditory subnetworks. However, undergoing epilepsy surgery and achieving seizure freedom did not lead to significant changes in network connectivity, with postoperative functional network abnormalities closely mirroring the preoperative state. Significance This result argues for a stable chronic effect of the disease on brain connectivity, with changes that are largely “burned in” by the time a patient with intractable TLE undergoes epilepsy surgery, which typically occurs years after the initial diagnosis. The result has potential implications for the treatment of intractable epilepsy, suggesting that delaying surgical intervention that may achieve seizure freedom may lead to functional network changes that are no longer reversible by the time of epilepsy surgery.

BACKGROUND AND PURPOSE To demonstrate the accuracy across different acquisition and analysis methods, we evaluated the variability in hippocampal volumetric and surface displacement measurements resulting from two different MRI (magnetic resonance imaging) acquisition protocols. METHODS Nine epilepsy patients underwent two independent T1-weighted magnetization prepared spoiled gradient sequences during a single 3T MRI session. Using high-dimension mapping-large deformation (HDM-LD) segmentation, we calculated volumetric estimates and generated a vector-based 3-dimensional surface model of each subject's hippocampi, and evaluated volume and surface changes, the latter using a cluster-based noise estimation model. RESULTS Mean hippocampal volumes and standard deviations for the left hippocampi were 2,750 (826) mm3 and 2,782 (859) mm3 (P = .13), and for the right hippocampi were 2,558 (750) mm3 and 2,547 (692) mm3 (P = .76), respectively for the MPR1 and MPR2 sequences. Average Dice coefficient comparing overlap for segmentations was 86%. There was no significant effect of MRI sequence on volume estimates and no significant hippocampal surface change between sequences. CONCLUSION Statistical comparison of hippocampal volumes and statistically thresholded HDM-LD surfaces in TLE patients showed no differences between the segmentations obtained in the two MRI acquisition sequences. This validates the robustness across MRI sequences of the HDM-LD technique for estimating volume and surface changes in subjects with epilepsy.

How epilepsy affects brain functional networks remains poorly understood. Here we investigated resting state functional connectivity of the temporal region in temporal lobe epilepsy. Thirty-two patients with unilateral temporal lobe epilepsy underwent resting state blood-oxygenation level dependent functional magnetic resonance imaging. We defined regions of interest a priori focusing on structures involved, either structurally or metabolically, in temporal lobe epilepsy. These structures were identified in each patient based on their individual anatomy. Our principal findings are decreased local and inter-hemispheric functional connectivity and increased intra-hemispheric functional connectivity ipsilateral to the seizure focus compared to normal controls. Specifically, several regions in the affected temporal lobe showed increased functional coupling with the ipsilateral insula and immediately neighboring subcortical regions. Additionally there was significantly decreased functional connectivity between regions in the affected temporal lobe and their contralateral homologous counterparts. Intriguingly, decreased local and inter-hemispheric connectivity was not limited or even maximal for the hippocampus or medial temporal region, which is the typical seizure onset region. Rather it also involved several regions in temporal neo-cortex, while also retaining specificity, with neighboring regions such as the amygdala remaining unaffected. These findings support a view of temporal lobe epilepsy as a disease of a complex functional network, with alterations that extend well beyond the seizure onset area, and the specificity of the observed connectivity changes suggests the possibility of a functional imaging biomarker for temporal lobe epilepsy., Highlights • We studied functional connectivity changes in patients with temporal lobe epilepsy. • Patients had decreased local and inter-hemispheric functional connectivity. • Patients had increased intra-hemispheric connectivity, ipsilateral to seizure focus. • Functional changes involved several neocortical sites, including the insula. • This pattern may have usefulness as a non-invasive method for presurgical planning.

Summary Objective Hippocampal atrophy in temporal lobe epilepsy (TLE) can indicate mesial temporal sclerosis and predict surgical success. Yet many patients with TLE do not have significant atrophy (magnetic resonance imaging (MRI) negative), which presents a diagnostic challenge. We used a new variant of high-dimensional large-deformation mapping to assess whether patients with apparently normal hippocampi have local shape changes that mirror those of patients with significant hippocampal atrophy. Methods Forty-seven patients with unilateral TLE and 32 controls underwent structural brain MRI. High-dimensional large-deformation mapping provided hippocampal surface and volume estimates for each participant, dividing patients into low versus high hippocampal atrophy groups. A vertex-level generalized linear model compared local shape changes between groups. Results Patients with low-atrophy TLE (MRI negative) had significant local hippocampal shape changes compared to controls, similar to those in the contralateral hippocampus of high-atrophy patients. These changes primarily involved the subicular and hilar/dentate regions, instead of the classically affected CA1 region. Disease duration instead co-varied with lateral hippocampal atrophy, co-localizing with the CA1 subfield. Significance These findings show that patients with “MRI-negative” TLE have regions of hippocampal atrophy that cluster medially, sparing the lateral regions (CA1) involved in high-atrophy patients. This suggests an overall effect of temporal lobe seizures manifesting as bilateral medial hippocampal atrophy, and a more selective effect of hippocampal seizures leading to disease-proportional CA1 atrophy, potentially reflecting epileptogenesis.

Frontal recruitment was characterized using functional magnetic resonance imaging (fMRI) during memory encoding in temporal lobe epilepsy (TLE) patients before and after unilateral medial temporal lobectomy. Twenty-four TLE patients and 12 healthy controls underwent a preoperative fMRI session consisting of verbal and nonverbal incidental memory-encoding tasks that typically lead to robust, lateralized frontal activity in controls. A similar postoperative fMRI session was performed in a subset of patients. Preoperatively, the verbal task resulted in significant additional recruitment of right frontal cortex in left TLE patients, compared with controls. Right TLE patients instead showed typically lateralized frontal activation. Bilateral frontal recruitment has been observed in older adults and in young adults in situations of difficult task demands. Typical right-lateralized patterns of frontal recruitment were found in both patient groups during the nonverbal task, indicating that the bilateral frontal recruitment pattern was engaged dynamically depending on the task. After surgery, left TLE patients regained more lateralized frontal activity. These results demonstrated differences in frontal recruitment in left and right TLE patients. Such differences emerged in specific task settings and were influenced by surgery, suggesting a dynamic mechanism of frontal recruitment that can be obtained in TLE patients, possibly as a response to presurgical dysfunction.

Summary Purpose Posttraumatic epilepsy (PTE) occurs in a proportion of traumatic brain injury (TBI) cases, significantly compounding the disability, and risk of injury and death for sufferers. To date, predictive biomarkers for PTE have not been identified. This study used the lateral fluid percussion injury (LFPI) rat model of TBI to investigate whether structural, functional, and behavioral changes post-TBI relate to the later development of PTE. Methods Adult male Wistar rats underwent LFPI or sham injury. Serial magnetic resonance (MR) and positron emission tomography (PET) imaging, and behavioral analyses were performed over 6 months postinjury. Rats were then implanted with recording electrodes and monitored for two consecutive weeks using video–electroencephalography (EEG) to assess for PTE. Of the LFPI rats, 52% (n = 12) displayed spontaneous recurring seizures and/or epileptic discharges on the video-EEG recordings. Key Findings MRI volumetric and signal analysis of changes in cortex, hippocampus, thalamus, and amygdala, 18F-fluorodeoxyglucose (FDG)–PET analysis of metabolic function, and behavioral analysis of cognitive and emotional changes, at 1 week, and 1, 3, and 6 months post-LFPI, all failed to identify significant differences on univariate analysis between the epileptic and nonepileptic groups. However, hippocampal surface shape analysis using large-deformation high-dimensional mapping identified significant changes in the ipsilateral hippocampus at 1 week postinjury relative to baseline that differed between rats that would go onto become epileptic versus those who did not. Furthermore, a multivariate logistic regression model that incorporated the 1 week, and 1 and 3 month 18F-FDG PET parameters from the ipsilateral hippocampus was able to correctly predict the epileptic outcome in all of the LFPI cases. As such, these subtle changes in the ipsilateral hippocampus at acute phases after LFPI may be related to PTE and require further examination. Significance These findings suggest that PTE may be independent of major structural, functional, and behavioral changes induced by TBI, and suggest that more subtle abnormalities are likely involved. However, there are limitations associated with studying acquired epilepsies in animal models that must be considered when interpreting these results, in particular the failure to detect differences between the groups may be related to the limitations of properly identifying/separating the epileptic and nonepileptic animals into the correct group.

In utero exposure to antiepileptic drugs carries teratogenic risks, but little is known about the potential effects of such agents on neurocognitive development. The results from a large prospective study that set out to address this issue add to the mounting evidence against the use of valproate in women with epilepsy during childbearing years.

Hematopoietic stem cell transplantation for the treatment of childhood cerebral X-linked adrenoleukodystrophy

Preclinical and clinical studies have demonstrated the significance of inflammation and autoantibodies in epilepsy, and the use of immunotherapies in certain situations has become an established practice. Temporal lobe epilepsy can follow paraneoplastic or nonparaneoplastic limbic encephalitis associated with antibodies directed against brain antigens. Here, we focus on a patient with worsening confusion and temporal lobe seizures despite treatment with antiepileptic medications. Serial brain MRIs did not conclusively reveal structural abnormalities, so the patient underwent brain PET/MRI to simultaneously evaluate brain structure and function, revealing bitemporal abnormalities. The patient was diagnosed with voltage-gated potassium channel antibody-related limbic encephalitis based on clinical presentation, imaging findings, and antibody testing. Treatment included the addition of a second antiepileptic agent and oral steroids. His seizures and cognitive deficits improved and stabilized.