Temporal lobe epilepsy represents a major cause of drug-resistant epilepsy. Cognitive impairment is a frequent comorbidity, but the mechanisms are not fully elucidated. We hypothesized that the ...cognitive impairment in drug-resistant temporal lobe epilepsy could be due to perturbations of amyloid and tau signalling pathways related to activation of stress kinases, similar to those observed in Alzheimer's disease. We examined these pathways, as well as amyloid-β and tau pathologies in the hippocampus and temporal lobe cortex of drug-resistant temporal lobe epilepsy patients who underwent temporal lobe resection (n = 19), in comparison with age- and region-matched samples from neurologically normal autopsy cases (n = 22). Post-mortem temporal cortex samples from Alzheimer's disease patients (n = 9) were used as positive controls to validate many of the neurodegeneration-related antibodies. Western blot and immunohistochemical analysis of tissue from temporal lobe epilepsy cases revealed increased phosphorylation of full-length amyloid precursor protein and its associated neurotoxic cleavage product amyloid-β*56. Pathological phosphorylation of two distinct tau species was also increased in both regions, but increases in amyloid-β1-42 peptide, the main component of amyloid plaques, were restricted to the hippocampus. Furthermore, several major stress kinases involved in the development of Alzheimer's disease pathology were significantly activated in temporal lobe epilepsy brain samples, including the c-Jun N-terminal kinase and the protein kinase R-like endoplasmic reticulum kinase. In temporal lobe epilepsy cases, hippocampal levels of phosphorylated amyloid precursor protein, its pro-amyloidogenic processing enzyme beta-site amyloid precursor protein cleaving enzyme 1, and both total and hyperphosphorylated tau expression, correlated with impaired preoperative executive function. Our study suggests that neurodegenerative and stress-related processes common to those observed in Alzheimer's disease may contribute to cognitive impairment in drug-resistant temporal lobe epilepsy. In particular, we identified several stress pathways that may represent potential novel therapeutic targets.
Summary
Objective
To describe mesial temporal lobe ablated volumes, verbal memory, and surgical outcomes in patients with medically intractable mesial temporal lobe epilepsy (mTLE) treated with ...magnetic resonance imaging (MRI)–guided stereotactic laser interstitial thermal therapy (LiTT).
Methods
We prospectively tracked seizure outcome in 20 patients at Thomas Jefferson University Hospital with drug‐resistant mTLE who underwent MRI‐guided LiTT from December 2011 to December 2014. Surgical outcome was assessed at 6 months, 1 year, 2 years, and at the most recent visit. Volume‐based analysis of ablated mesial temporal structures was conducted in 17 patients with mesial temporal sclerosis (MTS) and results were compared between the seizure‐free and not seizure‐free groups.
Results
Following LiTT, proportions of patients who were free of seizures impairing consciousness (including those with auras only) are as follows: 8 of 15 patients (53%, 95% confidence interval CI 30.1–75.2%) after 6 months, 4 of 11 patients (36.4%, 95% CI 14.9–64.8%) after 1 year, 3 of 5 patients (60%, 95% CI 22.9–88.4%) at 2‐year follow‐up. Median follow‐up was 13.4 months after LiTT (range 1.3 months to 3.2 years). Seizure outcome after LiTT suggests an all or none response. Four patients had anterior temporal lobectomy (ATL) after LiTT; three are seizure‐free. There were no differences in total ablated volume of the amygdalohippocampus complex or individual volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus between seizure‐free and non–seizure‐free patients. Contextual verbal memory performance was preserved after LiTT, although decline in noncontextual memory task scores were noted.
Significance
We conclude that MRI‐guided stereotactic LiTT is a safe alternative to ATL in patients with medically intractable mTLE. Individualized assessment is warranted to determine whether the reduced odds of seizure freedom are worth the reduction in risk, discomfort, and recovery time. Larger prospective studies are needed to confirm our preliminary findings, and to define optimal ablation volume and ideal structures for ablation.
Summary
Objective
To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE).
Methods
This ...randomized, single‐blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36‐month follow‐up.
Results
A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1‐sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English‐speaking, dominant‐hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients.
Significance
These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.
Summary
Objective
Electrical source imaging (ESI) is a well‐established approach to localizing the epileptic focus in drug‐resistant focal epilepsy. So far, ESI has been used primarily on interictal ...events. Emerging evidence suggests that ictal ESI is also feasible and potentially useful. We aimed to investigate the diagnostic accuracy of ESI on ictal events using high‐density electroencephalography (EEG).
Methods
We performed ictal ESI on 14 patients (9 with temporal lobe epilepsy) admitted for presurgical evaluation who presented seizures during a long‐term (≥18 h) high‐density EEG recording (13 with 256 electrodes and one with 128 electrodes), and subsequently 8 of them underwent epilepsy surgery (postoperative follow‐up >1 year). Artifact‐free EEG epochs at ictal οnset were selected for further analysis. The predominant ictal rhythm was identified and filtered (±1 Hz around the main frequency). ESI was computed for each time point using an individual head model and a distributed linear inverse solution, and the average across source localizations was localized. For validation, results were compared with the resection area and postoperative outcome.
Results
Ictal ESI correctly localized the epileptic seizure‐onset zone in the resection area in five of six postoperatively seizure‐free patients. Interictal and ictal ESI were concordant in 9 of 14 patients and partially concordant in additional 4 of 14 patients (93%). Divergent solutions were found in only one of the 14 patients (7%).
Significance
Ictal ESI is a promising localization technique in focal epilepsy.
Abstract
INTRODUCTION
Epilepsy surgery, while high successful for lesional epilepsy, can be associated with significant morbidity. The objective was to evaluate the safety profile of chronic ...subthreshold cortical stimulation in patients with seizure foci not amenable to surgical resection.
METHODS
Patients underwent intracranial electroencephalography monitoring. Those with seizure foci that were deemed unsafe for resection were offered trial of continuous subthreshold cortical stimulation via intracranial monitoring electrodes. After successful trial, trial electrodes were replaced with permanent stimulation. Patients with permanent implantation prior to February, 2016, reported their seizure severity and life satisfaction before and after stimulation.
RESULTS
>Eight patients from 2014 to 2016 were included in this study. Age ranged (19-56 years). Intracranial pathologies included: cortical dysplasia (n = 3), encephalomalacia (n = 3), cortical tubers (n = 1), and linear migrational anomaly (n = 1). The duration of intracranial monitoring ranged (3-20 days). All patients experienced were discharged to home (median length of stay: 10 days). No postoperative surgical complications have developed to date (median length of follow-up: 187 days). Patients (n = 4) reported a improvement in seizure severity (worst = 10) from mean 7.5 (SE 0.29) to 1.25 (SE 0.75) and life satisfaction (best = 10) from mean 4.25 (SE 1.03) to 7 (SE 1.1), mean follow-up 8.8 months
CONCLUSION
Our institutional experience shows that chronic cortical stimulation can be safely and effectively performed in appropriately selected patients without postoperative complications. Future investigation will hopefully provide further insight to recently published results into the efficacy of this novel and promising intervention.
The 2017 International League Against Epilepsy classification has defined a three‐tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all ...children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood onset epilepsy syndromes, most of which have both mandatory seizure type(s) and interictal electroencephalographic (EEG) features. Based on the 2017 Classification of Seizures and Epilepsies, some syndrome names have been updated using terms directly describing the seizure semiology. Epilepsy syndromes beginning in childhood have been divided into three categories: (1) self‐limited focal epilepsies, comprising four syndromes: self‐limited epilepsy with centrotemporal spikes, self‐limited epilepsy with autonomic seizures, childhood occipital visual epilepsy, and photosensitive occipital lobe epilepsy; (2) generalized epilepsies, comprising three syndromes: childhood absence epilepsy, epilepsy with myoclonic absence, and epilepsy with eyelid myoclonia; and (3) developmental and/or epileptic encephalopathies, comprising five syndromes: epilepsy with myoclonic–atonic seizures, Lennox–Gastaut syndrome, developmental and/or epileptic encephalopathy with spike‐and‐wave activation in sleep, hemiconvulsion–hemiplegia–epilepsy syndrome, and febrile infection‐related epilepsy syndrome. We define each, highlighting the mandatory seizure(s), EEG features, phenotypic variations, and findings from key investigations.
Summary
We convened an international group of experts to standardize definitions of New‐Onset Refractory Status Epilepticus (NORSE), Febrile Infection‐Related Epilepsy Syndrome (FIRES), and related ...conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in‐person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion‐Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super‐refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.
Objective
18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is widely used in presurgical assessment in patients with drug‐resistant focal epilepsy (DRE) if magnetic resonance imaging ...(MRI) and scalp electroencephalography (EEG) do not localize the seizure onset zone or are discordant.
Methods
In this multicenter, retrospective observational cohort study, we included consecutive patients with DRE who had undergone FDG‐PET as part of their presurgical workup. We assessed the utility of FDG‐PET, which was defined as contributing to the decision‐making process to refer for resection or intracranial EEG (iEEG) or to conclude surgery was not feasible.
Results
We included 951 patients in this study; 479 had temporal lobe epilepsy (TLE), 219 extratemporal epilepsy (ETLE), and 253 epilepsy of uncertain lobar origin. FDG‐PET showed a distinct hypometabolism in 62% and was concordant with ictal EEG in 74% in TLE and in 56% in ETLE (p < .001). FDG‐PET was useful in presurgical decision‐making in 396 patients (47%) and most beneficial in TLE compared to ETLE (58% vs. 44%, p = .001). Overall, FDG‐PET contributed to recommending resection in 78 cases (20%) and iEEG in 187 cases (47%); in 131 patients (33%), FDG‐PET resulted in a conclusion that resection was not feasible. In TLE, seizure‐freedom 1 year after surgery did not differ significantly (p = .48) between patients with negative MRI and EEG‐PET concordance (n = 30, 65%) and those with positive MRI and concordant EEG (n = 46, 68%). In ETLE, half of patients with negative MRI and EEG‐PET concordance and three quarters with positive MRI and concordant EEG were seizure‐free postsurgery (n = 5 vs. n = 6, p = .28).
Significance
This is the largest reported cohort of patients with DRE who received presurgical FDG‐PET, showing that FDG‐PET is a useful diagnostic tool. MRI‐negative and MRI‐positive cases with concordant FDG‐PET results (with either EEG or MRI) had a comparable outcome after surgery. These findings confirm the significance of FDG‐PET in presurgical epilepsy diagnostics.
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