How common is brain atrophy in patients with medial temporal lobe epilepsy?

Purpose: It is unclear whether extrahippocampal brain damage in patients with medial temporal lobe epilepsy (MTLE) is a homogeneous phenomenon, as most data relates to the average volume reduction in groups of patients. This study aimed to evaluate where and how much atrophy is to be expected in an individual patient with MTLE. Methods: High‐resolution T₁ magnetic resonance imaging (MRI) was obtained from 23 consecutive patients with unilateral MTLE and from a matched control group. Parametric tests of voxel‐based gray matter volume evaluated mean regional atrophy in MTLE compared with controls. Gray matter images were then submitted to a voxel by voxel calculation of the fitted receiver operating characteristic (ROC) curve area, plotting the sensitivity versus 1–specificity for a binary classifier (MTLE vs. controls). The area under the curve (AUC) was calculated for each voxel and a resulting three‐dimensional map of gray matter voxel‐wise AUCs was obtained. Results: On average, patients with MTLE showed atrophy in the ipsilateral hippocampus and on a limbic network. Elevated AUC was demonstrated in the ipsilateral hippocampus and medial temporal lobe, the ipsilateral thalamus and occipitotemporal cortex, the ipsilateral cerebellum, the cingulate, the contralateral insula, and the occipitoparietal and dorsolateral prefrontal cortex. Conclusion: This study suggests that the medial temporal lobe, occipitotemporal areas, the cerebellum, the cingulate cortex, the ipsilateral insula, and thalamus are more likely to be atrophied in randomly selected patients with MTLE. Structures such as the orbitofrontal cortex, the contralateral medial temporal areas and insula, the putamen, and the caudate may be atrophied, but not as consistently.     

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PurposeEpilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe.MethodsWe systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies.ResultsOverall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60 months, range 12–72); six patients (35.3%) were seizure free at least 12 month before observation points (median duration 120.5 months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p = 0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p = 0.116) and before reoperation (p = 0.622) was not poorer compared to patients with congruent Video-EEG results.ConclusionsReoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.     

Reduced Pumilio-2 expression in patients with temporal lobe epilepsy and in the lithium–pilocarpine induced epilepsy rat model

ObjectiveDrosophila Pumilio (Pum), a homolog of mammalian Pum2, plays an important role in translational regulation in the central nervous system (CNS), particularly for dendrite outgrowth and neuronal excitability. We investigated the expression pattern and cellular distribution of Pum2 in patients with drug-refractory temporal lobe epilepsy (TLE) and rats with lithium chloride–pilocarpine-induced epilepsy.MethodsReal-time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, and double-labeled immunofluorescence were utilized to determine the expression level and distribution of Pum2 in temporal neocortex tissues from patients with intractable TLE (n = 20) and patients with severe head trauma (n = 20) in addition to the hippocampus and adjacent cortex of rats with lithium chloride–pilocarpine-induced TLE and controls.ResultsPum2 was expressed in the cell bodies and dendrites of neurons but did not colocalize with glial fibrillary acidic protein-positive astrocytes or propidium iodide (PI) in nuclei. The expression of Pum2 was significantly reduced in patients and rats with TLE in comparison to controls (P < 0.05).ConclusionPum2 expression was less in patients with TLE and a rodent model of epilepsy, suggesting that decreased expression of Pum2 may be involved in the pathogenesis of TLE.     

Inositol-requiring protein 1α signaling pathway is activated in the temporal cortex of patients with mesial temporal lobe epilepsy

Accumulating evidence suggests that repeated seizures could induce endoplasmic reticulum (ER) stress. Inositol-requiring protein 1α (IRE1α) is a vital pro-apoptotic molecule in ER stress, but it remains unclear whether the signaling pathway mediated by IRE1α is involved in human temporal lobe epilepsy. In this report, we investigated IRE1α-mediated ER stress pro-apoptotic signaling pathway in resected anterior temporal neocortex from 32 patients with intractable mesial temporal lobe epilepsy by immunofluorescence and western blot analysis. Our results indicate that chronic epilepsy induces ER stress, and IRE1α-mediated ER stress apoptotic signaling pathway is involved in brain damage after repeated seizures, which may provide a new therapeutic target to prevent brain damage caused by epilepsy.     

Does early postoperative drug regimen impact seizure control in patients undergoing temporal lobe resections?

Objective

To evaluate the impact of postoperative antiepileptic drug (AED) load on seizure control in patients who underwent surgical treatment for pharmacoresistant mesiotemporal lobe epilepsy during the first two postoperative years.

Patients and methods

532 consecutive patients (48.7% males and 51.7% females) who underwent surgical treatment for mesiotemporal lobe epilepsy were retrospectively evaluated regarding effects of AED load on seizures control during the first 2 years following epilepsy surgery. We analyzed whether postoperative increases in postoperative AED load are associated with better seizure control in patients initially not seizure free, and if postoperative decreases in postoperative AED load would increase the risk for seizure persistence or recurrence. For statistical analyses, Fisher’s exact and Wilcoxon test were applied.

Results

68.9, 64.0 and 59.1% of patients were completely seizure free (Engel Ia) at 3, 12 and 24 months after surgery, respectively. Patients in whom daily drug doses were increased did not have a higher rate of seizure freedom at any of the three follow-up periods. Of 16 patients achieving secondary seizure control at 12 months after surgery, only one did so with an increase in drug load in contrast to 15 patients who experienced a running down of seizures independent of drug load increases. Decreases in drug load did not significantly increase the risk for seizure recurrence. Of postoperatively seizure free patients at 3 months after surgery in whom AED were consequently reduced, 85% remained completely seizure free at 1 year and 76% at 1 year after surgery, respectively, as opposed to 86% each when AED was not reduced (differences n.s.). Mean daily drug load was significantly lower in seizure free patients at 12 and 24 months compared to patients with ongoing seizures.

Conclusion

In this large patient cohort stratified to the epilepsy syndrome neither did a postoperative reduction in drug load significantly increase the risk for seizure relapse nor did increases in drug dosages lead to improved seizure control. Mean drug load was on average lower in seizure free- than non-seizure free patients at 12 and 24 months of follow-up. Secondary seizure control after initial postoperative seizures in > 90% of cases occurred as a running down, independent of an AED increase. Thus, the effect of the surgical intervention rather than the postoperative drug regimen was the key determinant for seizure control. This finding supports a curative role of temporal lobe surgery rather than an effect rendering the majority of patients’ pharmacoresponsive with a critical role of the antiepileptic drug regime for seizure control.

     

Idiopathic mesial temporal lobe epilepsy: a syndrome with complex inheritance?

Journal of Neurology -