Intractable Temporal Lobe Epilepsy Research Articles

3D bioprinted in vitro epilepsy models for pharmacological evaluation in temporal lobe epilepsy

This study introduces a novelin vitromodel for intractable temporal lobe epilepsy (TLE) utilizing 3D bioprinting technology, aiming to replicate the complex neurobiological characteristics of TLE more accurately. Primary neural cell constructs were fabricated and subjected to epileptiform-inducing conditions, fostering synaptic proliferation and neuronal loss. Systematically electrophysiological and immunofluorescent analyses indicated that significant synaptic connectivity and sustained epileptiform activities within the constructs akin to those observed in human epilepsy models. Notably, the model responded to treatments with phenytoin and tetrodotoxin, illustrating its potential utility in drug response kinetics studies. Furthermore, we performed drug permeability simulations using COMSOL Multiphysics to analyze the diffusion characteristics of these drugs within the constructs. These results confirm that our 3D bioprinted neural model provides a physiologically relevant and ethically sustainable platform, which is beneficial for studying TLE mechanisms and developing therapeutic strategies with high accuracy and clinical relevance.

De novo Postoperative Postictal Psychosis Improved with Vagal Nerve Stimulation: A Case Report

Post-ictal psychosis can manifest in patients with intractable temporal lobe epilepsy following temporal lobectomy, presenting with psychiatric symptoms such as hallucinations, depression, and aggressive behavior. This case study details a 43-year-old male with refractory focal epilepsy who developed de novo post-ictal psychosis after undergoing left anterior temporal lobectomy and hippocampal ablation. Initially, the patient achieved seizure control, but later experienced recurrent focal seizures and subsequent post-ictal psychosis, characterized by aggression, paranoia, and hallucinations. Despite multiple hospitalizations and trials of antipsychotic medications, no improvement was observed. Following the placement of a vagal nerve stimulator, the patient’s psychotic episodes ceased, allowing for the discontinuation of antipsychotic medications. This case highlights the critical need for psychiatric monitoring in epilepsy patients post temporal lobectomy and underscores the potential of vagal nerve stimulator in managing peri-ictal psychotic episodes. Further research is essential to elucidate the mechanisms by which vagal nerve stimulator exerts its antipsychotic effects and to establish guidelines for its use in this patient population.

Location-based selection of the surgical approach to preserve the hippocampus in lesion-associated temporal lobe epilepsy

Background and objectivesSurgical resections for lesions associated with intractable temporal lobe epilepsy (TLE) offers good seizure outcomes.However, the necessity of hippocampectomy in addition to lesionectomy is controversial, especially when the hippocampus is not involved by the lesion. Lesionectomy alone, preserving the hippocampus by an appropriate surgical approach, might offer good seizure outcomes while maintaining neurocognitive function. In the present study, the aims were to examine the surgical strategy for lesions associated with TLE and to present how to select surgical approaches to preserve the hippocampus. MethodsA total of 22 consecutive lesion-associated TLE patients who underwent lesionectomy alone were retrospectively reviewed. The surgical approach, transsylvian, transorbital, subtemporal, supracerebellar transtentorial, or transcortical approach, was selected based on the location of the lesion. Postoperative seizure outcomes were classified by the Engel classification. Neurocognitive outcomes were assessed before and after surgery if possible. The pathology, the extent of resection, and lesion recurrence were reviewed. ResultsThe transsylvian approach was selected in six patients, the transorbital approach in one patient, the subtemporal approach in three patients, the supracerebellar transtentorial approach in five patients, and the transcortical approach in seven patients. Eighteen of 22 (81.8 %) patients achieved Engel’s class I or II good seizure outcomes. No patients had neurocognitive deterioration after surgery. Twelve patients had various types of brain tumors, and ten patients had non-tumorous lesions. Gross total resection was achieved in 21 patients. All patients had no recurrence. ConclusionFor patients with lesion-associated TLE, lesionectomy alone by the appropriate surgical approach offers satisfactory seizure outcomes while preserving hippocampus.

Surgical treatment may improve depressive and hysterical traits in temporal lobe epilepsy with hippocampal sclerosis: Study using the Minnesota Multiphasic Personality Inventory.

The influence of surgeries on psychiatric symptoms and personality traits is not well known in patients with intractable temporal lobe epilepsy (TLE). We investigated changes in personality traits with respect to postoperative seizure outcomes, etiology, side of surgery, and sex differences. Clinical information was retrospectively collected for 44 patients whose Minnesota Multiphasic Personality Inventory (MMPI) was examined before and 1 year after surgical treatment for drug-resistant TLE. Postoperative changes in MMPI T-scores were analyzed using a paired t-test. Participants were divided into two groups based on postoperative seizure outcome, the presence or absence of hippocampal sclerosis (HS) as the etiology, side of surgery, and sex differences. The effect of these clinical factors on postoperative changes in MMPI T-scores was evaluated using analysis of covariance (P-values < 0.05). The hypochondria (Hs) scale decreased significantly in all patients (p = 0.022). The postoperative seizure-free group had a significant decrease in the depression (D) scale (p = 0.037). The HS group had significant decreases in the D scale and the hysteria (Hy) scale (p = 0.016 and 0.004, respectively), and a significant increase in the masculinity-femininity (Mf) scale (p = 0.009). No significant differences existed between the sides of surgery or sex. Depressive traits were improved in patients with postoperative seizure freedom. Depressive and hysterical traits were improved in patients with HS, which may be attributed to a reduction in anxiety and fear associated with aura. Most personality traits are not significantly changed or exacerbated by surgical treatment of TLE.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Effect of Sevoflurane Anesthesia on Intraoperative Spikes, High-Frequency Oscillations, and Phase-Amplitude Coupling in MRI-Normal Hippocampus.

The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFOs), and phase-amplitude coupling using a modulation index in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography in identifying the epileptogenic hippocampus during sevoflurane administration. Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography evaluation. Patients were assigned to the Ictal (+) or Ictal (-) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. Intraoperative electrocorticography was performed under 0.5 and 1.5 minimum alveolar concentration of sevoflurane. The rates of spikes, ripples, fast ripples (FRs), ripples on spikes, FRs on spikes, and MI HFO(3-4 Hz) were evaluated. During the intraoperative electrocorticography procedure, sevoflurane administration was found to significantly increase the rate of spikes, ripples on spikes, fast ripples on spikes, and MI HFO(3-4 Hz) in the Ictal (+) group (P < 0.01). By contrast, the Ictal (-) group exhibited a paradoxical increase in the rate of ripples and fast ripple (P < 0.05). Our findings indicate that the administration of sevoflurane during intraoperative electrocorticography in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, ripples on spikes, fast ripples on spikes, and MI (HFO 3-4)) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and fast ripple in the nonepileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the nonepileptogenic hippocampus.

Role of T2 relaxometry in localization of mesial temporal sclerosis and the degree of hippocampal atrophy in patients with intractable temporal lobe epilepsy: A cross sectional study.

Mesial temporal lobe epilepsy is one of the most common causes of refractory epilepsy worldwide. A good percentage of patients do not have detectable hippocampal atrophy on magnetic resonance imaging (MRI). The objective of this study is to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable temporal lobe epilepsy (TLE). T2 relaxometry can also be used to correlate the clinical severity of the disease with the relaxometry readings in those who have hippocampal atrophy as well as those who do not. Thirty two patients having clinical and electrophysiological features of TLE were enrolled and a MRI brain with T2 relaxometry was done. Hippocampal T2 relaxometry values were calculated in the head, body, and tail of the hippocampus and average T2 relaxometry values were calculated, and a comparison was done with the controls. For patients with unilateral involvement, the contralateral side was taken as control and in cases of bilateral involvement, controls were identified from normal subjects. T2 relaxometry is found to be superior to MR visual analysis in the early detection of cases of hippocampal sclerosis where there is no atrophy on visual analysis. Nine out of 32 patients (28%) were normal on MR visual analysis; however, showed increased values on T2 relaxometry, correlating with clinical and electrophysiological diagnosis. The rest of the patients with hippocampal atrophy showed a correlation of T2 relaxometry values with the degree of atrophy. The hippocampal T2 measurement is thus more sensitive and specific. The study was clinically significant (p < .0001). There was a mild female predilection of the disease and there was no significant correlation with comorbidities. There was a strong positive correlation with patients having a history of febrile seizures in childhood. T2 relaxometry may accurately lateralize the majority of patients with persistent TLE and offers evidence of hippocampus injury in those patients who do not show evidence of atrophy on MRI and also the T2 relaxometry values correlated with the degree of atrophy. Early identification of hippocampal sclerosis is crucial for prompt management which offers better outcomes.

Seizure and anatomical outcomes of repeat laser amygdalohippocampotomy for temporal lobe epilepsy: A single-institution case series

ObjectiveIn patients with treatment-refractory temporal lobe epilepsy (TLE), a single stereotactic laser interstitial thermotherapy (LITT) procedure is sometimes insufficient to ablate epileptogenic tissue, particularly the medial structures often implicated in TLE. In patients with seizure recurrence after initial ablation, the extent to which a second ablation may achieve improved seizure outcomes is uncertain. The objective of this study was to investigate the feasibility and potential efficacy of repeat LITT amygdalohippocampotomy as a worthwhile strategy for intractable temporal lobe epilepsy by quantifying changes to targeted mesial temporal lobe structures and seizure outcomes. MethodsPatients who underwent two LITT procedures for drug-resistant mesial TLE at our institution were included in the study. Lesion volumes for both procedures were calculated by comparing post-ablation intraoperative sequences to preoperative anatomy. Clinical outcomes after the initial procedure and repeat procedure were classified according to Engel scores. ResultsFive consecutive patients were included in this retrospective case series: 3 with right- and 2 with left-sided TLE. The median interval between LITT procedures was 294 days (range: 227–1918). After the first LITT, 3 patients experienced class III outcomes, 1 experienced a class IV, and 1 experienced a class IB outcome. All patients achieved increased seizure freedom after a second procedure, with class I outcomes (3 IA, 2 IB). ConclusionsRepeat LITT may be sufficient to achieve satisfactory seizure outcomes in some individuals who might otherwise be considered for more aggressive resection or palliative neuromodulation. A larger study to establish the potential value of repeat LITT amygdalohippocampotomy vs. other re-operation strategies for persistent, intractable temporal lobe epilepsy is worth pursuing.

SHORT-TERM SURGICAL OUTCOMES IN PATIENTS WITH DRUG-RESISTANT EPILEPSY DUE TO LESIONAL TEMPORA

Objectives: To describe the outcome of 35 cases of drug-resistant epilepsy due to the lesional temporal lobe surgery at Vietduc University Hospital from May 2018 to September 2022. Methods: A prospective description combined with retrospective, longitudinal follow-up of all patients diagnosed with drug resistance due to lesional temporal lobe epilepsy undergoing surgery at Vietduc University Hospital was conducted. Results: 35 cases of intractable lesional temporal lobe epilepsy surgery, male/female 1.5/1, partial seizures with loss of consciousness accounted for 99%, and 2/3 of cases occurred without aura. Seizure-free (post-operation 1 month) (Engel I) accounted for 74.3%, and the remaining (25.7%) had improved seizures (Engel 2, 3). Complications after surgery accounted for 17.1%, and there were no cases of death. Conclusion: Surgical treatment for drug resistance due to lesional temporal lobe epilepsy is safe and very effective, with a low complication rate.

The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1

Epilepsy, one of the most common neurological disorders, is characterized by spontaneous recurrent seizures. Temporal lobe epilepsy (TLE) is one of the most common medically intractable seizure disorders. Traf2-and NcK-interacting kinase (TNIK) has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders, but its role in epilepsy remains unclear. In this study, we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpine-induced rat model of epilepsy by western blotting, immunofluorescence, and immunohistochemistry. A pentylenetetrazole (PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy. Coimmunoprecipitation (Co-IP)/mass spectrometry (MS) was used to identify the potential mechanism. Through Co-IP, we detected and confirmed the main potential TNIK interactors. Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density (PSD) fractions. We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls. NCB-0846 delayed kindling progression and decreased seizure severity. Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi, notably CaMKII. Co-IP showed that TNIK might correlate with endogenous GRIA1, SYN2, PSD-95, CaMKIV, GABRG1, and GABRG2. In addition, the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling. Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

Metabolic profiles and correlation with surgical outcomes in mesial versus neocortical temporal lobe epilepsy.

Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.

Intractable Epilepsy Controlled by Neurofeedback and Adjunctive Treatments: A Case Report

This case report documents the treatment of a female patient with intractable temporal lobe epilepsy with secondary generalization. At the age of 13, the patient was hospitalized with ~120 seizures in a day, some of which were life-threatening. After hospital discharge, despite a regimen of multiple antiseizure medications, the patient still experienced ~90 seizures per day. After the interventions described in this work, over 500 neurofeedback sessions guided by EEG or qEEG data and adjunctive treatments including mental skills coaching, the patient became seizure- and medication-free, progressing from poor academic performance and inability to carry out normal daily life to attending university as a student athlete playing an NCAA Division I sport. This case emphasizes that, with professional guidance and supervision, it is possible for people with epilepsy or their caregivers to provide the extensive, long-term neurofeedback and adjunctive training necessary for reduction and control of intractable seizures.

Magnetoencephalographic spikes with small spikes on simultaneous electroencephalography have high spatial clustering in temporal lobe epilepsy

ObjectiveTo classify magnetoencephalographic (MEG) spikes according to the findings of simultaneous scalp electroencephalography (EEG) to study dipole estimation in patients with temporal lobe epilepsy. MethodsWe analyzed MEG and simultaneous scalp EEG in 27 patients with intractable temporal lobe epilepsy. We classified MEG spikes into three groups (H-EM-spikes, L-EM-spikes, M-spikes) based on the amplitude of simultaneous EEG (50 μV or higher, lower than 50 μV, no spike morphology on EEG, respectively). We calculated parameters of the dipoles, such as goodness of fit (GOF), current moment, and location. ResultsWe detected 707 MEG spikes, consisting of 175 H-EM-spikes, 245 L-EM-spikes, and 287 M-spikes. Dipoles of H-EM-spikes showed the highest current moment among the three spike groups. Dipoles of L-EM-spikes showed the highest GOF, a moderate current moment, the highest density to cluster, and the highest proportion of being located in the temporal lobe among the three groups. Dipoles of M-spikes showed the lowest GOF and current moment among the three groups. ConclusionsThe characteristics of the dipoles of the MEG spikes differ depending on the simultaneous scalp EEG findings, though most of the MEG spikes were located in the temporal lobe. MEG spikes with concurrent small spikes on simultaneous scalp EEG may have higher spatial clustering in temporal lobe epilepsy.

Epilepsy surgery for dominant-side mesial temporal lobe epilepsy without hippocampal sclerosis

Although anterior temporal lobectomy (ATL) is an established surgery for medically intractable mesial temporal lobe epilepsy (MTLE), it can harm memory function, especially in dominant-side MTLE patients without hippocampal sclerosis (HS). To avoid this complication, multiple hippocampal transection (MHT) was developed, but its efficacy has not been fully elucidated. We report the detailed treatment results of MHT compared with that of ATL. We retrospectively analysed the records of 30 patients who underwent surgery for dominant-side MTLE. ATL was completed for 23 patients with HS, and MHT was completed for 7 patients without HS. The seizure control status, number of anti-seizure medicines, neurocognitive function, and psychiatric disorders of each patient were reviewed. The mean follow-up period was 70 months. Seizure control of Engel class I was achieved in 16 patients (70%) in the ALT group versus 5 patients (71%) in the MHT group. The mean number of anti-seizure medicines administered in the ATL group changed significantly from 2.4 to 1.9 (p = 0.01), while that in the MHT group was unchanged (from 2.1 to 2.0, p = 0.77). Eleven patients (48%) in the ATL group developed psychiatric disorders during the postoperative follow-up period, whereas no psychological complications were observed in the MHT group. Neither group showed neurocognitive decline after the surgery in any of the WAIS-III or WMS-R subtests. In conclusion, MHT may achieve reasonable postoperative seizure reduction, preserve neurocognitive function, and reduce postoperative psychiatric complications. Therefore, it can be considered as a therapeutic option for dominant-side MTLE without HS.

Visual outcomes after anterior temporal lobectomy and transsylvian selective amygdalohippocampectomy: A quantitative comparison of clinical and diffusion data.

Anterior temporal lobectomy (ATL) and transsylvian selective amygdalohippocampectomy (tsSAHE) are effective treatment strategies for intractable temporal lobe epilepsy but may cause visual field deficits (VFDs) by damaging the optic radiation (OpR). Due to the OpR's considerable variability and because it is indistinguishable from surrounding tissue without further technical guidance, it is highly vulnerable to iatrogenic injury. This imaging study uses a multimodal approach to assess visual outcomes after epilepsy surgery. We studied 62 patients who underwent ATL (n=32) or tsSAHE (n=30). Analysis of visual outcomes was conducted in four steps, including the assessment of (1) perimetry outcome (VFD incidence/extent, n=44/40), (2) volumetric OpR tractography damage (n=55), and the (3) relation of volumetric OpR tractography damage and perimetry outcome (n=35). Furthermore, (4) fixel-based analysis (FBA) was performed to assess micro- and macrostructural changes within the OpR following surgery (n=36). Altogether, 56% of all patients had postoperative VFDs (78.9% after ATL, 36.36% after tsSAHE, p=.011). VFDs and OpR tractography damage tended to be more severe within the ATL group (ATL vs. tsSAHE, integrity of contralateral upper quadrant: 65% vs. 97%, p=.002; OpR tractography damage: 69.2 mm3 vs. 3.8 mm3 , p=.002). Volumetric OpR tractography damage could reliably predict VFD incidence (86% sensitivity, 78% specificity) and could significantly explain VFD extent (R2 =.47, p=.0001). FBA revealed a more widespread decline of fibre cross-section within the ATL group. In the context of controversial visual outcomes following epilepsy surgery, this study provides clinical as well as neuroimaging evidence for a higher risk and greater severity of postoperative VFDs after ATL compared to tsSAHE. Volumetric OpR tractography damage is a feasible parameter to reliably predict this morbidity in both treatment groups and may ultimately support personalized planning of surgical candidates. Advanced diffusion analysis tools such as FBA offer a structural explanation of surgically induced visual pathway damage, allowing noninvasive quantification and visualization of micro- and macrostructural tract affection.

Transplantation of neurogenic-fusionogenic embryonic stem cells modified to overexpress GABA into a model of temporal lobe epilepsy: Promises and potential pitfalls.

Cell-based therapy is likely to become a clinically useful tool to treat severe neurological disease. Disease states such as intractable temporal lobe epilepsy will be candidates for this type of therapeutic approach. Embryonic stem cells are pluripotent, and are considered a viable source for cell replacement strategies. Embryonic stem cells can be genetically manipulated to express reporter molecules, and they can be forced into neural differentiation by controlling the expression of key transcription factors. One strategy for the treatment of temporal lobe epilepsy is to transplant enriched populations of transplantable GABAergic neurons into the damaged, epileptogenic, hippocampus. The goal would be to suppress seizures, and to replace and repair damaged circuits. We genetically engineered an embryonic stem cell -derived neurogenic, fusionogenic cell line with GAD65 and transplanted them into an animal model of temporal lobe epilepsy. We found some evidence of seizure suppression, and also evidence of widespread dispersion from the transplantation site. The pattern of staining of embryonic stem cell reporter molecule that was detected, suggested a pathotropism, and selective involvement of reportedly fusionogenic cell populations within the host. We feel that the evidence suggests that embryonic stem cell-derived neural cells might have a significant capacity to fuse with host neurons, which can cloud the interpretation of cellular replacement and circuit repair. This study, and other investigations that have reported stem cell fusion events in the transplanted host, reveal embryonic stem cell capacities that may not be fully appreciated. More research is needed to fully reveal the potential of cellular therapies using stem cells.

Pre-surgical features of intrinsic brain networks predict single and joint epilepsy surgery outcomes

Despite the effectiveness of surgical interventions for the treatment of intractable focal temporal lobe epilepsy (TLE), the substrates that support good outcomes are poorly understood. While algorithms have been developed for the prediction of either seizure or cognitive/psychiatric outcomes alone, no study has reported on the functional and structural architecture that supports joint outcomes. We measured key aspects of pre-surgical whole brain functional/structural network architecture and evaluated their ability to predict post-operative seizure control in combination with cognitive/psychiatric outcomes. Pre-surgically, we identified the intrinsic connectivity networks (ICNs) unique to each person through independent component analysis (ICA), and computed: (1) the spatial–temporal match between each person’s ICA components and established, canonical ICNs, (2) the connectivity strength within each identified person-specific ICN, (3) the gray matter (GM) volume underlying the person-specific ICNs, and (4) the amount of variance not explained by the canonical ICNs for each person. Post-surgical seizure control and reliable change indices of change (for language [naming, phonemic fluency], verbal episodic memory, and depression) served as binary outcome responses in random forest (RF) models. The above functional and structural measures served as input predictors. Our empirically derived ICN-based measures customized to the individual showed that good joint seizure and cognitive/psychiatric outcomes depended upon higher levels of brain reserve (GM volume) in specific networks. In contrast, singular outcomes relied on systematic, idiosyncratic variance in the case of seizure control, and the weakened pre-surgical presence of functional ICNs that encompassed the ictal temporal lobe in the case of cognitive/psychiatric outcomes. Our data made clear that the ICNs differed in their propensity to provide reserve for adaptive outcomes, with some providing structural (brain), and others functional (cognitive) reserve. Our customized methodology demonstrated that when substantial unique, patient-specific ICNs are present prior to surgery there is a reliable association with poor post-surgical seizure control. These ICNs are idiosyncratic in that they did not match the canonical, normative ICNs and, therefore, could not be defined functionally, with their location likely varying by patient. This important finding suggested the level of highly individualized ICN’s in the epileptic brain may signal the emergence of epileptogenic activity after surgery.

Increased uptake of the P2X7 receptor radiotracer 18 F-JNJ-64413739 in the brain and peripheral organs according to the severity of status epilepticus in male mice.

The P2X7 receptor (P2X7R) is an important contributor to neuroinflammation, responding to extracellularly released adenosine triphosphate. Expression of the P2X7R is increased in the brain in experimental and human epilepsy, and genetic or pharmacologic targeting of the receptor can reduce seizure frequency and severity in preclinical models. Experimentally induced seizures also increase levels of the P2X7R in blood. Here, we tested 18 F-JNJ-64413739, a positron emission tomography (PET) P2X7R antagonist, as a potential noninvasive biomarker of seizure-damage and epileptogenesis. Status epilepticus was induced via an intra-amygdala microinjection of kainic acid. Static PET studies (30 min duration, initiated 30 min after tracer administration) were conducted 48 h after status epilepticus via an intravenous injection of 18 F-JNJ-64413739. PET images were coregistered with a brain magnetic resonance imaging atlas, tracer uptake was determined in the different brain regions and peripheral organs, and values were correlated to seizure severity during status epilepticus. 18 F-JNJ-64413739 was also applied to ex vivo human brain slices obtained following surgical resection for intractable temporal lobe epilepsy. P2X7R radiotracer uptake correlated strongly with seizure severity during status epilepticus in brain structures including the cerebellum and ipsi- and contralateral cortex, hippocampus, striatum, and thalamus. In addition, a correlation between radiotracer uptake and seizure severity was also evident in peripheral organs such as the heart and the liver. Finally, P2X7R radiotracer uptake was found elevated in brain sections from patients with temporal lobe epilepsy when compared to control. Taken together, our data suggest that P2X7R-based PET imaging may help to identify seizure-induced neuropathology and temporal lobe epilepsy patients with increased P2X7R levels possibly benefitting from P2X7R-based treatments.

Functional Anterior Temporal Lobectomy for Temporal Lobe Epilepsy: A Novel, Alternative, and Less Invasive Therapy.

Anterior temporal lobectomy is the most effective treatment for intractable temporal lobe epilepsy (TLE). However, patients are reluctant to choose this surgery for fear of risks after large frontotemporal craniotomy, and epileptologists likewise have a cautious attitude because of surgical trauma. Functional anterior temporal lobectomy (FATL) is a minimally invasive surgery procedure for addressing the above concerns. To report preliminary data on this procedure and its safety and efficacy for treating TLE. This consecutive case series study was conducted between October 2020 and September 2021. Patients with TLE underwent FATL by minicraniotomy with a diameter of 3 cm. Surgery duration, postoperative complications, and seizure control are described herein. Seizure outcomes were classified using Engel classifications. A total of 25 patients undergoing FATL for TLE were enrolled. The median epilepsy duration was 8 years. The median surgery duration was 165 min. The median blood loss was 100 mL. The median postoperative hospital stay was 8 days. No deaths occurred after surgery. Only 1 patient presented with a cerebrospinal fluid disorder that was successfully treated using a ventriculoperitoneal shunt. At the last follow-up, 23 patients (92%) were seizure-free (Engel-Ia), 1 patient remained substantially improved (Engel-II), and 1 patient obtained worthwhile seizure reduction (Engel-III). Our pilot study suggests that FATL is a viable surgical therapy for TLE. This method has the advantages of minimal invasiveness and high seizure-free rate. A controlled trial is warranted to verify the efficacy and safety of FATL comparing with anterior temporal lobectomy.

Transcortical selective amygdalohippocampectomy for intractable mesial temporal lobe epilepsy: a review of outcomes in a single center

Introduction: Various surgical procedures have been found to effectively treat intractable temporal lobe epilepsy (TLE), including transcortical selective amygdalohippocampectomy (SAH), which is intended to protect the temporal lobe and to prevent interference with vascular structure. This research analyzed the outcome of post-operative seizure-free with transcortical selective amygdalohippocampectomy for intractable mesial temporal lobe epilepsy patients in a minimum two-year follow-up after surgery. Methods: Data of one hundred ninety-two patients who had undergone transcortical selective amygdalohippocampectomy for non-lesional, medically intractable, temporal lobe epilepsy were analyzed. Result: The statistical analysis indicated that Focal to Bilateral Tonic-Clonic Seizure had a more significant outcome (p=0.019) than other seizures. In all research subjects, after three, six, and twelve years of follow-up, the chance for a seizure-free after surgery was respectively 93.2 percent, 67.9 percent, and 36.7 percent with a median average survival period for all subjects of 11.00 years (95 % CI: 8.55 – 13.44) Conclusions: Transcortical selective amygdalohippocampectomy is an effective therapy for intractable mesial temporal lobe epilepsy and provides a satisfactory outcome. The transcortical approach allows an appropriate operative field by careful dissection with limited retraction to eliminate the epileptogenic target while preventing damage to the underlying vascular and cortical structures.