Extratemporal Lobe Research Articles

NCOG-10. LONGITUDINAL MULTIDISCIPLINARY MONITORING OF NEUROCOGNITIVE FUNCTION FOR COLLOID CYST RESECTION: THE IMPACT OF SURGERY

Abstract Endoscopic resection of colloid cysts, a rare pathology of the third ventricle, is now accepted clinical practice. Owing to their location proximal to numerous deep gray nuclei and to the forniceal columns, colloid cysts have always been feared to cause cognitive decline, whether operated on or not. Detailed cognitive testing before and after endoscopic resection, however, has rarely been described. Thus, out objective was to determine the neurocognitive effects of endoscopic colloid cyst resection. We analyzed formal pre- and postoperative neuropsychological testing performed in 20 patients undergoing endoscopic colloid cyst resection. Performance was compared either for each individual patient on a test-by-test basis or according to aggregated neuropsychological factor scores grouped via expert census. A clinical change was defined significant if (i) reaching statistical significance, and (ii) it was greater than 1.5 times the standard deviation of the preoperative performance distribution. Overall, 20 adult patients with colloid cysts (diameter 13.3 ± 1.3 mm) underwent matched pre- and postoperative testing generating 679 data points. No patient had a significant change in cognitive performance. When neurocognitive metrics assessing cognitive functions typically subsumed by the temporal (p = 0.35), extratemporal (p = 0.20), occipitoparietal (p = 0.31), or frontal lobes (p = 0.11), no statistically significant difference was observed between pre- and postoperative cognitive performance. No significant differences emerged when factor scores were generated according to composite score of different neurocognitive domains: attention (p = 0.32), executive function (p = 0.14), language (p = 0.98), and visuospatial function (p = 0.42). In conclusion, neuropsychological testing allows for the careful longitudinal monitoring of cognitive status and the identification of patients who may benefit from pre- and postoperative cognitive rehabilitation, and should be used as a valuable surgical psychometric marker and adjuvant. No significant cognitive decline was observed, again confirming the safety of endoscopic colloid cyst resection.

Acute effects of Mozart K.448 on interictal epileptiform discharges in adult patients with drug-resistant focal epilepsy: A crossover randomized controlled trial

BackgroundThis study aimed to validly assess the efficacy of Mozart K.448 on reducing interictal epileptiform discharges (IEDs) in adult patients with drug-resistant focal epilepsy (DRE). MethodsThis is a crossover RCT study. Adults with DRE were included. Stratified 1:1 randomization by epileptic foci i.e., temporal versus extratemporal foci, was performed. Intervention consisted of two study arms i.e., “Mozart arm” and “Control arm”. Study period encompassed 2 consecutive nights, each night consisted of baseline and intervention period. Outcomes were IED number and proportion of patients with significant IED reduction i.e., reduction ≥ 25 %. Within-group, within-subject and between-group analyses were used to test differences of IED number when listened to the Mozart piece as compared with baseline or with Control. ResultsTwenty-six patients were randomized; 13 in Mozart and 13 in Control arm. Overall, 16 (61.54 %) out of 26 patients had significant IED reduction when listening to the Mozart piece, as compared with only 7 (26.92 %) when continuing sleep (silence). Between-group analysis showed that IED number during intervention period i.e., listening to the Mozart piece in Mozart arm and silence in Control arm was significantly different, with a lower number in Mozart arm, 39.5 (IQR 89) vs 56.5 (IQR 114); p = 0.007. ConclusionsOur study demonstrates an acute effect of the Mozart K.448 on reducing IEDs in adult patients with DRE. Patients with temporal rather than extratemporal lobe epilepsy better responded to the Mozart piece. Mozart K.448 is safe and feasible in real practice. Further RCT study assessing its long-term effect is warranted. Trial registrationThai Clinical Trials Registry, TCTR20231019005, 19 October 2023, “retrospectively registered”

Augmented Reality in Extratemporal Lobe Epilepsy Surgery.

Background: Epilepsy surgery for extratemporal lobe epilepsy (ETLE) is challenging, particularly when MRI findings are non-lesional and seizure patterns are complex. Invasive diagnostic techniques are crucial for accurately identifying the epileptogenic zone and its relationship with surrounding functional tissue. Microscope-based augmented reality (AR) support, combined with navigation, may enhance intraoperative orientation, particularly in cases involving subtle or indistinct lesions, thereby improving patient outcomes and safety (e.g., seizure freedom and preservation of neuronal integrity). Therefore, this study was conducted to prove the clinical advantages of microscope-based AR support in ETLE surgery. Methods: We retrospectively analyzed data from ten patients with pharmacoresistant ETLE who underwent invasive diagnostics with depth and/or subdural grid electrodes, followed by resective surgery. AR support was provided via the head-up displays of the operative microscope, with navigation based on automatic intraoperative computed tomography (iCT)-based registration. The surgical plan included the suspected epileptogenic lesion, electrode positions, and relevant surrounding functional structures, all of which were visualized intraoperatively. Results: Six patients reported complete seizure freedom following surgery (ILAE 1), one patient was seizure-free at the 2-year follow-up, and one patient experienced only auras (ILAE 2). Two patients developed transient neurological deficits that resolved shortly after surgery. Conclusions: Microscope-based AR support enhanced intraoperative orientation in all cases, contributing to improved patient outcomes and safety. It was highly valued by experienced surgeons and as a training tool for less experienced practitioners.

Multi-Graph Assessment of Temporal and Extratemporal Lobe Epilepsy in Resting-State fMRI

Epilepsy is a common neurological disorder that affects millions of people worldwide, disrupting brain networks and causing recurrent seizures. In this regard, investigating the distinctive characteristics of brain connectivity is crucial to understanding the underlying neural processes of epilepsy. However, the various graph-theory frameworks and different estimation measures may yield significant variability among the results of different studies. On this premise, this study investigates the brain network topological variations between patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE) using both directed and undirected network connectivity methods as well as different graph-theory metrics. Our results reveal distinct topological differences in connectivity graphs between the two epilepsy groups, with TLE patients displaying more disassortative graphs at lower density levels compared to ETLE patients. Moreover, we highlight the variations in the hub regions across different network metrics, underscoring the importance of considering various centrality measures for a comprehensive understanding of brain network dynamics in epilepsy. Our findings suggest that the differences in brain network organization between TLE and ETLE patients could be attributed to the unique characteristics of each epilepsy type, offering insights into potential biomarkers for type-specific epilepsy diagnosis and treatment.

Interictal blood-brain barrier dysfunction in piriform cortex of people with epilepsy.

The piriform cortex is considered to be highly epileptogenic. Its resection during epilepsy surgery is a predictor for postoperative seizure freedom in temporal lobe epilepsy. Epilepsy is associated with a dysfunction of the blood-brain barrier. We investigated blood-brain barrier dysfunction in the piriform cortex of people with temporal lobe epilepsy using quantitative T1-relaxometry. Gadolinium-based contrast agent was administered ictally and interictally in 37 individuals before undergoing quantitative T1-relaxometry. Postictal and interictal images were co-registered, and subtraction maps were created as biomarkers for peri-ictal (∆qT1interictal-postictal) and interictal (∆qT1noncontrast-interictal) blood-brain barrier dysfunction. Values were extracted for the piriform cortex, hippocampus, amygdala, and the whole cortex. In temporal lobe epilepsy (n = 14), ∆qT1noncontrast-interictal was significantly higher in the piriform cortex than in the whole cortex (p = 0.02). In extratemporal lobe epilepsy (n = 23), ∆qT1noncontrast-interictal was higher in the hippocampus than in the whole cortex (p = 0.05). Across all individuals (n = 37), duration of epilepsy was correlated with ∆qT1noncontrast-interictal (ß = 0.001, p < 0.001) in all regions, while the association was strongest inthe piriform cortex. Impaired verbal memory was associated with ∆qT1noncontrast-interictal only in the piriform cortex (p = 0.04). ∆qT1interictal-postictal did not show differences in any region. Interictal blood-brain barrier dysfunction occurs in the piriform cortex in temporal lobe epilepsy. This dysfunction is linked to longer disease duration and worse cognitive deficits, emphasizing the central role of the piriform cortex in the epileptogenic network of temporal lobe epilepsy.

The value of ictal scalp EEG in focal epilepsies surgery: a retrospective analysis.

To describe the association between preoperative ictal scalp electroencephalogram (EEG) results and surgical outcomes in patients with focal epilepsies. The data of consecutive patients with focal epilepsies who received surgical treatments at our center from January 2012 to December 2021 were retrospectively analyzed. Our data showed that 44.2% (322/729) of patients had ictal EEG recorded on video EEG monitoring during preoperative evaluation, of which 60.6% (195/322) had a concordant ictal EEG results. No significant difference of surgery outcomes between patients with and without ictal EEG was discovered. Among MRI-negative patients, those with concordant ictal EEG had a significantly better outcome than those without ictal EEG (75.7% vs. 43.8%, p = 0.024). Further logistic regression analysis showed that concordant ictal EEG was an independent predictor for a favorable outcome (OR = 4.430, 95%CI 1.175-16.694, p = 0.028). Among MRI-positive patients, those with extra-temporal lesions and discordant ictal EEG results had a worse outcome compared to those without an ictal EEG result (44.7% vs. 68.8%, p = 0.005). Further logistic regression analysis showed that discordant ictal EEG was an independent predictor of worse outcome (OR = 0.387, 95%CI 0.186-0.807, p = 0.011) in these patients. Furthermore, our data indicated that the number of seizures was not associated with the concordance rates of the ictal EEG, nor the surgical outcomes. The value of ictal scalp EEG for epilepsy surgery varies widely among patients. A concordant ictal EEG predicts a good surgical outcome in MRI-negative patients, whereas a discordant ictal EEG predicts a poor postoperative outcome in lesional extratemporal lobe epilepsy.

Seizure Outcome After Intraoperative Electrocorticography-Tailored Epilepsy Surgery: A Systematic Review and Meta-Analysis.

Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic method. We assessed the current evidence to use ioECoG-tailored epilepsy surgery for improving postsurgical outcome. PubMed and Embase were searched for original studies reporting on ≥10 cases who underwent ioECoG-tailored surgery for epilepsy, with a follow-up of at least 6 months. We used a random-effects model to calculate the overall rate of patients achieving favorable seizure outcome (FSO), defined as Engel class I, ILAE class 1, or seizure-free status. Meta-regression was used to investigate potential sources of heterogeneity. We calculated the odds ratio (OR) for estimating variables on FSO:ioECoG vs non-ioECoG-tailored surgery (if included studies contained patients with non-ioECoG-tailored surgery), ioECoG-tailored epilepsy surgery in children vs adults, temporal (TL) vs extratemporal lobe (eTL), MRI-positive vs MRI-negative, and complete vs incomplete resection of tissue that generated interictal epileptiform discharges (IEDs). A Bayesian network meta-analysis was conducted for underlying pathologies. We assessed the evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Eighty-three studies (82 observational studies, 1 trial) comprising 3,631 patients with ioECoG-tailored surgery were included. The overall pooled rate of patients who attained FSO after ioECoG-tailored surgery was 74% (95% CI 71-77) with significant heterogeneity, which was predominantly attributed to pathologies and seizure outcome classifications. Twenty-two studies contained non-ioECoG-tailored surgeries. IoECoG-tailored surgeries reached a higher rate of FSO than non-ioECoG-tailored surgeries (OR 2.10 [95% CI 1.37-3.24]; p < 0.01; very low certainty). Complete resection of tissue that displayed IEDs in ioECoG predicted FSO better compared with incomplete resection (OR 3.04 [1.76-5.25]; p < 0.01; low certainty). We found insignificant difference in FSO after ioECoG-tailored surgery in children vs adults, TL vs eTL, or MRI-positive vs MRI-negative. The network meta-analysis showed that the odds of FSO was lower for malformations of cortical development than for tumors (OR 0.47 95% credible interval 0.25-0.87). Although limited by low-quality evidence, our meta-analysis shows a relatively good surgical outcome (74% FSO) after epilepsy surgery with ioECoG, especially in tumors, with better outcome for ioECoG-tailored surgeries in studies describing both and better outcome after complete removal of IED areas.

Analysis of the performance of PET/CT using 18F-fluorodeoxyglucose in comparison with other diagnostic methods in drug-resistant epilepsy in children

Background. Epilepsy is one of the most common neurological diseases characterized by a persistent predisposition to epileptic seizures and the neurobiological, cognitive, psychological, and social consequences. In recent decades, despite the continuous development of antiepileptic drugs, there are still many patients with epilepsy that progresses to drug-resistant epilepsy. Currently, surgical treatment is one of the most important ways to treat such epilepsy. Collaboration between multidisciplinary teams and the combination of multiple neuroimaging methods are key to determining the exact localization of the epileptogenic zone. New diagnostic methods are being developed and the number of indications for their use is growing. The purpose of the study was to analyze the scientific literature on the effectiveness of positron emission tomography combined with computed tomography (PET/CT) using 18F-fluorodeoxyglucose compared to other diagnostic methods in drug-resistant epilepsy in children. Materials and methods. A literature search using keywords was conducted in Web of Science, Scopus, PubMed, and Elsevier databases. Results. Surgical treatment of drug-resistant epilepsy in children has become a specialized area in neurosurgery. Surgical removal or disconnection of a part of the brain, in which the epileptogenic zone is suspected, allows for a complete cure or a significant reduction in seizure frequency. It has been shown that a prerequisite for postoperative success is the accurate determination of the epileptogenic zone during a multistage preoperative diagnosis. Among many studies, nuclear medicine technologies play an important role in the presurgical examination of children with drug-resistant epilepsy. In combination with other methods, nuclear medicine helps identify the epileptogenic zone, especially in case of conflicting data, negative magnetic resonance imaging — negative epilepsy, focal cortical dysplasia or extratemporal lobe epilepsy. Single-photon emission CT and PET using functional neuroimaging with nuclear medicine indicators are classical methods and are recommended by neuroimaging specialists. In addition, one of the leading modern methods is PET/CT with 18F-fluorodeoxyglucose. It provides information that might be missed when using anatomical methods such as magnetic resonance imaging, and the area of hypometabolism detected with 18F-fluorodeoxyglucose PET/CT may be larger than the area of anatomical lesion detected on magnetic resonance imaging. Conclusions. For children with drug-resistant epilepsy, PET/CT using 18F-fluorodeoxyglucose is the most optimal method of preoperative diagnosis.

Lateralizing value and clinicoradiological features of asymmetric last clonic jerks in temporal and extratemporal epilepsy

Seizure semiology and electroencephalograph (EEG) are very important for determining seizure type, hemisphere lateralization, or localization. Clinical symptoms of focal seizures, as well as findings at the onset or end of a focal to bilateral tonic–clonic seizure (FBTCS), are highly informative for lateralization. This study aimed to investigate the relationship of asymmetric last clonic jerk in patients with temporal or extratemporal lobe epilepsy with pathologies, localization, lateralization, or other semiological findings detected in neuroimaging or neuro psychometric tests and its positive predictive value for the detection of hemisphere lateralization based on seizure onset ictal EEG activation. 44 patients with asymmetric last clonic jerks (aLCJ) who were followed up in our VEM unit were randomized 1:1 with epilepsy patients without. In patients with ipsilateral automatism and contralateral posture or gustatory and olfactory hallucinations aLCJ was less or absent. In patients with unilateral tonic activity, aLCJ was more common. The positive predictive value of aLCJ for ictal EEG activation lateralization was 86.36%. In conclusion, asymmetric last clonic beat is valuable for lateralization of FBTCS and should be considered. Its presence strongly and reliably lateralizes to the side of seizure onset.

Incidence, Severity, and Risk Factors of Hemorrhagic Complications of Epilepsy Surgery After 2026 Craniotomies from 2003 to 2019: A Single Center Experience

Surgery is effective in the treatment of epilepsy, particularly focal epilepsy. The aim of this work was to report the incidence and grade of severity of hemorrhagic complications after cranial epilepsy surgery, and investigate the risk factors. Patients who underwent epilepsy surgery via craniotomy between October 2003 and April 2019 were retrospectively analyzed. The incidence of hemorrhagic complications occurring in a 3-month period after cranial surgery was recorded. Other outcomes included the grade of hemorrhagic severity and risk factors. During the inclusion period, 2026 surgical procedures were performed. Sixty-six hemorrhagic complications were recorded. The total incidence of hemorrhagic complications after cranial epilepsy surgery was 3.3%. The most common type of hemorrhagic complications was epidural hemorrhage (57.6%), followed by intraparenchymal hemorrhage (33.3%). Forty-five patients (68.2%) had grade I complications, 4 (6.1%) grade II, 16 (24.2%) grade III, and 1 (1.5%) grade IV. The mortality due to hemorrhagic complications was 1.5% (1 of 66) and hemorrhagic mortality among all cranial surgery was 0.05% (1 of 2026). Left craniotomy induced a higher percentage of severe hemorrhage than the right (34.2% vs. 14.3%). Extratemporal lobe epilepsy induced a higher percentage of severe hemorrhage than other epilepsy type (34.2% vs. 14.3%). However, no statistically significant difference was observed between these two factors (P= 0.067). Hemorrhagic complications were uncommon after open surgery for epilepsy. Most hemorrhagic complications were mild while the severe were rare. Patients with hemorrhagic complications had a good prognosis after effective treatment.

Surgical Outcome of Pharmaco Refractory Epilepsy in the National Epilepsy Center of Sri Lanka

IntroductionThe National Epilepsy Center (NEC) in Sri Lanka was established in 2017. Seizure outcome, effects on quality of life (QOL) and surgical complications among non-pediatric patients who underwent epilepsy surgery from October 2017 to February 2023 are described. Material and methodsNineteen patients (≥14 years) underwent epilepsy surgery at the NEC. We used Engel classification and Quality of Life in Epilepsy 31 (QOLIE-31) questionnaire to assess seizure outcome and QOL respectively. Surgical complications were categorized into neurological and complications related to surgery. ResultsNine female and 10 male patients underwent surgery (mean age 27.5 years (range 14-44years). The mean follow-up duration was 10.5 months (range 6-55 months). Twelve patients underwent temporal lobe resections. At 6-months follow-up, 83.3% (10/12) had favorable seizure outcomes with Engel class I/II. At 1-year follow-up 6/8 patients (75.0 %) and at 2-year follow-up, 5/7 patients (71.4%) had a favorable outcome. Seven patients had extra-temporal lobe surgeries and one defaulted. Seizure freedom was observed in 6/6 at 6 months, 3/3 at one-year, and 2/2 at 2-year follow-up. Five patients (26.3%) experienced minor post-operative surgical site infection. Two (11.1%) had persistent quadrantanopia. Meaningful improvement in QOL (change in QOLIE-31 score ≥11.8) was observed irrespective of seizure outcome or type of surgery (P <0.001). ConclusionsEpilepsy surgery is effective in developing countries. Seizure outcomes in our patients are comparable to those worldwide. Clinically important QOL improvement was observed in our series. This is the first published data on epilepsy surgery outcomes in non-pediatric patients from Sri Lanka.

Factors influencing quality of life in extratemporal lobe epilepsy and mesial temporal lobe epilepsy: a cross-sectional study using medical records.

This study aimed to examine differences in factors influencing quality of life (QOL) in people with extratemporal lobe epilepsy (ETLE) and mesial temporal lobe epilepsy (MTLE). We obtained data from the medical records of 84 (47 ETLE and 37 MTLE) people with epilepsy. The data included age, sex, employment, seizure frequency, number of antiseizure medication (ASM), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) score, and Quality of Life in Epilepsy Inventory-31 (QOLIE-31) score. Multiple regression analyses were performed using QOLIE-31 as the dependent variable and age, sex, employment, seizure frequency, number of ASM, and NDDI-E score as the independent variables in ETLE or MTLE. From the results of the multiple regression analyses, QOLIE-31 in ETLE was associated with NDDI-E (β = -0.757, p < 0.001) and employment (β = 0.388, p = 0.008). Meanwhile, QOLIE-31 in MTLE was associated with NDDI-E (β = -0.625, p < 0.001), employment (β = 0.396, p = 0.041), and number of ASMs (β = -0.399, p = 0.018). Overall, our findings indicate that the number of ASMs is potentially an influence on QOL of MTLE but similar effect is not observed in ETLE.

Advocacy for Epilepsy Surgery in Africa: Moroccan Experience of 132 Cases

In Africa, epilepsy is a real burden. Temporal lobe epilepsy is the most common drug-resistant focal epilepsy disorder, and temporal lobectomy are the most common effective treatment on patients with drug-resistant epilepsy. We aim to highlight the Moroccan experience in epilepsy surgery and to ascertain its long-term outcome. Through the results of surgical treatment in our series, we expect to raise awareness of the need of epilepsy surgery in Africa and contribute to its development. We present a retrospective study of 132 patients who underwent surgery for epilepsy from January 2005 to December 2021 at our institution. The presurgical evaluation was based on clinical screening, interictal EEG, VEEG, neuropsychological tests, MRI and Pet Scan in some cases. Data are presented as the median and ranges. For all analyses, P-values < 0.05 were considered statistically significant. Our series includes 132 patients (69 males, 52.27%), median age at surgery was 24 years (range: 1-64). One hundred -fifteen patients (87%) were operated for temporal lobe epilepsy, among them, 98 (85%) had anterior temporal lobectomy, and 17 (15%) had a lesionectomy. Seventeen patients (13%) were operated for extratemporal epilepsy, among them, 4 had lesionectomy, 7 functional hemispherotomy, and 5 patients had Gamma Knife Stereotactic Radiosurgery. Our postoperative outcomes 3 months after surgery found 113 patients (85.6%), seizure-free (Engel I), 16 Engel II (12.1%), and 3 Engel III (2.3 %) in temporal lobe epilepsy. In extratemporal lobe epilepsy, 12 (70.5%) were Engel I, seizure-free, 4 Engel II (23.5%) and 1 Engel III (6%). These results confirm that a majority of patients with drug-resistant epilepsy may benefit from surgical treatment without submitting to preoperative invasive explorations. This should help develop epilepsy surgery widely in Africa.

Epileptogenic networks in extra temporal lobe epilepsy.

Extra temporal lobe epilepsy (eTLE) may involve heterogenous widespread cerebral networks. We investigated the structural network of an eTLE cohort, at the postulated epileptogenic zone later surgically removed, as a network node: the resection zone (RZ). We hypothesized patients with an abnormal connection to/from the RZ to have proportionally increased abnormalities based on topological proximity to the RZ, in addition to poorer post-operative seizure outcome. Structural and diffusion MRI were collected for 22 eTLE patients pre- and post-surgery, and for 29 healthy controls. The structural connectivity of the RZ prior to surgery, measured via generalized fractional anisotropy (gFA), was compared with healthy controls. Abnormal connections were identified as those with substantially reduced gFA (z < -1.96). For patients with one or more abnormal connections to/from the RZ, connections with closer topological distance to the RZ had higher proportion of abnormalities. The minority of the seizure-free patients (3/11) had one or more abnormal connections, while most non-seizure-free patients (8/11) had abnormal connections to the RZ. Our data suggest that eTLE patients with one or more abnormal structural connections to/from the RZ had more proportional abnormal connections based on topological distance to the RZ and associated with reduced chance of seizure freedom post-surgery.

Breath-Hold-Triggered BOLD fMRI in Drug-Resistant Nonlesional Focal Epilepsy-APilot Study.

Individuals with drug-resistant epilepsy may benefit from epilepsy surgery. In nonlesional cases, where no epileptogenic lesion can be detected on structural magnetic resonance imaging, multimodal neuroimaging studies are required. Breath-hold-triggered BOLD fMRI (bh-fMRI) was developed to measure cerebrovascular reactivity in stroke or angiopathy and highlights regional network dysfunction by visualizing focal impaired flow increase after vasodilatory stimulus. This regional dysfunction may correlate with the epileptogenic zone. In this prospective single-center single-blind pilot study, we aimed to establish the feasibility and safety of bh-fMRI in individuals with drug-resistant non-lesional focal epilepsy undergoing presurgical evaluation. In this prospective study, 10consecutive individuals undergoing presurgical evaluation for drug-resistant focal epilepsy were recruited after case review at amultidisciplinary patient management conference. Electroclinical findings and results of other neuroimaging were used to establish the epileptogenic zone hypothesis. To calculate significant differences in cerebrovascular reactivity in comparison to the normal population, bh-fMRIs of 16healthy volunteers were analyzed. The relative flow change of each volume of interest (VOI) of the atlas was then calculated compared to the flow change of the whole brain resulting in an atlas of normal cerebral reactivity. Consequently, the mean flow change of every VOI of each patient was tested against the healthy volunteers group. Areas with significant impairment of cerebrovascular reactivity had decreased flow change and were compared to the epileptogenic zone localization hypothesis in asingle-blind design. Acquisition of bh-fMRI was feasible in 9/10cases, with one patient excluded due to noncompliance with breathing maneuvers. No adverse events were observed, and breath-hold for intermittent hypercapnia was well tolerated. On blinded review, we observed full or partial concordance of the local network dysfunction seen on bh-fMRI with the electroclinical hypothesis in 6/9cases, including cases with extratemporal lobe epilepsy and those with nonlocalizing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This represents the first report of bh-fMRI in individuals with epilepsy undergoing presurgical evaluation. We found bh-fMRI to be feasible and safe, with apromising agreement to electroclinical findings. Thus, bh-fMRI may represent apotential modality in the presurgical evaluation of epilepsy. Further studies are needed to establish clinical utility.

Cannabidiol Modifies the Glutamate Over-Release in Brain Tissue of Patients and Rats with Epilepsy: A Pilot Study.

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as well as in a preclinical model of epilepsy. Synaptic terminals (synaptosomes) were obtained from the epileptic neocortex of patients with drug-resistant temporal lobe epilepsy (DR-TLE, n = 10) or drug-resistant extratemporal lobe epilepsy (DR-ETLE, n = 10) submitted to epilepsy surgery. Synaptosomes highly purified by Percoll-sucrose density gradient were characterized by confocal microscopy and Western blot. Synaptosomes were used to estimate the high KCl (33 mM)-evoked glutamate release in the presence of CBD at different concentrations. Our results revealed responsive tissue obtained from seven patients with DR-TLE and seven patients with DR-ETLE. Responsive tissue showed lower glutamate release (p < 0.05) when incubated with CBD at low concentrations (less than 100 µM) but not at higher concentrations. Tissue that was non-responsive to CBD (DR-TLE, n = 3 and DR-ELTE, n = 3) showed high glutamate release despite CBD exposure at different concentrations. Simultaneously, a block of the human epileptic neocortex was used to determine its viability through whole-cell and extracellular electrophysiological recordings. The electrophysiological evaluations supported that the responsive and non-responsive human epileptic neocortices used in the present study exhibited proper neuronal viability and stability to acquire electrophysiological responses. We also investigated whether the subchronic administration of CBD could reduce glutamate over-release in a preclinical model of temporal lobe epilepsy. Administration of CBD (200 mg/kg, p.o. every 24 h for 7 days) to rats with lithium-pilocarpine-evoked spontaneous recurrent seizures reduced glutamate over-release in the hippocampus. The present study revealed that acute exposure to low concentrations of CBD can reduce the glutamate over-release in synaptic terminals obtained from some patients with DRE. This effect is also evident when applied subchronically in rats with spontaneous recurrent seizures. An important finding was the identification of a group of patients that were non-responsive to CBD effects. Future studies are essential to identify biomarkers of responsiveness to CBD to control DRE.

Yield of non-invasive imaging in MRI-negative focal epilepsy.

The absence of MRI-lesion reduces considerably the probability of having an excellent outcome (International League Against Epilepsies [ILAE] class I-II) after epilepsy surgery. Surgical success in magnetic-resonance imaging (MRI)-negative cases relies therefore mainly on non-invasive techniques such as positron-emission tomography (PET), subtraction ictal/inter-ictal single-photon-emission-computed-tomography co-registered to MRI (SISCOM), electric source imaging (ESI) and morphometric MRI analysis (MAP). We were interested in identifying the optimal imaging technique or combination to achieve post-operative class I-II in patients with MRI-negative focal epilepsy. We identified 168 epileptic patients without MRI lesion. Thirty-three (19.6%) were diagnosed with unifocal epilepsy, underwent surgical resection and follow-up ⩾ 2 years. Sensitivity, specificity, predictive values, and diagnostic odds ratio (OR) were calculated for each technique individually and in combination (after co-registration). 23/33 (70%) were free of disabling seizures (75.0% with temporal and 61.5% extratemporal lobe epilepsy). None of the individual modalities presented an OR > 1.5, except ESI if only patients with interictal epileptiform discharges (IEDs) were considered (OR 3.2). On a dual combination, SISCOM with ESI presented the highest outcome (OR = 6). MAP contributed to detecting indistinguishable focal cortical dysplasia in particular in extratemporal epilepsies with a sensitivity of 75%. Concordance of PET, ESI on interictal epileptic discharges, and SISCOM was associated with the highest chance for post-operative seizure control (OR = 11). If MRI is negative, the chances to benefit from epilepsy surgery are almost as high as in lesional epilepsy, provided that multiple established non-invasive imaging tools are rigorously applied and co-registered together.

Real-Life Disability-Adjusted Life Years (DALY) Capture the Disability of Epilepsy Better from an Individual's Perspective.

For 1.3 billion population in India, there are only scarce reports on disability of epilepsy using disability-adjusted life year (DALY) as a measure. Our objective was to estimate DALY using real-life data over a period of time for a cohort of people with epilepsy (PWE) admitted to an Epilepsy Monitoring Unit (EMU) of a tertiary care epilepsy center. : We ascertained survival status as on December 31, 2016 of all eligible admissions to the EMU between 01/01/2005 and 12/31/2015. We examined the medical records of randomly selected 200 of the 1970 survivors and all the expired PWE (n = 40) for clinical characteristics. The cumulative real-life DALY (cr-DALY) for individual was calculated as the sum of the years lost to disability (YLD) and the years of life lost (YLL). Annual population-based DALY (p-DALY) was estimated from the cr-DALY, total patient-years of follow-up, and regional population prevalence. The cr-DALY per PWE was 17.63 (generalized seizures only). The cr-DALY increased by 23.7% when all seizure types were considered (23.12). PWE with epilepsy onset <10 years of age, focal epilepsy (particularly, extratemporal lobe epilepsy), and premature death had significantly higher cr-DALY. Those who underwent surgery for epilepsy or achieved remission had significantly lower cr-DALY. The computed p-DALY was 583/1,00,000 population (generalized epilepsy contributed 165/1,00,000 population; focal epilepsy contributed 418/1,00,000 population). Our study had identified, for the first time, several determinants that reduced DALY significantly. Real-life DALY, rather than prevalence-based DALY, captures the cumulative disability of affected individuals. Epilepsy leads to loss of 23 years of disability-adjusted life span for the affected person. This can be extrapolated to substantial economic benefits.

Classification of temporal lobe epilepsy based on neuropsychological tests and exploration of its underlying neurobiology.

To assist improving long-term postoperative seizure-free rate, we aimed to use machine learning algorithms based on neuropsychological data to differentiate temporal lobe epilepsy (TLE) from extratemporal lobe epilepsy (extraTLE), as well as explore the relationship between magnetic resonance imaging (MRI) and neuropsychological tests. Twenty-three patients with TLE and 23 patients with extraTLE underwent neuropsychological tests and MRI scans before surgery. The least absolute shrinkage and selection operator were firstly employed for feature selection, and a machine learning approach with neuropsychological tests was employed to classify TLE using leave-one-out cross-validation. A generalized linear model was used to analyze the relationship between brain alterations and neuropsychological tests. We found that logistic regression with the selected neuropsychological tests generated classification accuracies of 87.0%, with an area under the receiver operating characteristic curve (AUC) of 0.89. Three neuropsychological tests were acquired as significant neuropsychological signatures for the diagnosis of TLE. We also found that the Right-Left Orientation Test difference was related to the superior temporal and the banks of the superior temporal sulcus (bankssts). The Conditional Association Learning Test (CALT) was associated with the cortical thickness difference in the lateral orbitofrontal area between the two groups, and the Component Verbal Fluency Test was associated with the cortical thickness difference in the lateral occipital cortex between the two groups. These results showed that machine learning-based classification with the selected neuropsychological data can successfully classify TLE with high accuracy compared to previous studies, which could provide kind of warning sign for surgery candidate of TLE patients. In addition, understanding the mechanism of cognitive behavior by neuroimaging information could assist doctors in the presurgical evaluation of TLE.

Withdrawal of antiseizure medications after MRI–Guided laser interstitial thermal therapy in extra-temporal lobe epilepsy

PurposeThis study investigated the success rate of antiseizure medications (ASMs) withdrawal following MRI Guided Laser Interstitial Thermal Therapy (MRg-LITT) for extra-temporal lobe epilepsy (ETLE), and identified predictors of seizure recurrence. MethodsWe retrospectively assessed 27 patients who underwent MRg-LITT for ETLE. Patients’ demographics, disease characteristics, and post-surgical outcomes were evaluated for their potential to predict seizure recurrence associated with ASMs withdrawal. ResultsThe median period of observation post MRg-LITT was 3 years (range 18 - 96 months) and the median period to initial ASMs reduction was 0.5 years (range 1–36 months). ASMs reduction was attempted in 17 patients (63%), 5 (29%) of whom had seizure recurrence after initial reduction. Nearly all patient who relapsed regained seizure control after reinstitution of their ASMs regimen. Pre-operative seizure frequency (p = 0.002) and occurrence of acute post-operative seizures (p = 0.01) were associated with increased risk for seizure recurrence post ASMs reduction. At the end of the observation period, 11% of patients were seizure free without drugs, 52% were seizure free with drugs and 37% still experienced seizures despite ASMs. Compared with pre-operative status, the number of ASMs was reduced in 41% of patients, unchanged in 55% of them and increased in only 4% of them. ConclusionsSuccessful MRg-LITT for ETLE allows for ASMs reduction in a significant portion of patients and complete ASMs withdrawal in a subset of them. Patients with higher pre-operative seizure frequency or occurrence of acute post operative seizures exhibit higher chances relapse post ASMs reduction.