Epilepsy Surgery Patients Research Articles

Optimization of epilepsy surgery through virtual resections on individual structural brain networks

The success of epilepsy surgery in patients with refractory epilepsy depends upon correct identification of the epileptogenic zone (EZ) and an optimal choice of the resection area. In this study we developed individualized computational models based upon structural brain networks to explore the impact of different virtual resections on the propagation of seizures. The propagation of seizures was modelled as an epidemic process [susceptible-infected-recovered (SIR) model] on individual structural networks derived from presurgical diffusion tensor imaging in 19 patients. The candidate connections for the virtual resection were all connections from the clinically hypothesized EZ, from which the seizures were modelled to start, to other brain areas. As a computationally feasible surrogate for the SIR model, we also removed the connections that maximally reduced the eigenvector centrality (EC) (large values indicate network hubs) of the hypothesized EZ, with a large reduction meaning a large effect. The optimal combination of connections to be removed for a maximal effect were found using simulated annealing. For comparison, the same number of connections were removed randomly, or based on measures that quantify the importance of a node or connection within the network. We found that 90% of the effect (defined as reduction of EC of the hypothesized EZ) could already be obtained by removing substantially less than 90% of the connections. Thus, a smaller, optimized, virtual resection achieved almost the same effect as the actual surgery yet at a considerably smaller cost, sparing on average 27.49% (standard deviation: 4.65%) of the connections. Furthermore, the maximally effective connections linked the hypothesized EZ to hubs. Finally, the optimized resection was equally or more effective than removal based on structural network characteristics both regarding reducing the EC of the hypothesized EZ and seizure spreading. The approach of using reduced EC as a surrogate for simulating seizure propagation can suggest more restrictive resection strategies, whilst obtaining an almost optimal effect on reducing seizure propagation, by taking into account the unique topology of individual structural brain networks of patients.

A Commentary on “Can Neuroscience Provide a New Foundation for the Rorschach Variables?” (Jimura et al., 2021)

A Commentary on “Can Neuroscience Provide a New Foundation for the Rorschach Variables?” (Jimura et al., 2021)

MRI-guided stereotactic laser corpus callosotomy for epilepsy: distinct methods and outcomes.

Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames. The authors retrospectively reviewed sequential adult epilepsy surgery patients who underwent SLCC procedures at a single institution. They describe workflows, stereotactic errors, percentage disconnection, hospitalization durations, adverse events, and seizure outcomes after performing anterior, posterior, and complete SLCC procedures using a frameless stereotactic surgical robot versus direct MRI guidance platforms. Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20-49 years), the median duration of epilepsy was 21 years (range 9-48 years), and median postablation follow-up was 20 months (range 4-44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%-80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm (range 0.2-2.0 mm) versus 2.4 mm (range 0.6-6.1 mm; p = 0.0011). The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique. This is the largest reported series of SLCC for epilepsy to date. SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC. Methodological advancements and larger studies are needed.

The epileptogenic zone in children with tuberous sclerosis complex is characterized by prominent features of focal cortical dysplasia.

ObjectivePatients with tuberous sclerosis complex (TSC) present with drug‐resistant epilepsy in about 60% of cases, and evaluation for epilepsy surgery may be warranted. Correct delineation of the epileptogenic zone (EZ) among multiple dysplastic lesions on MRI represents a challenging step in pre‐surgical evaluation.MethodsTwo experienced neuroradiologists evaluated pre‐ and post‐surgical MRIs of 28 epilepsy surgery patients with TSC, assessing characteristics of tubers, cysts, calcifications, and focal cortical dysplasia (FCD)—resembling lesions. Utilizing multiple metrics, we compared MRI features of the EZ—defined as the resected area in TSC patients who achieved seizure‐freedom 2 years after epilepsy surgery—with features of other brain areas. Using combinatorial analysis, we identified combinations of dysplastic features that are most frequently observed in the epileptogenic zone in TSC patients.ResultsAll TSC‐associated dysplastic features were more frequently observed in the EZ than in other brain areas (increased cortical thickness, gray‐white matter blurring, transmantle sign, calcifications, and tubers; Kendal's tau 0.35, 0.25, 0.27, 0.26, and 0.23, respectively; P value <.001 in all). No single feature could reliably and independently indicate the EZ in all patients. Conversely, the EZ was indicated by the presence of the combination of three of the following features: tubers, transmantle sign, increased cortical thickness, calcifications, and the largest FCD‐affected area. Out of these, the largest FCD‐affected area emerged as the most reliable indicator of the EZ, combined either with calcifications or tubers.SignificanceThe epileptogenic zone in TSC patients harbors multiple dysplastic features, consistent with focal cortical dysplasia. A specific combination of these features can indicate the EZ and aid in pre‐surgical MRI evaluation in epilepsy surgery candidates with TSC.

Ultra-High Field 7-Tesla Magnetic Resonance Imaging and Electroencephalography Findings in Epilepsy

Assessment of patients for temporal lobe epilepsy (TLE) surgery requires multimodality input, including EEG recordings to ensure optimal surgical planning. Often EEG demonstrates abnormal foci not detected on 1.5T MRI. Ultra-high field MRI at 7T provides improved resolution of the brain. We investigated the utility of 7T MRI to detect potential anatomical abnormalities associated with EEG changes. Ultra-high field data were acquired on a 7T MRI scanner for 13 patients with history of drug resistant TLE who had had EEG telemetry recordings. Qualitative evaluation of 7T imaging for presence of focal abnormalities detected on EEG was performed. Correlation of 7T MRI findings with EEG recordings of focal slowing or interictal epileptic spikes (IEDs), and seizures was performed. Assessment of 7T MRI demonstrated concordance with TLE as determined by the multidisciplinary team in 61.5% of cases (n = 8). Among these, 3 patients exhibited supportive abnormal 7T MRI abnormalities not detected by 1.5T MRI. In patients who underwent surgery, 72.7% had concordant histopathology findings with 7T MRI findings (n = 8). However, qualitative assessment of 7T images revealed focal anatomical abnormalities to account for EEG findings in only 15.4% of patients (n = 2). Other regions that were found to have localized IEDs in addition to the lesional temporal lobe, included the contralateral temporal lobe (n = 5), frontal lobe (n = 3), and parieto-occipital lobe (n = 2). Ultra-high field 7T MRI findings show concordance with clinical data. However, 7T MRI did not reveal anatomical findings to account for abnormalities detected by EEG.

MEG detection of high frequency oscillations and intracranial-EEG validation in pediatric epilepsy surgery

ObjectiveTo assess the feasibility of automatically detecting high frequency oscillations (HFOs) in magnetoencephalography (MEG) recordings in a group of ten paediatric epilepsy surgery patients who had undergone intracranial electroencephalography (iEEG). MethodsA beamforming source-analysis method was used to construct virtual sensors and an automatic algorithm was applied to detect HFOs (80–250 Hz). We evaluated the concordance of MEG findings with the sources of iEEG HFOs, the clinically defined seizure onset zone (SOZ), the location of resected brain structures, and with post-operative outcome. ResultsIn 8/9 patients there was good concordance between the sources of MEG HFOs and iEEG HFOs and the SOZ. Significantly more HFOs were detected in iEEG relative to MEG t(71) = 2.85, p < .05. There was good concordance between sources of MEG HFOs and the resected area in patients with good and poor outcome, however HFOs were also detected outside of the resected area in patients with poor outcome. ConclusionOur findings demonstrate the feasibility of automatically detecting HFOs non-invasively in MEG recordings in paediatric patients, and confirm compatibility of results with invasive recordings. SignificanceThis approach provides support for the non-invasive detection of HFOs to aid surgical planning and potentially reduce the need for invasive monitoring, which is pertinent to paediatric patients.

The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature.

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.

Post-Surgical Outcome and Its Determining Factors in Patients Operated on With Focal Cortical Dysplasia Type II-A Retrospective Monocenter Study.

Purpose: Focal cortical dysplasias (FCDs) are a frequent cause of drug-resistant focal epilepsies. These lesions are in many cases amenable to epilepsy surgery. We examined 12-month and long-term post-surgical outcomes and its predictors including positive family history of epilepsy.Methods: Twelve-month and long-term outcomes regarding seizure control after epilepsy surgery in patients operated on with FCD type II between 2002 and 2019 in the Epilepsy Center of Bonn were evaluated based on patient records and telephone interviews.Results: Overall, 102 patients fulfilled the inclusion criteria. Seventy-one percent of patients at 12 months of follow-up (FU) and 54% of patients at the last available FU (63 ± 5.00 months, median 46.5 months) achieved complete seizure freedom (Engel class IA), and 84 and 69% of patients, respectively, displayed Engel class I outcome. From the examined variables [histopathology: FCD IIA vs. IIB, lobar lesion location: frontal vs. non-frontal, family history for epilepsy, focal to bilateral tonic–clonic seizures (FTBTCS) in case history, completeness of resection, age at epilepsy onset, age at surgery, duration of epilepsy], outcomes at 12 months were determined by interactions of age at onset, duration of epilepsy, age at surgery, extent of resection, and lesion location. Long-term post-surgical outcome was primarily influenced by the extent of resection and history of FTBTCS. Positive family history for epilepsy had a marginal influence on long-term outcomes only.Conclusion: Resective epilepsy surgery in patients with FCD II yields very good outcomes both at 12-month and long-term follow-ups. Complete lesion resection and the absence of FTBTCS prior to surgery are associated with a better outcome.

Clinical characteristics of low-grade tumor-related epilepsy and its predictors for surgical outcome.

ObjectivesLow‐grade tumors are the most common neoplasms inducing focal epilepsy; however, the short‐ and medium‐term efficacy of surgery in epilepsy patients with low‐grade tumors remains underappreciated. This study aims to summarize the clinical characteristics of epilepsy patients with low‐grade tumors and to identify factors associated with postsurgical seizure‐free outcomes.MethodsWe retrospectively reviewed consecutive patients with low‐grade tumors who underwent subsequent epilepsy surgery in our epilepsy center, between 2012 and 2018 with a minimum follow‐up of 1 year. Using Engel’s classification and Kaplan–Meier survival analysis, we assessed postoperative seizure freedom over time. Demographical, electroclinical, and other presurgical evaluations were then evaluated for association with postoperative seizure outcome.ResultsThe cohort included a total of 132 patients: 79 males and 53 females. Among them, 110 (83.33%) were seizure‐free through their last follow‐up. The Engel class I outcomes were 90.15%, 87.76%, 85.53%, 82.46%, and 73.17% at the end of the 1st, 2nd, 3rd, 4th, and 5th postoperative years, respectively. Multivariate logistic analysis revealed that longer epilepsy duration (p < 0.001, OR 1.091, 95% CI 1.040–1.144) and incomplete resection (p = 0.009, OR 3.673, 95% CI 1.393–9.684) were independently associated with seizure recurrence through the last follow‐up.ConclusionsSurgical treatment for seizure control in patients with low‐grade tumors provides excellent short‐ and median‐term outcomes.

Determination of language dominance in pediatric patients with epilepsy for clinical decision-making: Correspondence of intracarotid amobarbitol procedure and fMRI modalities

Identification of the language dominant hemisphere is an essential part of the evaluation of potential pediatric epilepsy surgery patients. Historically, language dominance has been determined using the intracarotid amobarbitol procedure (IAP), but use of functional Magnetic Resonance Imaging (fMRI) scanning is becoming more common. Few studies examine the correspondence between fMRI and IAP in pediatric samples. The current study examined the agreement of hemispheric lateralization as determined by fMRI and IAP in a consecutive sample of 10 pediatric patients with epilepsy evaluated for epilepsy surgery. Data showed a strong correlation between IAP and fMRI lateralilty indices (r=.91) and 70% agreement in determination of hemispheric dominance, despite increased demonstration of bilateral or atypical language representation in this pediatric sample. Clinical implications and interpretation challenges are discussed.

Surgically treatable adult epilepsy: a changing patient population. Experience from a level 4 epilepsy center.

Invasive monitoring has long been utilized in the evaluation of patients for epilepsy surgery, providing localizing information to guide resection. Stereoelectroencephalography (SEEG) was introduced at the authors' level 4 epilepsy surgery program in 2013, with responsive neurostimulation (RNS) becoming available the following year. The authors sought to characterize patient demographics and epilepsy-related variables before and after SEEG introduction to understand whether differences emerged in their patient population. This information will be useful in understanding how SEEG, possibly in conjunction with RNS availability, may have changed practice patterns over time. This is a retrospective cohort study of consecutive patients who underwent surgery for epilepsy from 2006 to 2018, comprising 7 years before and 5 years after the introduction of SEEG. The authors performed univariate analyses of patient characteristics and outcomes and used generalized estimating equations logistic regression for predictive analysis. A total of 178 patients were analyzed, with 109 patients in the pre-SEEG cohort and 69 patients in the post-SEEG cohort. In the post-SEEG cohort, more patients underwent invasive monitoring for suspected bilateral seizure onsets (40.6% vs 22.0%, p = 0.01) and extratemporal seizure onsets (68.1% vs 8.3%, p < 0.0001). The post-SEEG cohort had a higher proportion of patients with seizures arising from eloquent cortex (14.5% vs 0.9%, p < 0.001). Twelve patients underwent RNS insertion in the post-SEEG group versus none in the pre-SEEG group. Fewer patients underwent resection in the post-SEEG group (55.1% vs 96.3%, p < 0.0001), but there was no significant difference in rates of seizure freedom between cohorts for those patients having undergone a follow-up resection (53.1% vs 59.8%, p = 0.44). These findings demonstrate that more patients with suspected bilateral, eloquent, or extratemporal epilepsy underwent invasive monitoring after adoption of SEEG. This shift occurred coincident with the adoption of RNS, both of which likely contributed to increased patient complexity. The authors conclude that their practice now considers invasive monitoring for patients who likely would not previously have been candidates for surgical investigation and subsequent intervention.

The clinical utility of a memory specialization index in epilepsy surgery patients with unilateral hippocampal sclerosis.

Although group studies provide some support for the material-specific model of memory function, there are considerable individual variations in memory function in people with temporal lobe epilepsy, even in those with the same underlying pathology. In this proof-of-concept study, we examined the sensitivity and specificity of a single measure of an individual's relative strength for the encoding of verbal or visual learning. Six hundred ninety-two patients with left hemisphere language dominance and unilateral hippocampal sclerosis completed verbal and visual encoding tasks with similar test structures as part of their presurgical evaluation. Three hundred one patients had right hippocampal sclerosis (RHS), and 391 patients had left hippocampal sclerosis (LHS). A memory specialization index (MSI) was calculated by subtracting the Visual Learning z-score from the Verbal Learning z-score. A positive value on the MSI indicates a relative strength in verbal learning. A negative score indicates a relative strength in visual learning. Employing cut-offs of ±1, the MSI had a positive predictive value of 71% (confidence interval [CI] 95% 0.64-0.77) for LHS and 64% (CI 95% 0.55-0.74) for RHS and was superior to the standalone z-scores from the verbal and visual tests in each respect. In the LHS group, the MSI was significantly correlated with age and duration of epilepsy. Older patients who had a longer duration of epilepsy were more likely to demonstrate a similar level of impairment in both verbal and visual learning, with a decreasing discrepancy between the scores on the two tasks over time. Our MSI provides a measure with high specificity for RHS. The pattern of strengths and weaknesses in visual and verbal encoding may evolve with age and duration of epilepsy, and clinicians should be aware of these factors when interpreting the lateralizing significance of test scores, particularly in a presurgical setting.

Awake Epilepsy Surgery in Patients with Focal Cortical Dysplasia

Awake craniotomy (AC) and direct electric stimulation emerged together with epilepsy surgery >80 years ago. The goal of our study was to evaluate the benefits of awake surgery in patients with drug-resistant epilepsy caused by focal cortical dysplasia (FCD) affecting eloquent areas. Our material included 95 patients with drug-resistant epilepsy and FCD, who were operated on between January 2009 and December 2018. These 95 patients were assigned into 3 groups: AC; general anesthesia (GA) with intraoperative neuromonitoring; and GA without intraoperative neuromonitoring. We investigated the following variables: age at surgery, lesion side, eloquent cortex involvement, brain mapping success rate, epilepsy surgery success rate, intraoperative complications, postoperative complications, and intraoperative changes of the preoperative resection plan according to results of the brain mapping by direct electric stimulation. We found statistically significant differences between the AC and GA groups in the mean age at operation, lesion side, eloquent localization, and postoperative transient neurologic deficit. Seizure outcome in the AC was satisfactory (71% complete seizure control) and comparable to the seizure outcome in the GA groups. Our preoperative plan was changed because of functional constraints in 6 patients (43%) operated on during AC. AC during epilepsy surgery for FCD in eloquent areas may change the preoperative plan. The good rate of postoperative seizure control and the absence of permanent postoperative neurologic deficit in our series is the main proof that AC is a useful tool in patients with FCD involving the eloquent cortex.

Changes in fractional amplitude of low frequency fluctuations (fALFF) changes after epilepsy surgery in patients with temporal lobe epilepsy (4441)

Changes in fractional amplitude of low frequency fluctuations (fALFF) changes after epilepsy surgery in patients with temporal lobe epilepsy (4441)

Resective epilepsy surgery in patients aged 50 years and older – a retrospective study regarding seizure outcome, memory performance, and psychopathology

PurposeTo assess clinical and demographic characteristics in two cohorts of elderly patients with drug-resistant focal epilepsy, undergoing resective epilepsy surgery (RES). Further, to determine seizure, neuropsychological, and mental health outcomes after RES and evaluate possible influencing factors. MethodsConsecutive patients aged ≥50 years with temporal lobe epilepsy (TLE) who underwent curative RES in the Hamburg epilepsy surgery program (2004–2017) were identified. Data were retrospectively analyzed. Seizure outcome was classified according to ILAE and Engel outcome scales in patients with first-time surgeries and with reoperations. Previously reported predictors of the seizure outcome were evaluated using regression analyses. Changes in verbal memory were assessed for patients with complete pre- and postoperative datasets (n=30) using repeated-measures analysis of variance. For evaluation of possible predictors of psychopathologic changes after RES a regression analysis was conducted. ResultsFifty-one elderly patients underwent RES of the temporal lobe, including twelve aged ≥60 years, and five with reoperations. After one year, 65% of the patients with first-time surgeries were seizure free and 91% had a favorable outcome. At last follow-up, 49% were seizure free since surgery. Three reoperated patients had an Engel I outcome. Seizure outcome was not dependent on age at surgery, duration of epilepsy, or other evaluated variables. There was no significant decline in the memory performance after surgery. Significant improvements in mental health were found. ConclusionRES for drug-resistant TLE is safe, effective, and improves mental health also in patients aged ≥ 50 years. Thus, it should be evaluated as the treatment of choice also in this age group.

Predictors and Long-term Outcome of Resective Epilepsy Surgery in Patients with Tuberous Sclerosis Complex: A Single-centre Retrospective Cohort Study

Objective: To identify prognostic factors and long-term seizure outcomes for patients with tuberous sclerosis complex (TSC) who underwent resective treatment for epilepsy. Methods: We enrolled 81 patients with TSC who had undergone resective epilepsy surgery at Sanbo Brain Hospital, Capital Medical University, between April 2004 and June 2019. We estimated cumulative probability of remaining seizure-free and plotted survival curves. Variables were compared using Mann–Whitney U, Pearson's correlation, continuity correction, and Fisher's exact chi-square tests. Prognostic predictors were analysed using log-rank (Mantel–Cox) tests and Cox regression models. Results: At the last follow-up, 48 (59.3%) patients were classified as International League Against Epilepsy Class 1 (including 14 patients who had seizures <3 times postoperatively on the same or different day and were seizure-free at all other times). The estimated cumulative probability of remaining seizure-free postoperatively was 69.0% (95% confidence interval [CI] 58.8–79.2%), 61.9% (95% CI 51.1–72.7%), and 55.0% (95% CI 42.8–67.2%) at 2, 5, and 10 years, respectively. The mean time of remaining seizure-free was 7.24 ± 0.634 years (95% CI 6.00–8.49); en bloc resection was an essential positive predictor of postoperative seizure freedom, as was age at seizure onset, regional interictal video-electroencephalography pattern, and temporal lobe surgery. The longer the seizure-free time, the less likely a relapse. Patients who postoperatively experienced seizures remained likely to recover. Conclusions: We demonstrated the efficacy of surgical treatment for patients with TSC and intractable epilepsy. Detailed perioperative tests are a reliable predictor of postoperative seizure freedom.

Seizure outcome after epilepsy surgery for patients with normal MRI: A Single center experience

ObjectiveTo analyze the surgical outcome in non-lesional intractable focal epilepsies in our center and to find possible predictors for better outcome. MethodsThis is a retrospective study for 40 adult patients with intractable focal epilepsy following at KFSHRC-Riyadh, who underwent presurgical evaluation followed by resective surgery and continued follow up for a minimum of 2 years. The surgery outcome was evaluated based on the type of surgical procedure and histopathology results. ResultsOut of all 40 patients studied, seizure freedom was achieved in 19 (47.5 %) and 17 (42.5 %) patients at the first and second year respectively in all non-lesional cases. Seizure freedom in non-lesional temporal lobe surgery was achieved in 10 (45 %) of patients at 2 years, 5 (38 %) in non-lesional frontal lobe patients at 2 years and 8 (44 %), 7 (38 %) for all extratemporal at 1 and 2 years respectively. Good prognosis was seen in patients with localized positron emission tomography (PET), had no aura and had a clear ictal onset either on scalp electroencephalogram (EEG) or subdural invasive electroencephalogram. SignificanceThe best surgical outcome is achievable in patients with non-lesional focal epilepsy. This study highlights the prognostic value of the PET scan and ictal scalp/subdural invasive EEG.

Spatiotemporal distribution and age of seizure onset in a pediatric epilepsy surgery cohort with cortical dysplasia

ObjectiveFocal Cortical Dysplasias (CD) are a common etiology of refractory pediatric epilepsy and are amenable to epilepsy surgery. We investigated the association of lesion volume and location to age of seizure onset among children with CD who underwent epilepsy surgery. MethodsA retrospective study of epilepsy surgery patients with pathologically-confirmed CD. Regions of interest (ROI) determined preoperative lesion volumes on 1.5 T and 3 T T2 and SPGR MRIs, and location in 7 distributed neural networks. Descriptive and inferential statistics were used. ResultsFifty-five patients were identified: 35 girls (56.5 %). Median age of seizure onset: 19.0 months (range 0.02 months - 16.0 years). Median age of surgery: 7.8 years (range 2.89 months - 24.45 years). CD were frontal (n = 21, 38 %); temporal (n = 15, 27 %); parietal (n = 10, 18 %); occipital (n = 3, 5%); multilobar (n = 6, 11 %). Frontal FCD had seizure onset < 1-year-old (P = 0.10); temporal lobe CD seizure onset was more likely > 5-years-old (P= 0.06). Median lesion volume for CD was 23.23 cm3 (range: 1.87-591.73 cm3). Larger CD lesions were associated with earlier epilepsy (P = 0.01, r = -0.16). We did not find that lesions proximal to early maturing cortical regions were associated with earlier seizure onset. We found an association with CD location in the default mode network (DMN) and age onset < 5years old (P = 0.03). Age of seizure onset was negatively correlated with percent of CD overlapping motor cortex (P = 0.001, r =-0.794) but not with CD overlap of the visual cortex (P = 0.35). There was no effect of CD type on age of epilepsy onset. SignificanceLarger CD lesions are associated with earlier onset epilepsy. CD most commonly occurs within the DMN and Limbic network, and DMN is associated with seizure onset before 5-years-old. Percent of CD overlapping motor cortex correlates with earlier seizure onset. These observations may reflect patterns of brain maturation or regional differences in clinical expression of seizures.

Molecular changes tracking through multiscale fluorescence microscopy differentiate Meningioma grades and non-tumoral brain tissues

Meningioma is the most common primary intracranial extra-axial tumor. Total surgical removal is the standard therapeutic method to treat this type of brain tumors. However, the risk of recurrence depends on the tumor grade and the extent of the resection including the infiltrated dura mater and, if necessary, the infiltrated bone. Therefore, proper resection of all invasive tumor borders without touching eloquent areas is of primordial in order to decrease the risk of recurrence. Nowadays, none of the intraoperative used tools is able to provide a precise real-time histopathological information on the tumor surrounding areas to help the surgeon to achieve a gross total removal. To respond to this problem, our team is developing a multimodal two-photon fluorescence endomicroscope, compatible with the surgeon tool, to better delimitate tumor boundaries, relying on the endogenous fluorescence of brain tissues. In this context, we are building a tissue database in order to specify each brain tissue, whether healthy or tumoral, with its specific optical signature. In this study, we present a multimodal and multiscale optical measurements on non-tumoral control brain tissue obtained in epilepsy surgery patients and several meningioma grades. We investigated tissue auto-fluorescence to track the molecular changes associated with the tumor grade from deep ultra-violet (DUV) to near infrared (NIR) excitation. Micro-spectroscopy, fluorescence lifetime imaging, two-photon fluorescence imaging and Second Harmonic Generation (SHG) imaging were performed. Several optically derived parameters such as collagen crosslinks fluorescence in DUV, SHG emission in NIR and long lifetime intensity fraction of Nicotinamide Adenine Dinucleotide and Flavins were correlated to discriminate cancerous tissue from control one. While collagen response managed to discriminate meningioma grades from control samples with a 100% sensitivity and 90% specificity through a 3D discriminative algorithm.

Machine Learning for Localizing Epileptogenic-Zone in the Temporal Lobe: Quantifying the Value of Multimodal Clinical-Semiology and Imaging Concordance.

Background: Epilepsy affects 50 million people worldwide and a third are refractory to medication. If a discrete cerebral focus or network can be identified, neurosurgical resection can be curative. Most excisions are in the temporal-lobe, and are more likely to result in seizure-freedom than extra-temporal resections. However, less than half of patients undergoing surgery become entirely seizure-free. Localizing the epileptogenic-zone and individualized outcome predictions are difficult, requiring detailed evaluations at specialist centers.Methods: We used bespoke natural language processing to text-mine 3,800 electronic health records, from 309 epilepsy surgery patients, evaluated over a decade, of whom 126 remained entirely seizure-free. We investigated the diagnostic performances of machine learning models using set-of-semiology (SoS) with and without hippocampal sclerosis (HS) on MRI as features, using STARD criteria.Findings: Support Vector Classifiers (SVC) and Gradient Boosted (GB) decision trees were the best performing algorithms for temporal-lobe epileptogenic zone localization (cross-validated Matthews correlation coefficient (MCC) SVC 0.73 ± 0.25, balanced accuracy 0.81 ± 0.14, AUC 0.95 ± 0.05). Models that only used seizure semiology were not always better than internal benchmarks. The combination of multimodal features, however, enhanced performance metrics including MCC and normalized mutual information (NMI) compared to either alone (p < 0.0001). This combination of semiology and HS on MRI increased both cross-validated MCC and NMI by over 25% (NMI, SVC SoS: 0.35 ± 0.28 vs. SVC SoS+HS: 0.61 ± 0.27).Interpretation: Machine learning models using only the set of seizure semiology (SoS) cannot unequivocally perform better than benchmarks in temporal epileptogenic-zone localization. However, the combination of SoS with an imaging feature (HS) enhance epileptogenic lobe localization. We quantified this added NMI value to be 25% in absolute terms. Despite good performance in localization, no model was able to predict seizure-freedom better than benchmarks. The methods used are widely applicable, and the performance enhancements by combining other clinical, imaging and neurophysiological features could be similarly quantified. Multicenter studies are required to confirm generalizability.Funding: Wellcome/EPSRC Center for Interventional and Surgical Sciences (WEISS) (203145Z/16/Z).