Pharmacoresistant Focal Epilepsy Research Articles

Effects of cenobamate on cognitive performance of epilepsy patients

PurposeCenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance. MethodEfficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions. ResultsThe median CNB dose at T1 was 125 mg/day (range: 50 – 250 mg/day). Most patients received 2–3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p < .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency. ConclusionMost of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

Brain network analysis of interictal epileptiform discharges from ECoG to identify epileptogenic zone in pediatric patients with epilepsy and focal cortical dysplasia type II: A retrospective study.

ObjectiveFor patients with drug–resistant focal epilepsy, intracranial monitoring remains the gold standard for surgical intervention. Focal cortical dysplasia (FCD) is the most common cause of pharmacoresistant focal epilepsy in pediatric patients who usually develop seizures in early childhood. Timely removal of the epileptogenic zone (EZ) is necessary to achieve lasting seizure freedom and favorable developmental and cognitive outcomes to improve the quality of life. We applied brain network analysis to investigate potential biomarkers for the diagnosis of EZ that will aid in the resection for pediatric focal epilepsy patients with FCD type II.MethodsTen pediatric patients with focal epilepsy diagnosed as FCD type II and that had a follow–up after resection surgery (Engel class I [n = 9] and Engel class II [n = 1]) were retrospectively included. Time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation were combined to calculate brain network parameters based on interictal epileptiform discharges from ECoG.ResultsClustering coefficient, local efficiency, node out–degree, and node out–strength with higher values are the most reliable biomarkers for the delineation of EZ, and the differences between EZ and margin zone (MZ), and EZ and normal zone (NZ) were significant (p < 0.05; Mann–Whitney U-test, two–tailed). In particular, the difference between MZ and NZ was significant for patients with frontal FCD (MZ > NZ; p < 0.05) but was not significant for patients with extra–frontal FCD.ConclusionsBrain network analysis, based on the combination of time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation, can aid in the diagnosis of EZ for pediatric focal epilepsy patients with FCD type II.

Stereoelectroencephalography in pre-surgical evaluation of patients with drug-resistant focal epilepsy

Background. Surgical treatment has shown its effectiveness for patients with drug-resistant focal epilepsy: resection or disconnection of the epileptogenic zone leads to relief from epileptic seizures. However, in some cases non-invasive examination may not be sufficient for localization of epileptogenic zone boundaries. Hence, such patients undergo invasive encephalography (EEG) to clarify zone location accounting for seizure development. Objective: to evaluate effectiveness of invasive stereo-EEG in the diagnostics of drug-resistant focal epilepsy. Material and methods. The data collected from 65 patients who underwent stereo-EEG during pre-surgical examination for pharmacoresistant focal epilepsy were retrospectively analyzed within the period of 2016–2019. According to the results of magnetic resonance imaging (MRI), 34 patients had MRI-negative forms of epilepsy, and 31 patients had MRI-positive forms with multiple structural changes in the brain or discrepancies between electro-clinical data and MRI findings. Results. Based on the information obtained by stereo-EEG, 49 patients (75.4%) underwent resection operations. In 16 (24.6%) cases surgical treatment was not carried out due to detected bilateral epileptogenic zone, the lack of convincing data on its location or detecting an epileptogenic zone in a functionally significant region. In 44 operated patients, the follow-up comprised more than 12 months; it was not possible to contact 5 patients. Engel outcomes: I class – 27 (61.3%) patients, II class – 7 (15.9%), III class – 4 (9.1%), IV class – 6 (13.6%). As a result of stereo-EEG, hemorrhagic complications developed in 2 (3.1%) patients: epidural hematoma in 1 case (1.5%), and intracerebral hematoma in 1 case (1.5%). No persistent neurological deficit was noted during continued monitoring. Conclusion. The method of stereo-EEG is effective for determining the epileptogenic zone boundaries in patients with drug- resistant focal epilepsy.

Interictal epileptiform discharges show distinct spatiotemporal and morphological patterns across wake and sleep.

Presurgical evaluation of mesial temporal and neocortical focal pharmacoresistant epilepsy patients using intracranial EEG recordings has led to the generation of extensive data on interictal epileptiform discharges, located within or remotely from seizure onset zones. In this study, we used this data to investigate how interictal epileptiform discharges are modulated and how their spatial distribution changes during wake and sleep and analysed the relationship between these discharge events and seizure onset zones. Preoperative evaluation data from 11 adult patients with focal pharmacoresistant epilepsy were extracted from the Epilepsiae database. Interictal epileptiform discharges were automatically detected during wakefulness and over several hours of continuous seizure-free sleep (total duration of EEG recordings:106.7 h; mean per patient: 9.7 h), and analysed across four brain areas (mesial temporal, lateral neocortical, basal cortical and the temporal pole). Sleep stages were classified manually from scalp EEG. Discharge events were characterized according to their rate and morphology (amplitude, sharpness and duration). Eight patients had a seizure onset zone over mesial areas and three patients over lateral neocortical areas. Overall, discharge rates varied across brain areas during wakefulness and sleep [wake/sleep stages × brain areas interaction; Wald χ 2(df = 6) = 31.1, P < 0.0001]. N2-N3 non-rapid eye movement sleep increased interictal epileptiform discharges in mesial areas compared with wakefulness and rapid eye movement sleep (P < 0.0001), and to other areas (P < 0.0001 for all comparisons). This mesial pattern was observed both within and outside of seizure onset zones. During wakefulness, the rate of interictal epileptiform discharges was significantly higher than during N2-N3 non-rapid eye movement sleep (P = 0.04), and rapid eye movement sleep (P = 0.01) in lateral neocortical areas (referred to as lateral neocortical pattern), a finding that was more pronounced in seizures onset zones (P = 0.004). The morphological characteristics of the discharge events were modulated during wakefulness and sleep stages across brain areas. The effect of seizure onset zones on discharge morphology was conditioned by brain area and was particularly marked in temporal pole areas. Our analysis of discharge patterns in relation to cerebral localization, vigilance state and the anatomical affiliation of seizure onset zones revealed the global and local aspects of the complex relationship between interictal discharges, sleep and seizure onset zones. This novel approach may lead to a better understanding of cognitive decline and responses to therapy, as well as to adaptation of surgical interventions for epileptic patients.

Automated video analysis of emotion and dystonia in epileptic seizures

ObjectiveTo investigate the accuracy of deep learning methods applied to seizure video data, in discriminating individual semiologic features of dystonia and emotion in epileptic seizures. MethodsA dataset of epileptic seizure videos was used from patients explored with stereo-EEG for focal pharmacoresistant epilepsy. All patients had hyperkinetic (HKN) seizures according to ILAE definition. Presence or absence of (1) dystonia and (2) emotional features in each seizure was documented by an experienced clinician. A deep learning multi-stream model with appearance and skeletal keypoints, face and body information, using graph convolutional neural networks, was used to test discrimination of dystonia and emotion. Classification accuracy was assessed using a leave-one-subject-out analysis. ResultsWe studied 38 HKN seizure videos in 19 patients. By visual analysis based on ILAE criteria, 9/19 patients were considered to have dystonia and 9/19 patients were considered to have emotional signs. Two patients had both dystonia and emotional signs. Applying the deep learning multistream model, spatiotemporal features of facial appearance showed best accuracy for emotion detection (F1 score 0.84), while skeletal keypoint detection performed best for dystonia (F1 score 0.83). SignificanceHere, we investigated deep learning of video data for analyzing individual semiologic features of dystonia and emotion in hyperkinetic seizures. Automated classification of individual semiologic features is possible and merits further study.

Long-term deep intracerebral microelectrode recordings in patients with drug-resistant epilepsy: Proposed guidelines based on 10-year experience

PurposeHuman neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and pathophysiological mechanisms of brain diseases, in particular epilepsy. Continuous and long-term recordings are necessary to monitor non predictable pathological and physiological activities like seizures or sleep. Because of their high impedance, microelectrodes are more sensitive to noise than macroelectrodes. Low noise levels are crucial to detect action potentials from background noise, and to further isolate single neuron activities. Therefore, long-term recordings of multi-unit activity remains a challenge. We shared here our experience with microelectrode recordings and our efforts to reduce noise levels in order to improve signal quality. We also provided detailed technical guidelines for the connection, recording, imaging and signal analysis of microelectrode recordings. ResultsDuring the last 10 years, we implanted 122 bundles of Behnke-Fried hybrid macro-microelectrodes, in 56 patients with pharmacoresistant focal epilepsy. Microbundles were implanted in the temporal lobe (74%), as well as frontal (15%), parietal (6%) and occipital (5%) lobes. Low noise levels depended on our technical setup. The noise reduction was mainly obtained after electrical insulation of the patient's recording room and the use of a reinforced microelectrode model, reaching median root mean square values of 5.8 µV. Seventy percent of the bundles could record multi-units activities (MUA), on around 3 out of 8 wires per bundle and for an average of 12 days. Seizures were recorded by microelectrodes in 91% of patients, when recorded continuously, and MUA were recorded during seizures for 75 % of the patients after the insulation of the room. Technical guidelines are proposed for (i) electrode tails manipulation and protection during surgical bandage and connection to both clinical and research amplifiers, (ii) electrical insulation of the patient's recording room and shielding, (iii) data acquisition and storage, and (iv) single-units activities analysis. ConclusionsWe progressively improved our recording setup and are now able to record (i) microelectrode signals with low noise level up to 3 weeks duration, and (ii) MUA from an increased number of wires . We built a step by step procedure from electrode trajectory planning to recordings. All these delicate steps are essential for continuous long-term recording of units in order to advance in our understanding of both the pathophysiology of ictogenesis and the neuronal coding of cognitive and physiological functions.

Epilepsy related to focal neuronal lipofuscinosis: extra-frontal localization, EEG signatures and GABA involvement.

Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue.

Histopathological Findings in Brain Tissue of Patients with Pharmacoresistant Focal Epilepsy

Background: Pharmacoresistant epilepsy represents 30-40% of cases with intractable epilepsy in children, and up to 20% of adult cases. Various cerebral lesions can lead to drug-resistant focal epilepsy. They are medically refractory but the complete surgical resection correlates with good outcome.

Histopathological Correlations of Qualitative and Quantitative Temporopolar MRI Analyses in Patients With Hippocampal Sclerosis.

Hippocampal sclerosis (HS) is a common cause of pharmacoresistant focal epilepsy. Here, we (1) performed a histological approach to the anterior temporal pole of patients with HS to evaluate cortical and white matter (WM) cell populations, alteration of myelin integrity and markers of neuronal activity, and (2) correlated microscopic data with magnetic resonance imaging (MRI) findings. Our aim was to contribute with the understanding of neuroimaging and pathophysiological mechanisms of temporal lobe epilepsy (TLE) associated with HS. We examined MRIs and surgical specimens from the anterior temporal pole from TLE-HS patients (n = 9) and compared them with 10 autopsy controls. MRIs from healthy volunteers (n = 13) were used as neuroimaging controls. Histological techniques were performed to assess oligodendrocytes, heterotopic neurons, cellular proliferative index, and myeloarchitecture integrity of the WM, as well as markers of acute (c-fos) and chronic (ΔFosB) activities of neocortical neurons. Microscopic data were compared with neuroimaging findings, including T2-weighted/FLAIR MRI temporopolar blurring and values of fractional anisotropy (FA) from diffusion-weighed imaging (DWI). We found a significant increase in WM oligodendrocyte number, both in hematoxylin and eosin, and in Olig2-stained sections. The frequencies of oligodendrocytes in perivascular spaces and around heterotopic neurons were significantly higher in patients with TLE–HS compared with controls. The percentage of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; a marker of myeloarchitecture integrity) immunopositive area in the WM was significantly higher in TLE-HS, as well as the numbers of c-fos- and ΔFosB-immunostained neocortical neurons. Additionally, we demonstrated a decrease in axonal bundle integrity on neuroimaging, with a significant reduction in the FA in the anterior temporal pole. No differences were detected between individuals with and without temporopolar blurring on visual MRI analysis, considering the number of oligodendroglial cells and percentage of WM CNPase-positive areas. Also, there was no relationship between T2 relaxometry and oligodendrocyte count. In conclusion, our histopathological data support the following: (1) the hypothesis that repetitive neocortical neuronal activity could induce changes in the WM cellular constitution and myelin remodeling in the anterior temporal pole from patients with TLE-HS, (2) that oligodendroglial hyperplasia is not related to temporal blurring or T2 signal intensity on MRI, and (3) that reduced FA is a marker of increase in Olig2-immunopositive cells in superficial temporopolar WM from patients with TLE-HS.

ResectVol: A tool to automatically segment and characterize lacunas in brain images.

ObjectiveTo assess and validate the performance of a new tool developed for segmenting and characterizing lacunas in postoperative MR images of epilepsy patients.MethodsA MATLAB‐based pipeline was implemented using SPM12 to produce the 3D mask of the surgical lacuna and estimate its volume. To validate its performance, we compared the manual and automatic lacuna segmentations obtained from 51 MRI scans of epilepsy patients who underwent temporal lobe resections.ResultsThe code is consolidated as a tool named ResectVol, which can be run via a graphical user interface or command line. The automatic and manual segmentation comparison resulted in a median Dice similarity coefficient of 0.77 (interquartile range: 0.71‐0.81).SignificanceEpilepsy surgery is the treatment of choice for pharmacoresistant focal epilepsies, and despite the extensive literature on the subject, we still cannot predict surgical outcomes accurately. As the volume and location of the resected tissue are fundamentally relevant to this prediction, researchers commonly perform a manual segmentation of the lacuna, which presents human bias and does not provide detailed information about the structures removed. In this study, we introduce ResectVol, a user‐friendly, fully automatic tool to accomplish these tasks. This capability enables more advanced analytical techniques applied to surgical outcomes prediction, such as machine‐learning algorithms, by facilitating coregistration of the resected area and preoperative findings with other imaging modalities such as PET, SPECT, and functional MRI ResectVol is freely available at https://www.lniunicamp.com/resectvol.

Epilepsy imaging: New challenges on the diagnosis

Imaging is pivotal in the evaluation and management of patients with epilepsies. High-resolution structural neuroimaging with magnetic resonance imaging (MRI) plays a vital role in defining the etiology, epilepsy syndrome, and prognosis of seizure disorders. The type of lesion identified by MRI is associated with different probabilities of pharmacoresistance. It is essential that structural MRIs are optimally acquired, including 3D T1-weighted and FLAIR sequences, and carefully reviewed by trained experts within the context of all available clinical and EEG data. Multiplanar reformatting of high-resolution MRI and correlation with functional multimodal imaging improves the detection of subtle lesions. Detection of a lesion on a previous negative MRI has a substantial impact on determining the etiology of epilepsy, reducing the need for invasive investigations, and planning surgical treatment in patients with pharmacoresistant seizures and for the postoperative outcome. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures, including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms, and malformations of cortical development (MCD), has been well established. Quantitative postprocessing may help to complement the evaluation of subtle MCDs. Positron emission tomography (PET) is the most performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single-photon emission computed tomography (SPECT) studies may assist the performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy. Emerging functional imaging modalities, such as functional MRI (fMRI), and EEG-fMRI, may help to reduce the need for invasive investigations and predict prognosis.

Automated interictal source localisation based on high-density EEG

PurposeTo study the accuracy of automated interictal EEG source localisation based on high-density EEG, and to compare it to low-density EEG. MethodsThirty patients operated for pharmacoresistant focal epilepsy were retrospectively examined. Twelve months after resective brain surgery, 18 were seizure-free or had ‘auras’ only, while 12 had persistence of disabling seizures. Presurgical 257-channel EEG lasting 3–20 h was down-sampled to 25, 40, and 204 channels for separate analyses. For each electrode setup, interictal spikes were detected, clustered, and averaged automatically before validation by an expert reviewer. An individual 6-layer finite difference head model and the standardised low-resolution electromagnetic tomography were used to localise the maximum source activity of the most prevalent spike. Sublobar concordance with the resected brain area was visually assessed and related to favourable vs. unfavourable postsurgical outcome. ResultsDepending on the EEG setup, epileptic spikes were detected in 21-24 patients (70-80%). The median number of single spikes per average was 470 (range 17–15,066). Diagnostic sensitivity of EEG source localisation was 58-75%, specificity was 50-67%, and overall accuracy was 55-71%. There were no significant differences between low- and high-density EEG setups with 25 to 257 electrodes. ConclusionAutomated high-density EEG source localisation provides meaningful information in the majority of cases. With hundreds of single spikes averaged, diagnostic accuracy is similar in high- and low-density EEG. Therefore, low-density EEG may be sufficient for interictal EEG source localisation if high numbers of spikes are available.

Past Trauma Is Associated With a Higher Risk of Experiencing an Epileptic Seizure as Traumatic in Patients With Pharmacoresistant Focal Epilepsy.

Objective: The present study aimed to evaluate the prevalence of traumatic experienced seizures (TES) and of postepileptic seizure PTSD (PS-PTSD) in patients with pharmacoresistant focal epilepsy and to explore the determining factors of TES.Methods: We conducted an observational study enrolling 107 adult refractory epilepsy patients. We used the DSM-5 criteria of traumatic events and PTSD to define TES and PS-PTSD. We assessed all traumatic life events unrelated to epilepsy, general and specific psychiatric comorbidities, and quality of life.Results: Nearly half (n = 48) of the 107 participants reported at least one TES (44.85%). Among these, one-third (n = 16) developed PS-PTSD. The TES group was more likely to experience traumatic events unrelated to epilepsy (p < 0.001), to have generalized anxiety disorder (p = 0.019), and to have specific psychiatric comorbidities [e.g., interictal dysphoric disorder (p = 0.024) or anticipatory anxiety of seizures (p = 0.005)]. They reported a severe impact of epilepsy on their life (p = 0.01). The determining factors of TES according to the multifactorial model were the experience of trauma (p = 0.008), a history of at least one psychiatric disorder (p = 0.03), and a strong tendency toward dissociation (p = 0.03).Significance: Epileptic seizures may be a traumatic experience in some patients who suffer from pharmacoresistant epilepsy and may be the source of the development of PS-PTSD. Previous trauma unrelated to epilepsy and psychiatric history are determining factors of TES. These clinical entities should be explored systematically.

Focal epilepsy due to de novo SCN1A mutation.

Our aim was to identify patients with SCN1A-related epilepsy with a phenotype of pure focal epilepsy. We conducted a retrospective study and a systematic review in Pubmed to identify patients with focal epilepsy associated with SCN1A pathogenic variants. We found three patients among 1,191 in our rare epilepsy database in 2017. The literature search from January 2000 to September 2019 led to identification of four patients with limited data. Our three patients had a common phenotype with focal-onset seizures as the only seizure type. All patients showed normal psychomotor development in the first years of life, and no intellectual disability although they displayed some cognitive or behavioural problems. Fever or hyperthermia were triggers in all three patients. In addition, all had a history of brief recurrent febrile seizures in their first year, followed by a phenotype of pharmacoresistant focal epilepsy with normal brain imaging. Two of them were initially investigated for epilepsy surgery. Seizure precipitation by fever has also been reported in previously published patients. Focal epilepsy associated with SCN1A gene mutation should be recognized in patients with suggestive features, in particular among surgical candidates.

802 Seizure-Associated Central Respiratory Events: What’s Sleep Go To Do With It?

Abstract Introduction Seizure-related respiratory dysfunction has been reported in patients with epilepsy(PWE) on scalp EEG. We assessed this in Stereo-EEG(SEEG) recordings in patients with pharmacoresistant focal epilepsy. Methods PWE undergoing SEEG wore temperature/pressure-based airflow,RIP belts, SpO2, and EtCO2/TcpCO2. Interpretable recordings required SpO2 and at least one airflow and effort channel. Respiratory events including apneas, hypopneas(3%) and central pauses (5 to&amp;lt;10sec). Respiratory events, respiratory rate(RR), SpO2 nadir, total desaturation time, Peak EtCO2/TcpCO2, and hypercapnia duration were analyzed surrounding seizures. Frequency and duration of central events were compared in sleep-onset and awake seizures. Linear mixed-effects models evaluated relationships between respiratory variables and the frequency and duration of central events associated with seizures and compared respiratory variables between seizures with and without events. Results 44 seizures were recorded in 23 patients. Seizures were focal-onset in 79.5%(n=35), GTC in 20.5%(9). Respiratory events accompanied 61.4%(27) of the seizures with median duration/seizure duration of 0.40(IQR: 0.27, 0.61). Of the 47 respiratory events, 42 were central events, and 66.6%(28) were central apneas. Respiratory events occurred during the seizure in 73.8%, postictal in 26.2%; median SpO2 nadir was 90%(77.0, 93.0), total desaturation duration 104.3(50.3, 195.0)sec, peak TcpCO2 41.3(38.7, 44.8) mmHg, hypercapnia duration 157.6(51.0, 367.9) sec, and ictal-postictal RR change 3.3 ± 4.0bpm. For every 1 sec duration increase in central event duration, there was a significant increase in peak TcpCO2 0.35(95%CI [0.09,0.62],p=0.015) and TcpCO2 change 0.25(95%CI [0.02,0.49],p=0.037). Presence of central events were associated with increased peak TcpCO2(9.82[3.77,15.9], p=0.006). Seizures with central events trended greater changes in RR, SpO2, and EtCO2/TcpCO2, desaturation and hypercapnia time, with negative changes in SpO2 nadir. No significant difference on central event frequency was found between sleep-onset and awake seizures. Conclusion Central events including apneas and pauses are common in focal seizures arising from sleep and wake and are associated with hypercapnia. In addition to the significant association between TcpCO2 and the frequency and duration of central events, there is a positive trend of association of other respiratory dysfunction parameters. These findings suggest that central events may lead to a cascade of respiratory disturbance that may participate in the pathophysiology of sudden unexplained death in epilepsy. Support (if any):

Voxel-based morphometry for the evaluation of patients with pharmacoresistant epilepsy with apparently normal MRI.

Magnetic resonance imaging (MRI) is essential in the diagnosis of pharmacoresistant epilepsy (PRE), because patients with lesions detected by MRI have a better prognosis after surgery. Focal cortical dysplasia (FCD) is one of the most frequent etiologies of PRE but can be difficult to identify by MRI. Voxel-based morphometric analysis programs, like the Morphometric Analysis Program (MAP), have been developed to help improve MRI detection. Our objective was to evaluate the clinical usefulness of MAP in patients with PRE and an apparently normal MRI. We studied 70 patients with focal PRE and a nonlesional MRI. The 3DT1 sequence was processed with MAP, obtaining three z-score maps. Patients were classified as MAP+ if one or more z-score maps showed a suspicious area of brightness, and MAP- if the z-score maps did not show any suspicious areas. For MAP+ cases, a second-look MRI was performed with a dedicated inspection based on the MAP findings. The MAP results were correlated with the epileptogenic zone. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Thirty-one percent of patients were classified as MAP+ and 69% were MAP-. Results showed a sensitivity of 0.57, specificity of 0.8, PPV of 0.91, and NPV of 0.35. In 19% of patients, an FCD was found in the second-look MRI after MAP. MAP was helpful in the detection of lesions in PRE patients with a nonlesional MRI, which could have important repercussions for the clinical management and postoperative prognosis of these patients.

Stiripentol in the treatment of adults with focal epilepsy- a retrospective analysis

The aim of the present study was to evaluate the safety and efficacy of the add-on treatment of stiripentol (STP) in adult patients with severely pharmacoresistant focal or multifocal epilepsy. Data on adult patients treated with STP from March 2007 to July 2020 and with at least one clinical follow-up (FU) were retrospectively reviewed. Data on tolerability, efficacy and concomitant medication were evaluated at baseline, 6 months (5.5 ± 1.6 months (mean ± SD)) and 12 months (13.1 ± 3.9 months (mean ± SD)). Data of 22 patients (54.5% male, mean age 34.4 ± 17.79 years (mean ± SD), including mean duration of epilepsy 17.6 ± 25.5 years (mean ± SD), median seizure frequency 30 ± 20 (median ± MAD) per month, and 63.6% being severely intellectually disabled, with 3 to 18 previous anti-seizure-drugs (ASD), were collected. After 6 months, 72.7% of the patients were still taking STP, and 31% of the patients were responders, including 13% who were seizure-free. The 12-month retention rate was 54.4 %, the response rate was 36.4% and 13.6% of patients were seizure-free at the 12-month FU. Reasons for discontinuation were increased seizure frequency, hyperammonaemia and encephalopathy. STP seems to be a useful option in the treatment of patients with severely pharmacoresistant epilepsy. Prospective trials are necessary to examine the efficacy of STP in adult patients with pharmacoresistant focal epilepsy.

Radiological and Clinical Value of 7T MRI for Evaluating 3T-Visible Lesions in Pharmacoresistant Focal Epilepsies.

Objective: The recent FDA approval of the first 7T MRI scanner for clinical diagnostic use in October 2017 will likely increase the utilization of 7T for epilepsy presurgical evaluation. This study aims at accessing the radiological and clinical value of 7T in patients with pharmacoresistant focal epilepsy and 3T-visible lesions.Methods: Patients with pharmacoresistant focal epilepsy were included if they had a lesion on pre-operative standard-of-care 3T MRI and also a 7T research MRI. An epilepsy protocol was used for the acquisition of the 7T MRI. Prospective visual analysis of 7T MRI was performed by an experienced board-certified neuroradiologist and communicated to the patient management team. The clinical significance of the additional 7T findings was assessed by intracranial EEG (ICEEG) ictal onset, surgical resection, post-operative seizure outcome and histopathology. A subset of lesions were demarked with arrows for subsequent, retrospective comparison between 3T and 7T by 7 neuroradiologists using a set of quantitative scales: lesion presence, conspicuity, boundary, gray-white tissue contrast, artifacts, and the most helpful sequence for diagnosis. Conger's kappa for multiple raters was performed for chance-adjusted agreement statistics.Results: A total of 47 patients were included, with the main pathology types of focal cortical dysplasia (FCD), hippocampal sclerosis, periventricular nodular heterotopia (PVNH), tumor and polymicrogyria (PMG). 7T detected additional smaller lesions in 19% (9/47) of patients, who had extensive abnormalities such as PMG and PVNH; however, these additional findings were not necessarily epileptogenic. 3T−7T comparison by the neuroradiologist team showed that lesion conspicuity and lesion boundary were significantly better at 7T (p < 0.001), particularly for FCD, PVNH and PMG. Chance-adjusted agreement was within the fair range for lesion presence, conspicuity and boundary. Gray-white contrast was significantly improved at 7T (p < 0.001). Significantly more artifacts were encountered at 7T (p < 0.001).Significance: For patients with 3T-visible lesions, 7T MRI may better elucidate the extent of multifocal abnormalities such as PVNH and PMG, providing potential targets to improve ICEEG implantation. Patients with FCD, PVNH and PMG would likely benefit the most from 7T due to improved lesion conspicuity and boundary. Pathologies in the antero–inferior temporal regions likely benefit less due to artifacts.

Automated detection and segmentation of focal cortical dysplasias (FCDs) with artificial intelligence: Presentation of a novel convolutional neural network and its prospective clinical validation

PurposeFocal cortical dysplasias (FCDs) represent one of the most frequent causes of pharmaco-resistant focal epilepsies. Despite improved clinical imaging methods over the past years, FCD detection remains challenging, as FCDs vary in location, size, and shape and commonly blend into surrounding tissues without clear definable boundaries. We developed a novel convolutional neural network for FCD detection and segmentation and validated it prospectively on daily-routine MRIs. Material and methodsThe neural network was trained on 201 T1 and FLAIR 3 T MRI volume sequences of 158 patients with mainly FCDs, regardless of type, and 7 focal PMG. Non-FCD/PMG MRIs, drawn from 100 normal MRIs and 50 MRIs with non-FCD/PMG pathologies, were added to the training. We applied the algorithm prospectively on 100 consecutive MRIs of patients with focal epilepsy from daily clinical practice. The results were compared with corresponding neuroradiological reports and morphometric MRI analyses evaluated by an experienced epileptologist. ResultsBest training results reached a sensitivity (recall) of 70.1 % and a precision of 54.3 % for detecting FCDs. Applied on the daily-routine MRIs, 7 out of 9 FCDs were detected and segmented correctly with a sensitivity of 77.8 % and a specificity of 5.5 %. The results of conventional visual analyses were 33.3 % and 94.5 %, respectively (3/9 FCDs detected); the results of morphometric analyses with overall epileptologic evaluation were both 100 % (9/9 FCDs detected) and thus served as reference. ConclusionWe developed a 3D convolutional neural network with autoencoder regularization for FCD detection and segmentation. Our algorithm employs the largest FCD training dataset to date with various types of FCDs and some focal PMG. It provided a higher sensitivity in detecting FCDs than conventional visual analyses. Despite its low specificity, the number of false positively predicted lesions per MRI was lower than with morphometric analysis. We consider our algorithm already useful for FCD pre-screening in everyday clinical practice.

Associations of individual and structural socioeconomic status with cognition and mental distress in pharmacoresistant focal epilepsy

ObjectiveEpilepsy is often associated with low socioeconomic status (SES). People with epilepsy (PWE) also suffer from cognitive dysfunction and mental distress. In the general population, these constraints are related to individual and structural SES. However, in PWE, cognitive dysfunction and mental distress have been mainly attributed to biological factors such as brain lesions or pharmacological treatment, whereas comprehensive studies on possible social determinants are missing. Here, we study associations of individual and structural SES with cognition and mental distress in PWE. MethodsWe retrospectively studied 340 adult patients with pharmacoresistant focal epilepsy from Berlin treated at a tertiary epilepsy center. Individual SES (education, employment, and income), structural SES (social index of district and neighborhood), and their interactions were examined. Associations between social variables and verbal learning, psychomotor speed, and mental distress were analyzed with multiple regression analyses, controlling for demographic and medical variables and intelligence. ResultsOur sample had lower educational levels and lived more frequently in low SES neighborhoods compared to the general population of Berlin. Thirty percent showed reduced verbal learning, 31% had deficits in psychomotor speed, and 20% revealed significant mental distress. Lower structural SES was related to lower psychomotor speed (ΔR2 = 0.9%) and higher mental distress (ΔR2 = 1.6%). Employment was related to verbal learning (ΔR2 = 0.7%) and psychomotor speed (ΔR2 = 1.2%). Income and education were linked to mental distress (ΔR2 = 5%). Neighborhood and individual SES covered more than half of the explained variance in mental distress. Furthermore, interactions between individual and structural SES were identified. ConclusionWe confirm cognitive deficits, significant mental distress, and individual and structural social disadvantage in PWE. Our findings indicate that individual and structural SES are related to cognitive and emotional well-being beyond demographic and medical characteristics. As a clinical implication, individual and structural SES should be considered when interpreting neuropsychological findings.