Drug-resistant Partial Epilepsy Research Articles

Electrophysiological brain imaging based on simulation-driven deep learning in the context of epilepsy

Identifying the location, the spatial extent and the electrical activity of distributed brain sources in the context of epilepsy through ElectroEncephaloGraphy (EEG) recordings is a challenging task because of the highly ill-posed nature of the underlying Electrophysiological Source Imaging (ESI) problem. To guarantee a unique solution, most existing ESI methods pay more attention to solve this inverse problem by imposing physiological constraints. This paper proposes an efficient ESI approach based on simulation-driven deep learning. Epileptic High-resolution 256-channels scalp EEG (Hr-EEG) signals are simulated in a realistic manner to train the proposed patient-specific model. More particularly, a computational neural mass model developed in our team is used to generate the temporal dynamics of the activity of each dipole while the forward problem is solved using a patient-specific three-shell realistic head model and the boundary element method. A Temporal Convolutional Network (TCN) is considered in the proposed model to capture local spatial patterns. To enable the model to observe the EEG signals from different scale levels, the multi-scale strategy is leveraged to capture the overall features and fine-grain features by adjusting the convolutional kernel size. Then, the Long Short-Term Memory (LSTM) is used to extract temporal dependencies among the computed spatial features. The performance of the proposed method is evaluated through three different scenarios of realistic synthetic interictal Hr-EEG data as well as on real interictal Hr-EEG data acquired in three patients with drug-resistant partial epilepsy, during their presurgical evaluation. A performance comparison study is also conducted with two other deep learning-based methods and four classical ESI techniques. The proposed model achieved a Dipole Localization Error (DLE) of 1.39 and Normalized Hamming Distance (NHD) of 0.28 in the case of one patch with SNR of 10 dB. In the case of two uncorrelated patches with an SNR of 10 dB, obtained DLE and NHD were respectively 1.50 and 0.28. Even in the more challenging scenario of two correlated patches with an SNR of 10 dB, the proposed approach still achieved a DLE of 3.74 and an NHD of 0.43. The results obtained on simulated data demonstrate that the proposed method outperforms the existing methods for different signal-to-noise and source configurations. The good behavior of the proposed method is also confirmed on real interictal EEG data. The robustness with respect to noise makes it a promising and alternative tool to localize epileptic brain areas and to reconstruct their electrical activities from EEG signals.

PO036 / #609 REFINEMENT OF GRANULARITY OF CORTICAL ATLAS TO MODEL EPILEPTIC INTERICTAL SPIKE PROPAGATION: E-POSTER VIEWING

In patients with drug-resistant partial epilepsy, intracerebral recordings with stereoelectroencephalography (SEEG) are performed in order to localize the activity arising from epileptogenic tissues and its propagation patterns. The clinical interpretation of SEEG signals is crucial to delimit surgery boundaries or to design patient-specific neuromodulation protocols. To assist these interpretations, physiologically relevant computational and anatomical models can be combined to reconstruct in silico intracerebral SEEG signals and to link the signal morphology with the geometry of underlying epileptic regions.

Acute effects of brain-responsive neurostimulation in drug-resistant partial onset epilepsy

ObjectiveUnderstanding the acute effects of responsive stimulation (AERS) based on intracranial EEG (iEEG) recordings in ambulatory patients with drug-resistant partial epilepsy, and correlating these with changes in clinical seizure frequency, may help clinicians more efficiently optimize responsive stimulation settings. MethodsIn patients implanted with the NeuroPace® RNS® System, acute changes in iEEG spectral power following active and sham stimulation periods were quantified and compared within individual iEEG channels. Additionally, acute stimulation-induced acute iEEG changes were compared within iEEG channels before and after patients experienced substantial reductions in clinical seizure frequency. ResultsResponsive stimulation resulted in a 20.7% relative decrease in spectral power in the 2–4 second window following active stimulation, compared to sham stimulation. On several detection channels, the AERS features changed when clinical outcomes improved but were relatively stable otherwise. AERS change direction associated with clinical improvement was generally consistent within detection channels. ConclusionsIn this retrospective analysis, patients with drug-resistant partial epilepsy treated with direct brain-responsive neurostimulation showed an acute stimulation related reduction in iEEG spectral power that was associated with reductions in clinical seizure frequency. SignificanceIdentifying favorable stimulation related changes in iEEG activity could help physicians to more rapidly optimize stimulation settings for each patient.

HR-EEG Source localization

High-resolution EEG (HR-EEG) allows the recording of electric brain activities with excellent temporal resolution. Data have to be recorded with high temporal resolution (sampling rate) and high spatial resolution (number of channels). Data analyses are based on several steps including interictal and/or ictal selections, head model elaboration and use of several algorithms in order to solve the inverse problem. These tools now represent real methods of Electric Source Imaging. HR-EEG constitutes non-invasive and complementary examination with Magnetoencephalography (MEG), characterized by distinct sensitivities according to the location and orientation of intracerebral generators. In the presurgical assessment of drug-resistant partial epilepsies, HR-EEG can characterize and localize interictal activities and thus the irritative zone. HR-EEG often yields significant additional data that are complementary to other presurgical investigations. In some lesional epilepsy cases as epilepsies related to focal cortical dysplasia, localization of the irritative zone using HR-EEG is particularly relevant in presurgical evaluation, epileptogenic and irritative zones being characterized by an overlap. It has been demonstrated that HR-EEG more accurately estimated the epileptogenic zone in subgroups of patients who are often the most difficult cases in epilepsy surgery: frontal lobe epilepsy, negative MRI and the presence of malformation of cortical development [1] . Moreover, source localization results may help in identifying subtle focal cortical dysplasia abnormalities and increasing the diagnostic yield of conventional MRI visual analysis [3] . During presurgical evaluation of pharmacoresistant partial epilepsies, stereoelectroencephalography records interictal and ictal activities directly but is inherently limited in spatial sampling. In contrast, scalp-EEG and MEG are less sensitive but provide a global view on brain activity. Therefore, recording simultaneously these three modalities [2] should provide a better understanding of the underlying brain sources by taking advantage of the different sensitivities of the three recording techniques.

Surgical techniques and therapeutic effect of deep brain stimulation of anterior nucleus thalamus for refractory partial epilepsy

Objective To discuss the surgical techniques and therapeutic effect of deep brain stimulation of anterior nucleus thalamus for refractory partial epilepsy. Methods Eight drug-resistant partial epilepsy patients, with no indication of respective surgery, were treated at Neurosurgery Department of Beijing Tiantan Hospital, Capital Medical University from March 2015 to November 2016 and retrospectively enrolled into this study. The seizure frequency, severity of seizure, quality of life, depression and anxiety status and other clinical outcome features in pre-surgical and post-surgical periods were analyzed. Results Eight patients with refractory partial epilepsy were followed up for 18.0±2.4 months. The seizure frequency post surgery was significantly reduced (36.4±13.4 times per month prior to operation, 13.9±6.2 times per month post operation, P=0.012) and the remission rate was 54.3%±7.4%. The severity of seizure was improved based on the Liverpool seizure severity scale (38.4±5.3 points prior to operation, 22.3±4.9 points post operation, P=0.001) and the remission rate was 46.0%±8.4%. The quality of life was significantly improved based on the Quality of Life in Epilepsy Inventory-89 (71.2±2.7 points prior to operation, 80.0±2.9 points post operation, P=0.001) and the improvement rate was 12.6%±2.3%. Conclusion For patients with refractory partial epilepsy without indication of respective surgery, deep brain stimulation of anterior nucleus thalamus might have certain treatment effect, which still needs further clinical research. Key words: Epilepsy, partial; Anterior thalamic nuclei; Deep brain stimulation; Treatment outcome

Longitudinal imaging of Microglia-Astrocyte activation in mouse mesial temporal lobe epilepsy with TSPO PET to identify the best therapeutic time windows

Objectives Mesiotemporal lobe epilepsy (MTLE) is the most common type of drug-resistant partial epilepsy with a specific history which begins by a status epilepticus due to a neurological insult followed by a silent period before the recurrent seizures begin. Once established, these seizures can become resistant to medications. Along this period a specific lesion is often found, described as a unilateral hippocampal sclerosis (HS). Currently it is still challenging to determine when and which drugs can be most effective along the constitution of this epileptic process. Neuroinflammation has been reported to play an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation probes can be potent epilepsy biomarkers. The Translocator Protein 18 kDa (TSPO) expression is associated with neuroinflammatory processes involving reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral hippocampal sclerosis and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that TSPO PET imaging using 18F-DPA-714 TSPO-targeted PET could be a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and follow response to treatment in the mouse model of MTLE. Methods The model was induced by unilateral injection of kainic acid into the right dorsal hippocampus of male C57/Bl6 mice. μPET/CT scanning was performed before model induction and along the development of the HS at 7 days, 14 days, 1 month and 6 months. In vitro autoradiography and immunohistofluorescence were performed on additional mice at each time point. Results TSPO PET uptake reached the peak at 7 days and mostly correlated with microglial activation whereas after 14 days, reactive astrocytes were shown to be the main cells expressing TSPO which would be related to the increased PET uptake. Our studies suggest that mTOR signal pathways play an important role in the modulation of astrocyte activities. Our hypothesis is that the neurotoxicity during ictogenesis (aggravation phase) could be due to persistent mTOR reactive signaling in astrocytes. Conclusion : on this knowledge of TSPO expression over time in the MTLE model, TSPO PET imaging could be a valuable tool to evaluate efficacy of mTOR treatments.

Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: Toward identification of optimal treatment windows.

Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process. Neuroinflammation plays an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation biomarkers such as translocator protein 18 kDa (TSPO) can be potent epilepsy biomarkers. TSPO is associated with reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral HS and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that longitudinal imaging using TSPO positron emission tomography (PET) with 18 F-DPA-714 could identify optimal treatment windows in a mouse model during the formation of HS. The model was induced into the right dorsal hippocampus of male C57/Bl6 mice. Micro-PET/computed tomographic scanning was performed before model induction and along the development of the HS at 7 days, 14 days, 1 month, and 6 months. In vitro autoradiography and immunohistofluorescence were performed on additional mice at each time point. TSPO PET uptake reached peak at 7 days and mostly related to microglial activation, whereas after 14 days, reactive astrocytes were shown to be the main cells expressing TSPO, reflected by a continuing increased PET uptake. TSPO-targeted PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor response to treatment.

Neurostimulation for drug-resistant epilepsy: a systematic review of clinical evidence for efficacy, safety, contraindications and predictors for response.

Neurostimulation is becoming an increasingly accepted treatment alternative for patients with drug-resistant epilepsy (DRE) who are unsuitable surgery candidates. Standardized guidelines on when or how to use the various neurostimulation modalities are lacking. We conducted a systematic review on the currently available neurostimulation modalities primarily with regard to effectiveness and safety. For vagus nerve stimulation (VNS), there is moderate-quality evidence for its effectiveness in adults with drug-resistant partial epilepsies. Moderate-to-low-quality evidence supports the efficacy and safety of deep brain stimulation (DBS) and responsive neurostimulation (RNS) in patients with DRE. There is moderate-to-very low-quality evidence that transcranial direct current stimulation (tDCS) is effective or well tolerated. For transcutaneous vagus nerve stimulation (tVNS), transcranial magnetic stimulation (TMS) and trigeminal nerve stimulation (TNS), there are insufficient data to support the efficacy of any of these modalities for DRE. These treatment modalities, nevertheless, appear well tolerated, with no severe adverse events reported. Head-to-head comparison of treatment modalities such as VNS, DBS and RNS across different epileptic syndromes are required to decide which treatment modality is the most effective for a given patient scenario. Such studies are challenging and it is unlikely that data will be available in the near future. Additional data collection on potentially promising noninvasive neurostimulation modalities like tVNS, TMS, TNS and tDCS is warranted to get a more precise estimate of their therapeutic benefit and long-term safety.

Model-based sensitivity analysis for outcome reporting bias in the meta analysis of benefit and harm outcomes.

Outcome reporting bias occurs when outcomes in research studies are selectively reported, the selection being influenced by the study results. For benefit outcomes, we have shown how risk assessments using the Outcome Reporting Bias in Trials risk classification scale can be used to calculate bias-adjusted treatment effect estimates. This paper presents a new and simpler version of the benefits method, and shows how it can be extended to cover the partial reporting and non-reporting of harm outcomes. Our motivating example is a Cochrane systematic review of 12 studies of Topiramate add-on therapy for drug-resistant partial epilepsy. Bias adjustments for partially reported or unreported outcomes suggest that the review has overestimated the benefits and underestimated the harms of the test treatment.

MEG language lateralization in partial epilepsy using dSPM of auditory event-related fields.

Methods employed to determine hemispheric language dominance using magnetoencephalography (MEG) have differed significantly across studies in the choice of language-task, the nature of the physiological response studied, recording hardware, and source modeling methods. Our goal was to determine whether an analysis based on distributed source modeling can replicate the results of prior studies that have used dipole-modeling of event-related fields (ERFs) generated by an auditory word-recognition task to determine language dominance in patients with epilepsy. We analyzed data from 45 adult patients with drug-resistant partial epilepsy who performed an auditory word-recognition task during MEG recording and also completed a language fMRI study as part of their evaluation for epilepsy surgery. Source imaging of auditory ERFs was performed using dynamic statistical parametric mapping (dSPM). Language laterality indices (LIs) were calculated for four regions of interest (ROIs) by counting above-threshold activations within a 300-600ms time window after stimulus onset. Language laterality (LL) classifications based on these LIs were compared to the results from fMRI. The most lateralized MEG responses to language stimuli were observed in a parietal region that included the angular and supramarginal gyri (AngSmg). In this region, using a half-maximal threshold, source activations were left dominant in 32 (71%) patients, right dominant in 8 (18%), and symmetric in 5 patients (11%). The best agreement between MEG and fMRI on the ternary classification of regional language dominance into left, right, or symmetric groups was also found at the AngSmg ROI (69%). This was followed by the whole-hemisphere and temporal ROIs (both 62%). The frontal ROI showed the least agreement with fMRI (51%). Gross discordances between MEG and FMRI findings were disproportionately of the type where MEG favored atypical right-hemispheric language in a patient with right-hemispheric seizure origin (p<0.05 at three of the four ROIs). In a parietal region that includes the angular and supramarginal gyri, language laterality estimates based on dSPM of ERFs during auditory word-recognition shows a degree of MEG-fMRI concordance that is comparable to previously published estimates for MEG-Wada concordance using dipole counting methods and the same task. Our data also suggest that MEG language laterality estimates based on this task may be influenced by the laterality of epileptic networks in some patients. This has not been reported previously and deserves further study.

What are the benefits and harms of lamotrigine add-on in adults or children with drug-resistant partial epilepsy?

What are the benefits and harms of lamotrigine add-on in adults or children with drug-resistant partial epilepsy?

Rebuttal to the manuscript by R.J. Porter

• The ability of an AED suppressing the Photoparoxysmal EEG Response applies to a broader epilepsy spectrum than data gathered in drug resistant partial epilepsy patients alone.

SUrface-PRojected FLuid-Attenuation-Inversion-Recovery Analysis: A Novel Tool for Advanced Imaging of Epilepsy

The objective of this pilot retrospective study is to describe the SUrface-PRojected FLuid-Attenuation-Inversion-Recovery (SUPR-FLAIR) analysis, a novel method mainly aimed at revealing cortical areas with subtle signal hyperintensity. Images from 101 healthy controls and 10 patients suffering from drug-resistant partial epilepsy were retrospectively postprocessed. The brain surface was reconstructed from a 3-dimensional (3D) T1-weighted fast field echo (T1W-FFE) magnetic resonance imaging (MRI) scan. A turbo spin echo fluid attenuated inversion recovery axial scan was registered to the 3D T1W-FFE scan, and its intensity values were normalized. The cortical intensity signal was projected onto the brain surface, and surface-based analysis was performed, comparing each patient against the 101 controls. The localizations of the first positive lower P value cluster (PLPC) peak and the resection zone (RZ) were compared. We studied 5 patients with focal cortical dysplasia (3 of them with negative MRI) and 5 with hippocampal sclerosis. SUPR-FLAIR analysis localized the first PLPC peak in the RZ in all cases. Because all patients have been seizure free since surgery, it can be assumed that the epileptogenic zone (EZ) was included in the RZ. Therefore, SUPR-FLAIR analysis correctly aligned with the EZ, with 100% sensitivity. SUPR-FLAIR analysis is a noninvasive technique that could be helpful for the definition of the EZ, especially when MRI is negative. Its use could reduce the indications for invasive electroencephalography or could provide essential data to refine the strategy of intracerebral electrode implantation in the most challenging cases.

WITHDRAWN: Oxcarbazepine add-on for drug-resistant partial epilepsy.

Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field. Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome. Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine. Oxcarbazepine has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy, both in adults and children. However, trials reviewed were of relatively short duration, and provide no evidence about the long-term effects of oxcarbazepine. Results cannot be extrapolated to monotherapy or to patients with other epilepsy types.

Lamotrigine add-on for drug-resistant partial epilepsy.

This is an updated version of the Cochrane review published in The Cochrane Library 2010, Issue 1.Epilepsy is a common neurological disorder, affecting almost 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is refractory to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. Lamotrigine in combination with other antiepileptic drugs (add-on) can reduce seizures, but with some adverse effects. The aim of this systematic review was to overview the current evidence for the efficacy and tolerability of lamotrigine when used as an adjunctive treatment for people with refractory partial epilepsy. To determine the effects of lamotrigine on (1) seizures, (2) adverse effect profile, and (3) cognition and quality of life, compared to placebo controls, when used as an add-on treatment for people with refractory partial epilepsy. For the previous version of the review, the authors searched the Cochrane Epilepsy Group Specialized Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 1), MEDLINE (1950 to January 2010), and reference lists of articles.For this update, we searched the Cochrane Epilepsy Group Specialized Register (28 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Ovid, 1946 to May 2015), and reference lists of articles. We also contacted the manufacturers of lamotrigine (GlaxoSmithKline). No language restrictions were imposed. Randomised placebo-controlled trials of people with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant partial epilepsy. For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best and worse case analyses were undertaken to account for missing outcome data. Pooled Risk Ratios (RR) with 95% confidence intervals (95% Cl) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, pooled RRs and 99% Cls were calculated. We did not identify any new studies for this update, therefore, the results are unchanged.For the previous version of the review, the authors found five parallel add-on studies and eight cross-over studies in adults or children with refractory focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1958 participants (38 infants, 199 children, and 1721 adults). Baseline phases ranged from 4 to 12 weeks; treatment phases from 8 to 36 weeks. Overall, eleven studies (n = 1243 participants) were rated as having a low risk of bias, and three (n = 715 participants) had un unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in three studies (n = 504 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 RCTs) for twelve studies (n = 1322 participants, adults and children) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.90 to 1.36; 14 RCTs) for fourteen studies (n = 1958 participants). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia, and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 RCTs; n = 1524); dizziness 2.00 (99% Cl 1.51 to 2.64;13 RCTs; n = 1767); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 RCTs; n = 943); nausea 1.81 (99% Cl 1.22 to 2.68; 12 RCTs; n = 1486). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate quality, due to incomplete data for some outcomes. Lamotrigine as an add-on treatment for partial seizures appears to be effective in reducing seizure frequency, and seems to be fairly well tolerated. However, the trials were of relatively short duration and provided no evidence for the long-term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare it with other add-on drugs.Since we did not find any new studies, our conclusions remain unchanged.

Carisbamate add-on therapy for drug-resistant partial epilepsy

Carisbamate add-on therapy for drug-resistant partial epilepsy

Brivaracetam add-on for refractory focal epilepsy

To evaluate the efficacy and safety of the new antiepileptic drug brivaracetam (BRV) as add-on treatment for drug-resistant partial epilepsy using meta-analytical techniques. Randomized, placebo-controlled, single- or double-blind, add-on trials of BRV in adult patients with drug-resistant partial epilepsy were identified through a systematic literature search. The following outcomes were assessed: 50% or greater reduction in seizure frequency, seizure freedom, incidence of treatment-emergent adverse events (TEAEs), and treatment withdrawal. Risk ratio (RR) with 95% confidence interval was estimated for each outcome. Six trials were included involving 2,399 participants according to the intent-to-treat, 1,715 for BRV, and 684 for placebo groups, respectively. The pooled RRs for the 50% responders and seizure freedom were 1.79 (1.51-2.12) and 4.74 (2.00-11.25), respectively. The subanalysis by levetiracetam (LEV) status did not show a statistically significant difference in the 50% responder rate when comparing BRV with placebo in patients with concomitant assumption of LEV. The TEAEs significantly associated with BRV were irritability (2.99 [1.28-6.97]), fatigue (2.19 [1.44-3.33]), somnolence (1.97 [1.45-2.68]), and dizziness (1.66 [1.19-2.31]). The overall RRs for treatment withdrawal due to TEAEs or any reason were 1.58 (1.04-2.40) and 1.27 (0.93-1.73), respectively. In adults with drug-refractory focal epilepsy, add-on BRV was effective to reduce seizure frequency and fairly well-tolerated. Further studies are needed to draw definitive conclusions about its efficacy in non-LEV-naive participants and evaluate its long-term safety profile.

NEW OPPORTUNITIES PHARMACOTHERAPY PATIENTS WITH REFRACTORY EPILEPSY

Objective: to generalize the Russian experience with perampanel (PER) in routine clinical practice; to do this, the results of its use as an adjuvant partial epilepsy medication were retrospectively assessed. The study is still in progress now; therefore, the paper gives its preliminary results. Materials and methods. The investigation included 52 patients with drug-resistant partial epilepsy. Their mean age was 28.92±14.02 years (a small number of the patients had not attained the age of 12 years); the proportion of men was 56%; the disease duration was over 10 years (69.2%); symptomatic epilepsy was in 76.9% with an epileptic focus being in the frontal (46.2%) and temporal (44.2%) regions. PER was prescribed to the majority (71.2%) of patients after three previous therapy lines. The baseline monthly rates of all types of seizures were 127.29±82.29; those of generalized seizures were 6.72±1.90. Results. After addition of PER to therapy just within the first month, there was a significant reduction in the frequency of all types of seizures to 52.06±29.26 per month (Sign test; p=0.00001) and in that of secondary generalized seizures to 3.71±1.71 (Sign test; p=0.00001). The duration of PER administration was more than 6 months in the overwhelming majority of cases. In 58% of the patients, the frequency of seizures decreased by more than 50% (respondents). The lack of all types of seizures was noted in 8%; that of only secondary generalized seizures was in 31%. Adverse events were observed in 30.1% of the patients (aggression in 11.5% and somnolence in 9.6%; others were seen more rarely). The dose of PER was decreased because of side effects in 7 (13.5%) patients; the drug was discontinued in 4 (7.7%). The mean dose of PER for adults was as high as 6 mg.

Russian experience with perampanel in routine clinical practice

Objective: to generalize the Russian experience with perampanel (PER) in routine clinical practice; to do this, the results of its use as an adjuvant partial epilepsy medication were retrospectively assessed. The study is still in progress now; therefore, the paper gives its preliminary results. Patients and methods. The investigation included 52 patients with drug-resistant partial epilepsy. Their mean age was 28.92±14.02 years (a small number of the patients had not attained the age of 12 years); the proportion of men was 56%; the disease duration was over 10 years (69.2%); symptomatic epilepsy was in 76.9% with an epileptic focus being in the frontal (46.2%) and temporal (44.2%) regions. PER was prescribed to the majority (71.2%) of patients after three previous therapy lines. The baseline monthly rates of all types of seizures were 127.29±82.29; those of generalized seizures were 6.72±1.90. Results and discussion. After addition of PER to therapy just within the first month, there was a significant reduction in the frequency of all types of seizures to 52.06±29.26 per month (Sign test; p = 0.00001) and in that of secondary generalized seizures to 3.71±1.71 (Sign test; p=0.00001). The duration of PER administration was more than 6 months in the overwhelming majority of cases. In 58% of the patients, the frequency of seizures decreased by more than 50% (respondents). The lack of all types of seizures was noted in 8%; that of only secondary generalized seizures was in 31%. Adverse events were observed in 30.1% of the patients (aggression in 11.5% and somnolence in 9.6%; others were seen more rarely). The dose of PER was decreased because of side effects in 7 (13.5%) patients; the drug was discontinued in 4 (7.7%). The mean dose of PER for adults was as high as 6 mg.

A puzzling case without solution: isolated late-onset epileptic seizure

Focal cortical dysplasia type II (FCD II) is a highly epileptogenic lesion that is frequently associated with early-onset drug-resistant partial epilepsy [1]. Epilepsy can occur at any age, but most commonly develops in childhood. Histopathology is mandatory for diagnoses, however, there are MRI findings very suggestive of FCD type II such as increased cortical thickness, abnormal gyral/sulcal patterns, blurring of the gray/white junction and the transmantle sign, which is seen exclusively typical of FCD type II [1, 2]. Differential diagnosis with low-grade gliomas is often very difficult [3, 4]. Here, we report an unusual case of a patient who had a single late-onset epileptic seizure with a 3-Tesla MRI study showing several signs of type II FCD.