Drug-resistant Epileptic Patients Research Articles

Bifurcations and bursting in the Epileptor.

The Epileptor is a phenomenological model for seizure activity that is used in a personalized large-scale brain modeling framework, the Virtual Epileptic Patient, with the aim of improving surgery outcomes for drug-resistant epileptic patients. Transitions between interictal and ictal states are modeled as bifurcations, enabling the definition of seizure classes in terms of onset/offset bifurcations. This establishes a taxonomy of seizures grounded in their essential underlying dynamics and the Epileptor replicates the activity of the most common class, as observed in patients with focal epilepsy, which is characterized by square-wave bursting properties. The Epileptor also encodes an additional mechanism to account for interictal spikes and spike and wave discharges. Here we use insights from a more generic model for square-wave bursting, based on the Unfolding Theory approach, to guide the bifurcation analysis of the Epileptor and gain a deeper understanding of the model and the role of its parameters. We show how the Epileptor's parameters can be modified to produce activities for other seizures classes of the taxonomy, as observed in patients, so that the large-scale brain models could be further personalized. Some of these classes have already been described in the literature in the Epileptor, others, predicted by the generic model, are new. Finally, we unveil how the interaction with the additional mechanism for spike and wave discharges alters the bifurcation structure of the main burster.

Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy.

The locus coeruleus-norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This system is known to prevent seizure development and induce long-term plastic changes, particularly with the release of norepinephrine in the hippocampus. However, the requisites to become responder to the therapy and the mechanisms of action are still under investigation. Using MRI, we assessed the structural and functional characteristics of the locus coeruleus and microstructural properties of locus coeruleus-hippocampus white matter tracts in patients with drug-resistant epilepsy responding or not to the therapy. Twenty-three drug-resistant epileptic patients with cervical vagus nerve stimulation were recruited for this pilot study, including 13 responders or partial responders and 10 non-responders. A dedicated structural MRI acquisition allowed in vivo localization of the locus coeruleus and computation of its contrast (an accepted marker of LC integrity). Locus coeruleus activity was estimated using functional MRI during an auditory oddball task. Finally, multi-shell diffusion MRI was used to estimate the structural properties of locus coeruleus-hippocampus tracts. These characteristics were compared between responders/partial responders and non-responders and their association with therapy duration was also explored. In patients with a better response to the therapy, trends toward a lower activity and a higher contrast were found in the left medial and right caudal portions of the locus coeruleus, respectively. An increased locus coeruleus contrast, bilaterally over its medial portions, correlated with duration of the treatment. Finally, a higher integrity of locus coeruleus-hippocampus connections was found in patients with a better response to the treatment. These new insights into the neurobiology of vagus nerve stimulation may provide novel markers of the response to the treatment and may reflect neuroplasticity effects occurring in the brain following the implantation.

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now?

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy. However, such measures may not be sufficient to efficiently control seizure recurrence. Resective surgery, ablative procedures and non-resective neuromodulatory (deep-brain stimulation, vagus nerve stimulation) treatments are the available treatments for these kinds of patients. However, invasive procedures may involve lengthy inpatient stays for the patients, risks of long-term neurological impairment, general anesthesia, and other possible surgery-related complications (i.e., hemorrhage or infection). In the last few years, MR-guided focused ultrasound (MRgFUS) has been proposed as an emerging treatment for neurological diseases because of technological advancements and the goal of minimally invasive neurosurgery. By outlining the current knowledge obtained from both preclinical and clinical studies and discussing the technical opportunities of this therapy for particular epileptic phenotypes, in this perspective review, we explore the various mechanisms and potential applications (thermoablation, blood-brain barrier opening for drug delivery, neuromodulation) of high- and low-intensity ultrasound, highlighting possible novel strategies to treat drug-resistant epileptic patients who are not eligible or do not accept currently established surgical approaches. Taken together, the available studies support a possible role for lesional treatment over the anterior thalamus with high-intensity ultrasound and neuromodulation of the hippocampus via low-intensity ultrasound in refractory epilepsy. However, more studies, likely conceiving epilepsy as a network disorder and bridging together different scales and modalities, are required to make ultrasound delivery strategies meaningful, effective, and safe.

The Role of Ketogenic Diet in the Treatment of Neuroblastoma.

The ketogenic diet (KD) was initially used in 1920 for drug-resistant epileptic patients. From this point onward, ketogenic diets became a pivotal part of nutritional therapy research. To date, KD has shown therapeutic potential in many pathologies such as Alzheimer's disease, Parkinson's disease, autism, brain cancers, and multiple sclerosis. Although KD is now an adjuvant therapy for certain diseases, its effectiveness as an antitumor nutritional therapy is still an ongoing debate, especially in Neuroblastoma. Neuroblastoma is the most common extra-cranial solid tumor in children and is metastatic at initial presentation in more than half of the cases. Although Neuroblastoma can be managed by surgery, chemotherapy, immunotherapy, and radiotherapy, its 5-year survival rate in children remains below 40%. Earlier studies have proposed the ketogenic diet as a possible adjuvant therapy for patients undergoing treatment for Neuroblastoma. In this study, we seek to review the possible roles of KD in the treatment of Neuroblastoma.

Local neuronal excitation and global inhibition during epileptic fast ripples in humans.

Understanding the neuronal basis of epileptic activity is a major challenge in neurology. Cellular integration into larger scale networks is all the more challenging. In the local field potential, interictal epileptic discharges can be associated with fast ripples (200-600 Hz), which are a promising marker of the epileptogenic zone. Yet, how neuronal populations in the epileptogenic zone and in healthy tissue are affected by fast ripples remain unclear. Here, we used a novel 'hybrid' macro-micro depth electrode in nine drug-resistant epileptic patients, combining classic depth recording of local field potentials (macro-contacts) and two or three tetrodes (four micro-wires bundled together) enabling up to 15 neurons in local circuits to be simultaneously recorded. We characterized neuronal responses (190 single units) with the timing of fast ripples (2233 fast ripples) on the same hybrid and other electrodes that target other brain regions. Micro-wire recordings reveal signals that are not visible on macro-contacts. While fast ripples detected on the closest macro-contact to the tetrodes were always associated with fast ripples on the tetrodes, 82% of fast ripples detected on tetrodes were associated with detectable fast ripples on the nearest macro-contact. Moreover, neuronal recordings were taken in and outside the epileptogenic zone of implanted epileptic subjects and they revealed an interlay of excitation and inhibition across anatomical scales. While fast ripples were associated with increased neuronal activity in very local circuits only, they were followed by inhibition in large-scale networks (beyond the epileptogenic zone, even in healthy cortex). Neuronal responses to fast ripples were homogeneous in local networks but differed across brain areas. Similarly, post-fast ripple inhibition varied across recording locations and subjects and was shorter than typical inter-fast ripple intervals, suggesting that this inhibition is a fundamental refractory process for the networks. These findings demonstrate that fast ripples engage local and global networks, including healthy tissue, and point to network features that pave the way for new diagnostic and therapeutic strategies. They also reveal how even localized pathological brain dynamics can affect a broad range of cognitive functions.

Vagal nerve stimulation cycles alter EEG connectivity in drug-resistant epileptic patients: A study with graph theory metrics

ObjectiveVagal Nerve Stimulation (VNS) is an effective treatment for Drug-Resistant (DR) epilepsy. Albeit the corroborated effectiveness of VNS, little is known about how VNS works. We aim to leverage quantitative Electroencephalography (qEEG) to study how the brain responds to VNS cycles. MethodsEighteen subjects with DR epilepsy were enrolled in our study. 64-channel EEG was recorded during VNS stimulation. Periods of stimulation (VNS), preceding (preVNS) and following stimulation (postVNS) were identified via an electrode placed on the stimulator. We used qEEG analysis to assess changes in spectral and network activity that characterize these conditions. Graph theory metrics were used to calculate differences in network connectivity. ResultsNo differences were found in spectral activity between preVNS, VNS, and postVNS. Graph theory showed consistent changes in network organization expressed by Small World Index (SWI), Betweenness Centrality (BtwC), and Global Efficiency (gE). These changes were most significant in the slow EEG bands. ConclusionsIn DR epilepsy, VNS has a significant effect on brain network activity, as assessed by EEG connectivity, acting on widespread network distribution rather than band-power. SignificanceOur findings support the hypothesis that VNS acts on epilepsy by influencing diffuse network connectivity in the brain.

Epileptic electroencephalography classification using embedded dynamic mode decomposition

Objective. Seizure prediction devices for drug-resistant epileptic patients could lead to improved quality of life and new treatment options, but current approaches to classification of electroencephalography (EEG) segments for early identification of the pre-seizure state typically require many features and complex classifiers. We therefore propose a novel spatio-temporal EEG feature set that significantly aids in separation and easy classification of the interictal and preictal states. Approach. We derive key spectral features from the embedded dynamic mode decomposition (EmDMD) of the brain state system. This method linearizes the complex spatio-temporal dynamics of the system, describing the dynamics in terms of a spectral basis of modes and eigenvalues. The relative subband spectral power and mean phase locking values of these modes prove to be good indicators of the preictal state that precedes seizure onset. Main results. We analyze the linear separability and classification of preictal and interictal states based on our proposed features using seizure data extracted from the CHB-MIT scalp EEG and Kaggle American Epilepsy Society Seizure Prediction Challenge intracranial EEG databases. With a light-weight support vector machine or random forest classifier trained on these features, we classify the preictal state with a sensitivity of up to 92% and specificity of up to 89%. Significance. The EmDMD-derived features separate the preictal and interictal states, improving classification accuracy and motivating further work to incorporate them into seizure prediction algorithms.

Stereotactic Electroencephalography in Patients with Drug-resistant Epilepsy

Stereotactic electroencephalography (SEEG) is an important method for invasive presurgical exploration of candidates for epilepsy surgery by means of stereotactic implantation of intracerebral electrodes without craniotomy. Implantations of intracerebral electrodes through craniotomy in drug-resistant epileptic patients have been performed in Bulgaria in the 1980s, but no further development of epilepsy surgery followed. The aim of our study is to present the first Bulgarian series of patients with drug-resistant epilepsy explored by SEEG. Our study included 53 patients with drug-resistant epilepsy explored by SEEG. Stereotactic Leksell frame, stereotactic software for avascular trajectory planning and depth electrodes with diameter of 0.8 mm and 8–18 contacts were used in all patients. Subsequently, long-term video-SEEG monitoring of various duration was performed and registered interictal and ictal EEG activity in order to evaluate the putative epileptogenic zone. Fifty-three patients were explored by 62 SEEGs because one patient underwent three SEEG procedures and seven patients – two SEEG procedures. We implanted 753 electrodes in these 62 SEEGs (mean: 12 electrodes per exploration; range: 5–20 electrodes). The mean age in our cohort was 23.6 years (4–60 years). The main indication for SEEG was MRI-negative epilepsy (20 patients). Focal cortical dysplasia was found in 17 cases, and hippocampal sclerosis in 8 cases. Surgical intervention was done in 48 patients (91%). Surgical resection of the epileptogenic zone (EZ) as defined by the SEEG was performed in 27 patients; radiofrequency stereotactic thermocoagulation (RFTC) on selected electrode contacts was applied in seven patients, and both procedures (i.e. RFTC followed by resective surgery) were performed on 14 patients. Full seizure control (Engel class I) was achieved in 28 patients (58.3%) and significant improvement – in 17 patients (35.4%). Three patients (6.2%) had no effect from surgery. No complications were observed in our series of 62 SEEGs. SEEG is a major tool for the determination of the EZ in patients with drug-resistant epilepsy who are candidates for epilepsy surgery, including MRI-negative cases or such without congruent data from the clinical, neurophysiological and neuroimaging perspectives. SEEG is a low-risk invasive diagnostic and even a therapeutic method when performed by experienced epilepsy surgery team.

Preserved time but altered numerosity processing in epileptic patients with postoperative lesion in the inferior frontal gyrus

Previous researches have shown that the inferior frontal gyrus (IFG) is involved in time and numerosity processing. This study aimed at examining (i) interval timing and (ii) interaction between duration and numerosity processing in four drug-resistant epileptic patients with postoperative lesions in the IFG in comparison with thirteen healthy controls. The duration reproduction and discrimination tasks performed in the sub- and supra-second ranges did not reveal any significant differences between patients and controls. The duration discrimination task of stimuli varying in numerosity (DurN) and the numerosity discrimination task of stimuli varying in duration (NumD) revealed that only numerosity judgment was altered in IFG patients. A time-order effect was notably observed in the NumD task but in opposite directions for the two groups: The second patch was perceived as more numerous than the first patch in controls and conversely as less numerous in patients. Finally in the DurN task, we observed a congruency effect which was dependent on numerical distance in patients but not in controls. These converging results suggest that the IFG would be more specifically involved in numerosity than in duration processing, possibly playing a role in numerical decision.

Simultaneous stereo-EEG and high-density scalp EEG recordings to study the effects of intracerebral stimulation parameters

BackgroundCortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. ObjectiveTo demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. MethodsThe dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. ResultsWhile invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. ConclusionsCCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.

Tracing in vivo the dorsal loop of the optic radiation: convergent perspectives from tractography and electrophysiology compared to a neuroanatomical ground truth.

The temporo-parietal junction (TPJ) is a cortical area contributing to a multiplicity of visual, language-related, and cognitive functions. In line with this functional richness, also the organization of the underlying white matter is highly complex and includes several bundles. The few studies tackling the outcome and neurological burdens of surgical operations addressing TPJ document the presence of language disturbances and visual field damages, with the latter hardly recovered in time. This observation advocates for identifying and functionally monitoring the optic radiation (OR) bundles that cross the white matter below the TPJ. In the present study, we adopted a multimodal approach to address the anatomo-functional correlates of the OR's dorsal loop. In particular, we combined cadavers' dissection with tractographic and electrophysiological data collected in drug-resistant epileptic patients explored by stereoelectroencephalography (SEEG). Cadaver dissection allowed us to appreciate the course and topography of the dorsal loop. More surprisingly, both tractographic and electrophysiological observations converged on a unitary picture highly coherent with the data obtained by neuroanatomical observation. The combination of diverse and multimodal observations allows overcoming the limitations intrinsic to single methodologies, defining a unitary picture which makes it possible to investigate the dorsal loop both presurgically and at the individual patient level, ultimately contributing to limit the postsurgical damages. Notwithstanding, such a combined approach could serve as a model of investigation for future neuroanatomical inquiries tackling white matter fibers anatomy and function through SEEG-derived neurophysiological data.

OC20: Deep Intracerebral Electric Field Measurement with Stereoelectroencephalography during Transcranial Electrical Stimulations in Human in-vivo

Measuring the electric field generated in several deep brain structures during Transcranial electrical stimulation in humans in-vivo. In addition, we investigated the effects of TES intensities and montages on the intracerebral EF. Transcranial electrical stimulation (TES) has shown for the last decades promises as a treatment for several neurological and psychiatric disorders. Its efficiency is related to the amount of electric field (EF) magnitude delivered on the target. Very few studies (n=3) estimated the in-vivo intracerebral electric fields in human. They relied mainly on electrocorticographic recordings that require a craniotomy and did not precisely focus on targeting the deep cortical structures which can still lead to some discussion about the TES possibility to reach deep structures. We applied Transcranial alternating current stimulations simultaneously with intracerebral recordings (SEEG) in 7 drug-resistant epileptic patients. Two low intensities were used in 6 patients (0.5 and 1mA) and 15 different montages were used in 1 patient. We calculated the electric field by subtracting voltage measured on contiguous intracerebral contacts. We found EF magnitude up to 0.29, 0.38 and 0.54 V/m respectively in the amygdala, the hippocampus, and the cingulate gyrus. Among 91 montage combinations, the global EF difference in the brain was significant in 65% of cases. We also confirmed experimentally that EF magnitude is proportional to TES intensity. In conclusion, EF at a magnitude which can induces stochastic effects, is achievable in the deep brain structures using low intensities. EF is highly correlated to the stimulation intensity and depends on montages.

Genetic Analysis of Sodium Channel Genes in Pediatric Epilepsy Patients of Pakistan.

Epilepsy affects millions of people worldwide. Although antiepileptic drugs work for the majority of epileptic patients, these drugs do not work for some of the patients, subjecting them to drug-resistant epilepsy (DRE). Voltage-gated sodium channels act as targets for a number of antiepileptic drugs, and the genes encoding these channels can play a crucial role in developing drug-resistant epilepsy. This case-control (100 control: 101patients) study evaluated the association of sodium channel genes SCN1A and SCN2A with drug-resistant epilepsy. The cases were further accounted in two categories, drug-resistant and drug-responsive epileptic patients. The polymorphic sites rs794726754, rs1057518252, rs121918809, rs12191792, rs121917932, c.730 G > T, c.735 G > T, c.736 A > T, rs10167228, and rs2298771 of the SCN1A gene and rs17183814 of SCN2A gene were selected for mutational analysis. The DNA was isolated, amplified by PCR, and then, was run through 1% agarose gel. The sequencing was performed, and the sequences were observed through BioEdit software for any change in DNA sequence. In our study, no polymorphism was observed in the studied SNPs except for rs2298771. For rs2298771, a significant difference existed in the distribution of genotypic and allelic frequencies (p < 0.01) among the case and control group. Furthermore, the genotypic and allelic frequencies of the two categories of cases (drug responder drug resistant) were calculated. The genotypic and allelic frequencies of drug-responsive and drug-resistant epileptic patients did not differ significantly (p > 0.01). Our study indicated that the rs2298771 polymorphism of SCN1A may not be associated with chance of developing DRE in the Pakistani population.

Transcranial Electrical Stimulation generates electric fields in deep human brain structures

BackgroundTranscranial electrical stimulation (TES) efficiency is related to the electric field (EF) magnitude delivered on the target. Very few studies (n = 4) have estimated the in-vivo intracerebral electric fields in humans. They have relied mainly on electrocorticographic recordings, which require a craniotomy impacting EF distribution, and did not investigate deep brain structures. ObjectiveTo measure the electric field in deep brain structures during TES in humans in-vivo. Additionally, to investigate the effects of TES frequencies, intensities, and montages on the intracerebral EF. MethodsSimultaneous bipolar transcranial alternating current stimulation and intracerebral recordings (SEEG) were performed in 8 drug-resistant epileptic patients. TES was applied using small high-definition (HD) electrodes. Seven frequencies, two intensities and 15 montages were applied on one, six and one patients, respectively. ResultsAt 1 mA intensity, we found mean EF magnitudes of 0.21, 0.17 and 0.07 V·m−1 in the amygdala, hippocampus, and cingulate gyrus, respectively. An average of 0.14 ± 0.07 V·m−1 was measured in these deep brain structures. Mean EF magnitudes in these structures at 1Hz were 11% higher than at 300Hz (+0.03 V·m−1). The EF was correlated with the TES intensities. The TES montages that yielded the maximum EF in the amygdalae were T7-T8 and in the cingulate gyri were C3-FT10 and T7-C4. ConclusionTES at low intensities and with small HD electrodes can generate an EF in deep brain structures, irrespective of stimulation frequency. EF magnitude is correlated to the stimulation intensity and depends upon the stimulation montage.

Insular Cortex Response to Static Visual Sexual Stimuli

Abstract. According to previous research, the insula is important for processing salient and emotional stimuli, but its precise role remains elusive. By combining high spatial and temporal resolution, intracranial electroencephalography (iEEG) might contribute to filling this gap. Four drug-resistant epileptic patients with intracranial electrodes in the insula were instructed to watch and rate pictures with sexual content and neutral pictures. Event-related potentials (ERPs) were computed separately for both types of stimuli. Ninety-three percent of the anterior insula (AI) and 85% of the posterior insula (PI) contacts showed differences between ERPs. AI-positive deflections tended to have an earlier onset than PI-positive deflections. The results suggest that the AI generates a P300-like response and contributes to the early phase of the late positive potential, both components found enhanced while viewing emotional stimuli in the ERP literature. The present findings are interpreted as congruent with the role of the AI in maintaining attention to salient stimuli.

Localizing Epileptogenic Zone from High Density EEG Data Using Machine Learning

&lt;span&gt;Drug-resistant focal epilepsy is the failure of antiepileptic drugs scheduled to obtain epileptic free brain activities. In human brain, cerebral hemispheres are the most commonly involved brain regions in epilepsy. In case of antiepileptic drugs failure, surgical treatment is the best cure possible. However, correct localization of epileptogenic region is a challenging task for neurologists, while for computer scientists, automatic localization is. This research work’s aim is to explore the functional activities of all brain regions in drug-resistant focal epileptic patients and achieve high accuracy for the classification of epileptogenic region (ER) with the high-density electroencephalographic (hdEEG) data. The proposed system includes frequency analysis for feature extractions followed by individual subject’s registration of hdEEG signals with anatomical brain images for most precise localization of ER possible. The datasets attained from feature extraction process are then preprocessed for class imbalanced and then evaluated using different machine learning algorithms including the techniques under Bayesian networks, Lazy networks, Meta techniques, Rule based systems and Tree structured algorithms. Considering human brain as stationary object as well as dynamic object, frequency-based and time-frequency based features were considered in 12 subjects respectively. Through this novel approach, 99.70% accuracy is achieved to classify ER from healthy regions using KSTAR and using IBK algorithm, 91.60% accuracy has been achieved to classify generator from propagator.&lt;/span&gt;

Plasma fatty acid abnormality in Sudanese drug-resistant epileptic patients

Intervention studies have demonstrated that the n-3 fatty acids, docosahexaenoic and eicosapentaenoic acids, ameliorate seizure frequency in patients with drug-resistant epilepsy (DRE). There is a scarcity of fatty acid status of patients with epilepsy. We have investigated blood fatty acids of patients with DRE and assessed the indices of elongase and desaturase activities. DRE patients (n = 83) and healthy controls (n = 31) were recruited form Soba University Hospital Neurology Referral Clinic and Ibn-Auf paediatric Teaching Hospital Neurology Referral Clinic, Khartoum, Sudan. Fatty acid composition of plasma total lipids, phosphatidylcholine and neutral lipids were analysed. The patients compared with their healthy counterparts had higher levels of C14:0, C16:0, C18:0, C20:0, C22:0 (p<0.05) and C24:0, and total saturates (p<0.05). Similarly, the proportions of C16:1n-7, 18:1n-7, C18:1n-9, C20:1n-9, C24:1n-9 and total monounsaturated fatty acids; p<0.005) were higher in the drug-resistant patients. Conversely, the patients had lower levels of n-6 (C18:2n-6, C18:3n-6, C20:4n-6, n-6 metabolites and total n-6; p<0.005 and C20:2n-6 and C20:3n-6; p<0.05) and n-3 (C20:5n-3, C22:5n-3, C22:6n-3, ∑EPA and DHA, n-3 metabolites and total n-3; p<0.05) fatty acids. Indices of elongase and desaturase activities - The plasma total lipid ratios of C16:0/C14:0 (p = 0.001), C18:0/C16:0 (p = 0.001), C16:1n-7/C16:0 (p = 0.027), C18:1n-9/C18:0 (p = 0.022) and C22:4n-6/C20:4n-6 (p = 0.008) were higher and C18:3n-6/C18:2n-6 (p = 0.05), C20:4n-6/C20:3n-6 (p = 0.032) and C20:4n-6/C18:2n-6 (p>0.05) lower in the patients with drug-resistant epilepsy than in the healthy control subjects. DRE is associated with blood fatty acid perturbation and abnormal activities of long-chain fatty acid elongase (ELOVL-6), stearoyl-coenzyme A desaturase-1 (SCD-1), delta 6-fatty acid desaturase (D6D) and delta 5 fatty acid desaturase (D5D). N-3 fatty acids are known to ameliorate seizures frequency and dampen neuronal hyperexcitability. Therefore, patients with DRE should be regularly monitored and, if necessary, supplemented with n-3 fatty acids.

Histological assessment of a chronically implanted cylindrically-shaped, polymer-based neural probe in the monkey

Objective. Previous studies demonstrated the possibility to fabricate stereo-electroencephalography probes with high channel count and great design freedom, which incorporate macro-electrodes as well as micro-electrodes offering potential benefits for the pre-surgical evaluation of drug resistant epileptic patients. These new polyimide probes allowed to record local field potentials, multi- and single-unit activity (SUA) in the macaque monkey as early as 1 h after implantation, and yielded stable SUA for up to 26 d after implantation. The findings opened new perspectives for investigating mechanisms underlying focal epilepsy and its treatment, but before moving to possible human application, safety data are needed. In the present study we evaluate the tissue response of this new neural interface by assessing post-mortem the reaction of brain tissue along and around the probe implantation site. Approach. Three probes were implanted, independently, in the brain of one monkey (Macaca mulatta) at different times. We used specific immunostaining methods for visualizing neuronal cells and astrocytes, for measuring the extent of damage caused by the probe and for relating it with the implantation time. Main results. The size of the region where neurons cannot be detected did not exceed the size of the probe, indicating that a complete loss of neuronal cells is only present where the probe was physically positioned in the brain. Furthermore, around the probe shank, we observed a slightly reduced number of neurons within a radius of 50 µm and a modest increase in the number of astrocytes within 100 µm. Significance. In the light of previous electrophysiological findings, the present data suggest the potential usefulness and safety of this probe for human applications.

The gut microbiome in drug-resistant epilepsy.

Drug‐resistant epileptic patients make up approximately one‐third of the global epilepsy population. The pathophysiology of drug resistance has not been fully elucidated; however, current evidence suggests intestinal dysbiosis, as a possible etiopathogenic factor. Ketogenic diet, whose effect is considered to be mediated by alteration of gut microbiota synthesis, has long been administered in patients with medically refractory seizures, with positive outcomes. In this review, we present data derived from clinical studies regarding alterations of gut microbiome profile in drug‐resistant epileptic patients. We further attempt to describe the mechanisms through which the gut microbiome modification methods (including ketogenic diet, pre‐ or probiotic administration) improve drug‐resistant epilepsy, by reporting findings from preclinical and clinical studies. A comprehensive search of the published literature on the PubMed, Embase, and Web of science databases was performed. Overall, the role of gut microbiome in drug‐resistant epilepsy is an area which shows promise for the development of targeted therapeutic interventions. More research is required to confirm the results from preliminary studies, as well as safety and effectiveness of altering gut bacterial composition, through the above‐mentioned methods.

Frequency-domain identification of stereoelectroencephalographic transfer functions for brain tissue classification

Abstract In drug-resistant epileptic patients, direct electrical brain stimulation sessions may be needed to identify epileptic regions on the brain before surgery. In this context, the classification of the brain tissue in which the electrodes are implanted in is very important for the interpretation of observed responses. This paper presents a new method for tissue classification based on the study of the baseline data with signal processing methods and features estimated from non parametric frequency identification of transfer functions. The method is tested on actual data and compared to visual classification of contacts co-registered on magnetic resonance imaging. The results show that good separability between matters, with up to 80% accuracy, can be achieved when considering the pairing of two consecutive electrodes.