Refractory Epilepsy Research Articles

Vascular imaging for Stereoelectroencephalography: A safety and planning study

BackgroundStereoelectroencephalography (SEEG) is a procedure used to localize the epileptogenic zone in patients with medically refractory epilepsy, involving the stereotactic implantation of electrodes into brain parenchyma. Magnetic Resonance Imaging (MRI), Digital Subtraction Angiography, and Computed Tomography have been used preoperatively to prevent Intracranial Hemorrhage (ICH) by identifying electrode-vessel conflicts (EVC’s) on planned electrode trajectories. There is variation in the use of Digital Subtraction Angiography and non-invasive sequences for vascular planning. Digital Subtraction Angiography provides high spatial resolution, but carries risks of arterial dissection, groin and retroperitoneal hematoma, and a 0.5–1.9% risk of stroke. Our group has incorporated Intravenous Cone Beam Computed Tomography (CBCT A/V) Brain into our SEEG workflow, given its effective implementation in other neurosurgical domains. Primary aims include validating the safety of our CBCT A/V sequence for SEEG planning and determining if CBCT A/V is comparable to other modalities in detecting EVC’s. Secondary aims include elucidating the relationship of conflicting vessel calibre with ICH incidence in SEEG using CBCT A/V imaging. MethodsA single-center retrospective study was conducted of 20 patients who underwent preoperative CBCT A/V Brain and MRI Brain with gadolinium enhancement, encompassing 273 electrode implantations from August 2020 − July 2023. The incidence and grade of post-implant, post-explant symptomatic ICH and asymptomatic ICH was noted. The total number of EVC’s identifiable on MRI and CBCT A/V was recorded, along with average diameter of conflicting vessels. ResultsAcross 20 patients and 273 implanted electrodes, there were four ICH events, where two were symptomatic and two were asymptomatic. The mean diameter of EVC’s across all patients was 1.4 mm (±0.5). A significant difference (P < 0.0001) was observed between the number of EVC’s that CBCT A/V could identify (20) compared to MRI (6). Two EVC’s were identified in the region of two symptomatic ICH’s, with the mean diameter of these conflicted vessels being 1.5 mm (±0.4). The two symptomatic ICH-associated EVC’s were observed on CBCT A/V but not MRI. ConclusionsIn our series, CBCT A/V demonstrates an acceptable safety profile for SEEG planning compared to other imaging modalities. CBCT A/V identified significantly more EVC’s compared to MRI, including those contributing to transient symptomatic intracranial hemorrhage. A conflicting vessel calibre of less than 1.2 mm on CBCT A/V did not contribute to ICH in our SEEG series.

Exercise in patients with epilepsy and neurostimulation devices - physical activity levels, barriers, and beliefs

Exercise improves many comorbidities associated with epilepsy in addition to seizure control. Despite the ILAE consensus statement noting the positive effects of exercise in patients with epilepsy (PWE) and individual assessment of risks pertaining to these activities, many healthcare professionals, including neurologists, are unfamiliar with these guidelines. Neurostimulation is an increasingly prevalent treatment option for refractory epilepsy. To date, no literature exists regarding how PWE treated with neurostimulation devices view and participate in exercise. We surveyed 36 adult PWE treated with neurostimulation (11 VNS, 21 RNS, 3 DBS, 1 VNS+RNS) on their barriers, beliefs, activity levels, and interests in exercise. Forty-three percent of patients reported meeting AHA guidelines for physical activity. Ninety percent of participants noted at least one barrier to exercise with transportation being most common. Fear of embarrassment of a seizure during exercise was reported by 44% with 39% endorsing prior seizure while exercising. Device-specific barriers included fear of device damage or avoidance of specific exercises. There was a statistically significant effect on activity level and prior seizure while exercising. Only 8% of participants reported knowledge of exercise guidelines for PWE. This data provides insight into the views of PWE treated with neurostimulation devices on exercise.

Targeting Adipokines: A Promising Therapeutic Strategy for Epilepsy.

Epilepsy affects 65million people globally and causes neurobehavioral, cognitive, and psychological defects. Although research on the disease is progressing and a wide range of treatments are available, approximately 30% of people have refractory epilepsy that cannot be managed with conventional medications. This underlines the importance of further understanding the condition and exploring cutting-edge targets for treatment. Adipokines are peptides secreted by adipocyte's white adipose tissue, involved in controlling food intake and metabolism. Their regulatory functions in the central nervous system (CNS) are multifaceted and identified in several physiology and pathologies. Adipokines play a role in oxidative stress and neuroinflammation which are associated with brain degeneration and connected neurological diseases. This review aims to highlight the potential impacts of leptin, adiponectin, apelin, vaspin, visfatin, and chimerin in the pathogenesis of epilepsy.

SISCOS in focal cortical dysplasia: localization and comparative analysis with MRI.

This study evaluates the efficacy of SISCOS (Subtraction ictal-interictal SPECT coregistered to SPECT) in localizing the epileptogenic zone (EZ) in focal cortical dysplasia (FCD), comparing its predictive performance with MRI and post-surgical outcomes based on ILAE classification. 84 patients with drug refractory epilepsy (DRE) who were operated and had histopathology consistent with FCD, were included in the study. All patients had undergone a complete work-up including SISCOS and MRI for EZ localization, followed by discussion in the multidisciplinary epilepsy surgery meeting prior to surgery. Ictal & interictal perfusion SPECT studies were performed with Tc-99m Ethylene Cysteinate Dimer (Tc-99m ECD) followed by SISCOS analysis using SPM2 and Bioimage Suite 2.6. Concordance for localization was determined by comparing with the surgical resection site and post-surgical outcomes were assessed using the ILAE classification. The concordance for EZ localization demonstrated by SISCOS was 73.8% and MRI was 82.1%. 52 patients (61.9%) had good surgical outcome and 31(59%) of these were FCD type 2. In patients with discordant MRI findings, SISCOS was able to provide localisation in 86% (13/15), with 69.2% showing good surgical outcomes. Sensitivity of SISCOS and MRI was 73% (95% CI = 59-84.8%) and 78% (95% CI = 67.5-90.3%) respectively with no significant difference between the two. In FCD type I, both SISCOS and MRI revealed a similar a sensitivity of 76.4% (95%CI = 50.1-93.2%). Concordant cases exhibited higher seizure-free odds ratios for both modalities. SISCOS is effective in localizing the EZ in FCD patients, comparable to MRI. Integrating SISCOS and MRI enhances lesion detection, especially in MRI discordant cases. A comprehensive diagnostic approach utilizing SISCOS and MRI can optimize the non-invasive pre-surgical assessment in DRE thereby guiding surgical decision-making in a resource-limited setting.

The network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy.

Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or "irritative" network. Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups. There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment. The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.

Preliminary study on the mechanism of SAHA in the treatment of refractory epilepsy induced by GABRG2(F343L) mutation

Mutations in the γ-amino butyric acid type A (GABAA) receptor γ2 subunit gene, GABRG2, have been associated with refractory epilepsy. Increasing evidence indicates that suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone acetyltransferases (HDACs) inhibitor, can inhibit seizure onset. However, the mechanisms involved remains unknown. The present study aimed to explore the anti-epileptic effect and underlying mechanisms of SAHA in the treatment of refractory epilepsy induced by GABRG2 mutation. In the zebrafish line expressing human mutant GABRG2(F343L), Tg(hGABRG2F343L), SAHA was found to reduce seizure onset, swimming activity, and neuronal activity. In both Tg(hGABRG2F343L) zebrafish and HEK293T cells transfected with GABAA receptor subunits, SAHA could improve the pan-acetylation level and reduce the expression of HDAC1/10. The decreased expressions of GABAA receptor subunits could be rescued by SAHA treatment both in vivo and in vitro, which might be the result of increased gene transcription and protein trafficking. The up-regulated acetylation of histone H3 and H4 as well as Bip expression might be involved in the process. Taken together, our data proved that both histone and non-histone acetylation might contribute to the anti-epileptic effect of SAHA in refractory epilepsy caused by GABRG2(F343L) mutation, demonstrating SAHA as a promising therapeutic agent for refractory epilepsy.

Test-retest reliability of the "Home Town Walk" fMRI paradigm for memory activation and lateralization in the pre-surgical evaluation of patients with temporal lobe epilepsy.

Functional magnetic resonance imaging (fMRI) can be used to assess language and memory function as part of pre-surgical decision making in refractory epilepsy. Although language paradigms are well established, memory paradigms are not widely used in clinical practice due to a lack of evidence for robust and reliable methods. Here, we aim to investigate the clinical utility of the Home Town Walk (HTW) paradigm for personalized treatment decisions in medial temporal lobe epilepsy. A cohort of 123 consecutive patients having HTW-fMRI as part of routine MRI scans over a 7.5 year period were included in this retrospective study. Of these, 111 patients underwent repeated HTW-fMRI in two scanning sessions one to three days apart. fMRI analysis was performed at the time of the scans using clinically approved software and retrospectively validated using FSL. We assessed the test-retest within subject reliability of activations within the posterior parahippocampal gyri (pPHG) at the individual subject level. Activations within the pPHG region were observed for 101 patients (91%) in at least one of the fMRI sessions and for 88 patients (79%) in both fMRI sessions, with 82 patients showing overlapping unilateral or bilateral activations and 8 further patients showing overlapping activations in one of the hemispheres but not the other. Reproducibility was evaluated using metrics based on the concordance ratios for size (Rsize) and location (Roverlap) within the pPHG region, as well as the lateralization index (LI) metric to reflect the asymmetry of hemispheric activations, which is of crucial relevance to inform surgery. Test-retest reliability of visuospatial memory LIs, assessed by an intra-class correlation coefficient (ICC) yielded a value of 0.76, indicating excellent between session stability of memory lateralization. The HTW-fMRI paradigm shows reproducible activations in the medial temporal lobes of individual epilepsy patients sufficient to consistently lateralize visuospatial memory function, demonstrating the clinical utility of HTW memory fMRI and its potential for application in the pre-surgical assessment of people with temporal lobe epilepsy.

Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.

The Therapeutic Role of Perampanel in Treating Pediatric Patients With Dravet Syndrome: A Scoping Review.

Sodium channelopathies are genetic disorders caused by mutations in genes, including sodium voltage-gated channel alpha subunit 1 (SCN1A),that lead to several epilepsy syndromes. Traditional treatments with sodium channel blockers often have limited effectiveness and side effects. Dravet syndrome (DS), a severe epilepsy starting in infancy, presents significant treatment challenges. Perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, has shown promise for DS, reducing seizure frequency and improving quality of life (QoL). The limited availability of randomized controlled trials on PER among DS is challenging, but broader studies on refractory epilepsies offer insights. Real-world studies support PER's efficacy, underscoring its potential for managing refractory seizures in DS. Studies showed long-term effectiveness in reducing seizure frequency and enhancing QoL. While PER has minimal impact on cognitive development, it significantly improves seizure control. Numerous studies confirm the use of PER as an effective adjunctive treatment for DS; however, it is crucial to observe the safety profile, especially for pediatric sodium channelopathy patients. Common side effects include dizziness, drowsiness, and irritability, necessitating careful management. Long-term safety is generally favorable, but monitoring for behavioral and mood changes is essential. Additionally, the response to PER in DS varies widely, complicating its use. The limited clinical data and the need for careful dosage monitoring, especially in children, present significant challenges. Side effects, potential drug interactions, and high costs further complicate treatment. Despite increasing attention to its cost-effectiveness, accessibility remains limited in some regions, posing significant barriers for many families. In this paper, we review the role of PER in treating pediatric patients with DS, emphasizing clinical evidence and practical considerations.

INTS11-related neurodevelopmental disorder: a case report and literature review.

INTS11 is a critical catalytic component of the Integrator complex that regulates RNA polymerase II termination and modulates gene expression. Until recently, INTS11 mutations were associated with human neurodevelopmental disorders, characterized by global developmental and language delays, generalized hypotonia, and progressive brain atrophy. We report the case of a 2-year-old Chinese girl who presented with global developmental delay, generalized hypotonia, refractory epilepsy, craniofacial dysmorphism, and progressive brain atrophy. Novel variants were identified in exon 2 of INTS11 gene c.588_589del (p. Trp197AspfsTer2) and c.457_459del (p. Glu153del). We identified a compound heterozygous mutation in INTS11, a clinical feature consistent with two previous reports of the variants in human INTS11, but her recurrent seizures were more pronounced and refractory to most antiepileptic drugs and ketogenic diets.

Whole-brain simulation of interictal epileptic discharges for patient-specific interpretation of interictal SEEG data

In patients with refractory epilepsy, the clinical interpretation of stereoelectroencephalographic (SEEG) signals is crucial to delineate the epileptogenic network that should be targeted by surgery. We propose a pipeline of patient-specific computational modeling of interictal epileptic activity to improve the definition of regions of interest. Comparison between the computationally defined regions of interest and the resected region confirmed the efficiency of the pipeline. This result suggests that computational modeling can be used to reconstruct signals and aid clinical interpretation.

De Novo DNM1L Mutation in a Patient with Encephalopathy, Cardiomyopathy and Fatal Non-Epileptic Paroxysmal Refractory Vomiting.

Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic-dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L-related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. In patients with DNM1L mutations, careful evaluation for cardiac involvement is recommended.

Neurophysiologic Characteristics of the Anterior Nucleus of the Thalamus during Deep Brain Stimulation Surgery for Epilepsy

Introduction: Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an increasingly promising treatment option for refractory epilepsy. Optimal therapeutic benefit has been associated with stimulation at the junction of ANT and the mammillothalamic tract (mtt), but electrophysiologic markers of this target are lacking. The present study examined microelectrode recordings (MER) during DBS to identify unique electrophysiologic characteristics of ANT and the ANT-mtt junction. Methods: Ten patients with medically refractory epilepsy underwent MER during ANT-DBS implantation under general anesthesia. MER locations were determined based on coregistration of preoperative MRI, postoperative CT, and a stereotactic atlas of the thalamus (Morel atlas). Several neurophysiological parameters including single unit spiking rate, bursting properties, theta and alpha power and cerebrospinal fluid (CSF)-normalized root mean square (NRMS) of multiunit activity were characterized at recording depths and compared to anatomic boundaries. Results: From sixteen hemispheres, 485 recordings locations were collected from a mean of 30.3 (15.64 ± 5.0 mm) recording spans. Three-hundred and ninety-four of these recording locations were utilized further for analysis of spiking and bursting rates, after excluding recordings that were more than 8 mm above the putative ventral ANT border. The ANT region exhibited discernible features including: (1) mean spiking rate (7.52 Hz ± 6.9 Hz; one-way analysis of variance test, p = 0.014 when compared to mediodorsal nucleus of the thalamus [MD], mtt, and CSF), (2) the presence of bursting activity with 40% of ANT locations (N = 59) exhibited bursting versus 24% the mtt (χ2; p < 0.001), and 32% in the MD (p = 0.38), (3) CSF-NRMS, a proxy for neuronal density, exhibited well demarcated changes near the entry and exit of ANT (linear regression, R = −0.33, p < 0.001). Finally, in the ANT, both theta (4–8 Hz) and alpha band power (9–12 Hz) were negatively correlated with distance to the ventral ANT border (linear regression, p < 0.001 for both). The proportion of recordings with spiking and bursting activity was consistently highest 0–2 mm above the ventral ANT border with the mtt. Conclusion: We observed several electrophysiological markers demarcating the ANT superior and inferior borders including multiple single cell and local field potential features. A local maximum in neural activity just above the ANT-mtt junction was consistent with the previously described optimal target for seizure reduction. These features may be useful for successful targeting of ANT-DBS for epilepsy.

Robot-assisted deep brain stimulation

Deep brain stimulation (DBS) is recognised as a safe and effective treatment for several movement disorders, namely essential tremor, Parkinson's disease, and dystonia, as well as for obsessive–compulsive disorder and refractory epilepsy. The main anatomical target of DBS is the basal ganglia. The DBS system comprises a pulse generator and surgically implanted electrodes. Lead placements must be accurate because the effects of DBS rely on the spatial restriction of the stimulation. Neurosurgical centres have started adopting robot-assisted DBS surgery. The results so far have been promising, with lead placement accuracy comparable to that of frame-based procedures. Additionally, robot-assisted procedures are shorter and less demanding on patients. Robot-assisted DBS can be used on patients who are fully awake or under general anaesthesia, as well as on children.

Predictors of long-term memory and network connectivity 10 years after anterior temporal lobe resection.

Anterior temporal lobe resection (ATLR) effectively controls seizures in medically refractory temporal lobe epilepsy but risks significant episodic memory decline. Beyond 1 year postoperatively, the influence of preoperative clinical factors on episodic memory and long-term network plasticity remain underexplored. Ten years post-ATLR, we aimed to determine biomarkers of successful memory network reorganization and establish presurgical features' lasting impact on memory function. Twenty-five ATLR patients (12 left-sided) and 10 healthy controls underwent a memory-encoding functional magnetic resonance imaging paradigm alongside neuropsychometry 10 years postsurgery. Generalized psychophysiological interaction analyses modeled network functional connectivity of words/faces remembered, seeding from the medial temporal lobes (MTLs). Differences in successful memory connectivity were assessed between controls and left/right ATLR. Multivariate regressions and mixed-effect models probed preoperative phenotypes' effects on long-term memory outcomes. Ten years post-ATLR, lower baseline functioning (verbal and performance intelligence quotient) and a focal memory impairment preoperatively predicted worse long-term memory outcomes. Poorer verbal memory was significantly associated with longer epilepsy duration and earlier onset age. Relative to controls, successful word and face encoding involved increased functional connectivity from both or remnant MTL seeds and contralesional parahippocampus/hippocampus after left/right ATLR. Irrespective of surgical laterality, successful memory encoding correlated with increased MTL-seeded connectivity to frontal (bilateral insula, right anterior cingulate), right parahippocampal, and bilateral fusiform gyri. Ten years postsurgery, better memory performance was correlated with contralateral frontal plasticity, which was disrupted with longer epilepsy duration. Our findings underscore the enduring nature of functional network reorganizations to provide long-term cognitive support. Ten years post-ATLR, successful memory formation featured stronger connections near resected areas and contralateral regions. Preoperative network disruption possibly influenced effectiveness of postoperative plasticity. These findings are crucial for enhancing long-term memory prediction and strategies for lasting memory rehabilitation.

Navigating Dravet syndrome in Spain: A cross-sectional study of diagnosis, management, and care coordination.

Dravet syndrome (DS) is a rare form of refractory epilepsy that begins in the first year of life. Approximately 85% of patients have a mutation in the SCN1A gene, which encodes a voltage-gated sodium channel. The main objective of the present work was to assess the degree of knowledge of DS among Spanish primary care (PC) professionals, the communication flow between them and the pediatric neurologists (PNs), and the services available and resources offered to patients in Spain when searching for a diagnosis and adequate treatment. Two anonymized online surveys on DS diagnosis and patient management in PC were conducted with Spanish PC pediatricians (PCPs) and caregivers of DS patients in Spain. Most PCPs are aware of genetic epilepsy but lack full knowledge of DS and patient advocacy groups (PAGs). Access to epilepsy treatments varies among regions, with many referrals to hospitals and pediatric neurologists. Diagnosis is often delayed, with misdiagnoses and frequent emergency room (ER) visits. Treatment involves multiple drugs, and sodium channel blockers are used, which are contraindicated in DS treatment. Improved training, resources, and communication are needed for early diagnosis. To improve the care and treatment of DS patients in Spain, early diagnosis is required and, possibly, specific efforts aimed at identifying patients in adulthood, generating socio-sanitary structures that integrate social and health services to provide comprehensive care, taking into account the different features and comorbidities of the disease. Dravet syndrome (DS) is a form of genetic epilepsy that starts within the first year of life. We present a study showing that, while family doctors are aware of genetic epilepsies, many don't have a complete understanding of DS. Unfortunately, getting the right diagnosis can take a long time, leading to unnecessary visits to the emergency room. Patients often need several medications, and sometimes they're given drugs that aren't recommended for DS. The takeaway is that training for doctors, more resources, and improved communication could help creating better healthcare systems and therefore give easier access to the right therapies.

Phenotypic and mutational spectrum of 17 Chinese patients with Menkes Disease.

Menkes Disease (MD) is a fatal X-linked recessive disorder caused by mutations in the ATP7A gene. Severe cases typically die before the age of three. Mild MD and occipital horn syndrome are variants of MD characterized by a less severe phenotype and longer survival. This case series aims to validate previous findings, expand the clinical phenotype, identify novel ATP7A mutations of MD patients. Observational data with follow-up were collected from 17 genetically diagnosed Chinese MD patients. All 17 patients exhibited neurological symptoms, including delayed motor milestones (100%) and seizures (58.8%). Unspecific pregnancy or delivery complications occurred in 9 patients (52.9%). The most prevalent connective tissue problems were abnormal hair (76.5%), followed by skeletal and dental abnormalities (52.9%), skin problems (41.2%) and hernia (35.3%). Sensorineural hearing loss (17.6%) was previously unreported. Coronary artery aneurysm and patent foramen ovale (5.9%) were infrequent. One 16-year-old boy carries pathological exon 3-4 deletion, presents novel mild phenotype including short stature and cerebellar ataxia. Out of 13 patients with follow-up (median: 24 months), 7 patients (53.8%) died with median survival of 40 months (range: 21-48 months), 3 patients (23.1%) show severe motor development delay and 2 (15.4%) have refractory epilepsy, only the mild MD patient shows improved cerebellar ataxia. Sixteen ATP7A mutations were identified including 6 small indels (37.5%), 5 nonsense mutations (31.2%), 2 missense mutations (12.5%), 2 exon deletions (12.5%), and 1 splice site mutation (6.25%). Fourteen mutations were novel. Our study further broadens the phenotypic and genotypic spectrums of Menkes disease.

Endoscopic Transorbital Resection of Temporal Pole Cavernoma: 2-Dimensional Operative Video.

An endoscopic transorbital approach has been recently included in the neurosurgical armamentarium.1 We present a case of a 31-year-old female patient with a history of recent-onset refractory epilepsy related to a left temporal pole cavernoma operated through a superior eyelid endoscopic transorbital approach. The operative video shows the key surgical steps to ensure optimal surgical freedom, adequate exposure, and complete tumor resection.2 The postoperative course was uneventful, and the patient obtained seizure control and good cosmetic results without postoperative complications. The brain computed tomography and MRI showed the size of bone removal and confirmed the complete removal of the lesion, respectively. At 3-month follow-up, the patient is epileptic seizures-free without medications. An endoscopic transorbital approach provides adequate exposure of the temporal pole, allowing safe tumor resection. Complication avoidance encompasses careful dissection of palpebral muscles, dynamic orbital retraction, and neuronavigation guidance; sphenoidal drilling according to key anatomic landmarks (eg, sagittal crest3); and anatomic knowledge of the cavernous sinus and internal carotid artery and its tributaries course from a transorbital perspective4 and reconstruction filling the empty spaces using fat, fascia lata, or dural substitutes. All procedures performed were approved by the ethics committee of both centers and in accordance with Declaration of Helsinki and its later amendments. The patient consented to the procedure and to the publication of her images, and appropriate consent was obtained for publication of cadaveric images.

The Value of SINO Robot and Angio Render Technology for Stereoelectroencephalography Electrode Implantation in Drug-Resistant Epilepsy.

Stereoelectroencephalography (SEEG) electrodes are implanted using a variety of stereotactic technologies to treat refractory epilepsy. The value of the SINO robot for SEEG electrode implantation is not yet defined. The aim of the current study was to assess the value of the SINO robot in conjunction with Angio Render technology for SEEG electrode implantation and to assess its efficacy. Between June 2018 and October 2020, 58 patients underwent SEEG electrode implantation to resect or ablate their epileptogenic zone (EZ). The SINO robot and the Angio Render technology was used to guide the electrodes and visualize the individual vasculature in a three-dimensional (3D) fashion. The 3D view functionality was used to increase the safety and accuracy of the electrode implantation, and for reducing the risk of hemorrhage by avoiding blood vessels. In this study, 634 SEEG electrodes were implanted in 58 patients, with a mean of 10.92 (range: 5-18) leads per patient. The mean entry point localization error (EPLE) was 0.94 ± 0.23 mm (range: 0.39-1.63 mm), and the mean target point localization error (TPLE) was 1.49 ± 0.37 mm (range: 0.80-2.78 mm). The mean operating time per lead (MOTPL) was 6. 18 ± 1.80 minutes (range: 3.02-14.61 minutes). The mean depth of electrodes was 56.96 ± 3.62 mm (range: 27.23-124.85 mm). At a follow-up of at least 1 year, in total, 81.57% (47/58) patients achieved an Engel class I seizure freedom. There were two patients with asymptomatic intracerebral hematomas following SEEG electrode placement, with no late complications or mortality in this cohort. The SINO robot in conjunction with Angio Render technology-in SEEG electrode implantation is safe and accurate in mitigating the risk of intracranial hemorrhage in patients suffering from drug-resistant epilepsy.

Biochemical risk factors associated with refractory epilepsy: alpha synuclein and adenosine deaminase

Abstract Background Epilepsy is a common chronic neurological disorder affecting all age groups. A significant portion of children with epilepsy develop drug-resistant seizures. These children are at risk of cognitive and behavioral comorbidities and death. Some clinical features provide important information about the prognosis of epilepsy. However, currently, there is no objective biochemical indicator associated with refractory epilepsy. This study aimed to determine whether serum alpha-synuclein (αS), pglycoprotein (P-gp), and adenosine deaminase activity (ADA) were biochemical risk factors for refractory epilepsy. Methods The cross-sectional study included patients diagnosed with refractory epilepsy (n=32), non-refractory epilepsy (n=35) and 20 healthy children under the age of 18 who applied to the Pediatric Neurology outpatient clinic. In the serum samples, αS and P-gp were analyzed by ELISA and ADA activity was analyzed by spectrophotometric method. ROC analysis was applied and the area under the curve (AUC) was calculated to define cut-off values in distinguishing refractory epilepsy patients from non-refractory epilepsy patients. Binary logistic regression analysis was performed to define risk factors associated with resistance in patients with epilepsy. Results Children with epilepsy whose ADA activity and αS values were higher than the determined cut-off values had 10-fold and 5.3-fold increased risk of refractory epilepsy, respectively. Conclusions αS and ADA activity can be used as biochemical risk factors for refractory epilepsy. However, these results need to be confirmed by prospective studies with many patients.