Multimodal Approach for the Treatment of Complex Hypothalamic Hamartomas.

Hypothalamic hamartomas (HHs) are rare congenital lesions formed by heterotopic neuronal and glial cells attached to the mammillary bodies, tuber cinereum, and hypothalamus.They often present with an intractable epilepsy typically characterized by gelastic seizures but commonly associated with other types of refractory seizures. The clinical course is progressive in most of the cases, starting with gelastic seizures in infancy and deteriorating into complex seizure disorders that result in catastrophic epilepsy associated with cognitive decline and behavioral disturbances.Hamartomas are known to be intrinsically epileptogenic and the site of origin for the gelastic seizures. As antiepileptic drugs are typically ineffective in controlling HH-related epilepsy, different surgical options have been proposed as a treatment to achieve seizure control. Resection or complete disconnection of the hamartoma from the mammillothalamic tract has proved to achieve a long-lasting control of the epileptic syndrome.Usually, symptoms and their severity are typically related to the size, localization, and type of attachment. Precocious puberty appears mostly in the pedunculated type, while epileptic syndrome and behavioral decline are frequently related to the sessile type. For this reason, different classifications of HHs have been developed based on their size, extension, and type of attachment to the hypothalamus.The bigger and more complex hypothalamic hamartomas typically present with severe refractory epilepsy, behavioral disturbances, and progressive cognitive decline posing a formidable challenge for the control of these symptoms.We present here our experience with the multimodal treatment for complex hypothalamic hamartomas. After an in-depth review of the literature, we systematize our approach for the different types of hypothalamic hamartomas.

The impact of social determinants of health on utilization of pediatric epilepsy surgery: a systematic review.

OBJECTIVE: A minority of pediatric patients who may benefit from epilepsy surgery receive it. The reasons for this utilization gap are complex and not completely understood. Patient and caregiver social determinants of health (SDOH) may impact which patients undergo surgery and when. The authors conducted a systematic review examining SDOH and surgical intervention in children with drug-resistant epilepsy (DRE). They aimed to understand which factors influenced time to surgical program referral or receipt of epilepsy surgery among children with DRE, as well as identify areas to characterize the SDOH impacting epilepsy surgery in children and guide efforts aimed to promote health equity in epilepsy. METHODS: A systematic review was conducted using the PubMed, Embase, and Scopus databases in January 2022. Studies were analyzed by title and abstract, then full text, to identify all studies examining the impact of SDOH on utilization of epilepsy surgery. Studies meeting inclusion criteria were analyzed for SDOH examined, outcomes, and key findings. Quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Of 4545 resultant articles, 18 were included. Studies examined social, cultural, and environmental factors that contributed to SDOH impacting epilepsy surgery. Patients who underwent surgical evaluation were found to be most commonly White and privately insured and have college-educated caregivers. Five studies found differences in time to referral/surgery or rates of surgery by racial group, with most finding an increased time to referral/surgery or lower rates of surgery for those who were Hispanic and/or non-White. Four studies found that private insurance was associated with higher surgical utilization. Three studies found higher household income was related to surgical utilization. No studies examined biological, psychological, or behavioral factors that contributed to SDOH impacting epilepsy surgery. CONCLUSIONS: The authors conducted a systematic review exploring the impact of SDOH in DRE surgery utilization. They found that race, ethnicity, insurance type, caregiver educational attainment, and household income demonstrate relationships with pediatric epilepsy surgery. Further study is necessary to understand how these factors, and others not identified in this study, contribute to the low rates of utilization of epilepsy surgery and potential target areas for interventions aiming to increase equity in access to epilepsy surgery in children.

Design and validation of a diagnostic suspicion checklist to differentiate epileptic from psychogenic nonepileptic seizures (PNES-DSC).

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are complex clinical manifestations and misdiagnosis as status epilepticus remains high, entailing deleterious consequences for patients. Video-electroencephalography (vEEG) remains the gold-standard method for diagnosing PNES. However, time and economic constraints limit access to vEEG, and clinicians lack fast and reliable screening tools to assist in the differential diagnosis with epileptic seizures (ES). This study aimed to design and validate the PNES-DSC, a clinically based PNES diagnostic suspicion checklist with adequate sensitivity (Se) and specificity (Sp) to discriminate PNES from ES. METHODS: A cross-sectional study with 125 patients (n = 104 drug-resistant epilepsy; n = 21 PNES) admitted for a vEEG protocolised study of seizures. A preliminary PNES-DSC (16-item) was designed and used by expert raters blinded to the definitive diagnosis to evaluate the seizure video recordings for each patient. Cohen's kappa coefficient, leave-one-out cross-validation (LOOCV) and balance accuracy (BAC) comprised the main validation analysis. RESULTS: The final PNES-DSC is a 6-item checklist that requires only two to be present to confirm the suspicion of PNES. The LOOCV showed 71.4% BAC (Se = 45.2%; Sp = 97.6%) when the expert rater watched one seizure video recording and 83.4% BAC (Se = 69.6%; Sp = 97.2%) when the expert rater watched two seizure video recordings. CONCLUSION: The PNES-DSC is a straightforward checklist with adequate psychometric properties. With an integrative approach and appropriate patient history, the PNES-DSC can assist clinicians in expediting the final diagnosis of PNES when vEEG is limited. The PNES-DSC can also be used in the absence of patients, allowing clinicians to assess seizure recordings from smartphones.

Determination of oxidative stress level and some antioxidant activities in refractory epilepsy patients.

The aim of this study was to determine the levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) in patients with refractory epilepsy. Serum superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels were determined using the spectrophotometer method. Refractory epilepsy patients' serum superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels were statistically significant compared to the healthy control group (p < 0.05). In conclusion, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels may play an important role in the etiopathogenesis of refractory epilepsy. This study was the first to investigate some parameters in refractory epilepsy disease.

Assessing short-term and long-term security and efficacy of anterior nucleus of the thalamus deep brain stimulation for treating drug-resistant epilepsy: A systematic review and single-arm meta-analysis.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug-resistant epilepsy. Nonetheless, there is a persistent debate regarding the short-term and long-term efficacy and safety of ANT-DBS. Thus we conducted a systematic review and meta-analysis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Cochrane, Embase, and Web of Science for studies treating refractory epilepsy with ANT-DBS. Short-term analysis was considered for studies with a mean follow-up of 3 years or less. The following outcomes were assessed for data extraction: procedure responders and nonresponders, increased seizure frequency, complications, and procedure-related mortality. Of 650 studies, 25 fit our inclusion criteria, involving 427 patients. Previous surgical treatments have been reported in 214 patients (50.1%) and a median average baseline seizure frequency of 64.9 monthly seizures. In the short-term analysis, we observed a proportion of 67% (95% confidence interval [CI] 54%-79%) of responders and 33% (95% CI 21%-46%) of nonresponders. In addition, 4% (95% CI 0%-9%) of the patients presented increased seizure frequency. In the long-term analysis, we observed 72% (95% CI 66%-78%) responders and 27% (95% CI 21%-34%) nonresponders. Moreover, there was a 2% (95% CI 0%-5%) increase in seizure frequency. No procedure-related mortality was reported at any follow-up. ANT-DBS effectively treats refractory epilepsy, with lasting short-term and long-term benefits. It remains safe and efficient despite complications, showing no procedure-linked fatalities, high patient responsiveness, and minimal increased seizures. Consistent results over time and low morbidity/mortality rates emphasize its worth. Further research is necessary to diminish the discrepancy among results.

Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.

OBJECTIVE: This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD). METHODS: A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine differential gene expression between the FCD and control groups. RESULTS: Among the 40 patients included in the study, focal to bilateral tonic-clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET-CT) scans revealed hypometabolic lesions. Fused MRI/PET-CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET-CT alone, while 59.26% (16/27) yielded results consistent with PET-CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow-up, 38 patients were prescribed an average of 1.27 ± 1.05 anti-seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow-up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT-PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1. SIGNIFICANCE: This study highlights focal to bilateral tonic-clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD-related DRE showed a promising prognosis for seizure control post-surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD. PLAIN LANGUAGE SUMMARY: This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic-clonic seizures were the most prevalent seizure type in patients with drug-resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia-induced drug-resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia.

Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia-The Neonatal Type of Alexander Disease.

INTRODUCTION: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD. METHOD: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband's DNA extracted from blood. CASE DESCRIPTION: In the first weeks of life, the child presented with signs of increased intracranial pressure, which led to ventriculoperitoneal shunt implementation. Recurrent focal-onset motor seizures with secondary generalization occurred despite phenobarbital treatment. Therapy was modified with multiple anti-seizure medications. In MRI contrast-enhanced lesions in basal ganglia, midbrain and cortico-spinal tracts were observed. During the diagnostic process, GLUT-1 deficiency, lysosomal storage disorders, organic acidurias, and fatty acid oxidation defects were excluded. The NGS panel of EIEE revealed no abnormalities. In WES analysis, GFAP missense heterozygous variant NM_002055.5: c.1187C>T, p.(Thr396Ile) was detected, confirming the diagnosis of AxD. CONCLUSION: AxD should be considered in the differential diagnosis in all neonates with progressive, intractable seizures accompanied by macrocephaly.

Neuropsychological characteristics of drug resistant epilepsy patients with and without comorbid functional seizures.

INTRODUCTION: Neuropsychological testing is a mandatory component in the evaluation of drug resistant epilepsy. The results of testing may assist with both the localization of an epilepsy as well as assessment of surgical risk. Previous studies have demonstrated differences in the neuropsychological performance of patients with epilepsy and functional seizures. We hypothesized that comorbid functional seizures could potentially influence neuropsychological test performance. Therefore, we evaluated whether there is a difference in the neuropsychological test results between drug resistant epilepsy patients with and without comorbid functional seizures. METHOD: Neuropsychological test results were compared between 25 patients with drug resistant focal epilepsy and 25 patients that also had documented functional seizures. Univariate analyses and multiple logistic regression models were used to both assess performance differences between the groups and to assess whether test results could be used to accurately identify which patients had comorbid functional seizures. RESULTS: Epilepsy patients with comorbid functional seizures performed significantly worse on the FAS Verbal Fluency Test compared to ES patients (p = 0.047). Digit Span Backwards (p = 0.10), Digit Span Forwards (p = 0.14) and Working Memory Index (p = 0.10) tended to be lower in the epilepsy and functional seizures group but was not statistically significant. A multiple logistic regression model using the results of four neuropsychological tests was able to identify patients with comorbid functional seizures with 83.33% accuracy. CONCLUSIONS: There are appeared to be some differences in the neuropsychological performance among drug resistant epilepsy patients based on whether they have comorbid functional seizures. These findings may have relevant implications for the interpretation of neuropsychological test results.

Characterization of Vagus Nerve Stimulation (VNS) Dose-Dependent Effects on EEG Power Spectrum and Synchronization.

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy.

Complete Heart Block and Ventricular Asystole Caused by Vagus Nerve Stimulation Therapy.

Left vagus nerve stimulation (VNS) is an advanced therapeutic option for refractory, drug-resistant epilepsy. A 45-year-old woman with a history of refractory catamenial focal epilepsy since age 16, treated with a five-drug antiepileptic regimen and VNS (implanted eight and one-half years prior), presented with dyspnea, chest discomfort, and lightheadedness. During observation, symptoms recurred and were associated with bradycardia (<20 bpm) and a complete atrioventricular node (AVN) block. Following admission, she continued to experience recurrent symptomatic AVN block and transient ventricular asystole, temporally correlated with her baseline seizure activity and resultant activation of her VNS. Deactivation of VNS resolved her bradyarrhythmia, and she experienced no recurrence over 14 months of follow-up. This case highlights a therapeutic dilemma in cases of refractory epilepsy, with limited therapeutic options if seizure activity requires VNS to be controlled.

Drug resistant epilepsy and ketogenic diet: A narrative review of mechanisms of action.

Drug-resistant epilepsy (DRE) poses a significant global challenge, impacting the well-being of patients. Anti-epileptic drugs often fail to effectively control seizures in individuals with DRE. This condition not only leads to persistent seizures but also induces neurochemical imbalances, elevating the risk of sudden unexpected death in epilepsy and comorbidities. Moreover, patients experience mood and personality alterations, educational and vocational setbacks, social isolation, and cognitive impairments. Ketogenic diet has emerged as a valuable therapeutic approach for DRE, having been utilized since 1920. Various types of ketogenic diets have demonstrated efficacy in controlling seizures. By having a multimodal mechanism of action, the ketogenic diet reduces neuronal excitability and the frequency of seizure episodes. In our narrative review, we have initially provided a concise overview of the factors contributing to drug resistance in epilepsy. Subsequently, we have discussed the different available ketogenic diets. We have reviewed the underlying mechanisms through which the ketogenic diet operates. These mechanisms encompass decreased neuronal excitability, enhanced mitochondrial function, alterations in sleep patterns, and modulation of the gut microbiome. Understanding the complex mechanisms by which this diet acts is essential as it is a rigorous diet and requires good compliance. Hence knowledge of the mechanisms may help to advance research on achieving similar therapeutic effects through other less stringent approaches.

Dyke Davidoff Masson: A Case Report.

Dyke Davidoff-Masson syndrome is a rare neurological condition that results from brain injury during early childhood stages. The precise incidence of this condition is unknown, with a slight male predominance, and adult forms have been documented. Imaging findings reveal hemisphere atrophy along with ipsilateral compensatory skull changes and hyper-pneumatization of mastoid cells. The treatment approach involves anti-epileptic medications and hemispherectomy is reserved for cases with intractable seizures. This case report delineates the clinical manifestation and therapeutic approach employed in an 8-year-old male patient exhibiting pharmaco-resistant left hemi-body convulsive seizures. The magnetic resonance imaging (MRI) findings revealed right cerebral hemiatrophy, mesencephalon atrophy, ipsilateral calvarial hypertrophy and hyperpneumatization of mastoid cells. The objective of this study is to contribute to the existing literature by presenting this rare case report. We propose that in cases involving pediatric pharmaco-resistant epilepsy, it is essential to conduct further investigations to establish a comprehensive management strategy.

Deep learning-based automated lesion segmentation on pediatric focal cortical dysplasia II preoperative MRI: a reliable approach.

OBJECTIVES: Focal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II. METHODS: High-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance. RESULTS: The 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset. CONCLUSION: This pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection. CRITICAL RELEVANCE STATEMENT: Our fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes. KEY POINTS: • Simplified image processing promotes the DL model implemented in clinical practice. • The histopathological confirmed lesion masks enhance the clinical credibility of the AI model. • The voxel-level evaluation metrics benefit lesion detection and clinical decisions.

SEW2871 reduces seizures via the sphingosine 1-phosphate receptor-1 pathway in the pentylenetetrazol and phenobarbitone kindling model of drug-refractory epilepsy.

Epilepsy is a prevalent neurological disorder characterized by neuronal hypersynchronous discharge in the brain, leading to central nervous system (CNS) dysfunction. Despite the availability of anti-epileptic drugs (AEDs), resistance to AEDs is the greatest challenge in treating epilepsy. The role of sphingosine-1-phosphate-receptor 1 (S1PR1) in drug-resistant epilepsy is unexplored. This study investigated the effects of SEW2871, a potent S1PR1 agonist, on a phenobarbitone (PHB)-resistant pentylenetetrazol (PTZ)-kindled Wistar rat model. We measured the messenger ribonucleic acid (mRNA) expression of multi-drug resistance 1 (MDR1) and multi-drug resistance protein 5 (MRP5) as indicators for drug resistance. Rats received PHB + PTZ for 62 days to develop a drug-resistant epilepsy model. From day 48, SEW2871 (0.25, 0.5, 0.75 mg/kg, intraperitoneally [i.p.]) was administered for 14 days. Seizure scoring, behaviour, oxidative markers like reduced glutathione, catalase, superoxide dismutase, inflammatory markers like interleukin 1 beta tumour necrosis factor alpha, interferon gamma and mRNA expression (MDR1 and MRP5) were assessed, and histopathological assessments were conducted. SEW2871 demonstrated dose-dependent improvements in seizure scoring and neurobehavioral parameters with a reduction in oxidative and inflammation-induced neuronal damage. The S1PR1 agonist also downregulated MDR1 and MRP5 gene expression and significantly decreased the number of dark-stained pyknotic nuclei and increased cell density with neuronal rearrangement in the rat brain hippocampus. These findings suggest that SEW2871 might ameliorate epileptic symptoms by modulating drug resistance through downregulation of MDR1 and MRP5 gene expression.

Neurological function and drug-refractory epilepsy in Sturge-Weber syndrome children: a retrospective analysis.

Epilepsy in Sturge-Weber syndrome (SWS) is common, but drug-refractory epilepsy (DRE) in SWS has rarely been studied in children. We investigated the characteristics of epilepsy and risk factors for DRE in children with SWS. A retrospective study was conducted to analyze the clinical characteristics of children with SWS with epilepsy in our hospital from January 2013 to October 2022. Univariate and multivariate logistic analyses were performed to investigate the factors influencing DRE in children with SWS. A total of 35 SWS children with epilepsy were included (51% male; mean age of presentation 3.6 ± 0.5 years), 71% of children with SWS had their first seizure within the first year of life, and the most common type of seizure was focal seizure (77%). Eleven (31%) patients developed DRE. The median age of onset for the first seizure was 1.0 years and all these cases were of SWS type I. Multivariate logistic analysis revealed that stroke-like episodes and seizure clusters were risk factors for DRE in SWS children. A poor neurological function group was observed in twenty-five children with SWS. Status epilepticus was a risk factor that affected the neurological function of SWS children with epilepsy.  Conclusion: The study explored the epileptic features of children with SWS. The results revealed that stroke-like episodes and seizure clusters are risk factors for DRE in children with SWS. The occurrence of status epilepticus impacts the neurological function of SWS children with epilepsy. Thus, long-term follow-up is necessary to monitor outcomes. What is Known: • Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder, over 75% of children with SWS experience seizures, and 30-57% develop drug-refractory epilepsy (DRE), which leads to a poor outcome. • Drug-refractory epilepsy in SWS has been rarely studied in children, and the risk factors associated with DRE are unclear. What is New: • Clinical features of SWS children with drug-refractory epilepsy. • In SWS, stroke-like episodes and seizure clusters are risk factors of DRE, the occurrence of status epilepticus impacts the neurological function.

Hippocampal sclerosis is associated with celiac disease type immunity in patients with drug-resistant temporal lobe epilepsy.

BACKGROUND: A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies. METHODS: In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16-76 years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups. RESULTS: TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05). CONCLUSIONS: This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression.

Posterior Reversible Encephalopathy Syndrome (PRES) and the Uncommon Sequela: Mesial Temporal Sclerosis.

Posterior reversible encephalopathy syndrome is often linked to conditions like hypertension and is characterized by reversible brain edema. The development of mesial temporal sclerosis as a consequence of posterior reversible encephalopathy syndrome is an uncommon clinical outcome.  We report a 48-year-old female who initially presented with severe iron deficiency anemia, hypertension, and septic tenosynovitis requiring surgical drainage with subsequent development of posterior reversible encephalopathy syndrome accompanied by endocarditis. Although there was a question of one seizure episode during one of her hospital days, the patient experienced multiple seizure episodes three months after she left the hospital. Subsequent MRI demonstrated atrophy of the left mesial temporal lobe suggesting mesial temporal sclerosis.  The temporal development of mesial temporal sclerosis in a patient with posterior reversible encephalopathy syndrome highlights mesial temporal sclerosis as a potential long-term consequence of posterior reversible encephalopathy syndrome, and the need for imaging surveillance in patients diagnosed with posterior reversible encephalopathy syndrome.

GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation.

We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABAA receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception.

Epileptic tissue localization using graph-based networks in the high frequency oscillation range of intracranial electroencephalography.

PURPOSE: High frequency oscillations (HFOs) are an emerging biomarker of epilepsy. However, very few studies have investigated the functional connectivity of interictal iEEG signals in the frequency range of HFOs. Here, we study the corresponding functional networks using graph theory, and we assess their predictive value for automatic electrode classification in a cohort of 20 drug resistant patients. METHODS: Coherence-based connectivity analysis was performed on the iEEG recordings, and six different local graph measures were computed in both sub-bands of the HFO frequency range (80-250 Hz and 250-500 Hz). Correlation analysis was implemented between the local graph measures and the ripple and fast ripple rates. Finally, the WEKA software was employed for training and testing different predictive models on the aforementioned local graph measures. RESULTS: The ripple rate was significantly correlated with five out of six local graph measures in the functional network. For fast ripples, their rate was also significantly (but negatively) correlated with most of the local metrics. The results from WEKA showed that the Logistic Regression algorithm was able to classify highly HFO-contaminated electrodes with an accuracy of 82.5 % for ripples and 75.4 % for fast ripples. CONCLUSION: Functional connectivity networks in the HFO band could represent an alternative to the direct use of distinct HFO events, while also providing important insights about hub epileptic areas that can represent possible surgical targets. Automatic electrode classification through FC-based classifiers can help bypass the burden of manual HFO annotation, providing at the same time similar amount of information about the epileptic tissue.

Clinical and pathologic features of Sturge-Weber syndrome in patients with refractory epilepsy.

OBJECTIVES: We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. METHODS: Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. RESULTS: Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P = .015). CONCLUSIONS: Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS.