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Introduction: The aim of this study was to present a novel technique for subthalamic nucleus (STN) deep brain stimulation (DBS) implantation under general anesthesia by using intraoperative motor-evoked potentials (MEPs) through direct lead stimulation and determining their correlation to the thresholds of postoperative stimulation-induced side effects. Methods: This study included 22 consecutive patients with advanced Parkinson's disease who underwent surgery in our institution between January 2021 and September 2023. All patients underwent bilateral implantation in the STN (44 leads) under general anesthesia without microelectrode recordings (MERs) by using MEPs with electrostimulation directly through the DBS lead. No cortical stimulation was performed during this process. Intraoperative fluoroscopic guidance and immediate postoperative computed tomography were used to verify the electrode's position. The lowest MEP thresholds were recorded and were correlated to the postoperative stimulation-induced side-effect threshold. The predictive values of the MEPs were analyzed. Five DBS leads were repositioned intraoperatively due to the MEP results. Results: A moderately strong positive correlation was found between the MEP threshold and the capsular side-effect threshold (RS = 0.425, 95% CI, 0.17–0.67, p = 0.004). The highest sensitivity and specificity for predicting a side-effect threshold of 5 mA were found to be at 2.4 mA MEP threshold (sensitivity 97%, specificity 87.5%, positive predictive value 97%, and negative predictive value 87.5%). We also found high sensitivity and specificity (100%) at 1.15 mA MEP threshold and 3 mA side-effect threshold. Out of the total 44 leads, 5 (11.3%) leads were repositioned intraoperatively due to MEP thresholds lower than 1 mA (4 leads) or higher than 5 mA (1 lead). The mean accuracy on postoperative CT was 1.05 mm, and there were no postoperative side-effects under 2.8 mA. Conclusion: Intraoperative MEPs with electrostimulation directly through the contacts of the DBS lead correlate with the stimulation-induced capsular side effects. The lead reposition based on intraoperative MEP may enlarge the therapeutic window of DBS stimulation. [ABSTRACT FROM AUTHOR]

Purpose: We present our experience with the national epilepsy surgery program in Armenia by tracing the development of epilepsy surgery in the largest pediatric neurology department at “Arabkir” Medical Center. This development was possible on the basis of a strong collaboration with the Epilepsy Surgery center at the University Hospital “Sofia St. Ivan Rilski,” Sofia, Bulgaria. Materials and methods: Our material included 28 consecutive patients with lesional drug-resistant epilepsy evaluated. All patients underwent 3  T MRI and Video-EEG monitoring. Brain 18FDG-PET was done in 13 patients in St. Petersburg. Fifteen patients (53%) had preoperative neuropsychological examination before surgery. All operations were done by the same neurosurgical team on site in Arabkir Hospital. Results: The majority of the patients in our cohort benefited from the epilepsy surgery as 25 (89%) are free of disabling seizures (Engel class I) and three patients (11%) did not improve substantially (Engel class IV). Eleven patients (39%) are already ASM-free after surgery, 4 (14%) are on monotherapy, 11(39%) get two drugs, and 2(7%) are on polytherapy, one of them still continues having seizures. In 12 patients (43%), we were able either to withdraw therapy or to decrease one of the ASM. Conclusion: We believe that, although small, yet encompassing patients along the usual age spectrum and with the most frequent pathologies of drug-resistant epilepsies, our experience can serve as a model to develop epilepsy surgery in countries with limited resources. [ABSTRACT FROM AUTHOR]

Background: Each year, approximately two million adolescents and young adults in the world become infected with tuberculosis (TB). The problem is that the classification of the disease includes children in the age group 0–14 years and young adults aged 15 and over. The present study aims to analyze and compare the epidemiology and clinical presentation of TB in Bulgaria in the different age subgroups of childhood. Methods: A retrospective study was undertaken of the newly diagnosed children (n = 80) with TB treated onsite from January 2018 to December 2020 at the Multiprofile Hospital for Active Treatment of Pulmonary Diseases ("St. Sofia"). They were distributed into three age groups: aged 8–11 (prepuberty), aged 12–14 (younger adolescents), and aged above 15 (older adolescents). Results: A clear finding of the research indicated that adolescent children develop TB both as primary and secondary infections. In a large number of cases with the children under our care, we found enlarged intrathoracic lymph nodes as well as infiltrative changes in the lungs, i.e., we observed transitional forms. There were statistically significant differences between the age group >15 years old and each of the other two younger groups for diagnosis, the severity of intoxication, and BK spreading status. Conclusion: The course of tuberculosis in adolescence has its own specifics and differences between the three age groups in the current study. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related disease (IgG4-RD) is a lymphoproliferative disease which is described almost exclusively in adults. There are only a few pediatric patients who have been observed with this disorder. Here, we describe a rare case of IgG4-RD in a 17-year-old girl with a single manifestation—tracheal stenosis without previous intubation or other inciting event. She had mixed dyspnea and noisy and weakened breathing. Immunoproliferative hyper-IgG4 disease was diagnosed, based on elevated serum IgG4 and histological findings. Until now we have chosen to treat the girl only with corticosteroids with a good response so far. The general condition as well as the respiratory function are regularly monitored. The tracheal involvement of IgG4-RD is uncommon. Nonetheless, it is a manifestation that should be included in the differential diagnosis of tracheal stenosis. [ABSTRACT FROM AUTHOR]

Introduction: The orientation in the intracranial space remains a neurosurgical challenge and transition from slices to threedimensional (3D) imaging makes surgeon closer to the reality. New developments in magnetic resonance imaging (MRI) and the release of free softwares as 3DSlicer, Freesurfer and FSL improved dramatically the quality of 3D reconstruction. Our aim to present the possibilities of 3D cortico-vascular and stereotactic electroencephalography (SEEG) reconstructions using common MRI sequences and free softwares. Methods: This study has included fifty-five consecutive epilepsy patients operated on during the period between January 2015 and December 2016. All patients underwent 1.5 T preoperative MRI and DICOM data postprocessing using FSL, Freesurfer and 3DSlicer. Intraoperative neuronavigation was performed in 40 patients and SEEG was performed in 15 patients using postprocessed images and raw data. Results: Three-dimensional reconstruction improve preoperative planning and intraoperative orientation especially in extratemporal epilepsy patients where the sulcal pattern is more complex and tailored SEEG implantations and cortical resctions are needed. Conclusion: Postprocessing of raw MRI and CT DICOM sets could provide useful preoperative and intraoperative information. [ABSTRACT FROM AUTHOR]

Background: Stereo-electroencephalography (SEEG) requires high quality angiographic study because avascular trajectory planning is a prerequisite for the safety of this procedure. Some epilepsy surgery groups have started to use computed tomography angiography (CTA) and magnetic resonance T1- weighted sequence with contrast enhancement (CE T1). To the best of our knowledge there are no reports of avascular trajectory planning of SEEG based on magnetic resonance angiography (MRA). Objective: The goal of our study was to assess the quality and safety of MRA for avascular trajectory planning of SEEG. Methods: Thirty-six SEEG explorations for drug-resistant focal epilepsy have been performed from January 2013 to December 2015 in the Epilepsy Surgery Center in Sofia. MRI included MRA with modified contrast enhanced magnetic resonance venography (MRV) protocol with short acquisition delay allowing simultaneous arterial and venous visualization. Our criteria for satisfactory MRA were visualization of at least first-order branches of the angular artery, paracentral and calcarine artery and thirdorder tributaries of superficial Sylvian vein, vein of Labbe and vein of Trolard. Results: Thirty-four patients underwent thirty-six SEEG explorations with 369 electrodes carrying 4321 contacts. Contrast enhanced MRA using MRVprotocol was judged satisfactory for SEEG planning in all explorations. Postoperative complications were not observed in our series of 36 SEEG explorations. Conclusions: MRA using MRV protocol may be applied for avascular trajectory planning during SEEG procedures and appears to have satisfactory safety profile. This technique provides simultaneous visualisation of cortical arteries and veins without need of additional radiation exposure or intra-arterial catheter placement. [ABSTRACT FROM AUTHOR]

Objective: Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently described, histopathologically and molecularly defined (SLC35A2-mutated) type of cortical malformation. Although increasingly recognized, the diagnosis of MOGHE remains a challenge. We present the characteristics of the first six patients diagnosed in Bulgaria, with the aim to facilitate identification, proper presurgical evaluation, and surgical treatment approach in this disease., Methods: Revision of histopathological specimens of 202 patients operated on for drug-resistant focal epilepsy identified four cases with MOGHE. Another two were suggested, based on clinical characteristics and subsequently, were histologically confirmed. Sanger SLC35A2 sequencing on paraffin-embedded or fresh-frozen brain tissue was performed. Analysis of seizure types, neuropsychological profiles, electroencephalographic (EEG), imaging features and epilepsy surgery outcomes was done., Results: Three out of the six cases (50%) harbored pathogenic SLC35A2 mutations. One patient had a heterozygous somatic variant with uncertain significance. Clinical characteristics included epilepsy onset in infancy (in 100% under 3 years of age), multiple seizure types, and moderate or severe intellectual/developmental delay. Epileptic spasms with hypsarrhythmia on EEG were the initial seizure type in five patients. The subsequent seizure types resembled those in Lennox-Gastaut syndrome. The majority of the patients (n = 4) presented prominent and persisting autistic features. Magnetic resonance imaging (MRI) showed multilobar (n = 6) and bilateral (n = 3) lesions, affecting the frontal lobes (n = 5; bilaterally in three) and characterized by increased signal on T2/fluid-attenuated inversion recovery (FLAIR). Voxel-based morphometric MRI post-processing and positron emission tomography helped determining the localization and extent of the lesions and presumed epileptogenic zones. After surgery, four patients (66.7%) were seizure-free ≥2 years. Interestingly, all seizure-free patients carried somatic SLC35A2-alterations., Significance: Epileptic spasms, early prominent neuropsychological disturbances, MRI-T2/FLAIR hyperintense lesions with cortico-subcortical blurring, frequently multilobar and especially frontal, can preoperatively help to suspect MOGHE. Epilepsy surgery is still the only successful treatment option in MOGHE., (© 2024 International League Against Epilepsy.)

Objective: Stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) has the advantage of producing a lesion in the epileptogenic zone (EZ) at the end of SEEG. The majority of published SEEG-guided RFTCs have been bipolar and usually performed between contiguous contacts of the same electrode. In the present study, the authors evaluate the safety, efficacy, and benefits of monopolar RFTC at the end of SEEG., Methods: This study included a series of 31 consecutive patients who had undergone RFTC at the end of SEEG for drug-resistant focal epilepsy in the period of January 2013-December 2019. Post-RFTC seizure control was assessed after 2 months and at the last follow-up visit. Twenty-one patients underwent resective epilepsy surgery after the SEEG-guided RFTC, and the postoperative seizure outcome among these patients was compared with the post-RFTC seizure outcome., Results: Four hundred forty-six monopolar RFTCs were done in the 31 patients. Monopolar RFTCs were performed in all cortical areas, including the insular cortex in 11 patients (56 insular RFTCs). There were 31 noncontiguous lesions (7.0%) because of vascular constraints. The volume of one monopolar RFTC, as measured on T2-weighted MRI immediately after the procedure, was between 44 and 56 mm3 (mean 50 mm3). The 2-month post-RFTC seizure outcomes were as follows: seizure freedom in 13 patients (41.9%), ≥ 50% reduced seizure frequency in 11 (35.5%), and no significant change in 7 (22.6%). Seizure outcome at the last follow-up visit (mean 18 months, range 2-54 months) showed seizure freedom in 2 patients (6.5%) and ≥ 50% reduced seizure frequency in 20 patients (64.5%). Seizure freedom after monopolar RFTC was not significantly associated with the number or location of coagulated contacts. Seizure response after monopolar RFTC had a high positive predictive value (93.8%) but a low negative predictive value (40%) for seizure outcome after subsequent resective surgery. In this series, the only complication (3.2%) was a limited intraventricular hematoma following RFTC performed in the hippocampal head, with spontaneous resolution and no sequelae., Conclusions: The use of monopolar SEEG-guided RFTC provides more freedom in terms of choosing the SEEG contacts for thermocoagulation and a larger thermolesion volume. Monopolar thermocoagulation seems particularly beneficial in cases with an insular EZ, in which vascular constraints could be partially avoided by making noncontiguous lesions within the EZ.

The central hypothesis for the development of glioblastoma multiforme (GBM) postulates that the tumor begins its development by transforming neural stem cells into cancer stem cells (CSC). Recently, it has become clear that another kind of stem cell, the mesenchymal stem cell (MSC), plays a role in the tumor stroma. Mesenchymal stem cells, along with their typical markers, can express neural markers and are capable of neural transdifferentiation. From this perspective, it is hypothesized that MSCs can give rise to CSC. In addition, MSCs suppress the immune cells through direct contact and secretory factors. Photodynamic therapy aims to selectively accumulate a photosensitizer in neoplastic cells, forming reactive oxygen species (ROS) upon irradiation, initiating death pathways. In our experiments, MSCs from 15 glioblastomas (GB-MSC) were isolated and cultured. The cells were treated with 5-ALA and irradiated. Flow cytometry and ELISA were used to detect the marker expression and soluble-factor secretion. The MSCs' neural markers, Nestin, Sox2, and glial fibrillary acid protein (GFAP), were down-regulated, but the expression levels of the mesenchymal markers CD73, CD90, and CD105 were retained. The GB-MSCs also reduced their expression of PD-L1 and increased their secretion of PGE2. Our results give us grounds to speculate that the photodynamic impact on GB-MSCs reduces their capacity for neural transdifferentiation.

Low-grade epilepsy-associated neuroepithelial tumours (LEATs) encompass the broad spectrum of tumours associated with epilepsy. Since the postsurgical seizure outcome in LEATs is favourable, it is speculated that epileptological presurgical evaluation (EPE) might not be required for patients with LEATs. A multicentre study involving referring epilepsy and neurosurgery centres was performed, aimed at evaluating postsurgical epilepsy outcome in patients with LEATs, with and without EPE, including long-term video-EEG monitoring (vEEGM). In total, 149 surgically treated patients were enrolled (age: 31±14 years; age at surgery: 26.4±13.1 years; males; 55.7%) with histopathological confirmation of LEATs and follow-up of more than six months. All patients had undergone standard assessment: clinical, routine EEG and brain MRI. In addition to vEEGM, EPE included other additional investigations. Epileptologists did not assess patients treated in neurosurgical centres. The EPE was performed in 51% of patients. Histopathological diagnosis revealed ganglioglioma in 43.6%, DNET in 32.9%, pilocytic astrocytoma in 17.4%, and others in 6.1% of patients. The majority of patients were seizure-free (ILAE epilepsy surgery outcome Class 1; 71.1%). The median follow-up period was 36 months. Patients who were rendered seizure-free were younger (mean age: 24.2±12.2) than those who were not seizure-free (31.8±14.0) (p=0.001). No difference was identified between evaluated and non-evaluated patients with respect to seizure freedom (p=0.45). EPE patients had a longer epilepsy duration (median: 10 years) and a higher proportion of drug resistance (73.6%) compared to non-evaluated patients (median: two years; 26.4%) (p<0.001). Based on a significant difference in major clinical variables, that may well affect postoperative results, the similar postsurgical seizure outcome in groups with and without EPE observed in our study should be considered with caution, and conclusions as to whether there is value in formal presurgical evaluation in LEAT patients cannot be drawn. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences.