Clinical characteristics and multimodal imaging can help diagnosing and treating mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy.

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.

Mapping of Capsular Side Effects by using Intraoperative Motor-Evoked Potentials during Asleep Deep Brain Stimulation Surgery of the Subthalamic Nucleus for Parkinson's Disease.

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.

Is PDQ-39 a reliable measure of quality of life of patients at advanced stages of Parkinson's disease considered for Deep Brain Stimulation.

Purpose: Parkinson's disease (PD) significantly impedes, especially at its advanced stages, the health-related quality of life (QoL) of patients. The Parkinson's disease questionnaire (PDQ-39) is a widely-used measure assessing the impact of the disease on the patients' QoL. To date, the reliability of PDQ-39 has not been selectively evaluated for patients at a particular delineated stage of the PD progression. Against this backdrop, the study aimed firstly to evaluate comprehensively the internal consistency reliability of PDQ-39 and the constituent scales specifically for patients at the advanced stages of PD who were candidates for Deep Brain Stimulation (DBS) surgery, and secondly, to compare the Cronbach's alpha coefficients with those reported in other studies conducted with patients across all stages of the PD progression. Methods: The sample included 36 Bulgarian patients (29 men and 7 women) at advanced stages of PD (Hoehn and Yahr stage 4), PD duration, M = 11.06, SD = 3.50). The internal consistency reliability of the questionnaire and the constituent scales was assessed using three criteria: Cronbach's alpha coefficients, inter-item and item-total correlations. Results: The internal consistency reliability indicators were satisfactory for the entire instrument and for most of the scales and similar to those reported in previous studies. None of the scales had low internal consistency reliability results across the three criteria. Except for the Communication scale, seven of the eight scales had Cronbach's alpha values that were satisfactory or marginally below the cut off score. All scales had acceptable inter-item correlations. Three of the scales (Emotional Well-Being, Cognition and Communication) contained more than one item with non-satisfactory item-total correlations. With minor exceptions, the removal of the items with low item-total correlations either did not improve or improved marginally or even decreased the Cronbach's alpha coefficients of the respective scale. The Communication scale was the only scale with a Cronbach's alpha coefficient that was both low and comparatively different to other studies and had as well low item-total correlations for all constituent items, thus showing non-satisfactory results on two of the three internal consistency reliability estimates. In contrast, the Mobility scale met all three internal consistency reliability criteria. Conclusion: PDQ-39 is a reliable tool for assessing the QoL of patients at advanced stages of PD across multiple health-related domains. The questionnaire can be recommended for inclusion in the best practice guidelines for evaluating DBS candidacy and the efficacy of DBS treatment for patients' QoL.

Monopolar stereoelectroencephalography-guided radiofrequency thermocoagulation.

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.

Theoretical stereoelectroencephalography density on the brain convexity.

INTRODUCTION: Invasive electroencephalography (EEG) remains the "gold standard" for diagnosing the epileptogenic zone in patients with drug-resistant epilepsy and discrepancies between seizure semiology, video-EEG and magnetic resonance imaging (MRI) findings. However, the possibilities of stereoelectroencephalography (SEEG) to explore the brain surface remain a matter of debate and subdural EEG (SDEEG) is still preferred in some centers for cases when the supposed epileptogenic zone is on the brain convexity. The aim of our study was to evaluate the theoretical safe SEEG coverage on the brain convexity and to compare the theoretical SEEG cortical density with the usual SDEEG density. MATERIALS AND METHODS: Our material included 10 hemispheres in 5 patients, who had been already investigated with SEEG for drug-resistant epilepsy. We translated our previously described technique in a theoretical model in an attempt to calculate the maximal number of avascular windows for each cerebral hemisphere. The distance between every entry point and the other entry points for each hemisphere was calculated using a mathematical formula. Subsequently, the theoretical SEEG coverage on the brain convexity was described using the maximal, minimal and average distances between each entry point and the closest 4 neighboring points. This type of measurement allows a direct comparison between SEEG and SDEEG in their ability to explore the brain convexity. RESULTS: Ten hemispheres had 1328 safe entry points with a safety margin of 2.5 mm and a minimal distance of 2.5 mm between 2 entry points (average number of entry points: 132.8 (SD ± 5). The number of entry points in the explored 10 hemispheres varied from 104 to 156. The average distance between each entry point and its 4 neighbors was 11.47 mm. The maximal distance between two entry points in these 10 hemispheres was ranging from 20.28 to 27.23 mm (average: 24.67 mm). The closest entry points for the explored hemispheres were at an average distance of 4.67 mm (range: 2.82 - 5.96 mm). The average convexity surface was 223.68 cm2 (range: 204.63-238.77 cm2). The safe electrode density without electrode collision on the cortical surface was ranging from 0.46 to 0.69 electrodes per cm2 (average: 0.59 electrodes per cm2) (SD ± 0.023). CONCLUSION: The theoretical SEEG cortical density is comparable with the usual SDEEG density. These findings, combined with the better safety profile of SEEG and the possibilities to explore deep cortical structures, explain the progressive shift from SDEEG to SEEG during the last years.

Awake Epilepsy Surgery in Patients with Focal Cortical Dysplasia.

BACKGROUND: Awake craniotomy (AC) and direct electric stimulation emerged together with epilepsy surgery >80 years ago. The goal of our study was to evaluate the benefits of awake surgery in patients with drug-resistant epilepsy caused by focal cortical dysplasia (FCD) affecting eloquent areas. METHODS: Our material included 95 patients with drug-resistant epilepsy and FCD, who were operated on between January 2009 and December 2018. These 95 patients were assigned into 3 groups: AC; general anesthesia (GA) with intraoperative neuromonitoring; and GA without intraoperative neuromonitoring. We investigated the following variables: age at surgery, lesion side, eloquent cortex involvement, brain mapping success rate, epilepsy surgery success rate, intraoperative complications, postoperative complications, and intraoperative changes of the preoperative resection plan according to results of the brain mapping by direct electric stimulation. RESULTS: We found statistically significant differences between the AC and GA groups in the mean age at operation, lesion side, eloquent localization, and postoperative transient neurologic deficit. Seizure outcome in the AC was satisfactory (71% complete seizure control) and comparable to the seizure outcome in the GA groups. Our preoperative plan was changed because of functional constraints in 6 patients (43%) operated on during AC. CONCLUSIONS: AC during epilepsy surgery for FCD in eloquent areas may change the preoperative plan. The good rate of postoperative seizure control and the absence of permanent postoperative neurologic deficit in our series is the main proof that AC is a useful tool in patients with FCD involving the eloquent cortex.

Stereoelectroencephalography Using Magnetic Resonance Angiography for Avascular Trajectory Planning: Technical Report.

BACKGROUND: Stereoelectroencephalography (SEEG) requires high-quality angiographic studies because avascular trajectory planning is a prerequisite for the safety of this procedure. Some epilepsy surgery groups have begun to use computed tomography angiography and magnetic resonance T1-weighted sequence with contrast enhancement for this purpose. OBJECTIVE: To present the first series of patients with avascular trajectory planning of SEEG based on magnetic resonance angiography (MRA). METHODS: Thirty-six SEEG explorations for drug-resistant focal epilepsy were performed from January 2013 to December 2015. A retrospective analysis of this consecutive surgical series was then performed. Magnetic resonance imaging included MRA with a modified contrast-enhanced magnetic resonance venography (MRV) protocol with a short acquisition delay, which allowed simultaneous arterial and venous visualization. Our criteria for satisfactory MRA were the visualization of at least first-order branches of the angular artery, paracentral and calcarine artery, and third-order tributaries of the superficial Sylvian vein, vein of Labbe, and vein of Trolard. RESULTS: Thirty-four patients underwent 36 SEEG explorations with 369 electrodes carrying 4321 contacts. Contrast-enhanced MRA using the MRV protocol was judged satisfactory for SEEG planning in all explorations. Postoperative complications were not observed in our series of 36 SEEG explorations, which included 50 transopercular insular trajectories. CONCLUSION: MRA using an MRV protocol may be applied for avascular trajectory planning during SEEG procedures. This technique provides a simultaneous visualization of cortical arteries and veins without the need for additional radiation exposure or intra-arterial catheter placement.