Identifying responders to vagus nerve stimulation based on microstructural features of thalamocortical tracts in drug-resistant epilepsy.

The mechanisms of action of Vagus Nerve Stimulation (VNS) and the biological prerequisites to respond to the treatment are currently under investigation. It is hypothesized that thalamocortical tracts play a central role in the antiseizure effects of VNS by disrupting the genesis of pathological activity in the brain. This pilot study explored whether in vivo microstructural features of thalamocortical tracts may differentiate Drug-Resistant Epilepsy (DRE) patients responding and not responding to VNS treatment. Eighteen patients with DRE (37.11 â€‹± â€‹10.13 years, 10 females), including 11 responders or partial responders and 7 non-responders to VNS, were recruited for this high-gradient multi-shell diffusion Magnetic Resonance Imaging (MRI) study. Using Diffusion Tensor Imaging (DTI) and multi-compartment models - Neurite Orientation Dispersion and Density Imaging (NODDI) and Microstructure Fingerprinting (MF), we extracted microstructural features in 12 subsegments of thalamocortical tracts. These characteristics were compared between responders/partial responders and non-responders. Subsequently, a Support Vector Machine (SVM) classifier was built, incorporating microstructural features and 12 clinical covariates (including age, sex, duration of VNS therapy, number of antiseizure medications, benzodiazepine intake, epilepsy duration, epilepsy onset age, epilepsy type - focal or generalized, presence of an epileptic syndrome - no syndrome or Lennox-Gastaut syndrome, etiology of epilepsy - structural, genetic, viral, or unknown, history of brain surgery, and presence of a brain lesion detected on structural MRI images). Multiple diffusion metrics consistently demonstrated significantly higher white matter fiber integrity in patients with a better response to VNS (pFDR < 0.05) in different subsegments of thalamocortical tracts. The SVM model achieved a classification accuracy of 94.12%. The inclusion of clinical covariates did not improve the classification performance. The results suggest that the structural integrity of thalamocortical tracts may be linked to therapeutic effectiveness of VNS. This study reveals the great potential of diffusion MRI in improving our understanding of the biological factors associated with the response to VNS therapy.

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

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

Extradural malignant rhabdoid tumor of the spine in children: A case-based review.

BACKGROUND: Extradural malignant rhabdoid tumors of the spine are highly malignant and invasive tumors (WHO grade IV) with poor prognosis, most frequently occurring in young children before 2 years of age. Pain and motor deficit are the most common presenting signs. CASE DESCRIPTION: We report a case of a 2-year-old girl presenting with axial ataxia and paraparesis related to an extradural malignant rhabdoid tumor causing posterior thoracic spinal cord compression (D3-D6). She underwent two near-total removal of the tumor, adjuvant chemotherapy according to the Eu-Rhab protocol and proton beam therapy. She then developed multiple cranial nerve paresis (meningeal carcinomatosis) after 4 cycles of chemotherapy and died at 4.32 months of follow-up. DISCUSSION AND CONCLUSION: The role of the PET scan was essential to guide us to remove a residue, while two concomitant spinal MRIs were considered negative. We reviewed the 16 cases reported in the literature. Multiple surgeries and radiotherapy seem to be correlated with longer survival. No child younger than 2 years old had a documented survival higher than 4.32 months.

Clinical added value of interictal automated electrical source imaging in the presurgical evaluation of MRI-negative epilepsy: A real-life experience in 29 consecutive patients.

OBJECTIVE: During the presurgical evaluation, manual electrical source imaging (ESI) provides clinically useful information in one-third of the patients but it is time-consuming and requires specific expertise. This prospective study aims to assess the clinical added value of a fully automated ESI analysis in a cohort of patients with MRI-negative epilepsy and describe its diagnostic performance, by evaluating sublobar concordance with stereo-electroencephalography (SEEG) results and surgical resection and outcome. METHODS: All consecutive patients referred to the Center for Refractory Epilepsy (CRE) of St-Luc University Hospital (Brussels, Belgium) for presurgical evaluation between 15/01/2019 and 31/12/2020 meeting the inclusion criteria, were recruited to the study. Interictal ESI was realized on low-density long-term EEG monitoring (LD-ESI) and, whenever available, high-density EEG (HD-ESI), using a fully automated analysis (Epilog PreOp, Epilog NV, Ghent, Belgium). The multidisciplinary team (MDT) was asked to formulate hypotheses about the epileptogenic zone (EZ) location at sublobar level and make a decision on further management for each patient at two distinct moments: i) blinded to ESI and ii) after the presentation and clinical interpretation of ESI. Results leading to a change in clinical management were considered contributive. Patients were followed up to assess whether these changes lead to concordant results on stereo-EEG (SEEG) or successful epilepsy surgery. RESULTS: Data from all included 29 patients were analyzed. ESI led to a change in the management plan in 12/29 patients (41%). In 9/12 (75%), modifications were related to a change in the plan of the invasive recording. In 8/9 patients, invasive recording was performed. In 6/8 (75%), the intracranial EEG recording confirmed the localization of the ESI at a sublobar level. So far, 5/12 patients, for whom the management plan was changed after ESI, were operated on and have at least one-year postoperative follow-up. In all cases, the EZ identified by ESI was included in the resection zone. Among these patients, 4/5 (80%) are seizure-free (ILAE 1) and one patient experienced a seizure reduction of more than 50% (ILAE 4). CONCLUSIONS: In this single-center prospective study, we demonstrated the added value of automated ESI in the presurgical evaluation of MRI-negative cases, especially in helping to plan the implantation of depth electrodes for SEEG, provided that ESI results are integrated into the whole multimodal evaluation and clinically interpreted.

Stereoelectroencephalography Implantation Using Frameless Neuronavigation and Varioguide: Prospective Analysis of Accuracy and Safety in a Case Series of 11 Patients.

BACKGROUND: Stereoencephalography (SEEG) is becoming a widespread diagnostic procedure for drug-resistant epilepsy investigation. Techniques include frame-based and robot-assisted implantation, and more recently, frameless neuronavigated systems (FNSs). Despite its recent use, the accuracy and safety of FNS are still under investigation. OBJECTIVE: To assess in a prospective study the accuracy and safety of a specific FNS use for SEEG implantation. METHODS: Twelve patients who underwent SEEG implantation using FNS (Varioguide [Brainlab]) were included in this study. Data were collected prospectively and included demographic data, postoperative complications, functional results, and implantation characteristics (i.e., duration and number of electrodes). Further analysis included accuracy at entry point and target using measurements of the euclidean distance between planned and actual trajectories. RESULTS: Eleven patients underwent SEEG-FNS implantation from May 2019 to March 2020. One patient did not undergo surgery because of a bleeding disorder. The mean target deviation was 4.06 mm, and mean entry point deviation was 4.2 mm, with insular electrodes significantly more deviated. Results excluding insular electrodes showed a mean target deviation of 3.66 mm and a mean entry point deviation of 3.77 mm. No severe complications occurred; a few mild to moderate adverse events were reported (1 superficial infection, 1 seizure cluster, and 3 transient neurologic impairments). The mean implantation duration by electrodes was 18.5 minutes. CONCLUSIONS: Implantation of depth electrodes for SEEG using FNS seems to be safe, but larger prospective studies are needed to validate these results. Accuracy is sufficient for noninsular trajectories but warrant caution for insular trajectories with statistically significantly less accuracy.

Brain Surgery for Medically Intractable Epilepsy.

This review covers the broad topic of brain surgery in the treatment of pediatric intractable epilepsy. The authors review the latest advancements in the presurgical workup as well as the mandatory tests needed to explore the epilepsy workup in these children. They describe the different types of epilepsy from a surgical standpoint (temporal, extratemporal, multifocal, and hemispheric epilepsies) and various surgical procedures that can be proposed depending on the clinical scenario: lesionectomies, lobectomies, hemispherectomies, neuromodulation, and palliative surgeries. They also describe the key differences of the pediatric patient as compared with the adult patient in such pathologic conditions.

MRI-guided DBS of STN under general anesthesia for Parkinson's disease: results and microlesion effect analysis.

BACKGROUND: The efficacy of the subthalamic nucleus (STN) stimulation for Parkinson's disease has been widely established. The microlesion effect (MLE) due to deep brain stimulation (DBS) electrode implantation has been reputed to be a good predictor for long-term efficacy of the procedure but its analysis in asleep implantation is still unclear. We thus analyzed MLE rate in our strategy of targeting the STN on MRI under general anesthesia and its correlation with our long-term results. METHOD: We retrospectively analyzed 32 consecutive parkinsonian patients implanted with a DBS targeting the STN bilaterally under general anesthesia between October 2013 and December 2020. Targeting was performed after head frame and localizer placement using a stereotactic peroperative robotic 3D fluoroscopy (Artis Zeego, Siemens) fused with preoperative CT and MRI data. We collected intraoperative data, postoperative occurrence of MLE, modification of Unified Parkinson Disease Rating Scale item III (UPDRS III) postoperatively and at subsequent visit, as well as reduction of medication. RESULTS: The mean operative time was 223 min. No permanent complication occurred. MLE was observed in 90.7%. The mean follow-up time was 17 months. The UPDRS III for the off medication/on stimulation condition improved by 64.8% from baseline. The mean dose reduction of Prolopa after the surgical procedure was 31.3%. CONCLUSIONS: Direct targeting of STN under general anesthesia based on preoperative CT and MRI data fused with a preoperative 3D fluoroscopy is safe. It allows for a high rate of postoperative MLE (90.7%) and results in prolonged clinical improvement.

The Anterior Trans-Superior Temporal Gyrus Approach for Selective Amygdalohippocampectomy.

BACKGROUND: Different surgical approaches have been described for selective amygdalohippocampectomy in patients with pharmacoresistant temporal lobe epilepsy. The aim of this study was to report the results of the innovative anterior trans-superior temporal gyrus approach in a single-center series. METHODS: Patients' characteristics, postoperative outcomes, and complications were reviewed in a series of 8 consecutive patients with temporal lobe epilepsy operated on using the anterior trans-superior temporal gyrus approach between November 2015 and April 2017. RESULTS: Over a mean 2.5-year follow-up, 7 of 8 patients (87.5%) remained seizure-free (Engel class I). Only 1 patient (12.5%) was not cured (Engel class III) with no clear explanation for treatment failure. Mean operative time was 237 minutes, which was 80 minutes shorter compared with the classic transsylvian approach. No perioperative deaths were recorded and there were no visual field defects or visual acuity impairments secondary to the approach. One patient experienced a left posterior thalamocapsular stroke. CONCLUSIONS: The anterior trans-superior temporal gyrus approach is feasible, fast, and safe for selective amygdalohippocampectomy in patients with drug-refractory temporal lobe epilepsy. This approach allows preservation of the optic radiation but cuts part of the uncinate fasciculus and potentially the anterior aspect of the anterior bundle of the middle longitudinal fasciculus.

Large Epileptogenic Type IIIb Dysplasia: A Radiological and Anatomopathological Challenge.

BACKGROUND: Type IIIb dysplasia is a subtype of focal cortical dysplasia associated with a tumor, most frequently with gangliogliomas then with dysembryoplastic neuroepithelial tumors (DNETs). Their preoperative diagnosis often remains equivocal since specific features are missing. The functional results (i.e., seizure free) is good with 81%-87% of Engel Ia at 5-year follow-up. CASE DESCRIPTION: A 4-year-old boy presented with a 1-year history of severe, invalidating, drug-resistant epilepsy. Imaging workup demonstrated a huge left limbic lesion, of which diagnosis remained speculative. Because of worsening neurological status, resective surgery was recommended after multidisciplinary discussion. The resection was performed through left transtemporal approach under neuronavigation (C.R.). Postoperative magnetic resonance imaging assessed uncomplicated near-total resection. Histopathological analysis showed combined features of a DNET of nonspecific type and a focal cortical dysplasia. CONCLUSION: We describe a rare condition of type IIIb dysplasia combining a focal cortical dysplasia with a DNET. Preoperative diagnosis of the lesion was of utmost difficultly, thereby rendering mandatory a thorough histopathological examination of resected specimen in the vast majority of cases. Increased recognition of the condition brings up the hypothesis of a genetic continuum or linkage between the 2 conditions. Functional results on seizure activity after ablative surgery are good and maximal safe resection should be the goal.