Histopathological characterization of cerebral small vessel disease in epilepsy patients with temporal lobe epilepsy submitted to surgery: A case-control study.

BACKGROUND: Cerebrovascular disease (CVD) is a major contributor to epilepsy; however, patients with epilepsy also have a significantly increased risk of stroke. The way in which epilepsy contributes to the increased risk of stroke is still uncertain and is ill-characterized in neuropathological studies. A neuropathological characterization of cerebral small vessel disease (cSVD) in patients with chronic epilepsy was performed. METHODS: Thirty-three patients with refractory epilepsy and hippocampal sclerosis (HS) submitted to epilepsy surgery from a reference center were selected between 2010 and 2020 and compared with 19 autopsy controls. Five randomly selected arterioles from each patient were analyzed using a previously validated scale for cSVD. The presence of CVD disease imaging markers in pre-surgical brain magnetic resonance imaging (MRI) was studied. RESULTS: There were no differences in age (43.8 vs. 41.6 years; p = 0.547) or gender distribution (female gender 60.6% vs. male gender 52.6%; p = 0.575) between groups. Most CVD findings in brain MRI were mild. Patients had a mean time between the epilepsy onset and surgery of 26 ± 14.7 years and were medicated with a median number of three antiseizure medication (ASMs) [IQR 2-3]. Patients had higher median scores in arteriolosclerosis (3 vs. 1; p < 0.0001), microhemorrhages (4 vs. 1; p < 0.0001) and total score value (12 vs. 8.9; p = 0.031) in comparison with controls. No correlation was found between age, number of years until surgery, number of ASMs or cumulative defined daily dosage of ASM. CONCLUSION: The present study provides evidence supporting the increased burden of cSVD in the neuropathological samples of patients with chronic epilepsy.

Anterior Nucleus of Thalamus Deep Brain Stimulation: A Clinical-Based Analysis of the Ideal Target in Drug-Resistant Epilepsy.

INTRODUCTION: Deep brain stimulation of the anterior nucleus of thalamus (ANT-DBS) is an approved procedure for drug-resistant epilepsy. However, the preferred location inside ANT is not well known. In this study, we investigated the relationship between stereotactical coordinates of stimulated contacts and clinical improvement, in order to define the ideal target for ANT-DBS. METHODS: Individual contact's coordinates were obtained in the Montreal Neurological Institute (MNI) 152 space, with the utilization of advanced normalization tools and co-registration of pre- and postoperative MRI and CT images in open-source toolbox lead-DBS with the "Atlas of the Human Thalamus." Each contact's pair was either classified as a responder (≥50% seizure reduction and absence of intolerable adverse effects) or nonresponder, with a minimum follow-up of 11 continuous months of stimulation. RESULTS: A total of 19 contacts' pairs were tested in 14 patients. The responder rate was 9 out of 14 patients (64.3%). In 4 patients, a change in contacts' pairs was needed to achieve this result. A highly encouraging location inside ANT (HELIA) was delimited in MNI space, corresponding to an area in the anterior and inferior portion of the anteroventral (AV) nucleus, medially to the endpoint of the mammillothalamic tract (ANT-mtt junction) (x [3.8; 5.85], y [-2.1; -6.35] and z [6.2; 10.1] in MNI space). Statistically significant difference was observed between responders and nonresponders, in terms of the number of coordinates inside this volume. Seven responders and two nonresponders had at least 5 of 6 coordinates (2 electrodes) inside HELIA (77.8% sensitivity and 80% specificity). In 3 patients, changing to contacts that were better placed inside HELIA changed the status from nonresponder to responder. CONCLUSIONS: A relationship between stimulated contacts' coordinates and responder status was observed in drug-resistant epilepsy. The possibility to target different locations inside HELIA may help surpass anatomical variations and eventually obtain increased clinical benefit.

Functional hemispheric disconnection procedures for chronic epilepsy: history, indications, techniques, complications and current practice in Europe. A consensus statement on behalf of the EANS functional neurosurgery section.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

Tricellulin expression in brain endothelial and neural cells.

Tricellulin is a tight junction (TJ) protein, which is not only concentrated at tricellular contacts but also present at bicellular contacts between epithelial tissues. We scrutinized the brain for tricellulin expression in endothelial and neural cells by using real-time polymerase chain reaction, Western blot and immunohistochemical and immunocytochemical analysis of cultured brain cells and paraffin sections of brain. Tricellulin mRNA was detected in primary cultures and in a cell line of human brain microvascular endothelial cells. Protein expression was confirmed by Western blot and immunofluorescence analysis, which further highlighted the localization of tricellulin in the cell membrane at tricellular and along bicellular contacts, and in the nucleus and perinuclear region. Compared with the well-studied TJ protein, zonula occludens-1, tricellulin expression was less marked at the cell membrane but more evident in the nuclear and perinuclear regions. The presence of tricellulin in cultured endothelial cells was corroborated by immunohistochemical and immunofluorescence staining in brain blood vessels, where it was colocalized with another TJ protein, claudin-5. Tricellulin mRNA was detected in neurons and astrocytes, whereas protein expression was observed in astrocytes but not in neurons, as shown by immunofluorescence analysis. This study reveals the presence and subcellular distribution of tricellulin in brain endothelial cells, both in vitro and in situ and its colocalization with other relevant TJ proteins. Moreover, it demonstrates the expression of the protein in astrocytes opening new avenues for future research to establish the biological significance of tricellulin expression in glial cells.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe.

Background: People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients' well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe. Methods: An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan. Results: Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase. Conclusion: We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents' opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Intraventricular Ganglioglioma Presenting with Spontaneous Hemorrhage.

Intraventricular gangliogliomas presenting with spontaneous hemorrhage are rare. Due to high density of important tracts lateral to the ventricular atrium, the intraparietal trans sulcal approach is a good option to remove lesions in this location. These tracts are displaced and sometimes destroyed by the presence of large masses. A 33-year-old male presented with a sudden headache and a generalized seizure. He had a left visual field hemianopia and left visual field neglect. Brain computer tomography and magnetic resonance imaging revealed a hemorrhagic tumor located in his right atrium. With the help of tractography an optimal corridor to the tumor through the intraparietal sulcus was planned. Gross total removal of a ganglioglioma was possible with recovery of visual impairment and control of epilepsy. The efficacy in using tractography as a planning tool for safe tumor removal is demonstrated with clinical, imagiological and histological data, and a surgical video.

Os gangliogliomas Intraventriculares com hemorragia espontânea são raros. Devido à densidade elevada de tractos importantes localizados lateralmente ao átrio ventricular, o sulco intraparietal é a via preferencial de acesso para remoção de lesões nesta localização. Um homem de 33 anos recorreu à urgência por cefaleia súbita e crise tónico-clónica generalizada. No exame neurológico, apresentava hemianopsia homónima esquerda e negligência visual esquerda. Realizou tomografia computorizada cranioencefálica e ressonância magnética que revelaram lesão ocupando espaço com hemorragia, localizada no átrio do ventrículo lateral direito. O estudo por tractografia permitiu estabelecer o corredor ideal de acesso ao tumor através do sulco intraparietal. A remoção total do ganglioglioma foi possível sem instalação de défices e com recuperação do défice visual e controle das crises epilépticas. A eficácia do uso da tractografia como ferramenta de planeamento para remoção segura de tumores é aqui apresentada com detalhes clínicos, neurorradiológicos, neuropatológicos e um vídeo cirúrgico.

Stimulation of the bilateral anterior nuclei of the thalamus in the treatment of refractory epilepsy: two cases of subcortical band heterotopia.

Subcortical band heterotopia is a neuronal migration disorder that may cause refractory epilepsy. In these patients, resective surgery has yielded inadequate results. Deep brain stimulation of the anterior nuclei of the thalamus has been used for the treatment of refractory epilepsy with good results. We describe the first two patients with subcortical band heterotopia who were submitted to deep brain stimulation of the anterior nuclei of the thalamus, with evaluation of seizure outcome after 12 and 18 months of follow-up. At these times, both showed a >50% decrease in seizure frequency and an increase in seizure freedom. Both patients had a depressive syndrome after surgery that responded fully to anti-depressive medication in one patient and partly in the other. In both, deep brain stimulation of the anterior nuclei of the thalamus was associated with good seizure outcome. This procedure can therefore be considered in the treatment of patients with subcortical band heterotopia and refractory epilepsy. Depression may be a transient adverse event of the surgery or stimulation, however, its aetiology is probably multifactorial.

Amygdalohippocampotomy: surgical technique and clinical results.

OBJECT: The removal of mesial temporal structures, namely amygdalohippocampectomy, is the most efficient surgical procedure for the treatment of epilepsy. However, disconnection of the epileptogenic zones, as in temporal lobotomy or, for different purposes, hemispherotomy, have shown equivalent results with less morbidity. Thus, authors of the present study began performing selective amygdalohippocampotomy in cases of refractory mesial temporal lobe epilepsy (TLE) to treat mesial temporal lobe sclerosis (MTLS). METHOD: The authors conducted a retrospective analysis of all cases of amygdalohippocampotomy collected in a database between November 2007 and March 2011. RESULTS: Since 2007, 21 patients (14 males and 7 females), ages 20-58 years (mean 41 years), all with TLE due to MTLS, were treated with selective ablation of the lateral amygdala plus perihippocampal disconnection (anterior one-half to two-thirds in dominant hemisphere), the left side in 11 cases and the right in 10. In 20 patients the follow-up was 2 or more years (range 24-44 months, average 32 months). Clinical outcome for epilepsy 2 years after surgery (20 patients) was good/very good in 19 patients (95%) with an Engel Class I (15 patients [75%]) or II outcome (4 patients [20%]) and bad in 1 patient (5%) with an Engel Class IV outcome (extratemporal focus and later reoperation). Surgical morbidity included hemiparesis (capsular hypertensive hemorrhage 24 hours after surgery, 1 patient), verbal memory worsening (2 patients), and quadrantanopia (permanent in 2 patients, transient in 1). Late psychiatric depression developed in 3 cases. Operative time was reduced by about 30 minutes (15%) on average with this technique. CONCLUSIONS: Amygdalohippocampotomy is as effective as amygdalohippocampectomy to treat MTLS and is a potentially safer, time-saving procedure.