Deep brain stimulation in critical care conditions.

Some neurological conditions require admission to an intensive care unit (ICU) where deep sedation and mechanical ventilation are administered to improve the patient's condition. Nevertheless, these treatments are not always helpful in disease control. At this stage, deep brain stimulation (DBS) could become a viable alternative in the treatment of critical neurological conditions with long-lasting clinical benefit. The value of deep brain stimulation has been investigated in the treatment of patients who had undergone surgical electrode implants as an emergency procedure to treat acute life-threatening conditions requiring admission to neurological ICU (NICU). A before-and-after perspective study was examined of seven patients who were treated with DBS for status dystonicus (SD) and post-stroke severe hemiballismus. Bilateral globus pallidus internus (GPi) DBS was performed in five SD patients and unilateral ventralis oralis anterior and posterior (Voa/Vop) nucleus of the thalamus DBS in two post-stroke hemiballismus patients. Bilateral GPi-DBS allowed SD resolution in a time lapse varying from 1 week to 3 months. No clear improvements compared to the baseline clinical condition were observed. Unilateral Voa/Vop-DBS intervention controlled hemiballismus after 10 h, and the patient was discharged in 2 days. The other patient was transferred from the NICU to the neurosurgery ward after 13 days. No surgical complications were observed in any of the above procedures. Neurostimulation procedures could represent a valuable choice in critical care conditions, when involuntary movements are continuous, life-threatening and refractory to intensive care procedures. DBS is feasible, safe and effective in selected cases.

Putting our heads together: The future of craniopagus twin separation.

Computer-assisted design and computer-assisted modeling (CAD/CAM), virtual surgical planning (VSP) and augmented/virtual reality (AR/VR) aid our ability to plan and perform complex craniofacial procedures. This study seeks to define the role of the aforementioned techniques in the separation of craniopagus conjoined twins. Six teams were identified who had successfully performed craniopagus twin separation with the use of CAD/CAM, VSP and/or AR/VR. Surgeons involved in separating craniopagus twins have increasingly utilized tools such as CAD/CAM models, VSP and AR/VR to plan and execute successful separation, and these tools are associated with higher success rates than historical controls.

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.

Vertical Hemispherotomy: Contribution of Advanced Three-Dimensional Modeling for Presurgical Planning and Training.

Vertical hemispherotomy is an effective treatment for many drug-resistant encephalopathies with unilateral involvement. One of the main factors influencing positive surgical results and long-term seizure freedom is the quality of disconnection. For this reason, perfect anatomical awareness is mandatory during each step of the procedure. Although previous groups attempted to reproduce the surgical anatomy through schematic representations, cadaveric dissections, and intraoperative photographs and videos, a comprehensive understanding of the approach may still be difficult, especially for less experienced neurosurgeons. In this work, we reported the application of advanced technology for three-dimensional (3D) modeling and visualization of the main neurova-scular structures during vertical hemispherotomy procedures. In the first part of the study, we built a detailed 3D model of the main structures and landmarks involved during each disconnection phase. In the second part, we discussed the adjunctive value of augmented reality systems for the management of the most challenging etiologies, such as hemimegalencephaly and post-ischemic encephalopathy. We demonstrated the contribution of advanced 3D modeling and visualization to enhance the quality of anatomical representation and interaction between the operator and model according to a surgical perspective, optimizing the quality of presurgical planning, intraoperative orientation, and educational training.

Magnetic resonance imaging based neurosurgical planning on hololens 2: A feasibility study in a paediatric hospital.

Objective: The goal of this work is to show how to implement a mixed reality application (app) for neurosurgery planning based on neuroimaging data, highlighting the strengths and weaknesses of its design. Methods: Our workflow explains how to handle neuroimaging data, including how to load morphological, functional and diffusion tensor imaging data into a mixed reality environment, thus creating a first guide of this kind. Brain magnetic resonance imaging data from a paediatric patient were acquired using a 3 T Siemens Magnetom Skyra scanner. Initially, this raw data underwent specific software pre-processing and were subsequently transformed to ensure seamless integration with the mixed reality app. After that, we created three-dimensional models of brain structures and the mixed reality environment using Unity™ engine together with Microsoft® HoloLens 2™ device. To get an evaluation of the app we submitted a questionnaire to four neurosurgeons. To collect data concerning the performance of a user session we used Unity Performance Profiler. Results: The use of the interactive features, such as rotating, scaling and moving models and browsing through menus, provided by the app had high scores in the questionnaire, and their use can still be improved as suggested by the performance data collected. The questionnaire's average scores were high, so the overall experiences of using our mixed reality app were positive. Conclusion: We have successfully created a valuable and easy-to-use neuroimaging data mixed reality app, laying the foundation for more future clinical uses, as more models and data derived from various biomedical images can be imported.

Successful staged separation of total angular craniopagus.

BACKGROUND: Total craniopagus is an exceedingly rare condition in which surgical treatment is complex and potentially fatal. Over the last decades, a multistep surgical approach, which allows development of venous collateral circulation, has fostered a dramatic improvement of successful separation rates and neurological outcomes. Most of the experience derives from management of vertical craniopagus, the angular form being rarer and less amenable to successful surgical separation. METHODS: We present a case of total angular craniopagus twins observed at our Institution. Specific features included a large occipital fusion area with a bone defect, complete separation of brain and arterial vessels and a complex configuration of dural venous sinuses. The superior sagittal sinus of each twin preferentially drained to a single transverse sinus through a shared torcular. RESULTS: After an extensive diagnostic phase, including neuroimaging, tridimensional and virtual reality modelling, neurological, neurophysiological and rehabilitation assessment, a detailed multistep surgical plan, was proposed to a wide multidisciplinary team. The venous system was managed by taking advantage of the fact each twin's superior sagittal sinus was drained preferentially by the transverse sinus on the twin's left. The transverse sinuses were thus separated accordingly. CONCLUSIONS: Successful separation was achieved in three surgical steps over one year, with an excellent outcome for both twins.

Surgical management of pediatric intracranial CCM: a 10-year single center experience.

BACKGROUND: Cerebral cavernous malformations (CCMs) are low-flow vascular malformations made up of dilated vascular spaces without intervening parenchyma that can occur throughout the central nervous system. CCMs can occur sporadically or in familial forms. Presentation is diverse, ranging from asymptomatic discoveries to drug-resistant epilepsy and hemorrhages. METHODS: We describe the surgical management of CCMs in pediatric patients at Bambino Gesù Children's Hospital in Rome over the last 10 years. The cases have been stratified based on the clinical presentation and the relevant literature is discussed accordingly. RESULTS: We discuss the rationale and technique used in these cases based on their presentation, as well as the generally positive outcomes we achieved with early surgical management, use of intra-operative ultrasound (ioUS) and intraoperative neuromonitoring. CONCLUSIONS: Surgical management of pediatric CCMs is a safe and effective strategy, low rates of postoperative morbidity and partial resection were observed.

The inferior fronto-occipital fascicle: a century of controversies from anatomy theaters to operative neurosurgery.

Since its first description in the early 19th century, the inferior fronto-occipital fascicle (IFOF) and its anatomo-functional features were neglected in the neuroscientific literature for the last century. In the last decade, the rapid development of in-vivo imaging for the reconstruction of white matter (WM) connectivity (i.e., tractography) and the consequent interest in more traditional ex vivo methods (post-mortem dissection) have allowed a renewed debate about course, termination territories, anatomical relationships, and functional roles of this fascicle. We reviewed the main current knowledge concerning the structural and functional anatomy of the IFOF and possible implications in neurosurgical practice. The IFOF connects the occipital cortex, the temporo-basal areas, the superior parietal lobule, and the precuneus to the frontal lobe, passing through the ventral third of subinsular WM of the external capsule. This wide distribution of cortical terminations provides multimodal integration between several functional networks, including language, non-verbal semantic processing, object identification, visuo-spatial processing and planning, reading, facial expression recognition, memory and conceptualization, emotional and neuropsychological behavior. This anatomo-functional organization has important implication also in neurosurgical practice, especially when approaching the frontal, insular, temporo-parieto-occipital regions and the ventricular system. In conclusion, the IFOF is the most extensive associative bundle of the human connectome. Its multi-layer organization reflects important implications in many aspects of brain functional processing. Accurate awareness of IFOF functional anatomy and integration between multimodal datasets coming from different sources has crucial implications for both neuroscientific knowledge and quality of neurosurgical treatments.

The molecular landscape of glioma in patients with Neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of patients. The pattern of genetic and epigenetic alterations of glioma that develops in NF1 patients and the similarities with sporadic glioma remain unknown. Here, we present the molecular landscape of low- and high-grade gliomas in patients affected by NF1 (NF1-glioma). We found that the predisposing germline mutation of the NF1 gene was frequently converted to homozygosity and the somatic mutational load of NF1-glioma was influenced by age and grade. High-grade tumors harbored genetic alterations of TP53 and CDKN2A, frequent mutations of ATRX associated with Alternative Lengthening of Telomere, and were enriched in genetic alterations of transcription/chromatin regulation and PI3 kinase pathways. Low-grade tumors exhibited fewer mutations that were over-represented in genes of the MAP kinase pathway. Approximately 50% of low-grade NF1-gliomas displayed an immune signature, T lymphocyte infiltrates, and increased neo-antigen load. DNA methylation assigned NF1-glioma to LGm6, a poorly defined Isocitrate Dehydrogenase 1 wild-type subgroup enriched with ATRX mutations. Thus, the profiling of NF1-glioma defined a distinct landscape that recapitulates a subset of sporadic tumors.

Safety and efficacy of Endoscopic Third Ventriculostomy in Diffuse Intrinsic Pontine Glioma related hydrocephalus: a Systematic Review.

OBJECT: Diffuse Intrinsic Pontine Gliomas (DIPG) related hydrocephalus occurs as the result of tumor growth and Aqueduct obstruction. There is no consensus about the best surgical option, thus a review has been performed to clarify the rate of success, complications and possible issues of Endoscopic Third Ventriculostomy (ETV) in comparison to the other available techniques. METHODS: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and it was registered with the PROSPERO International Prospective Register of Systematic Reviews(CRD42018089001). MEDLINE, Web of Knowledge and EMBASE were searched for published series in which ETV was performed to treat hydrocephalus in DIPG patients. RESULTS: Six studies were included. Two further cases coming from our experience were added, for a total amount of 55 patients treated through either ETV, VPS or Ventriculocisternal shunt according to Torkildsen. 86% of patients who underwent ETV experienced clinical improvement after surgery (p-value 0.03). Torkildsen shunt placement was associated to 50% failure rate. Two patients implanted with VPS developed symptoms of shunt malfunction and increased ventricular sizes (10%). Fisher's exact test was applied to compare efficacy of VPS and ETV with no statistical difference between the two group (p-value 0,17). Patients who underwent ETV did not experienced major complications and no procedural abortion was observed. CONCLUSIONS: ETV is an effective and safe treatment option, associated to a low complications rate and a high success rate. Evidences from this review suggest to consider ETV as the first line treatment of hydrocephalus in DIPG patients.

Production and post-surgical modification of VEGF, tPA and PAI-1 in patients with glioma.

Malignant gliomas are associated with risk of thromboembolism, but the molecular link between tumor and peripheral pro-coagulant status has not been elucidated. Vascular Endothelial Growth Factor (VEGF), tissue-type Plasminogen Activator (tPA), Plasminogen Activator Inhibitor-1 (PAI-1) and lipoprotein (lp) (a) influence the pro-coagulant status. To assess whether the presence of the tumor influenced the peripheral levels of VEGF, tPA, PAI-1 and lp(a), we studied the expression and secretion of VEGF, tPA, PAI-1 and lp(a) in glioma specimens, in peripheral blood and in primary glioma-derived cultures. We also measured lp(a), VEGF, tPA and PAI-1 in the peripheral circulation of patients, before and after surgery for glioma. VEGF, tPA and PAI-1 were expressed in glioma specimens. Glioma cells were indeed a major source of tPA and PAI-1; these molecules were significantly more expressed in glioma than in patient's blood cells. Lp(a) was rarely expressed in glioma specimens and not expressed in blood cells. In glioma, VEGF, tPA and PAI-1 were localized mainly in tumor cells; tPA was localized also in the extracellular matrix and PAI-1 in tumor vascular lumen. Glioma cells were indeed able to produce and release VEGF, tPA and PAI-1. After surgery, peripheral levels of VEGF and PAI-1 were increased, while tPA and lp(a) were unchanged. The great amount of VEGF, tPA and PAI-1 produced by glioma could influence peripheral levels of these molecules. The partial resection of the tumor by surgery was not able to decrease plasma levels of these molecules.

Hemiconvulsion-Hemiplegia-Epilepsy syndrome associated with inflammatory-degenerative hystopathological findings in child with congenital adrenal hyperplasia.

Hemiconvulsion-Hemiplegia (HH) syndrome represents an uncommon consequence of prolonged unilateral clonic or hemiconvulsive status epilepticus in childhood, usually occurring during a febrile illness, followed by ipsilateral hemiplegia. The subsequent appearance of focal seizures configures the so called Hemiconvulsion-Hemiplegia-Epilepsy (HHE) syndrome. The pathogenesis of HH/HHE syndrome is still unclear. We describe the case of a 4 year-old girl with congenital adrenal hyperplasia (CAH) whom developed HH/HHE syndrome with drug resistant seizures at the age of 21 months and underwent left cerebral hemispherotomy at the age of 3 years and 6 months. Histopathological findings showed the presence of an underlying inflammatory-degenerative process. Disregulation of the inflammatory cascade has been proposed as one of the possible pathogenetic mechanisms underlying HH/HHE syndrome. To our knowledge however, this is the first report of an association with a histologically documented inflammatory process. The clinical and histopathological findings of our reported case lend support to the possible role of inflammation in the pathogenesis of HH/HHE syndrome.