The availability and integration of electrophysiological and molecular data from the living brain is critical to understand and diagnose complex human disease. Intracranial stereo electroencephalography (SEEG) electrodes used for identifying the seizure focus on epilepsy patients could enable the integration of such multimodal data. Here, we report MoPEDE (Multimodal Profiling of Epileptic Brain Activity via Explanted Depth Electrodes), a method that recovers extensive protein-coding transcripts, including cell-type markers, DNA methylation and short variant profiles from explanted SEEG electrodes matched with electrophysiological and radiological data allowing for high-resolution reconstructions of brain structure and function.
View Article and Find Full Text PDFBackground: Breast cancer brain metastasis is a rising occurrence, necessitating a better understanding of the mechanisms involved for effective management. Breast cancer brain metastases diverge notably from the primary tumor, with gains in kinase and concomitant losses of steroid signaling observed. In this study, we explored the role of the kinase receptor RET in promoting breast cancer brain metastases and provide a rationale for targeting this receptor.
View Article and Find Full Text PDFObjective: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy.
Methods: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy.
Here, we establish a CT-radiomics based method for application in invasive, orthotopic rodent brain tumour models. Twenty four NOD/SCID mice were implanted with U87R-Luc2 GBM cells and longitudinally imaged via contrast enhanced (CE-CT) imaging. Pyradiomics was employed to extract CT-radiomic features from the tumour-implanted hemisphere and non-tumour-implanted hemisphere of acquired CT-scans.
View Article and Find Full Text PDFObjective: Refractory idiopathic generalised epilepsy (IGE; also known as genetic generalised epilepsy) is a clinical challenge due to limited available therapeutic options. While vagus nerve stimulation (VNS) is approved as an adjunctive treatment for drug-resistant focal epilepsy, there is limited evidence supporting its efficacy for refractory IGE.
Methods: We conducted a single-centre retrospective analysis of adult IGE patients treated with VNS between January 2003 and January 2022.
Background: Glioblastoma (GBM) is an aggressive brain cancer that typically results in death in the first 15 months after diagnosis. There have been limited advances in finding new treatments for GBM. In this study, we investigated molecular differences between patients with extremely short (≤ 9 months, Short term survivors, STS) and long survival (≥ 36 months, Long term survivors, LTS).
View Article and Find Full Text PDFMalignant gliomas are a type of primary brain tumour that originates in glial cells. Among them, glioblastoma multiforme (GBM) is the most common and the most aggressive brain tumour in adults, classified as grade IV by the World Health Organization. The standard care for GBM, known as the Stupp protocol includes surgical resection followed by oral chemotherapy with temozolomide (TMZ).
View Article and Find Full Text PDFThe surgical management of brainstem glioma is challenging and has significant morbidity. Advances in surgical armamentarium has presented the opportunity to tackle these lesions. We present the case of a paediatric patient with a 2.
View Article and Find Full Text PDFBackground: The surgical management of deep brain lesions is challenging, with significant morbidity. Advances in surgical technology have presented the opportunity to tackle these lesions.
Methods: We performed a complete resection of a thalamic/internal capsule CM using a tubular retractor system via a parietal trans-sulcal para-fascicular (PTPF) approach without collateral injury to the nearby white matter tracts.
Glioblastoma (GBM), a highly invasive and vascular malignancy is shown to rapidly develop resistance and evolve to a more invasive phenotype following bevacizumab (Bev) therapy. Rho Guanine Nucleotide Exchange Factor proteins (RhoGEFs) are mediators of key components in Bev resistance pathways, GBM and Bev-induced invasion. To identify GEFs with enhanced mRNA expression in the leading edge of GBM tumours, a cohort of GEFs was assessed using a clinical dataset.
View Article and Find Full Text PDFSpontaneous extensive spinal epidural haematoma poses a unique challenge for the neurosurgeon. Performing extensive laminectomies to remove all of the compressive haematoma can destabilise the patient's spinal column, which may require fixation. This is further complicated in patients with significant coagulopathy.
View Article and Find Full Text PDFDNMT3A codes for a DNA methyl transferase enzyme that plays a central role embryogenesis. Somatic mutations in this gene have been associated with tumorigenesis and are associated with a number of cancers. The recently described Tatton-Brown-Rahman syndrome (TBRS) is due to heterozygous germline mutations in the DNMT3A gene.
View Article and Find Full Text PDFBackground: Postnatal closure of a myelomeningocele remains the standard of care in many countries. The prenatal closure has given hope for decreasing the damage to the neural placode and has challenged classic management. However, this technique presents potential sources of complications.
View Article and Find Full Text PDFIntroduction: Grade II and III intramedullary ependymomas [IME] are circumscribed with a plane of cleavage that should facilitate high gross total resection rates (GTR). Gross total resection of grade II/III IME is superior to subtotal resection (STR) and radiotherapy (RTx) for progression-free and overall survival. We sought to compare our GTR with other series that have utilised standard intraoperative monitoring techniques and we explored factors that may influence rates of resection.
View Article and Find Full Text PDFIsolated intracranial Rosai-Dorfman Disease is rare. Here, we describe a patient who developed an asymptomatic, right parietal RDD lesion over 18 months while being followed radiographically for another brain lesion. To our knowledge, rapid, de novo radiographic formation of isolated intracranial RDD has never been reported in an asymptomatic patient.
View Article and Find Full Text PDFBackground: Glioblastoma (GBM) is the most common and malignant primary brain tumour having a median survival of just 12-18 months following standard therapy protocols. Local recurrence, post-resection and adjuvant therapy occurs in most cases.
New Method: U87MG-luc2-bearing GBM xenografts underwent 4.
Current therapeutic strategies against glioblastoma (GBM) have failed to prevent disease progression and recurrence effectively. The part played by molecular imaging (MI) in the development of novel therapies has gained increasing traction in recent years. For the first time, using expertise from an integrated multidisciplinary group of authors, herein we present a comprehensive evaluation of state-of-the-art GBM imaging and explore how advances facilitate the emergence of new treatment options.
View Article and Find Full Text PDFObject: McLone and Knepper's unified theory of Chiari malformation Type II (CM-II) describes how the loss of CSF via the open posterior neuropore fails to create adequate distending pressure for the developing rhomboencephalic vesicle. The authors of the present article describe the relationship between the posterior fossa volume and intracranial cerebellar volume as being related to the distance from the obex of the fourth ventricle to the myelomeningocele lesion using a common mathematical model, the Hagen-Poiseuille law.
Methods: All newborns who required closure of a myelomeningocele at the authors' institution between 2008 and 2011 and who were between 4 weeks premature and 2 months, corrected gestational age, at the time of MRI were included in this study.