A5070197003- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Neuroblastoma Research and Treatments
- RNA Research and Splicing
- Chromatin Remodeling and Cancer
- Pituitary Gland Disorders and Treatments
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Epilepsy research and treatment
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Fetal and Pediatric Neurological Disorders
- Inflammatory Myopathies and Dermatomyositis
- Child and Adolescent Health
- Renal and related cancers
- Mitochondrial Function and Pathology
- Meningioma and schwannoma management
- Sarcoma Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Synthesis and biological activity
- Neonatal and fetal brain pathology
- Autopsy Techniques and Outcomes
Great Ormond Street Hospital for Children NHS Foundation Trust
2016-2025
University College London
2016-2025
Great Ormond Street Hospital
2016-2025
Stichting Epilepsie Instellingen Nederland
2024
University of Amsterdam
2024
Amsterdam Neuroscience
2024
University Medical Center Utrecht
2024
NIHR Great Ormond Street Hospital Biomedical Research Centre
2024
The Francis Crick Institute
2023
Institute of Child Health
2010-2022
Purpose: Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and very frequently associated with epilepsy in both children adults. A broad spectrum histopathology has been included the diagnosis FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities. Methods: Thirty-two Task Force members have reevaluated available data on electroclinical presentation, imaging,...
Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug-resistant temporal lobe epilepsy (TLE). Over past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes postsurgical outcome. However, no international consensus about definitions terminology has achieved. A task force reviewed previous classification schemes proposes a system based on semiquantitative that can be applied...
Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy.We report diagnoses made basis of resected specimens from 9523 patients who underwent epilepsy surgery in 36 centers 12 European countries over 25 years. Histopathological were determined through examination local hospitals (41%) or at German Neuropathology Reference Center Epilepsy Surgery (59%).The onset occurred before 18 years age 75.9%...
Although sepsis is the major cause of mortality and morbidity in critically ill, precise mechanism(s) causing multiorgan dysfunction remain unclear. Findings impaired oxygen utilization septic patients animals implicate nitric oxide-mediated inhibition mitochondrial respiratory chain. We recently reported a relationship between skeletal muscle dysfunction, clinical severity, poor outcome with shock. thus developed long-term, fluid-resuscitated, fecal peritonitis model utilizing male Wistar...
International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic DNA methylomic profiles. These subgroups have distinct clinicopathological features, underpin current disease subclassification initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity differences survival apparent within subgroup,...
Wingless (Wnt)/β-catenin signaling plays an essential role during normal development, is a critical regulator of stem cells, and has been associated with cancer in many tissues. Here we demonstrate that genetic expression degradation-resistant mutant form β-catenin early Rathke's pouch (RP) progenitors leads to pituitary hyperplasia severe disruption the pituitary-specific transcription factor 1-lineage differentiation resulting extreme growth retardation hypopituitarism. Mutant mice mostly...
Abstract Although manganese is an essential trace metal, little known about its transport and homeostatic regulation. Here we have identified a cohort of patients with novel autosomal recessive transporter defect caused by mutations in SLC39A14. Excessive accumulation these results rapidly progressive childhood-onset parkinsonism–dystonia distinctive brain magnetic resonance imaging appearances neurodegenerative features on post-mortem examination. We show that SLC39A14 impair vitro lead to...
Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous (AVM).To investigate the pathogenesis sporadic intracranial extracranial VMs in 160 children which known genetic causes had been excluded, we sequenced DNA from affected tissue optimized...
Human IFNAR2 deficiency causes fatal susceptibility to live viral vaccines.
Background. An 18-month-old boy developed encephalopathy, for which extensive investigation failed to identify an etiology, 6 weeks after stem cell transplant. To exclude a potential infectious cause, we performed high-throughput RNA sequencing on brain biopsy.
The HERBY trial was a phase II open-label, randomized, multicenter evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated pathology, radiology, immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency somatic POLE/POLD1 mutations) those biologically resembling pleomorphic...
Abstract Immune-therapy is an attractive alternative therapeutic approach for targeting central nervous system (CNS) tumors and the constituency of Tumor Immune Microenvironment (TIME) likely to predict patient response. Here, we describe TIME >6000 primarily pediatric CNS using a deconvolution (methylCIBERSORT). We produce validate custom reference signature defining 11 non-cancer cell types estimate relative proportions infiltration in panCNS tumor cohort spanning 80 subtypes. group...
ABSTRACT Proliferation and tangential migration of neural precursor cells are essential determinants CNS development. We have established cell culture models both these processes using grown as neurospheres. The pattern that we observe in is homotypic occurs the absence a glial or neuronal scaffold, therefore equivalent to previously described chain migration. To determine role integrins proliferation migration, analysed expression on neurosphere then performed blocking peptide antibody...
We report the clinical, genetic, and neuropathological findings of a seven generation-spanning pedigree with 196 individuals, 25 whom had levodopa-responsive parkinsonism. Genetic analyses indicated Parkin mutations in 77 subjects. Among patients, 5 carried compound heterozygous met criteria for definite Parkinson's disease (PD) according to UK PD Society Brain Bank guidelines; 8 subjects only mutation. The mutational status five deceased patients was unknown, no Survival showed significant...
OBJECTIVE To compare PGP9.5 and transient receptor potential vanilloid (TRPV1) suburothelial immunoreactivity between controls patients with spinal neurogenic detrusor overactivity (NDO) before after treatment intravesical resiniferatoxin, as PGP9.5‐staining nerve fibres decrease in NDO who respond to capsaicin, TRPV1 is present on these normal overactive human urinary bladder. PATIENTS AND METHODS Patients refractory were enrolled a prospective, randomized, parallel‐group, double‐blind,...
Objectives Most published articles are not cited and citation rates depend on many variables. We hypothesized that specific features of journal titles may be related to rates. Design reviewed the title characteristics 25 most least in 2005 general specialist medical journals including Lancet, BMJ Journal Clinical Pathology. The length construction were correlated number times papers have been May 2009. Setting Retrospective review a scientific database. Participants None. Main outcome...
Dravet syndrome is an epilepsy of infantile onset, frequently caused by SCN1A mutations or deletions.Its prevalence, long-term evolution in adults and neuropathology are not well known.We identified a series 22 adult patients, including three post-mortem cases with syndrome.For all we reviewed the clinical history, seizure types frequency, antiepileptic drugs, cognitive, social functional outcome results investigations.A systematic study was performed, material from syndrome, comparison...
A variety of analyses, including fluorescence in situ hybridization (FISH), quantitative PCR (qPCR) and array CGH (aCGH), have been performed on a series chordomas from 181 patients. Twelve (7%) tumours displayed amplification the T locus an additional two cases showed focal amplification; 70/181 (39%) were polysomic for chromosome 6, 8/181 (4.5%) primary minor allelic gain as assessed by FISH. No germline alteration was identified non-neoplastic tissue 40 Copy number seen similar percentage...