Publications by authors named "Roy Dudley"

Objective: Cerebral spinal fluid (CSF) diversion methods, including ventriculoperitoneal (VP) shunts, are the standard treatment for hydrocephalus. Hair clipping (HC) has been a routine neurosurgical practice of the great majority of neurosurgeons, due to the perception that this will either decrease the risk of shunt infection or allow for a faster, unimpeded opening and closing of the skin. The benefits of not cutting or clipping hair in terms of normalizing appearance and self-esteem are obvious.

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  • * The authors share a case where a child experienced near-complete spontaneous recovery from progressive cervical spine kyphosis without requiring spinal fusion surgery.
  • * This case highlights the possibility of spontaneous recovery in certain patients and suggests that a cautious monitoring approach could be beneficial for those without neurological deficits, avoiding unnecessary surgical risks.
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  • Recent studies suggest that oligodendrocyte lineage cells show varying functional and molecular characteristics during development and in diseases, notably multiple sclerosis, where grey matter lesions undergo more remyelination than white matter lesions.* -
  • Research comparing progenitor cells and mature oligodendrocytes from grey and white matter revealed that grey matter cells were better at ensheathing synthetic nanofibers and were more vulnerable to metabolic injury, indicating unique molecular profiles between the two types.* -
  • RNA sequencing demonstrated that differences in gene expression are more pronounced between cell types than regions, with grey matter cells showing higher levels of genes important for myelination, while both cell types exhibited up-regulated genes related to stress and injury response.*
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Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.

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Background And Objectives: Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables.

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  • Metformin has the potential to improve the myelination abilities of oligodendrocyte progenitor cells in aged rats and may aid recovery in children with brain injuries from radiation.
  • In experiments, human progenitor cells from both adults and children showed greater ensheathment capacity than mature oligodendrocytes, though metformin enhanced this capacity in adult cells while reducing it in pediatric cells.
  • The study revealed that metformin caused distinct changes in gene expression based on age, with adult cells benefiting in pathways related to growth and lipid synthesis, whereas pediatric cells experienced more down-regulation affecting their morphology and development.
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  • Scientists created a new way to grow special brain cells called microglia from a patient with a rare disease that affects their CSF1R gene.
  • The new method allowed them to produce more healthy microglia-like cells that behave more like natural brain cells, and the cells from the patient showed differences in how they work.
  • They found that the patient’s cells had problems with communication and movement, along with an increased response to inflammation, showing the impact of the faulty CSF1R gene.
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Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter.

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Background: Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype.

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We evaluated the utility of genetic testing in the pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy. This single-center retrospective study reviewed the charts of all pediatric patients referred for epilepsy surgery evaluation over a 5-year period. We extracted and analyzed results of genetic testing as well as clinical, EEG, and neuroimaging data.

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The K channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both and animal models of focal epilepsy. 4AP-induced effects are paralleled by an increase in both excitatory and inhibitory neurotransmitter release, but the mechanisms of action of 4AP on neuronal networks remain unclear. By employing simultaneous whole-cell patch clamp and field potential recordings from hippocampal CA3/4 pyramidal layer of acute brain slices obtained from mice (n = 30), we found that the appearance of epileptiform discharges induced by 4AP (100 μM) is consistently preceded by the transient recurrence of presumptive GABA outward currents, which are not mirrored by any field activity.

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Background And Objectives: Somatic and germline pathogenic variants in genes of the mammalian target of rapamycin (mTOR) signaling pathway are a common mechanism underlying a subset of focal malformations of cortical development (FMCDs) referred to as mTORopathies, which include focal cortical dysplasia (FCD) type II, subtypes of polymicrogyria, and hemimegalencephaly. Our objective is to screen resected FMCD specimens with mTORopathy features on histology for causal somatic variants in mTOR pathway genes, describe novel pathogenic variants, and examine the variant distribution in relation to neuroimaging, histopathologic classification, and clinical outcomes.

Methods: We performed ultra-deep sequencing using a custom HaloPlex Target Enrichment kit in DNA from 21 resected fresh-frozen histologically confirmed FCD type II, tuberous sclerosis complex, or hemimegalencephaly specimens.

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Mer tyrosine kinase (MerTK) is a receptor tyrosine kinase that mediates non-inflammatory, homeostatic phagocytosis of diverse types of cellular debris. Highly expressed on the surface of microglial cells, MerTK is of importance in brain development, homeostasis, plasticity and disease. Yet, involvement of this receptor in the clearance of protein aggregates that accumulate with ageing and in neurodegenerative diseases has yet to be defined.

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Oligodendrocyte (OL) injury and loss are central features of evolving lesions in multiple sclerosis. Potential causative mechanisms of OL loss include metabolic stress within the lesion microenvironment. Here we use the injury response of primary human OLs (hOLs) to metabolic stress (reduced glucose/nutrients) in vitro to help define the basis for the in situ features of OLs in cases of MS.

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Objectives: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy.

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Objective: Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors' knowledge, never been systematically reviewed.

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Background: Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis.

Method: In this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope.

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Background: We investigated the temporal evolution of post-hemorrhagic ventricular dilatation (PHVD) and compared neurodevelopmental impairments (NDI) in newborns with (Group 1) spontaneous resolution of PHVD, (Group 2) persistent PHVD without neurosurgical intervention, and (Group 3) progressive PHVD receiving neurosurgical intervention.

Methods: A multicenter retrospective cohort study of newborns born at ≤34 weeks with PHVD (ventricular index [VI] >97th centile for gestational age and anterior horn width [AHW] >6 mm) from 2012 to 2020. Severe NDI was defined as global developmental delay or cerebral palsy GMFCS III-V at 18 months.

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Purpose: Decompressive craniectomy immediately reduces intracranial pressure by increasing space to accommodate brain volumes. Any delay in reduction of pressure and signs of severe intracranial hypertension requires explanation.

Clinical Features: We present the case of a 13-yr-old boy presenting with a ruptured arteriovenous malformation resulting in a massive occipito-parietal hematoma and increased intracranial pressure (ICP) refractory to medical management.

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Objective: The aim of this study was to characterize a novel pathogenic variant in the transient receptor potential vanilloid 4 (TRPV4) gene, causing familial nonsyndromic craniosynostosis (CS) with complete penetrance and variable expressivity.

Methods: Whole-exome sequencing was performed on germline DNA of a family with nonsyndromic CS to a mean depth coverage of 300× per sample, with greater than 98% of the targeted region covered at least 25×. In this study, the authors detected a novel variant, c.

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Background: Although surgery within the tegmentum of the midbrain is challenging, resection of tegmental pilocytic astrocytomas (PAs) is a standard treatment because this has been shown to outperform chemotherapy and radiotherapy in terms of long-term tumor control. Gross total resection (GTR) assisted by intraoperative neuroelectrophysiological monitoring can be achieved with a reasonable risk-to-benefit ratio, especially for well-circumscribed tumors, but careful scrutiny of magnetic resonance imaging (MRI) is critical to surgical decision making. The authors present two cases of tegmental PAs, which appeared grossly similar on MRI and were operated on via the same surgical approach using the same intraoperative adjuncts.

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  • The study explores how different culture media impact human microglia (hMGL) functions compared to traditional rodent models, revealing that serum-free media can alter their behavior and gene expression.
  • Researchers found that adding fetal bovine serum helps maintain important gene functions related to phagocytosis, while growth factors had minimal impact on the transcriptome.
  • The results indicate that human microglia in culture have distinct characteristics compared to rodent microglia, highlighting the need for improved models to study their role in health and disease.
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Despite the widespread use of intraoperative electrocorticography (iECoG) during resective epilepsy surgery, there are conflicting data on its overall efficacy and inability to predict benefit per pathology. Given the heterogeneity of iECoG use in resective epilepsy surgery, it is important to assess the utility of interictal-based iECoG. This individual patient data (IPD) meta-analysis seeks to identify the benefit of iECoG during resective epilepsy surgery in achieving seizure freedom for various pathologies.

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