RET overexpression leads to increased brain metastatic competency in luminal breast cancer.

Background: 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.

Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.

Objective: 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.

Immunoproteasome deficiency results in age-dependent development of epilepsy.

The immunoproteasome is a central protease complex required for optimal antigen presentation. Immunoproteasome activity is also associated with facilitating the degradation of misfolded and oxidized proteins, which prevents cellular stress. While extensively studied during diseases with increasing evidence suggesting a role for the immunoproteasome during pathological conditions including neurodegenerative diseases, this enzyme complex is believed to be mainly not expressed in the healthy brain.

CPEB4-CLOCK crosstalk during temporal lobe epilepsy.

Objective: Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large-scale changes in mRNA polyadenylation in the hippocampus of mice during epilepsy development.

Comparative analysis of deeply phenotyped GBM cohorts of 'short-term' and 'long-term' survivors.

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).

Primary CNS EBV-positive post-transplant lymphoproliferative disorder with polymorphic and classic Hodgkin lymphoma features: A case report and literature review.

Post-transplant lymphoproliferative disorders (PTLD) are typically Epstein-Barr virus (EBV)-associated lymphoid or plasmacytic proliferations that occur when immunosuppressed after transplantation. Only 2 cases of primary central nervous system (PCNS) classic Hodgkin lymphoma PTLD and 1 case of PCNS Hodgkin lymphoma-like PTLD have been previously reported. A 59-year-old male presented with malaise, headaches, and dizziness; neuroimaging revealed a 1.

Brain biopsy in neurological disease of unknown etiology: A single-center 12-year retrospective analysis.

There are no international guidelines for brain biopsy in neurological disease of unknown etiology, yet most practicing neurologists will encounter difficult cases in which biopsy is considered. This patient cohort is heterogenous, and it is unclear in which circumstances biopsy is most useful. We performed an audit of brain biopsies reviewed in our neuropathology department from 2010 to 2021.

Establishing a committee for antemortem reviews of suspect Creutzfeldt-Jakob disease cases in Ireland.

Background: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, neurodegenerative disease. In Ireland, clinical diagnostics and laboratory testing remain the responsibility of the managing clinician and the Neuropathology Department at the Beaumont Hospital, respectively. Centralized review of individual cases is not undertaken.

MicroRNA inhibition using antimiRs in acute human brain tissue sections.

Antisense inhibition of microRNAs is an emerging preclinical approach to pharmacoresistant epilepsy. A leading candidate is an "antimiR" targeting microRNA-134 (ant-134), but testing to date has used rodent models. Here, we develop an antimiR testing platform in human brain tissue sections.

Microvascular stabilization via blood-brain barrier regulation prevents seizure activity.

Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB dysfunction remain to be elucidated. Tight junction proteins are important regulators of BBB integrity and in particular, the tight junction protein claudin-5 is the most enriched in brain endothelial cells and regulates size-selectivity at the BBB. Additionally, disruption of claudin-5 expression has been implicated in numerous disorders including schizophrenia, depression and traumatic brain injury, yet its role in epilepsy has not been fully deciphered.

Ondine's Curse in Frontotemporal Dementia with Parkinsonism Linked to Chromosome 17 Caused by Variants.

Background: "Ondine's curse" or central hypoventilation, induces an apparently spontaneous failure of automatic respiratory drive, henceforth necessitating a conscious effort to breathe and sleep induced hypoventilation. It is typically seen in congenital central hypoventilation syndrome, but may be acquired.

Objectives: To highlight Ondine's curse as part of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) secondary to microtubule associated protein tau () variants.

A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene.

We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We describe the clinical spectrum within this family and emphasize the association between MAPT gene variants and motor neuron disease.

Melanoma brain metastases in Ireland: surgical and systemic considerations.

Background: Cerebral metastases is a common complication in patients with melanoma. There is a paucity of information in the Republic of Ireland regarding the factors associated with melanoma brain metastases (MBM).

Methods: Patients diagnosed with melanoma brain metastases in Ireland were retrospectively identified in Beaumont Hospital between 1999 and 2018.

Primary intradural/extradural Ewing's sarcoma of the sacral spine: A case report and literature review.

Background: Ewing's sarcoma (ES) is a malignant mesenchymal tumor, most often found in the long bones, and usually affecting children and adolescents in the second decade of life. ES of the spine is a clinical rarity.

Case Description: A 45-year-old male presented with a 3-month history of lower back pain which acutely worsened in conjunction with urinary retention.

Comparative analysis of the AIB1 interactome in breast cancer reveals MTA2 as a repressive partner which silences E-Cadherin to promote EMT and associates with a pro-metastatic phenotype.

Steroid regulated cancer cells use nuclear receptors and associated regulatory proteins to orchestrate transcriptional networks to drive disease progression. In primary breast cancer, the coactivator AIB1 promotes estrogen receptor (ER) transcriptional activity to enhance cell proliferation. The function of the coactivator in ER metastasis however is not established.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

BACKGROUND Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. CASE REPORT We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma.

CNS lymphoma, the Irish experience: A retrospective review of neuropathologically confirmed cases over 10 years.

Background: Central nervous system (CNS) lymphoma is rare, representing 2% of all brain tumors. The commonest subtype is diffuse large B-cell lymphoma (DLBCL), with primary T-cell lymphomas (PCNSTL) accounting for ~ 2%.

Objective: To determine the frequency and describe the key features of CNS lymphoma over a 10-year period in an Irish population.

Impact of the 2016 World Health Organization Classification of Tumours of the Central Nervous System: an Irish experience.

The 2016 World Health Organization Classification of Tumours of the Central Nervous System Tumours represents the most significant update to neuro-oncological tumour classification to date, compared with previous updates. This update reflects the substantial advances in molecular and genetic understanding of both adult and childhood brain tumours which have occurred in recent years. These advances have meant that an increasing array of molecular tests are required to definitively classify a tumour, allowing for a more precise integrated pathological diagnosis, but at the expense of a more challenging pathology workup.

Metastasis of papillary thyroid carcinoma to the thoracic spine.

Introduction: Papillary thyroid carcinoma (PTC) is the most common form of well-differentiated thyroid carcinoma. Despite its well-differentiated microscopic features, PTC may be minimally or overtly invasive. We present the case of a patient in whom thoracic spinal cord compression was the first presentation of metastatic PTC.

Acute multiple sclerosis lesion pathology does not predict subsequent clinical course-a biopsy study.

Background: Knowledge of the clinical outcome in tumefactive demyelination remains limited.

Aims: This study aims to characterise the natural history of biopsy-proven, pathogen-free, cerebral demyelination in an adult Irish population.

Methods: We identified all patients with biopsy-proven demyelination in a single neuropathology centre between 1999 and 2017.

Evaluation of the specificity of the central diagnostic criterion for chronic traumatic encephalopathy.

Introduction: Chronic traumatic encephalopathy (CTE) is a postmortem diagnosis. Consensus postmortem, but not antemortem, diagnostic criteria have been established. A key factor in these criteria is evidence of phosphorylated-tau (p-tau) around sulcal vessels in the cortex.