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Tuberous sclerosis (TS) is a monogenic disorder which causes disabling neurological symptoms. Similarly, multiple sclerosis (MS) may result in disability, but in contrast, is diagnosed without genetic testing. Clinicians are advised to exercise caution in diagnosing MS in the presence of a pre-existing genetic disorder, as it may be a potential 'red flag'. A dual diagnosis of MS and TS has not previously been reported in the literature. We provide two cases of known cases of TS who presented with new neurological symptoms and associated physical signs compatible with a dual diagnosis of TS/MS. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate deaths among individuals with epilepsy recorded on the National Drug-Related Deaths Index (NDRDI).Method: A descriptive analysis of individuals with a known history of epilepsy in the NDRDI from 2004 to 2013 was undertaken.Results: Between 2004 and 2013, 225 (2%) of the recorded cases had a documented history of epilepsy, 82 (36%) of whom had epilepsy recorded as the cause of death. Of these 82 deaths, the majority were male (60-73%) and half (median age) were aged 47 years or younger. A post mortem toxicology report was available for 65 (79%) of these deaths, of which over two thirds (44-68%) did not have any antiepileptic drugs present on toxicology. Over two thirds of these deaths, (31-70%) were among people known to be alcohol dependent.Conclusion: The high percentage of individuals with a diagnosis of alcohol dependency that died as a result of epilepsy and who have no antiepileptic drugs in their system at the time of their death, highlights the need for preventative measures for this at-risk group. [ABSTRACT FROM AUTHOR]

Purpose: This study was undertaken to describe prescribing practice for the anti-convulsant drug (AED) Sodium Valproate (VPA) in an Irish population of woman of childbearing age during the period of the emergence of new data showing a high rate of developmental abnormalities in offspring of women who took VPA during pregnancy.Methods: All prescriptions dispensed from community pharmacies in Ireland between 2008 and 2013 inclusive were examined for women aged 16-44 years from all three drug reimbursement schemes in Ireland. Numbers of prescriptions and women on AEDs were identified, as was the rural/urban distribution of the drug along with co-prescribing of folic acid and the oral contraceptive pill. All data analysis was conducted using SAS v9.3.Results: The rate of prescribing of VPA in Ireland declined slightly from 3.5/1000 per eligible population in 2008 to 3.14/1000 in 2013. While rates of prescribing fell for epilepsy, there appeared to be a rise in prescription for other indications of VPA. In 2013, co-prescription of folic acid or oral contraceptives was relatively low across all community schemes. Finally, an address distant from academic specialist centers predicted a higher exposure to VPA.Conclusion: Recently the European Medicine's Agency suggested that alternatives to VPA be considered before prescribing to women of childbearing age. Despite this, the rate of VPA prescribing in Ireland appears to be increasing for indications other than epilepsy. It may be necessary to improve the dissemination of information about the potential negative effects of VPA in this population. [ABSTRACT FROM AUTHOR]

Background: Electronic patient record (EPR) technology is a key enabler for improvements to healthcare service and management. To ensure these improvements and the means to achieve them are socially and ethically desirable, careful consideration of the ethical implications of EPRs is indicated. The purpose of this scoping review was to map the literature related to the ethics of EPR technology. The literature review was conducted to catalogue the prevalent ethical terms, to describe the associated ethical challenges and opportunities, and to identify the actors involved. By doing so, it aimed to support the future development of ethics guidance in the EPR domain.Methods: To identify journal articles debating the ethics of EPRs, Scopus, Web of Science, and PubMed academic databases were queried and yielded 123 eligible articles. The following inclusion criteria were applied: articles need to be in the English language; present normative arguments and not solely empirical research; include an abstract for software analysis; and discuss EPR technology.Results: The medical specialty, type of information captured and stored in EPRs, their use and functionality varied widely across the included articles. Ethical terms extracted were categorised into clusters 'privacy', 'autonomy', 'risk/benefit', 'human relationships', and 'responsibility'. The literature shows that EPR-related ethical concerns can have both positive and negative implications, and that a wide variety of actors with rights and/or responsibilities regarding the safe and ethical adoption of the technology are involved.Conclusions: While there is considerable consensus in the literature regarding EPR-related ethical principles, some of the associated challenges and opportunities remain underdiscussed. For example, much of the debate is presented in a manner more in keeping with a traditional model of healthcare and fails to take account of the multidimensional ensemble of factors at play in the EPR era and the consequent need to redefine/modify ethical norms to align with a digitally-enabled health service. Similarly, the academic discussion focuses predominantly on bioethical values. However, approaches from digital ethics may also be helpful to identify and deliberate about current and emerging EPR-related ethical concerns. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Blood–brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals.We scanned 50 drug‐resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE‐MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls.Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10−7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI‐visible lesions compared with non‐lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10).These findings are consistent with pre‐clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

This article discusses POLR3A-related disorders, which encompass a range of clinical phenotypes beyond the classical triad of hypomyelinating leukodystrophy, hypodontia, and hypogonadotrophic hypogonadism. The case study presented focuses on a 46-year-old woman with walking difficulties, lower limb pain, weakness, and stiffness. The patient exhibited various neurological symptoms, including a waddling gait, dystonic posturing of the feet, and head tremors. The article highlights the importance of considering POLR3A-related disorders in the differential diagnosis of spastic or cerebellar ataxias in adolescents and adults. [Extracted from the article]

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. Participants were subdivided based on histopathology of the resected brain. Paired blood‐ and brain‐derived DNA samples were sequenced using high‐coverage targeted next generation sequencing to high depth (585× and 1360×, respectively). Variants were identified using Genome Analysis ToolKit (GATK4) MuTect‐2 and confirmed using high‐coverage Amplicon‐EZ sequencing. Results: Sequence data on 41 patients passed quality control. Four somatic variants were validated following amplicon sequencing: within CBL, ALG13, MTOR, and FLNA. The diagnostic yield across 41 patients was 10%, 9% in mesial temporal lobe epilepsy with hippocampal sclerosis and 20% in malformations of cortical development. Significance: This study provides novel insights into the etiology of mesial temporal lobe epilepsy with hippocampal sclerosis, highlighting a potential pathogenic role of somatic variants in CBL and ALG13. We also report candidate diagnostic somatic variants in FLNA in focal cortical dysplasia, while providing further insight into the importance of MTOR and related genes in focal cortical dysplasia. This work demonstrates the potential molecular diagnostic value of variants in both germline and somatic epilepsy genes. [ABSTRACT FROM AUTHOR]

Introduction: N-methyl-d-aspartate receptor antibody (NMDAR-Ab) encephalitis consensus criteria has recently been defined. We aimed to examine the prevalence of NMDAR-Ab encephalitis in patients with first episode psychosis (FEP) and treatment resistant schizophrenia (TRS) on clozapine, using clinical investigations, antibody testing and to retrospectively apply diagnostic consensus criteria.Methods: Adult (18-65 years old) cases of FEP meeting inclusion criteria were recruited over three years and assessed using the Structured Clinical Interview for DSM-IV disorders (SCID). NMDAR-Ab was identified using a live cell-based assay (L-CBA). Seropositive cases were clinically investigated for features of encephalitis including neuro-imaging, EEG and CSF where possible. Serum was retested using immunohistochemistry (IHC) as part of diagnostic criteria guidelines. A cohort of patients with TRS was also recruited.Results: 112 FEP patients were recruited over 3 years. NMDAR-Ab seroprevalence was 4/112 (3.5%) cases. One case (<1%) was diagnosed with definite NMDAR-Ab encephalitis and treated with immunotherapy. One of the three other seropositive cases met criteria for probable encephalitis. However all three were ultimately diagnosed with mood disorders with psychotic features. None have developed neurological features at three year follow up. 1/100 (1%) of patients with TRS was 100 patients with TRS were recruited. One case (1%) seropositive for NMDAR-Ab but did not meet criteria for encephalitis.Conclusions: NMDAR-Ab encephalitis as defined by consensus guidelines occured rarely in psychiatric services in this study. Further studies are needed to establish pathogenicity of serum NMDAR-Ab antibodies. Psychiatric services should be aware of the clinical features of encephalitis. [ABSTRACT FROM AUTHOR]

In line with healthcare reform across the world, the National Clinical Programme for Epilepsy (NCPE) in Ireland describes a model that aims to achieve holistic integrated person (patient)-centered care (PCC). While generally welcomed by stakeholders, the steps required to realize the NCPE ambition and the preparedness of those involved to make the journey are not clear. This study explored the perceptions of healthcare providers in the Irish epilepsy care ecosystem to understand their level of readiness to realize the benefits of an integrated PCC model. Ethnographic fieldwork including observations of different clinical settings across three regions in Ireland and one-to-one interviews with consultant epileptologists (n = 3), epilepsy specialist nurses (n = 5), general practitioners (n = 4), and senior healthcare managers (n = 3) were conducted. While there is a person-centered ambiance and a disposition toward advancing integrated PCC, there are limits to the readiness of the epilepsy care environment to fully meet the aspirations of healthcare reform. These are the following: underdeveloped healthcare partnerships;, poor care coordination;, unintended consequences of innovation;, and tension between pace and productivity. In the journey from policy to practice, the following multiple tensions collide: policy aims to improve services for all patients while simultaneously individualizing care; demands for productivity limit the time and space required to engage in incremental and iterative improvement initiatives. Understanding these tensions is an essential first step on the pathway to integrated PCC implementation. • Clinical readiness to execute healthcare reform recommendations cannot be assumed. • Healthcare practitioners face challenges to achieve integrated person-centered care. • Professional, disciplinary, and organizational boundaries limit collaboration. • Integrated person-centered care is affected by demand for pace and productivity. • Getting from policy to practice requires preparation, time, and space. [ABSTRACT FROM AUTHOR]