Publications by authors named "Colin P Doherty"

78 Publications

International Recommendations for the Management of Adults Treated With Ketogenic Diet Therapies.

Neurol Clin Pract 2021 Oct;11(5):385-397

Department of Neurology (MCC), Johns Hopkins University School of Medicine, Baltimore, MD; Matthew's Friends Clinics for Ketogenic Dietary Therapies (SW), Lingfield, Surrey, United Kingdom; Complex Epilepsy and Sleep Service (MB, JM), The Barberry, Birmingham, United Kingdom; Department of Neurology (AB, KR), Rush University Medical Center, Chicago, IL; Department of Neurology (EB), University of Toronto, Ontario, Canada; Department of Neurology (M-GB), University of Colorado, Denver; Department of Neurology (OD), New York University School of Medicine; Department of Medico-Surgical Sciences and Biotechnologies (CDL), Sapienza University of Rome Polo Pontino, Italy; Academic Unit of Neurology (CPD), Trinity College Dublin & FutureNeuro, Ireland; Department of Neurology (EF), UW Health, Madison; Department of Clinical Nutrition (LAH), St James' Hospital, Dublin, Ireland; Mid-Atlantic Epilepsy and Sleep Center (PK), Bethesda, MD; National Center for Epilepsy (MK), Oslo, Norway; Department of Neurology (DL), Academic Center for Epileptology, Kempenhaeghe and Maastricht University Medical Center, Heeze, The Netherlands; Department of Neurology (JL), University of Virginia, Charlottesville; Department of Neurology (JN), Shushrusha Hospital, Mumbai, India; Charles Dent Metabolic Unit (PN), University College London Hospitals NHS Foundation Trust, United Kingdom; Department of Neurology (MP), Waikato Hospital, Hamilton, New Zealand; Mercy Health Hauenstein Neurosciences (AT), Grand Rapids, MI; Department of Dietetics and Foodservices (CW), Mater Group, South Brisbane, QLD, Australia; and The Charlie Foundation for Ketogenic Therapies (BZ-K), Santa Monica, CA.

Objective: To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs).

Methods: A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs.

Results: Surveys were obtained from 20 medical institutions with >2,000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children, and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects, and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers.

Conclusions: KDTs may be safe and effective in treating adults with drug-resistant epilepsy, and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation.
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http://dx.doi.org/10.1212/CPJ.0000000000001007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610544PMC
October 2021

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.

Neuropathol Appl Neurobiol 2021 Aug 13. Epub 2021 Aug 13.

Neuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Aims: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis.

Methods: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy.

Results: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia.

Conclusions: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.
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http://dx.doi.org/10.1111/nan.12758DOI Listing
August 2021

Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study.

Neuroimage Clin 2021 24;31:102765. Epub 2021 Jul 24.

Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany; Institute for Diagnostic and Interventional Radiology, Pediatric and Neuroradiology, University Medical Centre Rostock, Rostock, Germany.

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.
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http://dx.doi.org/10.1016/j.nicl.2021.102765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346685PMC
September 2021

Democratizing epilepsy care: Utility and usability of an electronic patient portal.

Epilepsy Behav 2021 09 14;122:108197. Epub 2021 Jul 14.

FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Neurology, St. James's Hospital, Dublin, Ireland; Academic Unit of Neurology, Trinity College Dublin.

Objectives: Electronic patient portals (ePortals) can facilitate greater healthcare democratization by providing patients and/or their authorized care partners with secure access to their medical records when and where needed. Such democratization can promote effective healthcare provider-patient partnerships, shared decision-making, and greater patient engagement in managing their health condition. This study examined the usefulness of providing individualized services and care in epilepsy (PiSCES), an epilepsy ePortal, as an enabler of more democratized epilepsy care.

Methods: Seventy-two individuals with epilepsy and 18 care partners were invited to report on their experience of interacting via PiSCES with clinical documents (epilepsy care summary record; epilepsy clinic letters) authored about them by healthcare providers. The OpenNotes reporting tool was adapted to capture participant experience.

Results: Twenty-five percent of invited patients and 44% of invited care partners reported on interacting with their epilepsy care summary; 14% of patients and 67% of care partners invited reported on their epilepsy clinic letters. Participant testimonials illustrate the value of PiSCES in: promoting autonomy, aiding memory, developing the knowledgeable patient, and enhancing healthcare partnerships. Ninety-six percent and 100% of respondents, respectively, reported understanding their epilepsy care summary and epilepsy clinic letter; 77% said the summary described their epilepsy history to date; 96% indicated that the letter provided an accurate description of their clinical encounter; 92% and 96%, respectively, valued access to their summary record and clinic letters; 77% of summary record and 73% clinic letter respondents reported learning something about their epilepsy or the healthcare service via PiSCES. Illustrating their potential patient and care partner safety role, 42% respondents identified inaccuracies in their clinical documents which were subsequently resolved by a clinician.

Significance: In the post-digital world highly customized on-demand products and services have come to be expected. Similarly, in epilepsy care, technologies such as PiSCES can enable more personalized, transparent, and engaging services.
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http://dx.doi.org/10.1016/j.yebeh.2021.108197DOI Listing
September 2021

Computed tomography and emergency department frequency in homeless patients with seizures.

Seizure 2021 Oct 31;91:72-74. Epub 2021 May 31.

Academic Unit of Neurology Trinity College, Dublin, Ireland; FutureNeuro; an SFI Research Centre for Rare and Chronic Diseases, at RCSI, Dublin, Ireland.

Seizures are a common presentation to emergency departments in homeless patients. Seizures and epilepsy are often poorly managed in homeless patients. In this retrospective study, conducted in a large urban university hospital; we compared the number emergency department presentations and associated head computed tomography studies in a cohort of 88 homeless patients with seizures to an age and gender-matched housed cohort of patients over a five-year period. We found that homeless patients had a significantly increased number of presentations to the emergency department and a significantly higher number of head computed tomography, with a resulting increase in radiation exposure.
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http://dx.doi.org/10.1016/j.seizure.2021.05.021DOI Listing
October 2021

Awareness, knowledge and practice of healthcare professionals following implementation of a Pregnancy Prevention Program for sodium valproate in Ireland: a multi-stakeholder cross-sectional study.

Expert Opin Drug Saf 2021 Aug 23;20(8):965-977. Epub 2021 Aug 23.

Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.

Objectives: To establish awareness, knowledge, use and experience in practice of a sodium valproate pregnancy prevention program (PPP) in Ireland ("prevent") among three healthcare professional (HCP) groups.

Methods: A cross-sectional study using anonymous online surveys was conducted among general practitioners (GPs), pharmacists, and specialist consultants. Descriptive analyses are presented.

Results: HCP response rates were 5.8% for GPs (90/1544), 10.7% for pharmacists (219/2052), and 7.6% for specialists (17/224). Across HCP groups, there was high awareness (>90%) for specialist referral when female valproate patients are planning pregnancy, or become pregnant, but less awareness to refer annually for specialist review. While awareness of a possible teratogenic effect at any stage of pregnancy was high (>80%), most GPs (62.2%, 95% CI: 51.3, 71.9%) and community pharmacists (53.1%, 95% CI: 43.2, 62.8%) were unsure of the magnitude of risk for developmental disorders, while most specialists under-estimated this risk (46.7%, 95% CI: 24.8, 69.9%). Although >70% of the respondents identified valproate to be contraindicated in any woman of childbearing potential unless the conditions of the PPP are fulfilled, experience implementing key elements in practice varied.

Conclusions: Our findings suggest continued effort is needed to ensure optimal implementation of "prevent" into clinical practice in Ireland.
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http://dx.doi.org/10.1080/14740338.2021.1933429DOI Listing
August 2021

The anatomy of electronic patient record ethics: a framework to guide design, development, implementation, and use.

BMC Med Ethics 2021 02 4;22(1). Epub 2021 Feb 4.

FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, RCSI, 123 Stephen's Green, Dublin 2, Ireland.

Background: This manuscript presents a framework to guide the identification and assessment of ethical opportunities and challenges associated with electronic patient records (EPR). The framework is intended to support designers, software engineers, health service managers, and end-users to realise a responsible, robust and reliable EPR-enabled healthcare system that delivers safe, quality assured, value conscious care.

Methods: Development of the EPR applied ethics framework was preceded by a scoping review which mapped the literature related to the ethics of EPR technology. The underlying assumption behind the framework presented in this manuscript is that ethical values can inform all stages of the EPR-lifecycle from design, through development, implementation, and practical application.

Results: The framework is divided into two parts: context and core functions. The first part 'context' entails clarifying: the purpose(s) within which the EPR exists or will exist; the interested parties and their relationships; and the regulatory, codes of professional conduct and organisational policy frame of reference. Understanding the context is required before addressing the second part of the framework which focuses on EPR 'core functions' of data collection, data access, and digitally-enabled healthcare.

Conclusions: The primary objective of the EPR Applied Ethics Framework is to help identify and create value and benefits rather than to merely prevent risks. It should therefore be used to steer an EPR project to success rather than be seen as a set of inhibitory rules. The framework is adaptable to a wide range of EPR categories and can cater for new and evolving EPR-enabled healthcare priorities. It is therefore an iterative tool that should be revisited as new EPR-related state-of-affairs, capabilities or activities emerge.
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http://dx.doi.org/10.1186/s12910-021-00574-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859903PMC
February 2021

Attenuated CSF-1R signalling drives cerebrovascular pathology.

EMBO Mol Med 2021 02 22;13(2):e12889. Epub 2020 Dec 22.

Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.

Cerebrovascular pathologies occur in up to 80% of cases of Alzheimer's disease; however, the underlying mechanisms that lead to perivascular pathology and accompanying blood-brain barrier (BBB) disruption are still not fully understood. We have identified previously unreported mutations in colony stimulating factor-1 receptor (CSF-1R) in an ultra-rare autosomal dominant condition termed adult-onset leucoencephalopathy with axonal spheroids and pigmented glia (ALSP). Cerebrovascular pathologies such as cerebral amyloid angiopathy (CAA) and perivascular p-Tau were some of the primary neuropathological features of this condition. We have identified two families with different dominant acting alleles with variants located in the kinase region of the CSF-1R gene, which confer a lack of kinase activity and signalling. The protein product of this gene acts as the receptor for 2 cognate ligands, namely colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). Here, we show that depletion in CSF-1R signalling induces BBB disruption and decreases the phagocytic capacity of peripheral macrophages but not microglia. CSF-1R signalling appears to be critical for macrophage and microglial activation, and macrophage localisation to amyloid appears reduced following the induction of Csf-1r heterozygosity in macrophages. Finally, we show that endothelial/microglial crosstalk and concomitant attenuation of CSF-1R signalling causes re-modelling of BBB-associated tight junctions and suggest that regulating BBB integrity and systemic macrophage recruitment to the brain may be therapeutically relevant in ALSP and other Alzheimer's-like dementias.
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http://dx.doi.org/10.15252/emmm.202012889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863388PMC
February 2021

LoVE in a time of CoVID: Clinician and patient experience using telemedicine for chronic epilepsy management.

Epilepsy Behav 2021 02 17;115:107675. Epub 2020 Dec 17.

FutureNeuro SFI Research Centre, The Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland; Department of Neurology, St. James's Hospital, Dublin 8, Ireland.

As part of our ongoing interest in patient- and family-centered care in epilepsy, we began, before the onset of the CoVID-19 pandemic, to evaluate the concerns and preferences of those delivering and receiving care via telemedicine. CoVID-19 arrived and acted as an unexpected experiment in nature, catalyzing telemedicine's widespread implementation across many disciplines of medicine. The arrival of CoVID-19 in Ireland gave us the opportunity to record these perceptions pre- and post-CoVID. Data were extracted from the National Epilepsy Electronic Patient Record (EEPR). Power BI Analytics collated data from two epilepsy centers in Dublin. Analysis of data on reasons for using the telephone support line was conducted. A subset of patients and clinicians who attended virtual encounters over both periods were asked for their perception of telemedicine care through a mixed methods survey. Between 23rd December 2019 and 23rd March 2020 (pre-CoVID era), a total of 1180 patients were seen in 1653 clinical encounters. As part of a telemedicine pilot study, 50 of these encounters were scheduled virtual telephone appointments. Twenty eight surveys were completed by clinicians and 18 by patients during that period. From 24th March 2020 to 24th June 2020, 1164 patients were seen in 1693 encounters of which 729 (63%) patients were seen in 748 scheduled virtual encounters. 118 clinician impressions were captured through an online survey and 75 patients or carers completed a telephone survey during the post-CoVID era. There was no backlog of appointments or loss of care continuity forced by the pandemic. Clinicians expressed strong levels of satisfaction, but some doubted the suitability of new patients to the service or candidates for surgery receiving care via telemedicine. Patients reported positive experiences surrounding telephone appointments comparing them favorably to face-to-face encounters. The availability of a shared EEPR demonstrated no loss of care contact for patients with epilepsy. The survey showed that telemedicine is seen as an effective and satisfactory method of delivering chronic outpatient care.
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http://dx.doi.org/10.1016/j.yebeh.2020.107675DOI Listing
February 2021

Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study.

Sci Adv 2020 Nov 18;6(47). Epub 2020 Nov 18.

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria 3010, Australia.

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.
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http://dx.doi.org/10.1126/sciadv.abc6457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673818PMC
November 2020

Patients' Experiences of Remote Neurology Consultations during the COVID-19 Pandemic.

Eur Neurol 2020 4;83(6):622-625. Epub 2020 Nov 4.

Neurology Department, St. James's Hospital, Dublin, Ireland.

Telemedicine has been widely implemented during the COVID-19 global pandemic to enable continuity of care of chronic illnesses. We modified our general neurology clinic to be conducted using remote audio-only telephone consultations. We included all patients over a 10-week period who agreed to both a telephone consultation and a questionnaire afterwards in order to ascertain the patient's perspective of the experience. There were 212 participants consisting of men (43.8%) and women (56.2%). The mean ± standard deviation of age was 47.8 ± 17.0 (range 17-93) years. For the most part, patients found remote consultations either "just as good" (67.1%) or "better" (9.0%) than face-to-face consultations. Those who deemed it to be "not as good" were significantly older (52.3 ± 17.9 years vs. 46.6 ± 16.6 years, p =0.045) or were more likely to have a neurological disorder that required clinical examination, namely, a neuromuscular condition (66.7%, p = 0.002) or an undiagnosed condition (46.7%, p = 0.031). At the height of the COVID-19 global pandemic, most patients were satisfied with remote consultations. The positive feedback for remote consultations needs to be verified outside of this unique scenario because the results were likely influenced by the patients' apprehension to attend the hospital amongst other factors.
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http://dx.doi.org/10.1159/000511900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801972PMC
February 2021

Examination and diagnosis of electronic patient records and their associated ethics: a scoping literature review.

BMC Med Ethics 2020 08 24;21(1):76. Epub 2020 Aug 24.

FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, 123 Stephen's Green, Dublin 2, Ireland.

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.
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http://dx.doi.org/10.1186/s12910-020-00514-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446190PMC
August 2020

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study.

Brain 2020 08;143(8):2454-2473

Department of Neurology, Medical University of South Carolina, Charleston 29425 SC, USA.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
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http://dx.doi.org/10.1093/brain/awaa200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567169PMC
August 2020

Concussion and the severity of head impacts in mixed martial arts.

Proc Inst Mech Eng H 2020 Dec 16;234(12):1472-1483. Epub 2020 Aug 16.

Department of Bioengineering, Stanford University, Stanford, CA, USA.

Concern about the consequences of head impacts in US football has motivated researchers to investigate and develop instrumentation to measure the severity of these impacts. However, the severity of head impacts in unhelmeted sports is largely unknown as miniaturised sensor technology has only recently made it possible to measure these impacts in vivo. The objective of this study was to measure the linear and angular head accelerations in impacts in mixed martial arts, and correlate these with concussive injuries. Thirteen mixed martial arts fighters were fitted with the Stanford instrumented mouthguard (MiG2.0) participated in this study. The mouthguard recorded linear acceleration and angular velocity in 6 degrees of freedom. Angular acceleration was calculated by differentiation. All events were video recorded, time stamped and reported impacts confirmed. A total of 451 verified head impacts above 10g were recorded during 19 sparring events (n = 298) and 11 competitive events (n = 153). The average resultant linear acceleration was 38.0624.3g while the average resultant angular acceleration was 256761739 rad/s2. The competitive bouts resulted in five concussions being diagnosed by a medical doctor. The average resultant acceleration (of the impact with the highest angular acceleration) in these bouts was 86.7618.7g and 756163438 rad/s2. The average maximum Head Impact Power was 20.6kW in the case of concussion and 7.15kW for the uninjured athletes. In conclusion, the study recorded novel data for sub-concussive and concussive impacts. Events that resulted in a concussion had an average maximum angular acceleration that was 24.7% higher and an average maximum Head Impact Power that was 189% higher than events where there was no injury. The findings are significant in understanding the human tolerance to short-duration, high linear and angular accelerations.
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http://dx.doi.org/10.1177/0954411920947850DOI Listing
December 2020

Effectiveness and tolerability of adjunctive brivaracetam in patients with focal seizures: Second interim analysis of 6-month data from a prospective observational study in Europe.

Epilepsy Res 2020 09 9;165:106329. Epub 2020 Apr 9.

School of Medicine, University of Glasgow, Glasgow, G12 8QQ, United Kingdom. Electronic address:

Brivaracetam (BRV) is indicated for adjunctive treatment of focal (partial-onset) seizures with or without secondary generalisation in patients 4 years of age and older in the European Union (EU). An ongoing 12-month, prospective, non-interventional post-marketing study (EP0077; NCT02687711) is collecting real-world information on patients receiving treatment with adjunctive BRV in Europe. In this study, BRV is prescribed according to routine clinical practice and the EU Summary of Product Characteristics. This second interim analysis assessed effectiveness, tolerability and health-related quality of life outcomes for up to 6 months of treatment. At the cut-off date (13 April 2018), 266 patients from five countries had attended Visit 1, 24.1 % (64/266) had completed the study, 37.6 % (100/266) were ongoing, and 38.3 % (102/266) had discontinued. In total, 261 patients had at least one dose of BRV and were included in the analyses. Patients had a mean time since epilepsy diagnosis of 23.2 years, a mean of eight lifetime AEDs (sum of AEDs discontinued prior to study entry and concomitant at study entry), and a median of five focal seizures per 28 days during the 3-month retrospective Baseline. 66.3 % of patients initiated BRV at a dose within the recommended starting range (50-100 mg/day) and 87.1 % of patients received BRV modal doses within the recommended dose range (50-200 mg/day) during the study. Retention rates were 79.1 % (N = 239) at 3 months and 62.1 % (N = 211) at 6 months. The 50 % responder rates for focal seizures were 46.8 % (N = 139) at 3 months and 53.6 % (N = 97) at 6 months. The proportions of patients who were seizure-free were 10.7 % (21/196) and 7.5 % (15/199) at 3 and 6 months of treatment, respectively. Median percent reductions in focal seizure frequency per 28 days from Baseline to 3 and 6 months were 34.6 % (N = 139) and 53.3 % (N = 97), respectively. Overall, 44.2 % of patients had an improvement and 15.4 % had a worsening in Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 total score from Baseline to 6 months (N = 52). At least one treatment-emergent adverse event (TEAE) was reported in 51.0 % (133/261) of patients, and 34.5 % (90/261) of patients had drug-related TEAEs. The most common drug-related TEAEs (≥5% of patients) were drug ineffective (7.7 %), seizure (6.5 %), and fatigue (6.1 %). In this 6-month interim analysis, BRV showed effectiveness when used in clinical practice in five European countries. BRV was well tolerated, and no new safety signals were observed.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106329DOI Listing
September 2020

Prevalence of N-Methyl-d-Aspartate Receptor antibody (NMDAR-Ab) encephalitis in patients with first episode psychosis and treatment resistant schizophrenia on clozapine, a population based study.

Schizophr Res 2020 08 1;222:455-461. Epub 2020 Jun 1.

Department of Psychiatry, Trinity College Dublin, Ireland; Department of Psychiatry, St James's Hospital, Dublin, Ireland.

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.
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http://dx.doi.org/10.1016/j.schres.2019.11.023DOI Listing
August 2020

The genetic architecture of the human cerebral cortex.

Science 2020 03;367(6484)

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
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http://dx.doi.org/10.1126/science.aay6690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295264PMC
March 2020

Self-reported antiepilepsy medication adherence and its connection to perception of medication error.

Epilepsy Behav 2020 03 25;104(Pt A):106896. Epub 2020 Jan 25.

Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Dublin 2, Ireland; FutureNeuro SFI Research Centre, The Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Department of Neurology, St. James's Hospital, James's Street, Dublin 8, Ireland.

Although 70% of people with epilepsy (PWE) achieve seizure freedom following an appropriate antiepileptic drug (AED) regime, evidence suggests that adherence to AEDs by PWE is suboptimal. Nonadherence to AEDs is associated with increased morbidity, mortality, emergency department visits, and hospitalizations, with reduced adherence also correlating to a lower quality of life, decreased productivity, and loss of employment. Furthermore, research indicates that medication errors which are widespread in chronic disease are less well studied in epilepsy but are likely also to contribute to avoidable disease morbidity and mortality. The goals of this project were to determine rates of medication adherence by self-reported questionnaire and its links to perceived medication error in a cohort of PWE attending a general epilepsy outpatient clinic. Following a plan-do-study-act cycle, it was found that the most appropriate methodology for conducting was in the form of a bespoke 9-item self-administered questionnaire. One hundred eighty-six PWE completed a nine-question questionnaire asking patients about their own medication adherence habits and their perception that they were previously exposed to medication error. This study found that 41% of respondents reported suboptimal adherence to AED therapy, while 28.5% of respondents self-reported that they unintentionally do not take their AED medication on an occasional, regular, or frequent basis. A 5.9% of respondents self-reported that they intentionally do not take their medication as prescribed. A 6% of respondents self-reported that they are both unintentionally and intentionally nonadherent to their AED therapy. No significant associations were demonstrated between age, sex, perceived effectiveness of medication, feelings of stigma/embarrassment, adverse effects or additional neurological comorbidities, and unintentional or intentional nonadherence. A 28.5% of respondents to the questionnaire reported that they perceived themselves to have been subjected to medication error. Prescribing errors were the most common form of perceived medication error, followed by dispensing errors, then administration errors. Significant associations were found between ineffective medication and feelings of stigma or embarrassment about epilepsy with perceived prescribing errors. Intentional nonadherence to medication was significantly associated with perceived dispensing errors.
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http://dx.doi.org/10.1016/j.yebeh.2019.106896DOI Listing
March 2020

Corrigendum to "The rhetoric and reality of integrated patient-centered care for healthcare providers: An ethnographic exploration of epilepsy care in Ireland" [Epilepsy & Behavior (2019) 87-92].

Epilepsy Behav 2020 Feb 19;103(Pt A):106562. Epub 2019 Nov 19.

Research and Innovation, The Royal College of Surgeons in Ireland, 111 St. Stephen's Green, Ardilaun House, Block B Second Floor, St Stephen's Green, Dublin 2, Ireland. Electronic address:

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http://dx.doi.org/10.1016/j.yebeh.2019.106562DOI Listing
February 2020

Are patients ready for integrated person-centered care? A qualitative study of people with epilepsy in Ireland.

Epilepsy Behav 2020 01 15;102:106668. Epub 2019 Nov 15.

SFI FutureNeuro Research Centre, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland. Electronic address:

The National Clinical Programme for Epilepsy (NCPE) in Ireland aims to deliver a holistic model of integrated person-centered care (PCC) that addresses the full spectrum of biomedical and psychosocial needs of people with epilepsy (PwE). However, like all strategic plans, the model encompasses an inherent set of assumptions about the readiness of the environment to implement and sustain the actions required to realize its goals. In this study, through the lens of PwE, the Irish epilepsy care setting was explored to understand its capacity to adopt a new paradigm of integrated PCC. Focus groups and semi-structured one-to-one interviews were employed to capture the qualitative experiences of a sample of Irish PwE (n = 27) in the context of the care that they receive. Participants were from different regions of the country and were aged between 18 and 55 years with 1 to 42 years since diagnosis (YSD). Highlighting a gap between policy intent and action on the ground, findings suggest that patient readiness to adopt a new model of care cannot be assumed. Expectations, preferences, behaviors, and values of PwE may sustain the more traditional constructions of healthcare delivery rather than the integrated PCC goals of reform. These culturally constituted perceptions illustrate that PwE do not instinctively appreciate the goals of healthcare reform nor the different behavior expected from them within a reformed healthcare system. Recalibrating deep-rooted patient views is necessary to accomplish the aspirations of integrated PCC. Patient engagement emphasizing the meaningful role that they can play in shaping their healthcare services is vital.
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http://dx.doi.org/10.1016/j.yebeh.2019.106668DOI Listing
January 2020

Dynamic Blood-Brain Barrier Regulation in Mild Traumatic Brain Injury.

J Neurotrauma 2020 01 8;37(2):347-356. Epub 2019 Nov 8.

Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI.
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http://dx.doi.org/10.1089/neu.2019.6483DOI Listing
January 2020

Supporting and empowering people with epilepsy: Contribution of the Epilepsy Specialist Nurses (SENsE study).

Seizure 2019 Oct 10;71:42-49. Epub 2019 Jun 10.

School of Nursing and Midwifery, Trinity College Dublin, 24 D'Olier Street Dublin 2, Ireland. Electronic address:

Purpose: To explore how Epilepsy Specialist Nurses in the Republic of Ireland enacted their clinical role.

Methods: Qualitative descriptive design that involved individual and focus group interviews, observation and documentary analysis. Data were collected from 12 Epilepsy Specialist Nurses working in five hospital-based epilepsy services in Ireland, 24 multidisciplinary team members, and 35 people with epilepsy and their family members were involved. Data were analysed in NVivo using an inductive and deductive approach.

Results: Epilepsy Specialist Nurses work out of a value base that gives primacy to collaboration. active participation, relationship-based care, and respect for the voices of PWE and family members. They are key players in empowering people to self-manage their illness, Core dimensions of their clinical role includes: performing a comprehensive assessment to inform care and treatment; providing person-centred education; monitoring the impact of care and treatment; providing education to family members and significant others; providing psychosocial care to optimise psychological wellness; co-ordinating care to enhance patients' journey; and quality assuring patient information.

Conclusion: Findings from this study highlight the key role ESNs played as members of the MDT in building and supporting PWE's capacity to self-manage their illness. However, they also indicate deficits in the provision of information on sudden unexpected death in epilepsy and how to disclose a diagnosis of epilepsy by the ESN, as well deficits in their knowledge and confidence in supporting people experiencing significant mental health morbidities.
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http://dx.doi.org/10.1016/j.seizure.2019.06.008DOI Listing
October 2019

Eslicarbazepine acetate in epilepsy patients with psychiatric comorbidities and intellectual disability: Clinical practice findings from the Euro-Esli study.

J Neurol Sci 2019 Jul 2;402:88-99. Epub 2019 May 2.

Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Psychiatric and intellectual comorbidities are common in patients with epilepsy. However, data on the use of antiepileptic drugs in these patients are still lacking. This study assessed the real-world effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) in patients with intellectual disability and psychiatric comorbidities, including a separate analysis specifically in those with depression, using data from the Euro-Esli study. Effectiveness measures included responder and seizure freedom rates. Safety and tolerability were assessed by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Of the 2058 patients initially included in the Euro-Esli study, 952 patients had intellectual disability data available, 1138 had psychiatric comorbidity data available and 1134 had depression data available. Of those who had intellectual or psychiatric comorbidity data available, 11.3% (108/952) suffered from intellectual disability, 24.9% (283/1138) had a psychiatric disorder, including depression, and 12.4% (141/1134) specifically had depression. Responder and seizure freedom rates were generally comparable between patients with psychiatric comorbidity and those without, and patients with depression and those without. However, responder and seizure freedom rates were significantly lower in patients with intellectual disability compared with those without. Overall, patients with psychiatric and intellectual comorbidities experienced more AEs and AEs leading to ESL discontinuation than patients without these comorbidities. The incidence of psychiatric AEs was not significantly different for patients with psychiatric comorbidities or depression than those without, and the incidence of cognitive AEs was not significantly different for patients with intellectual disability than those without. These findings suggest that ESL is effective in patients with psychiatric and intellectual comorbidities and that its use in these patients is unlikely to exacerbate existing psychiatric or cognitive disturbances.
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http://dx.doi.org/10.1016/j.jns.2019.04.040DOI Listing
July 2019

The rhetoric and reality of integrated patient-centered care for healthcare providers: An ethnographic exploration of epilepsy care in Ireland.

Epilepsy Behav 2019 05 18;94:87-92. Epub 2019 Mar 18.

Research and Innovation, The Royal College of Surgeons in Ireland, 111 St. Stephen's Green, Ardilaun House, Block B Second Floor, St Stephen's Green, Dublin 2, Ireland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.yebeh.2019.02.011DOI Listing
May 2019

Extracranial and Intracranial Vasculopathy With "Moyamoya Phenomenon" in Association With Alagille Syndrome.

Front Neurol 2018 29;9:1194. Epub 2019 Jan 29.

Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating The National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland.

Alagille syndrome (AGS) is an autosomal-dominant, multisystem disorder caused by mutations in the JAG1 gene. A 34-year-old man was referred to our service 10 years ago with focal seizures with impaired awareness and transient slurred speech. He had a 5-year history of intermittent left monocular low-flow retinopathy. He has a family history of AGS. General examination revealed mild hypertension, aortic regurgitation, and livedo reticularis. Neurological examination was normal. He had mild hyperlipidaemia and persistently-positive lupus anticoagulant consistent with primary anti-phospholipid syndrome. Color Doppler ultrasound revealed low velocity flow in a narrowed extracranial left internal carotid artery (ICA). MR and CT angiography revealed a diffusely narrowed extracranial and intracranial left ICA. Formal cerebral angiography confirmed severe left ICA narrowing consistent with a left ICA "vasculopathy" and moyamoya phenomenon. Transthoracic echocardiogram revealed a bicuspid aortic valve and aortic incompetence. Molecular genetic analysis identified a missense mutation (A211P) in exon 4 of the JAG1 gene, consistent with AGS. AGS should be considered in young adults with TIAs/stroke and unexplained extracranial or intracranial vascular abnormalities, and/or moyamoya phenomenon, even in the absence of other typical phenotypic features. Gene panels should include JAG1 gene testing in similar patients.
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http://dx.doi.org/10.3389/fneur.2018.01194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362309PMC
January 2019

Evidence-based practice among epilepsy specialist nurses in the Republic of Ireland: Findings from the SENsE study.

J Nurs Manag 2019 May 13;27(4):840-847. Epub 2019 Feb 13.

School of Nursing and Midwifery, Trinity College Dublin, Dublin, Ireland.

Aim: To describe how epilepsy specialist nurses in Ireland enact the evidence-based practice dimension of their role.

Background: The importance of epilepsy specialist nurses (ESNs) delivering evidence-based care to people experiencing epilepsy is unquestionable, yet research into this aspect of the role is relatively sparse.

Methods: A qualitative design was used, involving 12 epilepsy specialist nurses working in five units in Ireland, 24 multidisciplinary team members working with them and 35 people with epilepsy and their family members. Data were collected using individual and focus group interviews, observation and documentary analysis.

Results: These ESNs were active in accumulating, translating, applying, generating and disseminating evidence. All were actively involved in, or leading audit and service evaluations, and used findings to improve practice. Their research activity mainly consisted of small-scale unfunded research projects.

Conclusions: These ESNs acted as opinion leaders and role models in relation to evidence-based practice, including the generation of new knowledge through audit and research.

Implications For Nursing Management: Organisations and managers need to support ESNs by ensuring that they have the necessary resources and competencies to accumulate, translate, apply, generate and disseminate relevant evidence. Future research should explore the impact of ESNs' evidence-based practice on patient outcomes.
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http://dx.doi.org/10.1111/jonm.12747DOI Listing
May 2019

Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients.

Neurology 2019 01 26;92(4):e351-e358. Epub 2018 Dec 26.

From the Department of Molecular and Cellular Therapeutics (S.A., G.L.C., N.D.) and FutureNeuro Research Centre (G.L.C., N.D.), the Royal College of Surgeons in Ireland, Dublin; Department of Neurology and Neurosurgery (S.A.), Montreal Neurological Institute and Hospital, Canada; The Florey Institute of Neuroscience and Mental Health (M.A.K., M.K.S., G.D.J.), Austin Campus, Melbourne, Australia; Neuroimaging Laboratory, Department of Neurology (C.L.Y., M.K., M.Z., T.Z., M.H.N., M.K.M.A., V.R.F., I.L.-C., F.C.), University of Campinas, São Paulo, Brazil; Department of Neurology (M.-H.T.), Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Brain Morphometry Laboratory (M.F.) and Division of Neurology (N.D.), Beaumont Hospital; Department of Neurology (C.P.D.), St James's Hospital, Dublin, Ireland; and Department of Neurology (G.D.J.), Austin Health, Melbourne, Australia.

Objective: To examine cerebral cortex thickness in asymptomatic first-degree relatives of patients with mesial temporal lobe epilepsy (MTLE).

Methods: We investigated 127 asymptomatic first-degree relatives of patients with MTLE due to hippocampal sclerosis (HS) (mean age ± SD = 39.4 ± 13 years) and 203 healthy control individuals (mean age ± SD = 36.0 ± 11 years). Participants underwent a comprehensive clinical evaluation and structural brain MRI at 3 study sites. Images were processed simultaneously at each site using a surface-based morphometry method to quantify global brain measures, hippocampal volumes, and cerebral cortical thickness. Differences in brain measures between relatives of patients and controls were examined using generalized models, while controlling for relevant covariates, including age and sex.

Results: None of the asymptomatic first-degree relatives of MTLE + HS patients showed evidence of HS on qualitative image assessments. Compared to the healthy controls, the asymptomatic relatives of patients displayed no significant differences in intracranial volume, average hemispheric surface area, or hippocampal volume. Similarly, no significant cerebral cortical thinning was identified in the relatives of patients. This was consistent across the 3 cohorts.

Conclusion: Lack of cortical thickness changes in the asymptomatic relatives of patients indicates that the previously characterized MTLE + HS-related cortical thinning is not heritable, and is likely driven by disease-related factors. This finding therefore argues for early and aggressive intervention in patients with medically intractable epilepsy.
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http://dx.doi.org/10.1212/WNL.0000000000006834DOI Listing
January 2019

Rising to the challenge: Epilepsy specialist nurses as leaders of service improvements and change (SENsE study).

Seizure 2018 Dec 1;63:40-47. Epub 2018 Nov 1.

School of Nursing and Midwifery, Trinity College Dublin, 24 D'Olier Street, Dublin 2, Ireland. Electronic address:

Purpose: To report the leadership role and change activities of epilepsy specialist nurses (ESNs) in Ireland; findings from the SENsE study.

Method: A mixed methods study design was used, involving 12 epilepsy specialist nurses working in five units in Ireland, 24multidisciplinary team members working with them, and 35 people with epilepsy and their family members. Data were collected using individual and focus group interviews, observation and documentary analysis.

Results: Five key areas in which ESNs demonstrated leading on the change agenda were identified. These included: Initiating new clinical practice developments; Building capability within the multidisciplinary team; Developing education programmes and resources for people with epilepsy, family and the public; Exerting influence through membership of committees and lobbying; and Advancing the ESN role.

Conclusion: Though the epilepsy specialist nurse role was first established in the UK in 1988, much of the literature that discusses or describes the ESN role is founded on anecdotal evidence, or focusses on their clinical expertise. Findings from this study provide empirical evidence that the ESNs were involved as key players in leading changes within the services, in the education of others, and the continuous advancement of epilepsy care.
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http://dx.doi.org/10.1016/j.seizure.2018.10.013DOI Listing
December 2018

Neuropolypathology as a result of severe traumatic brain injury?

Clin Neuropathol 2019 Jan/Feb;38(1):14-22

A history of brain trauma has long been acknowledged as increasing an individual's risk of developing dementia in later life. The underlying mechanisms that belie this pre-disposition are, however, very poorly understood. Here, we report a clinical-neuropathological correlation of a man who presented at the age of 66 with a progressive complex atypical dementia with early and prominent neurobehavioral symptoms. His neurological condition continued to decline up to his death at the age of 74. During the compilation of his clinical history, it was established that the subject had experienced a single severe traumatic brain injury (TBI) aged 12 years in 1954 resulting in loss of consciousness, hospitalization, and coma for a number of days after which he was deemed to have recovered. Following post-mortem neuropathological analysis, numerous distinct neuropathologies were observed in various brain regions and these included i) widespread Braak stage VI neurofibrillary tangle formation, ii) widespread α-synuclein positive Lewy bodies and Lewy neurites and iii) diffuse amyloid plaques and severe cerebral amyloid angiopathy (CAA). Added to this, a comprehensive analysis of blood-brain barrier (BBB) integrity, known to be disrupted during and after TBI, showed iv) distinct BBB breakdown with extravasated IgG and activated microglia present. This report represents an interesting documented case of neuropolypathology that may be associated with prior history of severe TBI. We propose one testable theory that a history of brain trauma may be a potential trigger for late onset dementia due to damage and unresolved functioning of the cerebral microvasculature.
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http://dx.doi.org/10.5414/NP301131DOI Listing
April 2019

Using Neuroimaging to Detect Covert Awareness and Determine Prognosis of Comatose Patients: Informing Surrogate Decision Makers of Individual Patient Results.

Semin Neurol 2018 10 15;38(5):555-560. Epub 2018 Oct 15.

School of Psychology, Trinity College Dublin, Dublin, Ireland.

Robust prognostic indicators of neurological recovery are urgently needed for acutely comatose patients. Functional neuroimaging is a highly sensitive tool for uncovering covert cognition and awareness in behaviorally nonresponsive patients with prolonged disorders of consciousness, and may be applicable to acutely comatose patients. Establishing a link between early detection of covert awareness in acutely comatose patients and eventual recovery of function could have significant implications for patient prognosis, treatment, and end-of-life decisions. Because functional neuroimaging of acutely comatose patients is currently limited to the research context, ethical guidelines for disseminating a patient's individual research results to clinical teams and surrogate decision makers are needed. We propose an ethical framework composed of four conditions that can guide ethical disclosure of individual results of neuroimaging research in the acute care context.
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http://dx.doi.org/10.1055/s-0038-1667385DOI Listing
October 2018
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