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.
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. Here we report that claudin-5 protein levels are significantly diminished in surgically resected brain tissue from patients with treatment-resistant epilepsy. Concomitantly, dynamic contrast-enhanced MRI in these patients showed widespread BBB disruption. We show that targeted disruption of claudin-5 in the hippocampus or genetic heterozygosity of claudin-5 in mice exacerbates kainic acid-induced seizures and BBB disruption. Additionally, inducible knockdown of claudin-5 in mice leads to spontaneous recurrent seizures, severe neuroinflammation, and mortality. Finally, we identify that RepSox, a regulator of claudin-5 expression, can prevent seizure activity in experimental epilepsy. Altogether, we propose that BBB stabilizing drugs could represent a new generation of agents to prevent seizure activity in epilepsy patients.
Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition associated with repetitive mild traumatic brain injury. In recent years, attention has focused on emerging evidence linking the ...development of CTE to concussive injuries in athletes and military personnel; however, the underlying molecular pathobiology of CTE remains unclear. Here, we provide evidence that the blood–brain barrier (BBB) is disrupted in regions of dense perivascular p-Tau accumulation in a case of CTE. Immunoreactivity patterns of the BBB-associated tight junction components claudin-5 and zonula occludens-1 were markedly discontinuous or absent in regions of perivascular p-Tau deposition; there was also immunohistochemical evidence of a BBB in these foci. Because the patient was diagnosed premortem clinically as having progressive supranuclear palsy (PSP), we also compromised that the CTE alterations appear to be distinct from those in the brain of a patient with PSP. This report represents the first description of BBB dysfunction in a pathologically proven CTE case and suggests a vascular component in the postconcussion cascade of events that may ultimately lead to development of a progressive degenerative disorder. BBB dysfunction may represent a correlate of neural dysfunction in live subjects suspected of being at risk for development of CTE.
Highlights • We identified 575 cases in the literature describing seizure induced acute MRI changes. • The most common abnormalities are restricted diffusion and reduced ADC values in the mesial ...temporal structures and neocortex. • Patients who have cytotoxic oedema on imaging are more likely to have long lasting sequelae. • Clinicians need to be aware of the need for careful imaging follow up to monitor resolution especially of any ictal related oedema or contrast enhancement to ensure neoplastic lesions are not missed.
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.
The use of mobile devices for delivering health-related services (mobile health mHealth) has rapidly increased, leading to a demand for summarizing the state of the art and practice through ...systematic reviews. However, the systematic review process is a resource-intensive and time-consuming process. Generative artificial intelligence (AI) has emerged as a potential solution to automate tedious tasks.
This study aimed to explore the feasibility of using generative AI tools to automate time-consuming and resource-intensive tasks in a systematic review process and assess the scope and limitations of using such tools.
We used the design science research methodology. The solution proposed is to use cocreation with a generative AI, such as ChatGPT, to produce software code that automates the process of conducting systematic reviews.
A triggering prompt was generated, and assistance from the generative AI was used to guide the steps toward developing, executing, and debugging a Python script. Errors in code were solved through conversational exchange with ChatGPT, and a tentative script was created. The code pulled the mHealth solutions from the Google Play Store and searched their descriptions for keywords that hinted toward evidence base. The results were exported to a CSV file, which was compared to the initial outputs of other similar systematic review processes.
This study demonstrates the potential of using generative AI to automate the time-consuming process of conducting systematic reviews of mHealth apps. This approach could be particularly useful for researchers with limited coding skills. However, the study has limitations related to the design science research methodology, subjectivity bias, and the quality of the search results used to train the language model.
Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how ...blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.
Highlights • This study describes prescribing practice of Valproate (VPA) in Irish women. • Numbers of prescriptions and women on Valproate were identified. • The overall prescribing of Valproate in ...women has dropped. • An address distant from specialist centers predicted higher exposure to Valproate. • The prescribing of Valproate is increasing for other health disorders.
•Epilepsy Specialist Nurses provide a range of service and clinical roles.•They are central to empowering people with epilepsy to self-manage their illness.•They require support to increase their ...competence around mental health morbidities.•They need to include strategies on how to disclose a diagnosis of epilepsy to others.
To explore how Epilepsy Specialist Nurses in the Republic of Ireland enacted their clinical role.
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.
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.
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.
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.
Synopsis
Two familial cohorts of ALSP, with novel pathological CSF1R variants were examined and an associating cerebrovascular amyloid‐β pathology identified. Deficits in peripheral macrophage function and blood‐brain barrier maintenance identified and suggested to contribute to ALSP.
Two novel pathological CSF1R mutations were identified and characterised, indicating the observed pathology to be driven by CSF1R haploinsufficiency.
Cerebral amyloid angiopathy (CAA) was identified as a novel accompanying pathology in ALSP, providing a potential single‐gene mutation capable of driving CAA itself.
CSF1R heterozygosity was shown to negatively impact macrophage differentiation, phagocytosis and chemotaxis to the brain in response to amyloid‐β.
Microglia heterozygous for Csf1r were shown to be uniquely capable of downregulating tight junction expression in brain endothelial cells.
Two familial cohorts of ALSP, with novel pathological CSF1R variants were examined and an associating cerebrovascular amyloid‐β pathology identified. Deficits in peripheral macrophage function and blood‐brain barrier maintenance identified and suggested to contribute to ALSP.
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