ORCID Profile
0000-0001-6404-9768
Current Organisations
Alfred Health
,
Melbourne Health
,
Monash University
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Publisher: Elsevier BV
Date: 07-2021
Publisher: Consortium of Multiple Sclerosis Centers
Date: 31-12-2021
DOI: 10.7224/1537-2073.2020-075
Abstract: People with multiple sclerosis and neuroimmunologic disorders (herein referred to as patients) are increasingly treated with infusible monoclonal antibodies. This rise in demand has placed increased loads on current infusion services and mandates careful strategic planning. This study examined patient preferences for the timing and location of infusions and their association with demographic and disease variables to facilitate patient-focused strategic planning. Ninety-one patients receiving an infusible therapy at an infusion service during March 2019 were asked to complete a questionnaire exploring eight domains, including preferences for time of infusions and location of infusion centers. Potential access to home-based treatment was included as an option. Unstructured (free-text) feedback on current service was also obtained. Eighty-three patients completed the survey (mean age, 42 years 75% women). Infusions were predominantly natalizumab (66%) and ocrelizumab (25%). Of these patients, 71% were engaged in some form of work or study, and 83% of this group had to arrange time off from work or study to attend treatment. Seventy percent of patients would prefer their infusion before noon, and 60% would consider home-based infusions. Most used a car as their transport to the infusion service. These results suggest that patients are more likely to prefer infusible treatment in the morning and are open to home-based infusions. This study provides information for health services to target service delivery at peak preference times and consider alternate ways of delivering infusible treatments.
Publisher: Mary Ann Liebert Inc
Date: 15-05-2020
Abstract: It is increasingly reported that a history of concussion may be associated with chronic deleterious consequences. While the pathophysiology that contributes to these consequences is not well understood, neuroinflammation is postulated to be critical. Activation of multi-protein complexes termed inflammasomes, a key component of this inflammatory response, has been reported in more severe TBIs however, it has not been investigated in milder TBIs, such as concussion. This study investigated serum levels of interleukin (IL)-1β and IL-18 (key proteins activated downstream of these inflammasomes) at acute, sub-acute, and chronic time-points post-concussion. We recruited 105 Australian footballers (65 male, 40 female) during the pre-season, then prospectively followed these players for the occurrence of concussion during the season. At baseline, 58 footballers reported a previous concussion history, and 47 reported no previous concussion history. Additionally, 25 players sustained a mid-season concussion and were s led at 2, 6, and 13 days post-concussion. Serum levels of IL-1β and IL-18 were quantified using highly sensitive Simoa HD-X Analyzer assays. At baseline, IL-1β levels were higher in male, but not female, footballers with a previous concussion history compared with footballers with no concussion history. There was also a positive correlation between years of collision sport participation and IL-18 levels in males. No evidence was found in males or females to indicate that IL-1β or IL-18 levels differed at 2, 6, or 13 days post-concussion. These findings provide novel insights into potential sex-specific physiological consequences of concussion, and suggest that neuroinflammation may be persistent chronically following concussion in male athletes.
Publisher: Society for Neuroscience
Date: 25-03-2009
DOI: 10.1523/JNEUROSCI.5512-08.2009
Abstract: Microglial activation is an integral part of neuroinflammation associated with many neurodegenerative conditions. Interestingly, a number of neurodegenerative conditions exhibit enhanced P2X 7 receptor (P2X 7 R) expression in the neuroinflammatory foci where activated microglia are a coexisting feature. Whether P2X 7 R overexpression is driving microglial activation or, conversely, P2X 7 R overexpression is a consequence of microglial activation is not known. We report that overexpression alone of a purinergic P2X 7 R, in the absence of pathological insults, is sufficient to drive the activation and proliferation of microglia in rat primary hippoc al cultures. The trophic responses observed in microglia were found to be P2X 7 R specific as the P2X 7 R antagonist, oxidized ATP (oxATP), was effective in markedly attenuating microgliosis. oxATP treatment of primary hippoc al cultures expressing exogenous P2X 7 Rs resulted in a significant decrease in the number of activated microglia. P2X 7 R is unusual in exhibiting two conductance states, a cation channel and a plasma membrane pore, and there are no pharmacological agents capable of cleanly discriminating between these two states. We used a point mutant of P2X 7 R (P2X7R G345Y ) with intact channel function but ablated pore-forming capacity to establish that the trophic effects of increased P2X 7 R expression are exclusively mediated by the pore conductance. Collectively, and contrary to previous reports describing P2X 7 R as a “death receptor,” we provide evidence for a novel trophic role for P2X 7 R pore in microglia.
Publisher: Science and Education Publishing Co., Ltd.
Date: 28-08-2017
DOI: 10.12691/NOVN-2-1-1
Publisher: Hindawi Limited
Date: 08-02-2020
DOI: 10.1155/2020/8454532
Abstract: Anti-GAD antibody syndrome is a result of the production of antibodies against glutamic acid decarboxylase (GAD), the main enzyme responsible for the production of gamma-aminobutyric acid (GABA). Several neurological manifestations including cerebellar ataxia and stiff person syndrome have been reported in association with anti-GAD antibodies. In this paper, we present a case of a young woman with anti-GAD antibodies who initially presented with cerebellar ataxia followed by stiff person syndrome three and a half years later. Having both cerebellar ataxia and stiff person syndrome is a rare occurrence in anti-GAD antibody syndrome. We emphasise the importance of long-term follow-up of patients with anti-GAD antibody syndrome, as delayed neurological manifestations can occur.
Publisher: JMIR Publications Inc.
Date: 12-10-2020
Abstract: ladribine tablets (marketed as Mavenclad) are a new oral therapy, which has recently been listed on the pharmaceutical benefits scheme in Australia for the treatment of relapsing multiple sclerosis (MS). The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS for up to 4 years in 75% of patients (based on annualized relapse rate). However, the reinitiation of therapy after year 4 has not been studied. his study aims to evaluate the safety and efficacy of cladribine tablets over a 6-year period, according to no evidence of disease activity 3. his will be a multicenter, 6-year, phase IV, low interventional, observational study that incorporates clinical, hematological, biochemical, epigenetic, radiological and cognitive biomarkers of disease. Participants considered for treatment with cladribine as part of their routine clinical care will be consented to take part in the study. They will be monitored at regular intervals during the initial course of medication administration in years 1 and 2. After year 3, patients will have the option of redosing, if clinically indicated, or to switch to another disease-modifying therapy. Throughout the duration of the study, we will assess blood-based biomarkers including lymphocyte subsets, serum neurofilament light chain, DNA methylation, and RNA analysis as well as magnetic resonance imaging findings (brain volume and/or lesion load) and cognitive performance. his study has been approved by the Hunter New England Local Health District Human Research Ethics Committee. Recruitment began in March of 2019 and was completed by June 2021. his will be the first long-term efficacy trial of cladribine, which offers reinitiation of therapy in the 3rd year, based on disease activity, after the initial 2 courses. We expect that this study will indicate whether any of the assessed biomarkers can be used to predict treatment efficacy or the need for future reinitiation of cladribine in people with MS. his study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619000257167) with Universal Trial Number (U1111-1228-2165). ERR1-10.2196/24969
Publisher: Springer Science and Business Media LLC
Date: 13-04-2021
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.57
Abstract: Myelin oligodendrocyte glycoprotein (MOG) antibody mediated disease is an autoimmune demyelinating disorder which can resemble multiple sclerosis (MS). 1 2 Thus, this condition can be misdiagnosed and treated as MS. 3 We present the clinical trajectory of two cases initially diagnosed as MS, treated with Alemtuzumab followed by clinical and radiological deterioration. Both were subsequently found to have anti MOG antibody in their serum. This is a retrospective case study based on a medical record search of neuroimmunology clinics in two teaching hospitals in Victoria. We searched for patients treated with Alemtuzumab who subsequently tested positive for MOG antibody. We found two young women who fulfilled the eligibility criteria. One patient presented with dizziness and vertigo, the other with unilateral optic neuritis. Both had supratentorial MRI lesions and were both diagnosed as having MS. Both patients experienced multiple relapses while on treatment for MS. Hence, they were commenced on Alemtuzumab therapy. Unexpectedly, both patients experienced a decline in their clinical status with worsening of expanded disability status scale (EDSS) and an increasing lesion load on MRI brain. Their serum anti MOG antibodies were then found to be positive. Subsequently, patients were treated with rituximab and plasma exchange with a favorable response. These two cases demonstrate that Alemtuzumab is ineffective and in fact can worsen cases of anti-MOG antibody associated encephalomyelitis. This highlights the importance of anti MOG antibody testing when patients diagnosed with MS do not respond to Alemtuzumab and in those patients presenting with atypical features of MS. Weber MS, Derfuss T, Metz I, Bruck W. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther Adv Neurol Disord . 2018 :1756286418762083. Narayan R, Simpson A, Fritsche K, Salama S, Pardo S, Mealy M, et al. MOG antibody disease: A review of MOG antibody seropositive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord . 2018 :66–72. Wildemann B, Jarius S, Schwarz A, Diem R, Viehover A, Hahnel S, et al . Failure of alemtuzumab therapy to control MOG encephalomyelitis. Neurology 2017 (2):207–9.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.10
Abstract: Neuroimaging and CSF analysis compose essential steps in evaluating patients with autoimmune encephalitis (AE). No study has compared the magnitude and prognostic implications of these findings between different subtypes. Herein we examine cases of AE with neuronal cell surface antibodies, and contrast the results of early investigations. We performed medical records search from 2008–2018 in 5 Victorian hospitals. Cases of AE were established in accordance with diagnostic criteria by Graus et al. 1 Clinical and laboratory data was collected. All neuroimaging was evaluated independently by a neuroradiologist. We identified 52 patients with AE with neuronal cell surface antibodies (21 NMDAR, 27 VGKC, 3 AMPAR, 1 GABAb). We found that among patients with anti-LGI1 antibodies the presence of abnormal CSF correlated with increased rates of mortality (50% vs 0%). This effect was largely mediated by CSF lymphocytosis, which was present in 2 patients who both died within 12 months of diagnosis. We found that the development of hippoc al atrophy was more common amongst patients with abnormal MRI findings, but in particular those with changes affecting the medial temporal lobe. This effect was evident both in the cases with anti-VGKC antibodies (60% vs 18%, 75% vs 17%) and the cohort as a whole (56% vs 15%, 83% vs 13%). This is the first study of its kind in Australia, and identifies some unique correlation between early investigation findings, and the clinical and radiological outcome. A larger cohort is required to determine if these findings are statistically significant. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Hoftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Pruss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostasy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016 :391–404.
Publisher: Springer Science and Business Media LLC
Date: 09-10-2021
DOI: 10.1186/S10194-021-01330-7
Abstract: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.19
Abstract: Long-term exposure of women with Multiple sclerosis (MS, wwMS) to immunomodulatory or immunosuppressive treatments may increase the risk of cervical dysplasia. However, little is known about cervical dysplasia risk and Human Papillomavirus (HPV)-vaccine coverage in wwMS. Adult wwMS were recruited from two tertiary MS clinics. To explore the association between MS treatments (DMTs) and abnormal cervical screening tests (CSTs), we linked in idual data from MSBase, the Victorian Cervical Screening Registry, and National HPV vaccination program registry (NHPVPR). To date, we have recruited 208 wwMS of whom 102 had complete data (vaccination status, cervical screening tests, MSBase data) and no previous history of abnormal CST at MS onset for this interim analysis. The average age was 33.8 (18 to 59 yrs) and most (n=58, 88%) were unvaccinated. 19 wwMS (19%) had an abnormal CST after MS onset (incidence rate 20.6 cases/1000 person-years, 95% confidence interval 12.4–32.1) over average 9.0 years of follow-up. 57 wwMS were treated with lower-efficacy therapies (56%), 73 with a high-efficacy therapy (72%), and 44 were exposed to both. Eight abnormal CSTs were detected before starting high-efficacy therapy (rate 12.6, 95% CI (5.4–24.8)) and 11 were detected after starting high-efficacy therapy (rate 38.6, 95% CI (19.3–69.0), p=0.022. We provide preliminary data that high efficacy DMTs may increase the risk of abnormal CSTs over time. A larger cohort and inclusion of additional cervical dysplasia risk factors are required to fully elucidate risk in wwMS.
Publisher: Elsevier BV
Date: 10-2017
Publisher: JMIR Publications Inc.
Date: 19-10-2021
DOI: 10.2196/24969
Abstract: Cladribine tablets (marketed as Mavenclad) are a new oral therapy, which has recently been listed on the pharmaceutical benefits scheme in Australia for the treatment of relapsing multiple sclerosis (MS). The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS for up to 4 years in 75% of patients (based on annualized relapse rate). However, the reinitiation of therapy after year 4 has not been studied. This study aims to evaluate the safety and efficacy of cladribine tablets over a 6-year period, according to no evidence of disease activity 3. This will be a multicenter, 6-year, phase IV, low interventional, observational study that incorporates clinical, hematological, biochemical, epigenetic, radiological and cognitive biomarkers of disease. Participants considered for treatment with cladribine as part of their routine clinical care will be consented to take part in the study. They will be monitored at regular intervals during the initial course of medication administration in years 1 and 2. After year 3, patients will have the option of redosing, if clinically indicated, or to switch to another disease-modifying therapy. Throughout the duration of the study, we will assess blood-based biomarkers including lymphocyte subsets, serum neurofilament light chain, DNA methylation, and RNA analysis as well as magnetic resonance imaging findings (brain volume and/or lesion load) and cognitive performance. This study has been approved by the Hunter New England Local Health District Human Research Ethics Committee. Recruitment began in March of 2019 and was completed by June 2021. This will be the first long-term efficacy trial of cladribine, which offers reinitiation of therapy in the 3rd year, based on disease activity, after the initial 2 courses. We expect that this study will indicate whether any of the assessed biomarkers can be used to predict treatment efficacy or the need for future reinitiation of cladribine in people with MS. This study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619000257167) with Universal Trial Number (U1111-1228-2165). DERR1-10.2196/24969
Publisher: BMJ
Date: 21-04-2018
Publisher: Wiley
Date: 06-09-2023
DOI: 10.1002/EPI4.12822
Abstract: Differentiating status epilepticus (SE) from prolonged psychogenic non‐epileptic seizures (pPNES) can be difficult clinically. We aimed to define the utility of peripheral cell counts, cell ratios, and lactate levels in distinguishing SE from pPNES. Retrospective two‐centre study investigating the sensitivity and specificity of acute (≤12 hours of event offset) peripheral cell counts, cell ratios (neutrophil‐lymphocyte ratio, neutrophil‐monocyte ratio, monocyte‐lymphocyte ratio, platelet‐lymphocyte ratio, systemic immune inflammatory index [SII], systemic inflammatory response index [SIRI]), and lactate levels in differentiating SE from pPNES. Patients were identified from two tertiary hospitals, with one forming the development cohort and the other the validation cohort. Using generalised additive models to generate biomarker versus time curves, optimal blood collection times were defined for set parameters. Three diagnostic scores combining neutrophil count, SII or SIRI with lactate levels were developed and validated in separate cohorts. For the development cohort, 1262 seizure‐like events were reviewed and 79 SE and 44 pPNES events included. For the validation cohort, 241 events were reviewed and 20 SE and 11 pPNES events included. In idually, the biomarkers generally had low sensitivity and reasonable specificity for differentiating SE from pPNES, with neutrophil count, SIRI and SII performing best with sensitivities of 0.65‐0.84, specificities of 0.64‐0.89, and ROC AUCs of 0.78‐0.79. Lactate levels peaked at 60 minutes, while cell counts and ratios peaked after 240 minutes. Combining early peaking lactate levels and later peaking neutrophil count, SIRI or SII resulted in three scores that improved predictive potential with sensitivities of between 0.75‐0.79, specificities between 0.93‐1.00, and ROC AUCs of 0.89‐0.91. Lactate levels peak early post‐SE, whereas cell counts and ratios do so later. The differing post‐event time profiles of lactate levels versus neutrophil count, SIRI and SII allows incorporation into three separate scores which can assist in differentiating SE from pPNES.
Publisher: Elsevier BV
Date: 07-2021
Publisher: SAGE Publications
Date: 08-10-2022
DOI: 10.1177/13524585211049986
Abstract: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1-2 months or 2-6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57-11.11, The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.116
Abstract: Cladribine Tablets (Mavenclad®) is nucleoside analogue of deoxyadenosine, and an oral treatment for relapsing remitting MS (RRMS). In RRMS clinical trials, Cladribine has been shown to reduce brain atrophy, relapse rates, and new lesions on brain MRI. P2X7R is a purinergic receptor expressed in innate immune cells, and is thought to play a critical role in neuroinflammation. The mechanism of action of Cladribine on peripheral innate immune cells (monocytes), and its effect on P2X7R, is unclear, and forms the basis of this study. This will be a Phase IV, multi-centre, 3 year, translational trial. Patients who are starting Cladribine as part of their routine clinical care will consent to take part in the study. Monocyte numbers and activation states will be measured at various times prior and after commencement of therapy. In addition, and in an in vitro setting the effect of Cladribine on P2X7R expression and function will be assessed, as well as measuring various cytokines/chemokines in serum. The laboratory data will also be correlated with clinical data from another long-term Cladribine study, CLOBAS. This study has been approved by Alfred Health Human Research Ethics Committee. The study is to commence in April 2019. This study will shed light on whether Cladribine is exerting its beneficial effects via action on peripheral monocytes and alterations of their P2X7Rs. The laboratory and clinical data will be analysed to understand the relationship between innate immune parameters and patient outcome.
Publisher: SAGE Publications
Date: 27-07-2022
DOI: 10.1177/13524585221111677
Abstract: Patients with relapsing–remitting multiple sclerosis commonly switch between disease-modifying therapies (DMTs). Identifying predictors of relapse when switching could improve outcomes. To determine predictors of relapse hazard when switching to cladribine. Data of patients who switched to cladribine, grouped by prior disease-modifying therapy (pDMT interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab (NTZ)), were extracted from the MSBase Registry. Predictors of relapse hazard during the treatment gap and the first year of cladribine therapy were determined. Of 513 patients, 22 relapsed during the treatment gap, and 38 within 1 year of starting cladribine. Relapse in the year before pDMT cessation predicted treatment gap relapse hazard (hazard ratio (HR) = 2.43, 95% confidence interval (CI) = 1.03–5.71). After multivariable adjustment, relapse hazard on cladribine was predicted by relapse before pDMT cessation (HR = 2.00, 95% CI = 1.01–4.02), treatment gap relapse (HR = 6.18, 95% confidence interval (CI) = 2.65–14.41), switch from NTZ (HR compared to injectable therapies 4.08, 95% CI = 1.35–12.33) and age at cladribine start (HR = 0.96, 95% CI = 0.91–0.99). Relapse during or prior to the treatment gap, and younger age, are of prognostic relevance in the year after switching to cladribine. Switching from NTZ is also independently associated with greater relapse hazard.
Publisher: Springer Science and Business Media LLC
Date: 09-09-2020
DOI: 10.1038/S41598-020-71887-X
Abstract: Glioblastoma is the most aggressive form of primary brain cancer, with a median survival of 12–15 months. The P2X receptor 7 (P2X7R) is upregulated in glioblastoma and is associated with increased tumor cell proliferation. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is also upregulated in glioblastoma and has been shown to have both pro- and anti-tumor functions. This study investigates the potential mechanism linking P2X7R and GM-CSF in the U251 glioblastoma cell line and the therapeutic potential of P2X7R antagonism in this setting. P2X7R protein and mRNA was demonstrated to be expressed in the U251 cell line as assessed by immunocytochemistry and qPCR. Its channel function was intact as demonstrated by live cell confocal imaging using a calcium indicator Fluo-4 AM. Inhibition of P2X7R using antagonist AZ10606120, decreased both GM-CSF mRNA (P 0.05) and protein (P 0.01) measured by qPCR and ELISA respectively. Neutralization of GM-CSF with an anti-GM-CSF antibody did not alter U251 cell proliferation, however, P2X7R antagonism with AZ10606120 significantly reduced U251 glioblastoma cell numbers (P 0.01). This study describes a novel link between P2X7R activity and GM-CSF expression in a human glioblastoma cell line and highlights the potential therapeutic benefit of P2X7R inhibition with AZ10606120 in glioblastoma.
Publisher: Wiley
Date: 13-09-2011
DOI: 10.1111/CEN3.12651
Abstract: Neurocognitive compromise, neuropsychiatric symptoms and psychopathology are all evident in the acute stages of autoimmune encephalitides. These factors considerably affect functional independence after discharge. Drawing on psychometric assessments and qualitative descriptions, this review explores the nature, extent and diagnosis of cognitive disorder in autoimmune encephalitides. Potential pathophysiological and neuroanatomical architecture related to neurocognitive compromise in the acute and chronic stages of this illness is examined. In regard to outcomes, the review highlights clinicodemographic factors currently known to be associated with poorer cognitive outcome. Finally, the review delves into neuropsychiatric symptomology and psychological concerns that should be considered at diagnosis and during follow up of these patients.
Publisher: MDPI AG
Date: 22-01-2020
DOI: 10.3390/MPS3010011
Abstract: Glioblastoma is a heterogeneous glial cell malignancy with extremely high morbidity and mortality. Current treatment is limited and provide minimal therapeutic efficacy. Previous studies were reliant on cell lines that do not accurately reflect the heterogeneity of the glioma microenvironment. Developing reliable models of human glioblastoma is therefore essential. Direct culture of human brain tumours is often difficult and there is a limited number of protocols available. Hence, we have developed an effective method for the primary culture of human glioblastoma s les obtained during surgical resection. Culturing tumour tissue direct from human brain is advantageous in that cultures (1) more closely resemble true human disease, relative to the use of cell lines (2) comprise a range of cellular components present in the natural tumour microenvironment and (3) are free of added antibodies and reagents. Additionally, primary glioblastoma cultures are valuable in studies examining the effects of anti-cancer pharmaceuticals and therapeutic agents, and can be further used in live cell imaging, immunocytochemistry, flow cytometry and immunoassay experiments. Via this protocol, cells are maintained in supplemented medium at 37 °C (5% CO2) and are expected to achieve sufficient confluency within 7 days of initial culture.
Publisher: BMJ
Date: 08-2020
DOI: 10.1136/BMJNO-2020-000069
Abstract: Gliomas are the most common central nervous system malignancies and present with significant morbidity and mortality. Treatment modalities are currently limited to surgical resection, chemotherapy and radiotherapy. Increases in survival rate over the previous decades are negligible, further pinpointing an unmet clinical need in this field. There is a continual struggle with the development of effective glioma diagnostics and therapeutics, largely due to a multitude of factors, including the presence of the blood–brain barrier and significant intertumoural and intratumoural heterogeneity. Importantly, there is a lack of reliable biomarkers for glioma, particularly in aiding tumour subtyping and measuring response to therapy. There is a need for biomarkers that would both overcome the complexity of the disease and allow for a minimally invasive means of detection and analysis. This is a comprehensive review evaluating the potential of current cellular, proteomic and molecular biomarker candidates for glioma. Significant hurdles faced in glioma diagnostics and therapy are also discussed here.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JNEUROIM.2019.04.010
Abstract: Gliomas are the most prevalent tumours of the central nervous system and present with high morbidity and mortality. The most common and most aggressive form of glioma is glioblastoma multiforme, of which patients have a median survival time of only 12 to 15 months. Current treatment options are limited and have a small impact on clinical outcome and prognosis. There is accumulating evidence that microglia, the immunocompetent cells of the central nervous system, and the purinergic P2X7 receptor (P2X7R) may contribute to tumour progression and pathology. Importantly, P2X7R on both tumour cells and infiltrating microglia is overexpressed in animal and human glioma cultures. Factors released by glioma cells and P2X7R activation recruit microglia into the largely immunosuppressive tumour microenvironment where they have been demonstrated to contribute to either tumour proliferation or tumour suppression. It is likely that P2X7R mediates a range of microglia effector functions in the glioma setting, potentially increasing tumour growth and proliferation. This review evaluates current evidence on the roles of microglia and P2X7R in glioma pathogenesis. Understanding the nature, mechanisms and outcomes of microglia and P2X7R activation in gliomas is necessary for the development of more therapies with increased efficacy and specificity.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2020
Publisher: AMPCo
Date: 05-2014
DOI: 10.5694/MJA2.51012
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.119
Abstract: Cladribine tablets (marketed as Mavenclad®) is a new oral therapy, which has recently been listed on the pharmaceuticals benefit scheme (PBS) in Australia for treatment of relapsing MS. The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS up to 4 years in 75% of patients (based on annualised relapse rate). However, re-initiation of therapy after year 4 has not been studied. This will be a multicentre, 6-year, phase IV, low interventional trial. Subjects considered for treatment with cladribine will receive an initial treatment course in year 1 and a continuing treatment course in year 2. After year 3, patients will have the option for re-dosing, if clinically indicated or to switch to another disease modifying therapy. Throughout the duration of the study we will assess blood based biomarkers including lymphocyte subsets, serum neurofilament light chain, DNA methylation and RNA analysis as well as MRI findings (brain volume/lesion load) and cognitive performance. This study has been approved by the Hunter New England Local Health District Human Research Ethics Committee. The study is due to commence on March 14 th . This will be the first long-term efficacy trial of cladribine which offers re-initiation of therapy after the initial two courses. We expect this study will be an indication if any of the assessed biomarkers can be used to predict treatment efficacy or the need for re-initiation of Cladribine in MS patients.
Publisher: Wiley
Date: 14-12-2020
DOI: 10.1111/EPI.16788
Abstract: Epilepsy is seen historically as a disease of aberrant neuronal signaling manifesting as seizures. With the discovery of numerous auto‐antibodies and the subsequent growth in understanding of autoimmune encephalitis, there has been an increasing emphasis on the contribution of the innate and adaptive immune system to ictogenesis and epileptogenesis. Pathogenic antibodies, complement activation, CD8+ cytotoxic T cells, and microglial activation are seen, to various degrees, in different seizure‐associated neuroinflammatory and autoimmune conditions. These aberrant immune responses are thought to cause disruptions in neuronal signaling, generation of acute symptomatic seizures, and, in some cases, the development of long‐term autoimmune epilepsy. Although early treatment with immunomodulatory therapies improves outcomes in autoimmune encephalitides and autoimmune epilepsies, patient identification and treatment selection are not always clear‐cut. This review examines the role of the different components of the immune system in various forms of seizure disorders including autoimmune encephalitis, autoimmune epilepsy, Rasmussen encephalitis, febrile infection–related epilepsy syndrome (FIRES), and new‐onset refractory status epilepticus (NORSE). In particular, the pathophysiology and unique cytokine profiles seen in these disorders and their links with diagnosis, prognosis, and treatment decision‐making are discussed.
Publisher: BMJ Publishing Group Ltd
Date: 08-2021
Publisher: Elsevier BV
Date: 11-2020
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/JNNP-2019-ANZAN.5
Abstract: Seizures are a common characteristic of Autoimmune encephalitis (AIE). The use of the electroclinical characteristics to assist in the diagnosis of AIE has been explored 1 however use of specific electroencephalogram (EEG) changes has not been examined with regards to outcome prediction. Patients with AIE were recruited retrospectively across 4 hospitals in Victoria. Clinical Data was collected during admission and at final follow-up. EEGs of patients were reviewed using an objective proforma. Associations between EEG biomarkers and clinical outcomes were demonstrated using logistic regression modelling. We recruited 88 patients with AIE and available EEGs. Presence of rhythmic delta, superimposed fast activity and an abnormal background were significantly more common in N-methyl-D-aspartame receptor (NMDAR) antibody associated AIE patients (p .05). ICU admission was associated with rhythmic delta epileptiform activity (OR 3.25, p=0.046), sharp elements in the EEG abnormality (OR 3.55, p=0.05), and an abnormal background rhythm (OR 3.56, p=0.03). Development of drug resistant epilepsy was associated with prolonged duration of abnormality on EEG (OR 11.99, p=0.013), and sharp elements in the EEG abnormality (OR 7.29, p=0.02). We have identified EEG biomarkers that differentiate NMDAR AIE from other subtypes, and likely represents an objective description of extreme delta brush which has previously been described in NMDAR AIE. 2 We have also demonstrated biomarkers associated with important outcomes that can be used to help guide treatment and prognosis. Limotai C, Denlertchaikul C, Saraya AW, Jirasakuldej S. Predictive values and specificity of electroencephalographic findings in autoimmune encephalitis diagnosis. Epilepsy Behav 2018 :29–36. Veciana M, Becerra JL, Fossas P, Muriana D, Sansa G, Santamarina E, et al. EEG extreme delta brush: An ictal pattern in patients with anti-NMDA receptor encephalitis. Epilepsy Behav 2015 :280–5.
Publisher: BMJ Publishing Group Ltd
Date: 08-2021
Publisher: Sciedu Press
Date: 07-2019
DOI: 10.5430/CRIM.V6N2P5
Abstract: Glutamic acid decarboxylase (GAD) is becoming increasingly recognised as an antigenic target in autoimmune disorders of the central nervous system. There are currently no reports of weight loss being a manifestation in such disorders. We describe two cases of anti-GAD associated neurological disorders with profound and otherwise unexplained weight loss. Both patients had incomplete response to immunotherapy, as is becoming typical of these disorders. The variable disease associations of anti-GAD antibodies is incompletely understood, and leads us to question whether weight loss in these patients could possibly be immune-mediated.
Publisher: Humana Press
Date: 24-08-2012
DOI: 10.1007/978-1-62703-086-1_19
Abstract: Within single cells there is a complex myriad of signaling which controls physiological process many of which are modulated, or signaled directly, by intracellular calcium ions. Understanding the exquisitely sensitive, and spatially restricted, changes in calcium has been of interest to the researcher for a number of years. Recent advances in this field have been driven by the development of genetically encoded calcium probes for detecting calcium changes within the cells specifically targeting organelles such as mitochondria, endoplasmic reticulum, and the nucleus. In this chapter the authors outline some of the available fluorescent probes, with particular emphasis on an endoplasmic reticulum targeted calcium biosensor in cell signaling studies with astrocytes, detailing experimental protocols and the interpretation of data from such probes.
Publisher: Wiley
Date: 12-2004
DOI: 10.1111/J.1440-1681.2004.04098.X
Abstract: 1. Our aim is to measure near-membrane Ca(2+) flux within the presynaptic terminals of central neurons by modifying new genetically encoded Ca(2+) sensors to develop tools capable of measuring localized Ca(2+) signals. 2. We used standard recombinant DNA technologies to generate the DNA coding for a fusion construct of a modified fluorescent 'pericam' Ca(2+) biosensor with a presynaptic P2X7 receptor (P2X7R). The Ca(2+) sensitivity of the biosensor was modified by rational site-directed mutagenesis of the calmodulin portion of the pericam. 3. Biosensor-receptor fusions were transfected into expression systems for evaluation. Expression studies in HEK-293 cells showed that biosensor-receptor fusion construct-delivered protein was localized exclusively to the plasma membrane, confirming that fusion did not affect the ability of the receptor to undergo normal protein synthesis and trafficking. 4. The Ca(2+)-dependent fluorescence of the pericam portion of the fusion protein was also retained. Site-direct mutagenesis within the calmodulin moiety of the pericam significantly reduced the Ca(2+) affinity of the complex. The dynamic range of the sensor following this modification is better matched to the higher Ca(2+) levels expected within presynaptic Ca(2+) microdomains.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 17-03-2021
Publisher: MDPI AG
Date: 26-04-2022
Abstract: Many medical applications have arisen from the technological advancement of three-dimensional (3D) bioprinting, including the printing of cancer models for better therapeutic practice whilst imitating the human system more accurately than animal and conventional in vitro systems. The objective of this systematic review is to comprehensively summarise information from existing studies on the effectiveness of bioinks in mimicking the tumour microenvironment of glioblastoma and their clinical value. Based on predetermined eligibility criteria, relevant studies were identified from PubMed, Medline Ovid, Web of Science, Scopus, and ScienceDirect databases. Nineteen articles fulfilled the inclusion criteria and were included in this study. Alginate hydrogels were the most widely used bioinks in bioprinting. The majority of research found that alginate bioinks had excellent biocompatibility and maintained high cell viability. Advanced structural design, as well as the use of multicomponent bioinks, recapitulated the native in vivo morphology more closely and resulted in bioprinted glioblastoma models with higher drug resistance. In addition, 3D cell cultures were superior to monolayer or two-dimensional (2D) cell cultures for the simulation of an optimal tumour microenvironment. To more precisely mimic the heterogenous niche of tumours, future research should focus on bioprinting multicellular and multicomponent tumour models that are suitable for drug screening.
Publisher: SAGE Publications
Date: 2021
Abstract: To determine the prevalence of epileptic seizures in multiple sclerosis (MS) at an Australian tertiary hospital and to define their clinical features. We retrospectively analysed adult patients at the Royal Melbourne Hospital electronically identified to have ICD codes for MS and seizures and/or epilepsy between 1996 to 2019, utilising paper and electronic-based records. Of the 2,125 MS patients identified, 16 (0.75%) experienced epileptic seizures during a mean follow-up period of 12.9 years. Median age of MS diagnosis (SD) was 38 (9.3) years. Four patients had relapsing remitting MS (25%), 10 secondary progressive MS (63.5%), and 2 primary progressive MS (12.5%). More than two-thirds of patients had seizure onset following the diagnosis of MS, and the majority of these had advanced disease (approximate EDSS ) at the time of seizure onset. Focal onset-seizures occurred in 87.5% of patients with seizures. The estimated prevalence of seizures in our cohort was lower than in previous studies (0.75 vs 2–4%). In most cases, seizures occurred after the diagnosis of MS in the context of advanced disease. Further studies are required to determine if MS disease modifying treatments reduce the risk of seizures in this cohort.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JAUT.2018.10.014
Abstract: To perform a systematic review of the current scientific literature in order to identify variables associated with patient prognosis in autoimmune encephalitis. We performed a systematic literature search using MEDLINE, Embase, PubMed and PsychInfo databases. We selected studies that explored the correlation between early clinical and paraclinical findings, and patient outcomes. Data was extracted, analyzed and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Forty four publications detailing 2823 subjects matched our inclusion criteria. There was considerable heterogeneity in methodology, patient profile, investigation results and clinical outcome measures. Findings were often discrepant for cases of anti-NMDAR encephalitis when compared with other causes of autoimmune encephalitis. Delay in immunotherapy contributed to a variety of worse outcomes for patients with different subsets of autoimmune encephalitis. Altered consciousness, ICU admission and no use of immunotherapy were variables associated with poor prognosis in anti-NMDAR encephalitis. Older age, sex, the presence of status epilepticus, CSF abnormalities and MRI changes were unlikely to have significant prognostic value. The influence of antibody titers, autonomic dysfunction and underlying malignancy was unclear. A number of variables were identified to have potential predictive value for outcomes in autoimmune encephalitis. Heterogeneous study design, size and quality were major limiting factors in this review.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JNEUROIM.2019.03.004
Abstract: Multiple sclerosis (MS) is characterized by neuroinflammatory infiltrates and central nervous system demyelination. In the neuroinflammatory foci of MS there is increased expression of a purinergic receptor, P2X7R. Although implicated in the neuroinflammation, the exact role of P2X7R in the context of MS is unclear and forms the basis of this review. In this review, we also introduce the immunopathologies and inflammatory processes in MS, with a focus on P2X7R and the possible immunomodulatory role of vitamin D deficiency in this setting.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Springer Science and Business Media LLC
Date: 06-04-2020
DOI: 10.1186/S12974-020-01778-5
Abstract: There is a great clinical need to identify the underlying mechanisms, as well as related biomarkers, and treatment targets, for traumatic brain injury (TBI). Neuroinflammation is a central pathophysiological feature of TBI. NLRP3 inflammasome activity is a necessary component of the innate immune response to tissue damage, and dysregulated inflammasome activity has been implicated in a number of neurological conditions. This paper introduces the NLRP3 inflammasome and its implication in the pathogenesis of neuroinflammatory-related conditions, with a particular focus on TBI. Although its role in TBI has only recently been identified, findings suggest that priming and activation of the NLRP3 inflammasome are upregulated following TBI. Moreover, recent studies utilizing specific NLRP3 inhibitors have provided further evidence that this inflammasome is a major driver of neuroinflammation and neurobehavioral disturbances following TBI. In addition, there is emerging evidence that circulating inflammasome-associated proteins may have utility as diagnostic biomarkers of neuroinflammatory conditions, including TBI. Finally, novel and promising areas of research will be highlighted, including the potential involvement of the NLRP3 inflammasome in mild TBI, how factors such as biological sex may affect NLRP3 activity in TBI, and the use of emerging biomarker platforms. Taken together, this review highlights the exciting potential of the NLRP3 inflammasome as a target for treatments and biomarkers that may ultimately be used to improve TBI management.
Publisher: BMJ Publishing Group Ltd
Date: 08-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-12-2020
DOI: 10.1212/NXI.0000000000000924
Abstract: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody–associated disorders (MOGAD), we performed detailed characterization of an Australasian MOGAD cohort. Using a live cell–based assay, we diagnosed 271 adults with MOGAD (2013–2018) and performed detailed clinical and immunologic characterization on those with likely PNS involvement. We identified 19 adults with MOGAD and PNS involvement without prior TM. All patients had CNS involvement including ON (bilateral [n = 3], unilateral [n = 3], and recurrent [n = 7]), a cortical lesion (n = 1), meningoencephalitis (n = 1), and subsequent TM (n = 4). Clinical phenotyping and neurophysiology were consistent with acute inflammatory demyelinating polyneuropathy (n = 1), myeloradiculitis (n = 3), multifocal motor neuropathy (n = 1), brachial neuritis (n = 2), migrant sensory neuritis (n = 3), and paresthesia and/or radicular limb pain (n = 10). Onset MRI spine was consistent with myeloradiculitis with nerve root enhancement in 3/19 and normal in 16/19. Immunotherapy resulted in partial/complete PNS symptom resolution in 12/15 (80%) (steroids and/or IV immunoglobulin n = 9, rituximab n = 2, and plasmapheresis n = 1). We identified serum antibodies targeting neurofascin 155, contactin-associated protein 2, or GM1 in 4/16 patients with MOGAD PNS compared with 0/30 controls ( p = 0.01). There was no binding to novel cell surface antigens using an in vitro myelinating sensory neuronal coculture model. Myeloradiculitis, combined central and peripheral demyelination syndromes, and inflammatory neuropathies may be associated with MOGAD and may be immunotherapy responsive. We identified a subgroup who may have pathology mediated by coexistent autoantibodies.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2022
DOI: 10.1186/S12883-022-02612-6
Abstract: Myelin Oligodendrocyte Glycoprotein antibody-associated disease (MOGAD) is most classically associated in both children and adults with phenotypes including bilateral and recurrent optic neuritis (ON) and transverse myelitis (TM), with the absence of brain lesions characteristic of multiple sclerosis (MS). ADEM phenotype is the most common presentation of MOGAD in children. However, the presence of clinical phenotypes including unilateral ON and short TM in some patients with MOGAD may lead to their misdiagnosis as MS. Thus, clinically and radiologically, MOGAD can mimic MS and clinical vigilance is required for accurate diagnostic workup. We present three cases initially diagnosed as MS and then treated with alemtuzumab. Unexpectedly, all three patients did quite poorly on this medication, with a decline in their clinical status with worsening of expanded disability status scale (EDSS) and an increasing lesion load on magnetic resonance imaging of the brain. Subsequently, all three cases were found to have anti-MOG antibody in their serum. These cases highlight that if a patient suspected to have MS does not respond to conventional treatments such as alemtuzumab, a search for alternative diagnoses such as MOG antibody disease may be warranted.
Publisher: Frontiers Media SA
Date: 14-01-2021
DOI: 10.3389/FIMMU.2020.597858
Abstract: To examine the utility of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) as biomarkers of prognosis in seropositive autoimmune encephalitis (AE). In this multicenter study, we retrospectively analyzed 57 cases of seropositive AE with hospital admissions between January 2008 and June 2019. The initial full blood examination was used to determine each patients’ NLR and MLR. The modified Rankin Scale (mRS) was utilized to assess the patients’ follow-up disability at 12 months and then at final follow-up. Primary outcomes were mortality and mRS, while secondary outcomes were failure of first line treatment, ICU admission, and clinical relapse. Univariate and multivariable regression analysis was performed. During initial hospital admission 44.7% of patients had unsuccessful first line treatment. After a median follow-up of 700 days, 82.7% had good functional outcome (mRS ≤2) while five patients had died. On multivariable analysis, high NLR was associated with higher odds of first line treatment failure (OR 1.32, 95% CI 1.03–1.69, p = 0.029). Increased MLR was not associated with any short or long-term outcome. NLR on initial hospital admission blood tests may be provide important prognostic information for cases of seropositive AE. This study demonstrates the potential use of NLR as a prognostic marker in the clinical evaluation of patients with seropositive AE.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.NEUBIOREV.2019.12.027
Abstract: Neurological conditions such as traumatic brain injury, stroke, Parkinson's disease, epilepsy, multiple sclerosis, and Alzheimer's disease are serious clinical problems that affect millions of people worldwide. The majority of clinical trials for these common conditions have failed, and there is a critical need to understand why treatments in preclinical animal models do not translate to patients. Many patients with these conditions are middle-aged or older, however, the majority of preclinical studies have used only young-adult animals. Considering that aging involves biological changes that are relevant to the pathobiology of neurological diseases, the lack of aged subjects in preclinical research could contribute to translational failures. This paper details how aging affects biological processes involved in neurological conditions, and reviews aging research in the context of traumatic brain injury, stroke, Parkinson's disease, epilepsy, multiple sclerosis, and Alzheimer's disease. We conclude that aging is an important, but often overlooked, factor that influences biology and outcomes in neurological conditions, and provide suggestions to improve our understanding and treatment of these diseases in aged patients.
Publisher: Wiley
Date: 13-05-2020
DOI: 10.1111/EPI.16515
Abstract: Epilepsy is a common neurological disorder that increases the risk of morbidity and mortality. Autoimmune epilepsy is a subset of epilepsy that occurs in the setting of autoimmunity, such as in autoimmune encephalitis (AIE). AIE is an autoimmune disorder characterized by immune‐mediated neuroinflammation resulting in a variety of neurological symptoms, including psychiatric disturbance, cognitive dysfunction, and seizures. Seizures in AIE are thought to be a result of antibodies directed against neuronal cell‐surface proteins involved in synaptic transmission. The role of blood‐brain barrier dysfunction, myeloid cell infiltration, and the initiation of proinflammatory cascades in epileptogenesis has been shown to be important in animal models and human patients with epilepsy. Epileptogenesis in AIE is likely to arise from the synergistic effect of both innately driven neuroinflammation and antibody‐induced hyperexcitability. Together, these processes produce persistent drug‐resistant seizures that contribute to the morbidity seen in AIE. Understanding the proinflammatory pathways involved in this process may improve diagnostics and provide alternative treatment targets in AIE.
Publisher: Frontiers Media SA
Date: 10-09-2019
Publisher: Springer Science and Business Media LLC
Date: 03-09-2019
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.BRAINRESBULL.2019.10.010
Abstract: Inflammatory response through interleukin-1β (IL-1β) plays a key role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanism of pro-IL-1β processing in AD is not clearly defined. The current study was designed to investigate which of the inflammasome complexes are critical for IL-1β production in AD. An experimental model for Alzheimer like disease was induced in male Wistar rats and Morris Water Maze was used to evaluate the function of learning and memory. The expression of genes involved in inflammasome complex including NLRP1, NLRP3, NLRC4, AIM2, ASC, IL18, IL-1β and caspase-1 was determined via Real-time PCR. Hematoxylin and Eosin (H&E) staining and Immunohistochemistry (IHC) for CD45 was applied to assess inflammatory cells infiltration. Furthermore, caspase-1, IL-1β and phosphorylated tau (p-Tau) protein expressing cells were investigated in the lesion area using immunofluorescence staining technique. The behavioral study revealed that streptozotocin (STZ) injection significantly impaired learning and memory function. In addition, the infiltration of inflammatory cells was confirmed in the hippoc us region of STZ-treated animals. Furthermore, a significant increase in the expression level of NLRC4 inflammasome, ASC and IL-1β was identified in STZ-treated animals. In contrast, no significant difference was observed in other inflammasome components including NLRP1, NLRP3, AIM2, IL-18 and caspase-1 in STZ-treated group compared with the control group. Moreover, the number of caspase-1, IL-1β and p-Tau protein positive cells were remarkably increased in STZ-treated animals. Based on the obtained results, it can be concluded that increased production of IL-1β, caspase-1 and p-Tau through association with NLRC4 inflammasome may be involved in neuroinflammation and memory impairment in AD, which creates a new horizon in this regard. Hence, strategies targeting NLRC4 inflammasome could be beneficial for the treatment of AD.
Publisher: Springer Science and Business Media LLC
Date: 30-06-2016
Publisher: Springer Science and Business Media LLC
Date: 28-08-2014
Publisher: BMJ Publishing Group Ltd
Date: 08-2021
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.JNEUROIM.2021.577754
Abstract: To evaluate the ability for pre-treatment NLR and MLR to predict overall survival (OS) and modified Rankin Scale (mRS) and to explore their relationship with clinicopathological parameters. Retrospective analysis of pretreatment NLR and MLR from 64 glioma patients. Higher pretreatment NLR (>4.7) predicted higher mean admission mRS (p 0.35) was a risk factor for poorer OS in glioma patients (p = 0.024). Higher pretreatment NLR was significantly associated with larger tumor diameter (p = 0.02). NLR and MLR can serve as prognostic markers to predict functional outcomes and OS in glioma patients.
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/IMJ.5_13457
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.BIOCEL.2010.06.021
Abstract: Microglial activation is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD), Parkinsons' disease, prion disease, multiple sclerosis, and ischemic and traumatic brain injury. The molecular mechanism of microglial activation is largely unknown. The expression of the purinergic, P2X7 receptor (P2X7R), is known to be enhanced in many brain pathologies where presence of activated microglia is a concurrent feature. This review focuses on the links between P2X7R expression and microglial activation and proliferation. The P2X7R is identified as a key player in the process of microgliosis, where by driving microglial activation, it can potentially lead to a deleterious cycle of neuroinflammation and neurodegeneration.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2023
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-032567
Abstract: To investigate whether sex, age, medical specialty and seasonal variations in serum concentration of 25-hydroxy vitamin D (25(OH)D) are evident among an Australian patient population. Retrospective study analysing the results of serum 25(OH)D lab tests and vitamin D supplementation from Royal Melbourne Hospital (RMH) between 2014 and 2017. Tertiary healthcare centre in Victoria, Australia. 30 023 patients (inpatient and outpatient) who had their serum 25(OH)D levels measured at RMH between 2014 and 2017. Serum 25(OH)D levels stratified according to patients’ sex, age and medical specialty admitted to, as well as the season and year (2014 to 2017) 25(OH)D level was measured. Mean serum 25(OH)D level of study population was 69.9 nmol/L (95% CI 69.5 to 70.2). Only 40.2% patients in this cohort were sufficient in vitamin D ( nmol/L). On average, 25(OH)D levels in male patients were 6.1 units (95% CI 5.4 to 6.9) lower than in females. Linear regression analysis found that 25(OH)D levels increased by 0.16 unit (95% CI 0.14 to 0.18) for every year increase in age. One-way analysis of variance showed patients from neurology had the highest average 25(OH)D level, 76.8 nmol/L (95% CI 74.2 to 79.3) compared with other medical specialties. Mean 25(OH)D level during winter, 64.9 nmol/L (95% CI 64.2 to 65.6) was significantly lower compared with other seasons despite supplementation. Average 25(OH)D level measured in 2014, 71.5 nmol/L (95 CI% 70.8 to 72.2) was significantly higher than levels measured in 2016–2017. There is a sex, age, medical specialty, seasonal and yearly variation in vitamin D status in an Australian patient population. The association between low vitamin D status and winter despite supplementation suggests other interventions are required to boost serum 25(OH)D levels.
Publisher: Wiley
Date: 08-0012
DOI: 10.1111/AJD.12239
Abstract: Mal de Meleda is a rare autosomal recessive genodermatosis caused by mutations in the ARS B (SLURP1) gene, with possible founder effects in the Mediterranean and Adriatic regions. We report an affected in idual from Indonesia without known consanguinity in the family, suggesting that SLURP1 gene mutations are ubiquitous. Recognition of the phenotype can be confirmed by genetic testing, thus facilitating genetic counselling.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JOCN.2017.08.014
Abstract: The routine outpatient electroencephalogram (EEG) is most often used in the diagnosis and classification of epilepsy. The diagnostic yield of outpatient EEGs is low and the clinical factors contributing to the EEG outcome have not been well established. In this study, we sought to determine the yield and the factors predicting the EEG outcome. We retrospectively analyzed 1092 routine adult EEGs that were performed in a tertiary referral center over a period of 1year. Patient demographics, sources of referral, and indications for EEG were recorded. The majority of the referrals were from neurologists (54.7%), followed by the emergency department (15.4%). The indications for requesting an EEG included patients with a provisional or established diagnosis of epilepsy (56.3%), first seizure (10.7%), and seizure mimickers (29.1%). The majority (66.7%) of the EEGs were normal, whereas 13.2% demonstrated epileptiform discharges. At the time of recording, epileptic seizures occurred in 0.6% of the cases. With logistic regression analysis, three factors were found to be significantly associated with an abnormal (epileptiform) EEG: no antiepileptic drug therapy, the age of the patient, and indication for EEG (pre-test provisional diagnosis). Patients who are not on antiepileptic drug therapy and with a diagnosis of epilepsy or seizures are more likely to have epileptiform abnormalities in EEGs. Our findings suggest that careful selection of patients is likely to improve the diagnostic yield and cost-effectiveness of routine outpatient EEG.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2022
Publisher: Elsevier BV
Date: 12-2018
No related grants have been discovered for Mastura Monif.