Recently proposed diagnostic criteria for iatrogenic cerebral amyloid angiopathy (iCAA) have sparked increased recognition of cases across the globe. Whilst these patients tend to have a tumultuous ...course, much like sporadic CAA, there is a high degree of variability. What is unique in this case is the breadth of clinicoradiological data available, including handwritten surgical notes from 1985. In retrospect, early imaging changes of what would ultimately lead to profound morbidity, were apparent 30 years after inoculation with cadaveric dural tissue.
In this case study we examine the clinicoradiological features of a case of probable iCAA and draw awareness to the presence of this disease in Australia.
This case was admitted under the care of the author at the Royal Brisbane and Women's Hospital (RBWH). Clinical details and data were gathered during the patient's care and consent for publication provided by the enduring power of attorney.
This 56-year-old female presented in 2018 with left hemiparesis, neglect, and dysarthria secondary to a large right frontal lobe intracerebral hemorrhage (ICH) without an underlying macrovascular cause. MRI brain demonstrated diffuse superficial siderosis assumed related to previous surgical interventions during the mid-1980s for a Chiari malformation and cervical syrinx. There was evidence of extensive white matter disease, discordant with her lack of cerebrovascular disease risk factors. Brain biopsy confirmed CAA. Archived surgical notes confirmed exposure to Lyodura in 1985 and 1986. Two decades of MRI data were available for review and illustrate the evolution of CAA, from normal post-operative findings to marked and unrecognized abnormalities 4 years prior to her first ICH.
This is the first Australian case of probable iatrogenic CAA (iCAA) to have such extensive documentation of clinicoradiological evolution. It demonstrates the aggressive course iCAA can take and provides insights into early disease manifestations, relevant to the more common sporadic cases. A brief review of the history of commercial cadaveric tissue use in Australia highlights enormous changes in medical practice over the last 50 years. Awareness within Australia should be raised for this clinical phenomenon, and cases collated to contribute to the growing international pool of evidence.
Early math skills matter for later formal mathematical performances, academic and professional success. Accordingly, it is important to accurately assess mathematical school readiness (MSR) at the ...beginning of elementary school. This would help identifying children who are at risk of encountering difficulties in math and then stimulate their acquisition of mathematical skills as soon as possible. In the present study, we present a new test that allows professionals working with children (e.g., teachers, school psychologists, speech therapists, and school doctors) to assess children's MSR when they enter formal schooling in a simple, rapid and efficient manner. 346 children were assessed at the beginning of 1st Grade (6-to-7-year-olds) with a collective test assessing early mathematical abilities (T1). In addition, children's math skills were evaluated with classical curriculum math tests at T1 and a year later, in 2nd Grade (T2, 7-to-8-year-olds). After assessing internal consistency, three tasks were retained for the final version of the MSR test. Test performance confirmed to be essentially unidimensional and systematically related to the scores children obtained in classical tests in 1st and 2nd Grade. By using the present MSR test, it is possible to identify pupils at risk of developing low math skills right from the start of formal schooling in 1st Grade. Such a tool is needed, as children's level in math at school beginning (or school readiness) is known to be foundational for their future academic and professional carrier.
Abstract Background The metabolism of cancer cells generally differs from that of normal cells. Indeed, most cancer cells have a high rate of glycolysis, even at normal oxygen concentrations. These ...metabolic properties can potentially be exploited for therapeutic intervention. In this context, we have developed troglitazone derivatives to treat hormone-sensitive and triple-negative breast cancers, which currently lack therapeutic targets, have an aggressive phenotype, and often have a worse prognosis than other subtypes. Here, we studied the metabolic impact of the EP13 compound, a desulfured derivative of Δ2-troglitazone that we synthetized and is more potent than its parent compounds. Methods EP13 was tested on two triple-negative breast cancer cell lines, MDA-MB-231 and Hs578T, and on the luminal cell line MCF-7. The oxygen consumption rate (OCR) of the treated cell lines, Hs578T mammospheres and isolated mitochondria was measured using the XFe24 Seahorse analyser. ROS production was quantified using the MitoSOX fluorescent probe. Glycolytic activity was evaluated through measurement of the extracellular acidification rate (ECAR), glucose consumption and lactate production in extracellular medium. The synergistic effect of EP13 with glycolysis inhibitors (oxamate and 2-deoxyglucose) on cell cytotoxicity was established using the Chou-Talalay method. Results After exposure to EP13, we observed a decrease in the mitochondrial oxygen consumption rate in MCF7, MDA-MB-231 and Hs578T cells. EP13 also modified the maximal OCR of Hs578T spheroids. EP13 reduced the OCR through inhibition of respiratory chain complex I. After 24 h, ATP levels in EP13-treated cells were not altered compared with those in untreated cells, suggesting compensation by glycolysis activity, as shown by the increase in ECAR, the glucose consumption and lactate production. Finally, we performed co-treatments with EP13 and glycolysis inhibitors (oxamate and 2-DG) and observed that EP13 potentiated their cytotoxic effects. Conclusion This study demonstrates that EP13 inhibits OXPHOS in breast cancer cells and potentiates the effect of glycolysis inhibitors.
Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease ...by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia.
We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected.
Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABA
receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability.
Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery.
ObjectiveWe report a favourable outcome following early treatment with rituximab in a patient with probable Susac’s syndrome (SuS).BackgroundDelayed treatment of SuS leads to significant morbidity, ...however there is no consensus in its management.ResultsA 34-year-old man presented with severe headache, subacute confusion and blurred vision developing over 4 months. The MRI brain revealed multiple supratentorial and infratentorial FLAIR/T2 hyperintense lesions in white and gray matter, including characteristic corpus collosum ‘snow ball’ lesions. The fundus fluorescein angiography (FFA) showed typical branch retinal artery occlusion, consistent with his bilateral decrease in visual fields. CSF showed high protein (3000mg/L) and pleocytosis (18X106/L). Following diagnosis of probable SuS, he was treated with high-dose corticosteroids on day 3 of presentation, followed by IVIG, mycophenolate and rituximab. He had significant improvement within 1 week. By 3 months, he returned to his neuropsychological baseline in majority of cognitive domains from moderate-severe dysfunction, with concurrent MRI demonstrating resolving white matter lesions and FFA showing less evident vasculitis. The treatment response was maintained with tapering of steroids (25mg at 12 months). He was able to return to his previous occupation as a paramedic by 1 year.ConclusionSuS is a rare, immune-mediated microangiopathy in which early recognition with aggressive immunosuppression is required to achieve optimal outcome. No randomized controlled trial (RCT) exists for the management of this condition. In this report, early recognition through multidisciplinary input and aggressive immunotherapy with rituximab resulted in a favourable outcome. However, RCT evidence is needed to guide management.
While numerical skills are fundamental in modern societies, some estimated 5-7% of children suffer from mathematical learning difficulties (MLD) that need to be assessed early to ensure successful ...remediation. Universally employable diagnostic tools are yet lacking, as current test batteries for basic mathematics assessment are based on verbal instructions. However, prior research has shown that performance in mathematics assessment is often dependent on the testee's proficiency in the language of instruction which might lead to unfair bias in test scores. Furthermore, language-dependent assessment tools produce results that are not easily comparable across countries. Here we present results of a study that aims to develop tasks allowing to test for basic math competence without relying on verbal instructions or task content. We implemented video and animation-based task instructions on touchscreen devices that require no verbal explanation. We administered these experimental tasks to two samples of children attending the first grade of primary school. One group completed the tasks with verbal instructions while another group received video instructions showing a person successfully completing the task. We assessed task comprehension and usability aspects both directly and indirectly. Our results suggest that the non-verbal instructions were generally well understood as the absence of explicit verbal instructions did not influence task performance. Thus we found that it is possible to assess basic math competence without verbal instructions. It also appeared that in some cases a single word in a verbal instruction can lead to the failure of a task that is successfully completed with non-verbal instruction. However, special care must be taken during task design because on rare occasions non-verbal video instructions fail to convey task instructions as clearly as spoken language and thus the latter do not provide a panacea to non-verbal assessment. Nevertheless, our findings provide an encouraging proof of concept for the further development of non-verbal assessment tools for basic math competence.
IntroductionStroke reperfusion therapies, comprising intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), are best practice treatments for eligible acute ischemic stroke patients. ...In Australia, EVT is provided at few, mainly metropolitan, comprehensive stroke centres (CSC). There are significant challenges for Australia’s rural and remote populations in accessing EVT, but improved access can be facilitated by a ‘drip and ship’ approach. TACTICS (Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship) aims to test whether a multicomponent, multidisciplinary implementation intervention can increase the proportion of stroke patients receiving EVT.Methods and analysisThis is a non-randomised controlled, stepped wedge trial involving six clusters across three Australian states. Each cluster comprises one CSC hub and a minimum of three primary stroke centre (PSC) spokes. Hospitals will work in a hub and spoke model of care with access to a multislice CT scanner and CT perfusion image processing software (MIStar, Apollo Medical Imaging). The intervention, underpinned by behavioural theory and technical assistance, will be allocated sequentially, and clusters will move from the preintervention (control) period to the postintervention period.Primary outcomeProportion of all stroke patients receiving EVT, accounting for clustering.Secondary outcomesProportion of patients receiving IVT at PSCs, proportion of treated patients (IVT and/or EVT) with good (modified Rankin Scale (mRS) score 0–2) or poor (mRS score 5–6) functional outcomes and European Quality of Life Scale scores 3 months postintervention, proportion of EVT-treated patients with symptomatic haemorrhage, and proportion of reperfusion therapy-treated patients with good versus poor outcome who presented with large vessel occlusion at spokes.Ethics and disseminationEthical approval has been obtained from the Hunter New England Human Research Ethics Committee (18/09/19/4.13, HREC/18/HNE/241, 2019/ETH01238). Trial results will be disseminated widely through published manuscripts, conference presentations and at national and international platforms regardless of whether the trial was positive or neutral.Trial registration numberACTRN12619000750189; UTNU1111-1230-4161.
Compared to other ethnic groups in the UK, Black people have the highest rates of psychosis. This may partly be explained by both assessment bias and structural racism. Mental health services often ...find it difficult to develop therapeutic relationships with Black people with psychosis. Attachment theory posits that the quality of previous caregiving experiences influence current interpersonal functioning and emotional regulation. In this study, we applied the theory to improve the understanding of therapeutic relationships with people with psychosis.
This is the first study to examine associations between attachment difficulties, therapeutic alliance, and service engagement in a Black sample with psychosis.
Fifty-one participants completed self-report measures of attachment and alliance. Staff completed measures of alliance and service engagement.
Higher attachment avoidance was related to poorer alliance ratings. These significant findings were not upheld in a regression model controlling for total symptom scores and perceived ethnic/racial discrimination in services. Attachment anxiety was generally not associated with alliance ratings. Neither attachment anxiety nor attachment avoidance was significantly associated with service engagement.
Staff should be supported to better understand the needs of service users with avoidant attachment behaviours and to develop mutually-agreed treatment goals and therapeutic bonds.
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