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1.
Front Netw Physiol ; 4: 1424004, 2024.
Article in English | MEDLINE | ID: mdl-39114571

ABSTRACT

Introduction: Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or "irritative" network. Methods: Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups. Results: There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment. Discussion: The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.

2.
Front Netw Physiol ; 4: 1425329, 2024.
Article in English | MEDLINE | ID: mdl-39055857

ABSTRACT

We present two cases with focal seizures where scalp electroencephalography (EEG) had prominent features of a developmental and epileptic encephalopathy (DEE): Case 1: a 17-year-old male with complex motor seizures whose EEG demonstrated a slow spike-and-wave pattern and generalized paroxysmal fast activity (GPFA). Case 2: a 12-year-old male with startle-induced asymmetric tonic seizures whose EEG also had a slow spike-and-wave pattern. Both patients had intracranial EEG assessment, and focal cortical resections resulted in long-term seizure freedom and resolution of generalized findings. These cases exemplify patients with focal epilepsy with networks that share similarities to generalized epilepsies, and importantly, these features did not preclude curative epilepsy surgery.

3.
Lipids Health Dis ; 23(1): 59, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38414008

ABSTRACT

Cancer cells need constant supplies of lipids to survive and grow. Lipid dependence has been observed in various types of cancer, including high-grade serous ovarian carcinomas (HGSOC), which is a lethal form of gynecological malignancy. ANGPTL3, PCSK9, and Apo CIII are pivotal lipid-modulating factors, and therapeutic antibodies have been developed against each one (Evinacumab, Evolocumab and Volanesorsen, respectively). The roles -if any- of ANGPTL3, PCSK9, and Apo CIII in HGSOC are unclear. Moreover, levels of these lipid-modulating factors have never been reported before in HGSOC. In this study, circulating levels of ANGPTL3, PCSK9, and Apo CIII, along with lipid profiles, are examined to verify whether one or many of these lipid-regulating factors are associated with HGSOC. Methods ELISA kits were used to measure ANGPTL3, PCSK9 and Apo CIII levels in plasma samples from 31 women with HGSOC and 40 women with benign ovarian lesions (BOL) before treatment and surgery. A Roche Modular analytical platform measured lipid panels, Apo B and Lp(a) levels.Results ANGPTL3 levels were higher in women with HGSOC (84 ng/mL, SD: 29 ng/mL, n = 31) than in women with BOL (67 ng/mL, SD: 31 ng/mL, n = 40; HGSOC vs. BOL P = 0.019). Associations between the lipid panel and ANGPTL3, and the inverse relationship between HDL-cholesterol and triglycerides, were present in women with BOL but not with HGSOC. PCSK9 and Apo CIII were not associated with HGSOC.Conclusions In this cohort of 71 women, ANGPTL3 levels were increased in HGSOC patients. The presence of HGSOC disrupted the classic inverse relationship between HDL and triglycerides, as well as the association between the lipid panel and ANGPTL3. These associations were only maintained in cancer-free women. Given the availability of Evinacumab, a therapeutic antibody against ANGPTL3, the current finding prompts an assessment of whether ANGPTL3 inhibition has therapeutic potential in HGSOC.


Subject(s)
Carcinoma , Ovarian Cysts , Ovarian Neoplasms , Humans , Female , Proprotein Convertase 9 , Angiopoietin-like Proteins/genetics , Angiopoietin-Like Protein 3 , Ovarian Neoplasms/drug therapy , Triglycerides , Angiopoietins/genetics
4.
Epileptic Disord ; 25(4): 534-544, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37265017

ABSTRACT

OBJECTIVE: Epilepsy surgery success is dependent on accurate localization of the epileptogenic zone. Despite the use of invasive EEG using subdural grids and strips, surgical failures can occur. In this series, we explore the utility of a second evaluation with stereoelectroencephalography in patients whose initial invasive evaluation with subdural grid electrodes was unsuccessful in localizing seizure origin. METHODS: We conducted a retrospective review of patients who underwent subdural grid evaluation (SDE) at our center and identified patients who underwent a re-evaluation with stereoelectroencephalography (SEEG). RESULTS: We identified three patients who had both subdural and SEEG electrodes in the region of the identified epileptogenic zone in whom the initial SDE evaluation failed to make the patients seizure-free. Two of these patients underwent a second resection and became seizure-free. SIGNIFICANCE: Stereoelectroencephalography can be useful in the re-evaluation and re-operation of patients who previously had surgical failure using SDE.


Subject(s)
Electroencephalography , Epilepsy , Humans , Electrodes, Implanted , Stereotaxic Techniques , Epilepsy/diagnosis , Epilepsy/surgery , Seizures/surgery , Retrospective Studies , Treatment Outcome
5.
Res Pract Thromb Haemost ; 7(1): 100011, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36891523

ABSTRACT

Background: Patients with antiphospholipid syndrome (APS) receive anticoagulant therapy with vitamin K antagonists (VKAs) to prevent recurrent thrombosis. VKA treatment requires strict monitoring with an international normalized ratio (INR). It is known that lupus anticoagulants (LAs) can lead to elevated INR results with point-of-care-testing (POCT) devices, which could result in inadequate adaptation of anticoagulant therapy. Objective: To determine discrepancies between POCT-INR and laboratory-INR in patients who are LA-positive on VKA therapy. Methods: Paired INR testing was performed with 1 POCT device (CoaguChek XS) and 2 laboratory assays (Owren and Quick method) in 33 patients with LA-positive APS on VKA in a single-center cross-sectional study. Patients were tested for anti-ß2-glycoprotein I, anticardiolipin, and antiphosphatidylserine/prothrombin immunoglobulin (Ig) G and IgM antibodies. Agreement between assays was evaluated with Spearman's correlation, Lin's correlation coefficient, and Bland-Altman plots. Agreement limits were considered satisfactory if differences were ≤20% as determined by the Clinical and Laboratory Standards Institute. Results: We found poor agreement between POCT-INR and laboratory-INR based on Lin's concordance correlation coefficient (ρc) of 0.42 (95% CI, 0.26-0.55) between POCT-INR and Owren-INR, a ρc of 0.64 (95% CI, 0.47-0.76) between POCT-INR and Quick-INR, and a ρc of 0.77 (95% CI, 0.64-0.85) between Quick-INR and Owren-INR. High anti-ß2-glycoprotein I IgG antibody titers correlated with INR disagreement between POCT-INR and laboratory-INR. Conclusion: There is a disagreement between INR values measured with the CoaguChek XS and laboratory-INR in a proportion of patients with LA. Consequently, laboratory-INR monitoring should be preferred over POCT-INR monitoring in patients with LA-positive APS, especially in patients with high anti-ß2-glycoprotein IgG antibody titers.

7.
J Clin Nurs ; 32(13-14): 3730-3745, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36494199

ABSTRACT

AIMS AND OBJECTIVES: The aim of this study is to enhance the understanding of the core elements and influencing factors on the community-based epilepsy nurse's role and responsibilities. BACKGROUND: Internationally, epilepsy nurse specialists play a key role in providing person-centred care and management of epilepsy but there is a gap in understanding of their role in the community. DESIGN: A national three-stage, mixed-method study was conducted. METHODS: One-on-one, in-depth semi-structured qualitative interviews were conducted online with 12 community-based epilepsy nurses (Stage 1); retrospective analysis of data collected from the National Epilepsy Line, a nurse-led community helpline (Stage 2); and focus group conducted with four epilepsy nurses, to delve further into emerging findings (Stage 3). A thematic analysis was conducted in Stages 1 and 3, and a descriptive statistical analysis of Stage 2 data. Consolidated Criteria for Reporting Qualitative studies checklist was followed for reporting. RESULTS: Three key themes emerged: (1) The epilepsy nurse career trajectory highlighted a lack of standardised qualifications, competencies, and career opportunities. (2) The key components of the epilepsy nurse role explored role diversity, responsibilities, and models of practice in the management of living with epilepsy, and experiences navigating complex fragmented systems and practices. (3) Shifting work practices detailed the adapting work practices, impacted by changing service demands, including COVID-19 pandemic experiences, role boundaries, funding, and resource availability. CONCLUSION: Community epilepsy nurses play a pivotal role in providing holistic, person-centred epilepsy management They contribute to identifying and addressing service gaps through innovating and implementing change in service design and delivery. RELEVANCE TO CLINICAL PRACTICE: Epilepsy nurses' person-centred approach to epilepsy management is influenced by the limited investment in epilepsy-specific integrated care initiatives, and their perceived value is impacted by the lack of national standardisation of their role and scope of practice. NO PATIENT OR PUBLIC CONTRIBUTION: Only epilepsy nurses' perspectives were sought.


Subject(s)
COVID-19 , Epilepsy , Nurses , Humans , Pandemics , Retrospective Studies , Nurse's Role , Qualitative Research
8.
J Asthma Allergy ; 15: 1491-1510, 2022.
Article in English | MEDLINE | ID: mdl-36303891

ABSTRACT

Background: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics. Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson's chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons. Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147). Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

9.
BMC Cancer ; 22(1): 1049, 2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36203122

ABSTRACT

BACKGROUND / SYNOPSIS: Cholesterol and lipids play an important role in sustaining tumor growth and metastasis in a large variety of cancers. ANGPTL3 and PCSK9 modify circulating cholesterol levels, thus availability of lipids to peripheral cells. Little is known on the role, if any, of circulating lipid-related factors such as PCSK9, ANGPTL3 and lipoprotein (a) in cancers. OBJECTIVE/PURPOSE: To compare circulating levels of PCSK9, ANGPTL3, and Lp(a) in women with stage III breast cancer versus women with premalignant or benign breast lesions. METHODS: Twenty-three plasma samples from women diagnosed with a stage III breast cancer (ductal, lobular or mixed) were matched for age with twenty-three plasma samples from women bearing premalignant (stage 0, n = 9) or benign (n = 14) breast lesions. The lipid profile (Apo B, total cholesterol, HDL cholesterol and triglycerides levels) and Lp(a) were measured on a Roche Modular analytical platform, whereas LDL levels were calculated with the Friedewald formula. ANGPTL3 and PCSK9 plasma levels were quantitated by ELISA. All statistical analyses were performed using SAS software version 9.4. RESULTS: PCSK9 levels were significantly higher in women with stage III breast cancer compared to age-matched counterparts presenting a benign lesion (95.9 ± 27.1 ng/mL vs. 78.5 ± 19.3 ng/mL, p < 0.05, n = 14). Moreover, PCSK9 levels positively correlated with breast disease severity (benign, stage 0, stage III) (Rho = 0.34, p < 0.05, n = 46). In contrast, ANGPTL3 and Lp(a) plasma levels did not display any association with breast disease status and lipids did not correlate with disease severity. CONCLUSION: In this small cohort of 46 women, PCSK9 levels tended to increase with the severity of the breast disease. Given that PCSK9 plays an important role in maintaining cholesterolemia, and a potential role in tumor evasion, present results warrant further investigation into a possible association between PCSK9 levels and breast cancer severity in larger cohorts of women.


Subject(s)
Breast Neoplasms , Proprotein Convertase 9 , Angiopoietin-Like Protein 3 , Angiopoietin-like Proteins , Apolipoproteins B , Cholesterol , Cholesterol, HDL , Female , Humans , Lipoprotein(a) , Triglycerides
10.
Epilepsy Behav Rep ; 19: 100561, 2022.
Article in English | MEDLINE | ID: mdl-35899185

ABSTRACT

There is a paucity of data on longitudinal seizure outcome of children undergoing epilepsy surgery. All children (n = 132) who underwent resective epilepsy surgery from January 1998 to December 2015 were identified. Relevant clinical, neurophysiological, imaging, surgical and seizure outcome data were extracted. Multivariable logistic regression analysis and Kaplan-Meier survival with Cox proportional hazard modelling were performed. The mean age at surgery was 7.8 years (range 0.2-17.9). 71% were seizure-free at a mean follow up of 5.3 ± 2.7 years. Of those who were seizure-free, 65 patients were able to completely wean off anti- seizure medications successfully. Using survival analysis, the probability of Engel Class I outcome at one year after surgery was 81% (95% confidence interval [CI] 87%-75%). This dropped to 73% at two years (95% CI 81%-65%), 58% at five years (95% CI 67.8%-48%), and 47% at ten years. Proportional hazard modelling showed that the presence of moderate to severe developmental disability (HR 6.5; p = 0.02) and lack of complete resection (HR 0.4; p = 0.02) maintain association as negative predictors of seizure-free outcome. Our study demonstrates favorable long-term seizure control following pediatric epilepsy surgery and highlights important predictors of seizure outcome guiding case selection and counseling of expectations prior to surgery.

11.
BMJ Open ; 12(4): e057537, 2022 04 05.
Article in English | MEDLINE | ID: mdl-35383079

ABSTRACT

INTRODUCTION: Precision medicine (PM) involves gene testing to identify disease risk, enable early diagnosis or guide therapeutic choice, and targeted gene therapy. We aim to perform a systematic review and meta-analysis to quantify the cost-effectiveness profile of PM stratified by intervention type, identify sources of heterogeneity in the value-for-money of PM. METHODS AND ANALYSIS: We will perform a systematic search in Embase, MEDLINE, EconLit and CRD databases for studies published in English language or with translation in English between 1 January 2011 and 8 July 2021 on the topic of cost-effectiveness analysis of PM interventions. The focus will be on studies that reported health and economic outcomes. Study quality will be assessed using the Biases in Economic Studies checklist. The incremental net benefit of PM screening, diagnostic, treatment-targeting and therapeutic interventions over conventional strategies will be respectively pooled across studies using a random-effect model if heterogeneity is present, otherwise a fixed-effect model. Subgroup analyses will be performed based on disease area, WHO region and World Bank country-income level. Additionally, we will identify the potential sources of heterogeneity with random-effect meta-regressions. Finally, biases will be detected using jackknife sensitivity analysis, funnel plot assessment and Egger's tests. ETHICS AND DISSEMINATION: For this type of study ethics approval or formal consent is not required. The results will be disseminated at various presentations and feedback sessions, in conference abstracts and manuscripts that will be submitted to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021272956.


Subject(s)
Mass Screening , Precision Medicine , Cost-Benefit Analysis , Humans , Meta-Analysis as Topic , Systematic Reviews as Topic
12.
Front Hum Neurosci ; 16: 815749, 2022.
Article in English | MEDLINE | ID: mdl-35280209

ABSTRACT

Objective: To prospectively study the cingulate cortex for the localization and role of the grasping action in humans during electrical stimulation of depth electrodes. Methods: All the patients (n = 23) with intractable focal epilepsy and a depth electrode stereotactically placed in the cingulate cortex, as part of their pre-surgical epilepsy evaluation from 2015 to 2017, were included. Cortical stimulation was performed and examined for grasping actions. Post-implantation volumetric T1 MRIs were co-registered to determine the exact electrode position. Results: Five patients (male: female 4:1; median age 31) exhibited contralateral grasping actions during electrical stimulation. All patients had electrodes implanted in the ventral bank of the right cingulate sulcus adjacent to the vertical anterior commissure (VAC) line. Stimulation of other electrodes in adjacent regions did not elicit grasping. Conclusion: Grasping action elicited from a localized region in the mid-cingulate cortex (MCC) directly supports the concept of the cingulate cortex being crucially involved in the grasping network. This opens an opportunity to explore this region with deep brain stimulation as a motor neuromodulation target for treatment in specific movement disorders or neurorehabilitation.

13.
Epileptic Disord ; 24(2): 404-410, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-34874268

ABSTRACT

Localisation of the human parietal eye fields (PEF) has not been as well studied as the human frontal eye fields (FEF). Stimulation studies in rhesus monkeys have suggested the localisation of the PEF to be within the intraparietal sulcus. Functional MRI studies have demonstrated this region to be highly active and potentially connected in saccadic and gaze shifting tasks. Here, we present a case of a patient with left versive seizures evaluated with SEEG, in whom electrical stimulation within the right intraparietal sulcus resulted in horizontal and downward conjugate eye movements contralateral to stimulation. We illustrate clinical differences between the FEF and PEF on cortical stimulation. In addition to the frontal eye field, it is important to recognise other cortical regions involved in eye movement which can cause conjugate contralateral eye movement.


Subject(s)
Parietal Lobe , Saccades , Animals , Brain Mapping/methods , Electric Stimulation , Frontal Lobe , Humans , Macaca mulatta , Photic Stimulation
14.
Langmuir ; 37(27): 8167-8176, 2021 Jul 13.
Article in English | MEDLINE | ID: mdl-34176271

ABSTRACT

Janus particles contain two or more chemical properties typically on opposing faces. With various property combinations possible, there are several potential applications, such as surfactants and drug delivery. However, scaling up the particle production process at reasonable cost is a limiting factor, and the method reported here aims to circumvent this issue. The process is based on a top-down destructive strategy that consists of two steps. Photocatalytic titanium dioxide particles prefunctionalized with a surface coating were assembled as particle films via spin-coating on a substrate. The particle films were placed directly under an ultraviolet light source, which induced the photodegradation of the surface coating only on the particle surfaces exposed to the light. The generated Janus particles were amphiphobic-amphiphilic in character. The Janus particles had a theoretical Janus balance close to ideal and remained attached at a hexane/water interface after disruption. They were able to make Pickering emulsions of water in silicone oil with a low energy input. The reported method may be easily scaled up to facilitate the production of gram-scale yields. The use of UV is clean and efficient and can be applied to semiconductor particles with surface coatings that are susceptible to photodegradation, making this method highly versatile.

15.
World J Clin Cases ; 9(5): 1139-1147, 2021 Feb 16.
Article in English | MEDLINE | ID: mdl-33644178

ABSTRACT

BACKGROUND: Thymic epithelial carcinomas are rare and have a poor prognosis. Treatment of thymic epithelial carcinoma is multimodal and includes surgery, post-operative radiation therapy, adjuvant and neoadjuvant chemotherapy, or exclusive chemotherapy based on disease resectability. However, there is currently no standard treatment regimen for metastatic and recurrent thymic carcinoma. CASE SUMMARY: A 45-year-old Caucasian male, with no past medical history, presented with hepatalgia and a cervical mass. A computed tomography (CT) scan showed multiple suspect lesions in the lungs, liver, and anterior mediastinum associated with mediastinal and cervical adenopathy. CT-guided percutaneous biopsies of the liver lesions and anterior mediastinal mass were performed, confirming the histopathology of thymic epithelial carcinoma. Management consisted of several chemotherapy regimens and radiation therapy, administered between April 2016 and December 2018. The patient achieved complete metabolic response. Fluorodeoxyglucose positron emission tomography/CT performed in June 2019 showed disease relapse, with reappearance of a large hypermetabolic hepatic mass and involvement of mediastinal and axillary lymph nodes. Intravenous pembrolizumab (200 mg, every 3 wk) was administered after two prior systemic therapies. The patient's response to treatment was last documented on March 5, 2020. CONCLUSION: Pembrolizumab was successful in treatment of a patient with programmed death-ligand 1-negative metastatic thymic carcinoma, pretreated with chemotherapy.

16.
BMJ Open ; 11(1): e043553, 2021 01 25.
Article in English | MEDLINE | ID: mdl-33495260

ABSTRACT

INTRODUCTION: Epilepsy is a common neurological condition affecting between 3% and 3.5% of the Australian population at some point in their lifetime. The effective management of chronic and complex conditions such as epilepsy requires person-centred and coordinated care across sectors, from primary to tertiary healthcare. Internationally, epilepsy nurse specialists are frequently identified as playing a vital role in improving the integration of epilepsy care and enhancing patient self-management. This workforce has not been the focus of research in Australia to date. METHODS AND ANALYSIS: This multistage mixed-method study examines the role and responsibilities of epilepsy nurses, particularly in primary and community care settings, across Australia, including through the provision of a nurse helpline service. A nationwide sample of 30 epilepsy nurses will be purposively recruited via advertisements distributed by epilepsy organisations and through word-of-mouth snowball sampling. Two stages (1 and 3) consist of a demographic questionnaire and semistructured interviews (individual or group) with epilepsy nurse participants, with the thematic data analysis from this work informing the areas for focus in stage 3. Stage 2 comprises of a retrospective descriptive analysis of phone call data from Epilepsy Action Australia's National Epilepsy Line service to identify types of users, their needs and reasons for using the service, and to characterise the range of activities undertaken by the nurse call takers. ETHICS AND DISSEMINATION: Ethics approval for this study was granted by Macquarie University (HREC: 52020668117612). Findings of the study will be published through peer-reviewed journal articles and summary reports to key stakeholders, and disseminated through public forums and academic conference presentations. Study findings will also be communicated to people living with epilepsy and families.


Subject(s)
Epilepsy , Research Design , Australia , Humans , Retrospective Studies , Surveys and Questionnaires
17.
RSC Adv ; 11(31): 18757-18767, 2021 May 24.
Article in English | MEDLINE | ID: mdl-35478622

ABSTRACT

NADPH and NADH are well known for their role in antioxidant defense and energy metabolism, respectively, however distinguishing their cellular autofluorescence signals is a challenge due to their nearly identical optical properties. Recent studies applying spectral phasor analysis to autofluorescence emission during chemically induced metabolic responses showed that two-component spectral behavior, i.e., spectral change acting as a superposition of two spectra, depended on whether one or multiple metabolic pathways were affected. Here, we use this property of spectral behavior to show that metabolic responses primarily involving NADPH or NADH can be distinguished. We start by observing that the cyanide-induced response at micro- and millimolar concentrations does not follow mutual two-component spectral behavior, suggesting their response mechanisms differ. While respiratory inhibition at millimolar cyanide concentration is well known and associated with the NADH pool, we find the autofluorescence response at micromolar cyanide concentration exhibits two-component spectral behavior with NADPH-linked EGCG- and peroxide-induced responses, suggesting an association with the NADPH pool. What emerges is a spectral phasor map useful for distinguishing cellular autofluorescence responses related to oxidative stress versus cellular respiration.

18.
Epileptic Disord ; 22(5): 633-641, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-33146141

ABSTRACT

Evaluating the candidacy for epilepsy surgery in patients with tuberous sclerosis can be challenging, particularly when non-invasive investigations do not show a clear epileptogenic zone. Stereoencephalography may be useful in such cases. We present a case in which the primary epileptogenic tuber was successfully identified by stereoencephalography, which resulted in seizure freedom following epilepsy surgery. [Published with video sequences].


Subject(s)
Electroencephalography , Epilepsy/surgery , Neurosurgical Procedures , Tuberous Sclerosis/surgery , Adolescent , Electroencephalography/methods , Epilepsy/complications , Epilepsy/diagnosis , Humans , Male , Neurosurgical Procedures/methods , Treatment Outcome , Tuberous Sclerosis/complications , Tuberous Sclerosis/diagnosis
19.
Epilepsy Behav ; 111: 107232, 2020 10.
Article in English | MEDLINE | ID: mdl-32640412

ABSTRACT

OBJECTIVES: This mixed-method feasibility study conducted in New South Wales (NSW), Australia, aimed to explore clinical practices around the identification of patients with refractory epilepsy and referral from primary care to Tertiary Epilepsy Centers. The perceptions of general practitioners, neurologists, and adults living with refractory epilepsy were considered. METHODS: Fifty-two data collection events were achieved through 22 semi-structured interviews with six neurologists and 12 adults who currently have, or have had refractory epilepsy, and four family members, 10 clinical observations of patient consultations and 20 surveys with general practitioners. A thematic analysis was conducted on the qualitative data alongside assessment of observational fieldnotes and survey data. FINDINGS: Two main themes emerged: 1) Patient healthcare pathways and care experiences highlighted the complex and deeply contextualized experiences of both patients and healthcare professionals, from first identification of people's seizures, in primary and community care settings, to referral to Tertiary Epilepsy Centers, shedding light on a fragmented, nonstandardized referral process, influenced by both individual and shared-care practices. 2) Factors impacting referrals and patient pathways indicated that onward referral to a Tertiary Epilepsy Center is affected by the knowledge, or the lack thereof, of healthcare professionals regarding treatment options. Barriers include limited person-centered care, shared decision-making, and refractory epilepsy education for healthcare professionals, which can delay patients' disease identification and can hinder speedy referral pathways and processes, in Australia for up to 17 years. In addition, person-centered communication around care pathways is affected by relationships between clinicians, patients, and family members. CONCLUSION: This study has identified a noticeable lack of standardized care across epilepsy-related healthcare sectors, which recognizes a need for developing and implementing clearer epilepsy-related guidelines and Continuing Professional Development in the primary and community care settings. This, however, requires greater collaboration and commitment in the primary, community, and tertiary care sectors to address the ongoing misconceptions around professional roles and responsibilities to optimize shared-care practices. Ultimately, prioritizing person-centered care on both patients' and professionals' agendas, in order to improve satisfaction with care experiences of people living with complex epilepsy.


Subject(s)
Drug Resistant Epilepsy/epidemiology , Drug Resistant Epilepsy/therapy , Primary Health Care/methods , Referral and Consultation , Surveys and Questionnaires , Tertiary Healthcare/methods , Adult , Aged , Drug Resistant Epilepsy/psychology , Family/psychology , Feasibility Studies , Female , General Practitioners/psychology , General Practitioners/trends , Humans , Male , Middle Aged , Neurologists/psychology , Neurologists/trends , New South Wales/epidemiology , Primary Health Care/trends , Qualitative Research , Referral and Consultation/trends , Tertiary Healthcare/trends
20.
Epileptic Disord ; 21(4): 347-352, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31366450

ABSTRACT

Small encephaloceles of the anterior temporal pole have been increasingly recognised as an underlying epileptogenic substrate in patients with medically refractory epilepsy. The current report aims to expand on the current knowledge by emphasising that seizure semiology in such patients can vary significantly. Patients were selected from an epilepsy surgery database between 2012 and 2017. Of the 143 patients who underwent epilepsy surgery, six patients had a temporal encephalocele. Four of these patients had stereo-EEG implantation. Of the four patients studied, each had a seizure semiology discordant with an ictal focus in the temporal lobe. Intracranial EEG assessment demonstrated, irrespective of this semiology, seizures originated from the anterior temporal pole. Seizures were observed to rapidly propagate to the orbitofrontal cortex, insula, temporo-occipital junction, and posterior language regions. Engagement of the mesial temporal structures could occur early or late, however, a good surgical outcome was achieved following a focused lesionectomy in either situation. The major finding was that seizures arising from anterior temporal encephaloceles can have an extra-temporal semiology. The varied clinical semiology and the rapid propagation to seemingly distant cortical regions could be explained by the connectivity of the anterior temporal lobe.


Subject(s)
Electroencephalography , Encephalocele/physiopathology , Epilepsy/physiopathology , Seizures/physiopathology , Drug Resistant Epilepsy/physiopathology , Electrocorticography/methods , Electroencephalography/methods , Epilepsy/surgery , Female , Humans , Magnetic Resonance Imaging/methods , Male
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