Evaluating the Contributions of State of the Art Assessment Techniques to Predicting Memory Outcome after Unilateral Anterior Temporal Lobectomy

Purpose:Although anterior temporal lobectomy (ATL) is an effective treatment for many patients with medically refractory temporal lobe epilepsy (TLE), one risk associated with this procedure is postsurgical decline in memory. A substantial number of past studies examined factors that predict memory decline after surgery, but few have investigated multiple predictors simultaneously or considered measures that are currently in use. Methods: This study compared the relative contributions made by presurgical neuropsychological test scores, MRI-based hippocampal volumetric analysis, and Wada test results to predicting memory outcome after ATL in a group of 87 patients. Results: Logistic regression analyses indicated that noninvasive procedures (neuropsychological testing and MRI) made significant contributions to improving the prediction of memory outcome in this sample. The results from the Wada procedure did not significantly improve prediction once these other factors were considered. The only exception was in predicting memory for visual information after a delay, in which Wada results improved prediction accuracy from 78% to 81%. Conclusions: Current neuropsychological tests and MRI volumetric measures predict changes in verbal and visual memory after ATL. The relatively small change in correct classification rates when Wada memory scores are considered calls into question the benefits of using Wada test results to predict memory outcome when the results of noninvasive procedures are available

APOE ɛ4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy

This study examined the relationship between the APOE ɛ4 allele and postictal confusion in patients with medically intractable temporal lobe epilepsy (TLE). Patients with at least one ɛ4 allele (n = 22) were three times more likely to exhibit postictal confusion (68%) than the 63 patients without ɛ4 (43%). These preliminary results demonstrate that APOE ɛ4 is associated with an increased risk of postictal confusion in patients with medically intractable TLE, suggesting possible dysfunction in neuronal recovery mechanisms

Assessment of Trace Estrogenic Contaminants Removal by Coagulant Addition, Powdered Activated Carbon Adsorption and Powdered Activated Carbon/Microfiltration Processes

Increasing attention is being paid to health and environmental risk as a result of the presence of trace steroid estrogens in the effluent discharged from municipal sewage treatment plants. This paper focuses on assessment of removal of these trace compounds using 3H-labelled estrone as the model compound. Jar tests over a range of ferric chloride dosage and pH conditions showed that coagulation was ineffective in removal of estrone from secondary effluent. The experiments showed that the combination of PAC and microfiltration could be effective for removal of trace estrone from water. The rate and extent of estrone removal by PAC are functions of PAC dosage and retention time of PAC in the system. Mathematical analysis of the results using a homogeneous surface diffusion model (HSMD) indicates that the adsorption of estrone on PAC can be limited by film diffusion and internal surface diffusion. The surface and film mass transfer coefficients were determined to be 9.72 x 10-10 cm2/min and 1.963 cm/min, respectively, under the conditions used

AMR, stability and higher accuracy

Efforts to achieve better accuracy in numerical relativity have so far focused either on implementing second order accurate adaptive mesh refinement or on defining higher order accurate differences and update schemes. Here, we argue for the combination, that is a higher order accurate adaptive scheme. This combines the power that adaptive gridding techniques provide to resolve fine scales (in addition to a more efficient use of resources) together with the higher accuracy furnished by higher order schemes when the solution is adequately resolved. To define a convenient higher order adaptive mesh refinement scheme, we discuss a few different modifications of the standard, second order accurate approach of Berger and Oliger. Applying each of these methods to a simple model problem, we find these options have unstable modes. However, a novel approach to dealing with the grid boundaries introduced by the adaptivity appears stable and quite promising for the use of high order operators within an adaptive framework

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial.

OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. METHODS: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. RESULTS: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. SIGNIFICANCE: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future

EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19

OBJECTIVES: Severe systemic inflammation associated with some stages of COVID-19 and in fatal cases led therapeutic agents developed or used frequently in Rheumatology being at the vanguard of experimental therapeutics strategies. The aim of this project was to elaborate EULAR Points to consider (PtCs) on COVID-19 pathophysiology and immunomodulatory therapies. METHODS: PtCs were developed in accordance with EULAR standard operating procedures for endorsed recommendations, led by an international multidisciplinary Task Force, including rheumatologists, translational immunologists, haematologists, paediatricians, patients and health professionals, based on a systemic literature review up to 15 December 2020. Overarching principles (OPs) and PtCs were formulated and consolidated by formal voting. RESULTS: Two OPs and fourteen PtCs were developed. OPs highlight the heterogeneous clinical spectrum of SARS-CoV-2 infection and the need of a multifaceted approach to target the different pathophysiological mechanisms. PtCs 1-6 encompass the pathophysiology of SARS-CoV-2 including immune response, endothelial dysfunction and biomarkers. PtCs 7-14 focus on the management of SARS-CoV-2 infection with immunomodulators. There was evidence supporting the use of glucocorticoids, especially dexamethasone, in COVID-19 cases requiring oxygen therapy. No other immunomodulator demonstrated efficacy on mortality to date, with however inconsistent results for tocilizumab. Immunomodulatory therapy was not associated with higher infection rates. CONCLUSIONS: Multifactorial pathophysiological mechanisms, including immune abnormalities, play a key role in COVID-19. The efficacy of glucocorticoids in cases requiring oxygen therapy suggests that immunomodulatory treatment might be effective in COVID-19 subsets. Involvement of rheumatologists, as systemic inflammatory diseases experts, should continue in ongoing clinical trials delineating optimal immunomodulatory therapy utilisation in COVID-19

Comparative Effectiveness of Stereo-EEG versus Subdural Grids in Epilepsy Surgery

OBJECTIVE: To compare the outcomes of subdural electrode (SDE) implantations versus stereo-electroencephalography (SEEG), the two predominant methods of intracranial EEG (iEEG) performed in difficult to localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005-2019 with ≥ 1 year follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints: 1) likelihood of resection after iEEG; 2) seizure-freedom at last follow-up; and 3) complications (composite of either post-operative infection, symptomatic intracranial hemorrhage, or permanent neurologic deficit). RESULTS: Ten study sites from seven countries and three continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE, 942 SEEG) of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio OR = 1.4, 95% CI 1.05 - 1.84), and higher odds of complications (OR=2.24, 95% CI 1.34-3.74; unadjusted: 9.6% after SDE vs. 3.3% after SEEG). Odds of seizure-freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared to SDE (unadjusted: 55% seizure-free after SEEG-guided resections vs. 41% after SDE) INTERPRETATION: Compared to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy, but have more surgical complications and lower probability of seizure-freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. This article is protected by copyright. All rights reserved

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial

Objective: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. Methods: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. Results: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa =.65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. Significance: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype–phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype–phenotype diagnosis in the near future

Automated detection of focal cortical dysplasia type II with surface-based magnetic resonance imaging postprocessing and machine learning

Objective Focal cortical dysplasia (FCD) is a major pathology in patients undergoing surgical resection to treat pharmacoresistant epilepsy. Magnetic resonance imaging (MRI) postprocessing methods may provide essential help for detection of FCD. In this study, we utilized surface‐based MRI morphometry and machine learning for automated lesion detection in a mixed cohort of patients with FCD type II from 3 different epilepsy centers. Methods Sixty‐one patients with pharmacoresistant epilepsy and histologically proven FCD type II were included in the study. The patients had been evaluated at 3 different epilepsy centers using 3 different MRI scanners. T1‐volumetric sequence was used for postprocessing. A normal database was constructed with 120 healthy controls. We also included 35 healthy test controls and 15 disease test controls with histologically confirmed hippocampal sclerosis to assess specificity. Features were calculated and incorporated into a nonlinear neural network classifier, which was trained to identify lesional cluster. We optimized the threshold of the output probability map from the classifier by performing receiver operating characteristic (ROC) analyses. Success of detection was defined by overlap between the final cluster and the manual labeling. Performance was evaluated using k‐fold cross‐validation. Results The threshold of 0.9 showed optimal sensitivity of 73.7% and specificity of 90.0%. The area under the curve for the ROC analysis was 0.75, which suggests a discriminative classifier. Sensitivity and specificity were not significantly different for patients from different centers, suggesting robustness of performance. Correct detection rate was significantly lower in patients with initially normal MRI than patients with unequivocally positive MRI. Subgroup analysis showed the size of the training group and normal control database impacted classifier performance. Significance Automated surface‐based MRI morphometry equipped with machine learning showed robust performance across cohorts from different centers and scanners. The proposed method may be a valuable tool to improve FCD detection in presurgical evaluation for patients with pharmacoresistant epilepsy

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part I: Extraarticular Pathologies

The first part of the guidelines and recommendations for musculoskeletal ultrasound, produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), provides information about the use of musculoskeletal ultrasound for assessing extraarticular structures (muscles, tendons, entheses, ligaments, bones, bursae, fasciae, nerves, skin, subcutaneous tissues, and nails) and their pathologies. Clinical applications, practical points, limitations, and artifacts are described and discussed for every structure. After an extensive literature review, the recommendations have been developed according to the Oxford Centre for Evidence-based Medicine and GRADE criteria and the consensus level was established through a Delphi process. The document is intended to guide clinical users in their daily practice