Longitudinal Multiparametric Quantitative MRI Evaluation of Acute and Chronic Multiple Sclerosis Paramagnetic Rim Lesions.

BACKGROUND: Multiple sclerosis (MS) paramagnetic rim lesions (PRLs) are markers of chronic active biology and exhibit complex iron and myelin changes that may complicate quantification when using conventional MRI approaches. PURPOSE: To conduct a multiparametric MRI analysis of PRLs. STUDY TYPE: Retrospective/longitudinal. SUBJECTS: Ninety-five progressive MS subjects with at least one persistent PRL who were enrolled in the CONSONANCE trial. FIELD STRENGTH/SEQUENCE: 3-T/Susceptibility-weighted, T1-weighted, T2-weighted, and fluid-attenuated inversion recovery. ASSESSMENT: Acute/chronic PRLs and non-PRLs were measured at screening, 24, 48, and 96 weeks using quantitative magnetic susceptibility (QS), R2*, and standardized T1w/T2w ratio (sT1w/T2w). PRL analyses were performed for whole lesion, core, and rim. The correlations between PRL core and rim sT1w/T2w, QS, and R2* were assessed. STATISTICAL TESTS: Linear mixed models. A P-value <0.05 was considered significant. RESULTS: There was a significant decrease in sT1w/T2w (-0.24 ± -5.3 × 10-3) and R2* (-3.6 ± 2.2 Hz) but a significant increase in QS (+21 ± 1.3 ppb) using whole-lesion analysis of chronic PRLs compared to non-PRLs at screening. Tissue damage accumulated at the 96-week time point was more evident in acute/chronic PRLs compared to acute/chronic non-PRLs (ΔsT1w/T2w = -0.21/-0.24 ± 0.033/0.0053; ΔR2* = -4.4/-3.6 ± 1.4/2.2 Hz). New, acute PRL sT1w/T2w significantly increased in lesion core (+4.3 × 10-3 ± 1.2 × 10-4) and rim (+5.6 × 10-3 ± 1.2 × 10-4) 24 weeks post lesion inception, suggestive of partial recovery. Chronic PRLs, contrastingly, showed significant decreases in sT1w/T2w over the initial 24 weeks for both core (-2.1 × 10-4 ± 2.0 × 10-5) and rim (-2.4 × 10-4 ± 2.0 × 10-5), indicative of irreversible tissue damage. Significant positive correlations between PRL core and rim sT1w/T2w (R2 = 0.53), R2* (R2 = 0.69) and QS (R2 = 0.52) were observed. DATA CONCLUSION: Multiparametric assessment of PRLs has the potential to be a valuable tool for assessing complex iron and myelin changes in chronic active PRLs of progressive MS patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Spinal cord compression by cystic IgG4-related spinal pachymeningitis mimicking neurocysticercosis: a case report.

BACKGROUND: To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. CASE PRESENTATION: A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. CONCLUSIONS: This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.

Lesion-level correspondence and longitudinal properties of paramagnetic rim and slowly expanding lesions in multiple sclerosis.

BACKGROUND: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs). OBJECTIVE: To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time. METHODS: MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs. RESULTS: In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage. CONCLUSIONS: Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage. TRIAL REGISTRATION: AFFINITY [NCT03222973].

Development and validation of a video-assisted liver biopsy technique using a minimally-invasive device.

BACKGROUND: Percutaneous liver biopsy is the gold standard technique for establishing the cause of cirrhosis and liver disease activity assessment. However, some cases of steatohepatitis or other chronic liver diseases show a high number of false negative results in samples obtained via the percutaneous route. This fact justifies performing a liver biopsy via the laparoscopic route. However, this is an expensive technique, with morbidities associated with pneumoperitoneum and anesthetic complications. The main objective of this study is to develop a video-assisted technique that uses only a minimally-invasive device for the liver biopsy and the optical trocar. Without additional trocars, this technique constitutes a less invasive procedure than the existing techniques in clinical practice. METHODS: This is a device development and validation study and patients submitted to abdominal laparoscopic surgery and required liver biopsy for moderate to severe steatosis were recruited. The patients were randomized into two groups: laparoscopic liver biopsy technique (n = 10, control group) and mini-laparoscopic liver biopsy technique (n = 8, experimental group). The times associated with procedure performance in both groups were evaluated using the Mann-Whitney or Kruskal-Wallis tests according to data distribution. RESULTS: At baseline, there was no statistical difference regarding gender and type of surgery. The experimental group had a significantly shorter time compared with the group that underwent the traditional procedure in mean procedure time (p = 0.003), biopsy time (p = 0.002) and hemostasis time (p = 0.003). CONCLUSIONS: The mini-laparoscopic biopsy device and technique showed to be capable of safely obtaining sufficient tissue samples, which was minimally invasive and in a shorter time than the classic technique.

Controversies in immunotherapy for anti-NMDA receptor encephalitis: a scoping review with a proposal of operational definitions.

Anti-NMDA receptor encephalitis (NMDARE), an autoimmune encephalitis associated with autoantibodies against the N-methyl-D-aspartate (NMDA) receptor, affects predominantly young women and is associated with psychiatric symptoms, seizures, movement disorders, and autonomic instability. Traditional treatments of anti-NMDA receptor encephalitis involve corticosteroids, intravenous immunoglobulin, plasmapheresis, cyclophosphamide, and rituximab. However, many controversies remain in the treatment for NMDA receptor encephalitis, such as optimal timing and combination of different immunotherapies, the role of newer strategies (e.g., bortezomib or tocilizumab) for severe and refractory patients, and the need or not for long-term immunosuppression. Our goal was to perform a scoping review to discuss the controversial topics of immunotherapy for NMDA receptor encephalitis and propose operational definitions to guide clinical practice and future research in the field.

Impact of the COVID-19 pandemic on maternal mental health, early childhood development, and parental practices: a global scoping review.

BACKGROUND: In March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO), generating stark economic and social repercussions that directly or indirectly affected families' wellbeing and health status. AIMS: This review aims at mapping the existing evidence on the impact of the COVID-19 pandemic on maternal mental health, early childhood development, and parental practices, worldwide, to identify evidence gaps and better inform future delivery of care and health policy measures. METHODS: Following the protocol defined by PRISMA-ScR, this scoping review has searched for relevant studies published between January 2020 and June 2021, selecting evidence sources based on pre-established criteria. From a total of 2,308 articles, data were extracted from 537 publications from 35 countries on all three health domains. RESULTS: The combined stressors brought forth by the pandemic have exerted a heavy burden on the mental health of mothers and the development of young children, partly mediated by its impact on parental practices. CONCLUSIONS: Despite remaining gaps, we have identified sufficient evidence pointing to an urgent need for more concerted global research efforts and rapid policy responses to timely address severe and pervasive negative impacts to the mental health of mothers and children at a key developmental stage.

Development and perceived usability evaluation of an interactive smartphone application for the teaching of hemodynamics and evaluation of arterial pulse pressure variation.

BACKGROUND: The use of fluids is the most frequently used therapy for circulatory shock. Its inadequate use has adverse effects, requiring hemodynamic goals, highlighting the use of pulse pressure variation due to its high accuracy. One of the problems related to this method is the difficulties in measuring the pulse pressure variation (PPV) in most monitors for clinical use. We assessed the qualitative aspects of perceived usability of a smartphone application (app), which, based on a photograph of the patient's arterial pulse wave, can help measure PPV and help in the diagnosis and management of shock cases. METHODS: To assess the software perceived usability, we used the System Usability Scale (SUS) applied to 30 physicians in 2 tertiary hospitals in Brazil. The software accuracy was measured using a sequence of 3 images with different values ​​of pulse pressure variation, comparing the obtained values ​​ with the gold standard. The educational interface of the app was evaluated qualitativelyfrom the spontaneous testimonies of the selected test participants.The project was approved by the Research Ethics Committee of Centro Universitário Christus. RESULTS: The analysis showed an average SUS of 86.3 points on a scale of 1-100 (above 80.3 is considered the best in terms of interface). The assessment of the application's accuracy when evaluating pulse pressure variation showed that the average variation of the measurements taken by the participants was small, with a good measure of repeatability and reproducibility. The app's educational interface was qualitatively evaluated, being praised by the users. CONCLUSIONS: It can be concluded that the developed mobile application showed excellent qualitative aspects of perceived usability results. More studies with this app will be required to evaluate the potential to help professionals with hemodynamic evaluation in emergency and intensive care settings.

Modified Glasgow Prognostic Score predicts survival among advanced non-small cell lung carcinoma patients treated with anti-PD1 agents.

Immune checkpoint inhibitors were approved for advanced nonsmall cell lung cancer (NSCLC) treatment. Despite improved survival, not all patients benefit from these agents. Here, the prognostic impact of pretreatment modified Glasgow Prognostic Score (mGPS) and neutrophil-to-lymphocyte ratio (NLR) was assessed. From 77 patients included, 83.2% received at least one prior systemic therapy. Immune-related adverse events (irAE) occurred in 20 patients. A lower mGPS was associated with higher median overall survival (OS), and a lower Eastern Cooperative Oncology Group (ECOG), irAE and fewer metastatic sites with better survival. A trend towards greater OS and progression-free survival (PFS) was stated among patients with NLR <5. mGPS 0 was associated with better survival; ≥3 metastatic sites with worse PFS and OS; ECOG >2 with worse OS and irAE with better survival. Pretreatment mGPS seems to be useful for predicting survival among advanced NSCLC patients treated with anti-programmed cell death 1 drugs, with ECOG performance status, irAE occurrence, and number of metastatic sites acting as survival predictors.

Prevalence, socioeconomic factors and obstetric outcomes associated with adolescent motherhood in Ceará, Brazil: a population-based study.

BACKGROUND: Adolescent motherhood (AM) remains a public health problem, especially in low and middle income countries, where approximately 95% of these births occur. Evidence from studies with population representativeness about events associated with AM is limited. We assessed the prevalence of AM, as well as its association with Socioeconomic Factors and Obstetric Outcomes. METHODS: A population-based cross-sectional study on maternal and child health of women aged 10 to 49 years, living in the state of Ceará, in northeastern Brazil was carried out to assess the prevalence of AM, as well as its association with Socioeconomic Factors and Obstetric Outcomes. The definition of adolescence used in the study was the one utilized by the WHO. In addition to the interview, data were double-checked according to the information in the government's pregnancy health booklet. Sample-adjusted logistic models to determine the association of socioeconomic factors and AM, as well as the association of AM with obstetric outcomes, with a causal approach to multivariate analyses, were used. RESULTS: The prevalence of adolescent motherhood was 18.6%. Poverty and household crowding were associated with greater chances of AM (p values of 0.038 and <  0.001, respectively), as well as not being in a stable relationship (OR 2.26 (95%CI: 1.67, 3.07), p <  0.001). AM showed a greater chance of not using community health services (p <  0.001), had fewer prenatal consultations (ß - 0.432 (95%CI: - 0.75, - 0.10)) and started prenatal care at a later date (ß 0.38 (95%CI: 0.21, 0.55), p <  0.001)). AM are also less likely to be tested for HIV and more likely to have urinary tract infections. CONCLUSIONS: Interventions aimed at socially-vulnerable adolescents are suggested. However, if pregnant, adolescents should receive proactive and differentiated prenatal care.

Delivery of essential surgery by family physicians.

Primary health care provides the framework for delivering the socially-informed, comprehensive and patient-centred care underlying robust health-care systems and is, therefore, central to achieving universal health coverage. Family physicians are best placed to embody primary health care's dual focus on community and population health because they are often employed in rural or district hospitals with limited human resources, particularly a lack of specialists. Here we want to illustrate how additional training for family physicians, the key clinicians in primary care, can play a critical role in reducing disparities in access to surgical, obstetric and anaesthesia care in low- and middle-income countries and in rural or remote settings. Examples are given of how training programmes can be developed in low-resource settings to equip family physicians with life-saving surgical skills and of how family physicians in high-income countries can be trained in the surgical skills essential for working overseas in low-income settings. Policy-makers should promote surgical practice among family physicians by supporting family medicine programmes that include additional surgical skills training and by expanding opportunities and incentives for family physicians to serve in rural areas. Moreover, national surgical plans should include a primary health care strategy for surgical care and, globally, family physicians should be considered in discussions of surgical care. Finally, surgeons, anaesthesiologists, obstetricians and family physicians should be encouraged to collaborate in ensuring that all patients, regardless of place of residence, receive safe and timely surgical care.

Les soins de santé primaires établissent le cadre requis pour des soins complets adaptés aux patients, gages d'un système de santé solide. Ils jouent donc un rôle central dans la mise en place d'une couverture maladie universelle. Dans ce contexte, les médecins de famille sont les mieux placés pour incarner une double perspective, la santé communautaire et la santé des populations, car ils travaillent souvent dans des hôpitaux ruraux ou de district qui disposent de ressources humaines limitées, surtout en termes de spécialistes. Le présent document montre dans quelle mesure une formation complémentaire dédiée aux médecins de famille, acteurs clés des soins de santé primaires, peut avoir un impact décisif sur la diminution des inégalités d'accès aux interventions chirurgicales, obstétriques et anesthésiques dans les pays à faible et moyen revenu, ainsi que dans les milieux ruraux ou isolés. Il existe de nombreux exemples qui illustrent la façon dont les programmes de formation peuvent être mis en œuvre dans les endroits manquant de ressources afin que les médecins de famille acquièrent des compétences chirurgicales vitales, et qui indiquent comment les médecins de famille des pays à haut revenu peuvent apprendre des techniques de chirurgie essentielles pour travailler outre-mer ou dans des régions plus défavorisées. Les législateurs devraient promouvoir la pratique chirurgicale chez les médecins de famille en soutenant les programmes qui incluent une formation complémentaire aux techniques de chirurgie, et en multipliant les opportunités et sources de motivation pour que les médecins de famille exercent dans les zones rurales. Par ailleurs, les projets nationaux devraient comporter une stratégie de soins de santé primaires pour les actes chirurgicaux et, globalement, les médecins de famille devraient être pris en compte dans les discussions consacrées aux interventions chirurgicales. Enfin, chirurgiens, anesthésistes, obstétriciens et médecins de famille devraient être encouragés à collaborer pour s'assurer que tous les patients, quel que soit leur lieu de résidence, puissent bénéficier de soins chirurgicaux au moment opportun et en toute sécurité.

La atención primaria de salud establece el marco para la prestación de una atención socialmente informada, integral y centrada en el paciente, que es la base de los sistemas sólidos de atención sanitaria y, por lo tanto, es fundamental para lograr la cobertura sanitaria universal. Los médicos de familia son los que mejor pueden asumir el doble enfoque de la atención primaria en la salud de la comunidad y de la población porque trabajan con frecuencia en hospitales rurales o de distrito que tienen recursos humanos limitados, en especial por la falta de especialistas. En este documento, se pretende ilustrar cómo la capacitación adicional de los médicos de familia, quienes son los profesionales clínicos clave en la atención primaria, puede desempeñar una función esencial en la reducción de las desigualdades que existen para acceder a los procedimientos quirúrgicos, obstétricos y de anestesia en los países de ingresos bajos y medios y en los zonas rurales o remotas. También se dan ejemplos de cómo se pueden elaborar programas de capacitación en entornos de bajos recursos para preparar a los médicos de familia con técnicas quirúrgicas que salvan vidas y de cómo se puede capacitar a los médicos de familia de los países de altos ingresos sobre las técnicas quirúrgicas esenciales para que trabajen en el extranjero en entornos de bajos ingresos. Los responsables de formular políticas deben promover la práctica quirúrgica entre los médicos de familia mediante su apoyo a los programas de medicina familiar que incluyan una capacitación adicional sobre técnicas quirúrgicas, así como la ampliación de las oportunidades y de los incentivos para que los médicos de familia presten servicios en las zonas rurales. Además, los planes quirúrgicos nacionales deben incluir una estrategia de atención primaria de salud para la intervención quirúrgica y, a nivel mundial, los médicos de familia se deben tener en cuenta en los debates sobre la intervención quirúrgica. Por último, se debe alentar a los cirujanos, anestesiólogos, obstetras y médicos de familia a que colaboren para garantizar que todos los pacientes, sea cual sea su lugar de residencia, reciban servicios quirúrgicos seguros y oportunos.

Effect of sex on carcass yield and meat quality of guinea pig.

The aim of this study was to evaluate the effect of sex on carcass yield and meat quality of guinea pig (Cavia porcellus). Twenty animals (10 males and 10 females) Criollos, with initial body weight of 286 ± 4.26 g and 2 months of age were distributed in a completely randomized design. The guinea pigs fed a diet based on vegetables and concentrate in a roughage:concentrate ratio of 80:20. After 60 days, animals were slaughtered and their carcasses and meat were evaluated. Males had higher slaughter weight, total weight gain, hot carcass weight, cold carcass weight, cold carcass yield, meat weight, meat yield, leg weight, loin + flank weight and front weight (P < 0.05). Females showed higher carcass chilling loss, liver yield, cooking loss and protein and ash content in meat (P < 0.05). The use of male guinea pigs for meat production provides higher yields of carcasses, meat and commercial cuts, and lower losses during carcass chilling and meat cooking.

Detection and clinical correlation of leukocortical lesions in pediatric-onset multiple sclerosis on multi-contrast MRI.

OBJECTIVE: To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sclerosis (POMS) using multi-contrast magnetic resonance imaging (MRI), and the relationship between frontal CL load and upper limb dexterity assessed with the Nine-Hole Peg Test (9-HPT). METHODS: Participants completed the 9-HPT and were imaged on a 3T MRI scanner to collect T1-weighted three-dimensional (3D) magnetization prepared rapid gradient echo (MPRAGE), proton density-weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. CLs were manually segmented using all MRI contrasts. RESULTS: We enrolled 24 participants with POMS (mean (standard deviation) age at first symptom: 13.3 (±2.7) years; mean age at scan: 18.8 (±3) years; mean disease duration of 5 (±3.2) years). A total of 391 CLs (mean, 16.3 ± 27.2; median, 7) were identified in 19 of 24 POMS patients (79%). The total number of CLs was positively associated with white matter lesion volume ( p = 0.04) but not with thalamic volume, age at the time of the scan, or disease duration. The number of frontal CLs was associated with slower performance on the 9-HPT ( p = 0.05). CONCLUSION: Multi-contrast 3T MRI led to a high rate of CL detection, demonstrating that cortical pathology occurs even in pediatric-onset disease. Frontal lobe CL count was associated with reduced manual dexterity, indicating that these CLs are clinically relevant.

Value of Central Venous to Arterial CO2 Difference after Early Goal-directed Therapy in Septic Shock Patients.

BACKGROUND AND AIMS: Venous to arterial difference of carbon dioxide (Pv-aCO2) tracks tissue blood flow. We aimed to evaluate if Pv-aCO2 measured from a superior central vein sample is a prognostic index (ICU length of stay, SOFA score, 28th mortality rate) just after early goal-directed therapy (EGDT)comparing its ICU admission values between patients with normal and abnormal (>6 mm Hg) Pv-aCO2. As secondary objectives, we evaluated the relationship of Pv-aCO2 with other variables of perfusion during the 24 hours that followed EGDT. MATERIALS AND METHODS: Prospective observational study conducted in an academic ICU adult septic shock patients after a 6-hour complete EGTD. Hemodynamic measurements, arterial/central venous blood gases, and arterial lactate were obtained on ICU admission and after 6, 18 and 24 hours. RESULTS: Sixty patients were included. Admission Pv-aCO2 values showed no prognostic value. Admission Pv-aCO2 (ROC curve 0.527 [CI 95% 0.394 to 0.658]) values showed low specificity and sensitivity as predictors of mortality. There was a difference observed in the mean Pv-aCO2 between nonsurvivors (NS) and survivors (S) after 6 hours. Central venous oxygen saturation (ScvO2) and Pv-aCO2 showed significant correlation (R2 = -0.41, P < 0.0001). Patients with normal ScvO2 (>70%) and abnormal Pv-aCO2 (>6 mm Hg) showed higher SOFA scores. Normal Pv-aCO2 group cleared their lactate levels in comparison to the abnormal Pv-aCO2 group. CONCLUSION: In septic shock, admission Pv-aCO2 after EGDT is not related to worse outcomes. An abnormal Pv-aCO2 along with a normal ScvO2 is related to organ dysfunction. HOW TO CITE THIS ARTICLE: Araujo DT, Felice VB, Meregalli AF, Friedman G. Value of Central Venous to Arterial CO2 Difference after Early Goal-directed Therapy in Septic Shock Patients. Indian J Crit Care Med 2019;23(10):449-453.

Histological Underpinnings of Grey Matter Changes in Fibromyalgia Investigated Using Multimodal Brain Imaging.

Chronic pain patients present with cortical gray matter alterations, observed with anatomical magnetic resonance (MR) imaging. Reduced regional gray matter volumes are often interpreted to reflect neurodegeneration, but studies investigating the cellular origin of gray matter changes are lacking. We used multimodal imaging to compare 26 postmenopausal women with fibromyalgia with 25 healthy controls (age range: 50-75 years) to test whether regional gray matter volume decreases in chronic pain are associated with compromised neuronal integrity. Regional gray matter decreases were largely explained by T1 relaxation times in gray matter, a surrogate measure of water content, and not to any substantial degree by GABAA receptor concentration, an indirect marker of neuronal integrity measured with [18F] flumazenil PET. In addition, the MR spectroscopy marker of neuronal viability, N-acetylaspartate, did not differ between patients and controls. These findings suggest that decreased gray matter volumes are not explained by compromised neuronal integrity. Alternatively, a decrease in neuronal matter could be compensated for by an upregulation of GABAA receptors. The relation between regional gray matter and T1 relaxation times suggests decreased tissue water content underlying regional gray matter decreases. In contrast, regional gray matter increases were explained by GABAA receptor concentration in addition to T1 relaxation times, indicating perhaps increased neuronal matter or GABAA receptor upregulation and inflammatory edema. By providing information on the histological origins of cerebral gray matter alterations in fibromyalgia, this study advances the understanding of the neurobiology of chronic widespread pain. SIGNIFICANCE STATEMENT: Regional gray matter alterations in chronic pain, as detected with voxel-based morphometry of anatomical magnetic resonance images, are commonly interpreted to reflect neurodegeneration, but this assumption has not been tested. We found decreased gray matter in fibromyalgia to be associated with T1 relaxation times, a surrogate marker of water content, but not with GABAA receptor concentration, a surrogate of neuronal integrity. In contrast, regional gray matter increases were partly explained by GABAA receptor concentration, indicating some form of neuronal plasticity. The study emphasizes that voxel-based morphometry is an exploratory measure, demonstrating the need to investigate the histological origin of gray matter alterations for every distinct clinical entity, and advances the understanding of the neurobiology of chronic (widespread) pain.

The independent contribution of Pseudomonas aeruginosa infection to long-term clinical outcomes in bronchiectasis.

Pseudomonas aeruginosa is responsible for chronic infection in many bronchiectasis patients but it is not known whether it is associated with worse clinical outcomes independent of the underlying severity of disease.This study analysed data from 2596 bronchiectasis patients included from 10 different bronchiectasis clinical centres across Europe and Israel, with a 5-year follow-up period. Prevalence of P. aeruginosa chronic infection and its independent impact on exacerbations, hospitalisations, quality of life and mortality was assessed.The prevalence of P. aeruginosa chronic infection was 15.0% (n=389). P. aeruginosa was associated with a higher mortality in a univariate analysis (hazard ratio (HR) 2.02; 95% (confidence interval) CI 1.53-2.66; p<0.0001) but an independent impact on mortality was not found in a multivariate analysis (HR 0.98; 95% CI 0.70-1.36; p=0.89). P. aeruginosa was independently associated with increased mortality only in patients with frequent exacerbations (two or more per year) (HR 2.03; 95% CI 1.36-3.03; p=0.001). An independent association with worse quality of life of 7.46 points (95% CI 2.93-12.00; p=0.001) was found in a multivariable linear regression. P. aeruginosa was therefore found to be independently associated with exacerbation frequency, hospital admissions and worse quality of life. Mortality was increased in patients with P. aeruginosa particularly in the presence of frequent exacerbations.

Thalamic and hippocampal volume associated with memory functions in multiple sclerosis.

OBJECTIVES: Although multiple sclerosis (MS) has long been considered to primarily affect white matter, it is now recognized that cognitive deficits in MS are also related to neocortical, thalamic and hippocampal damage. However, the association between damage to these structures and memory deficits in MS is unclear. This study examines whether MS patients with cognitive impairment have a reduction of hippocampal and/or thalamic volumes compared to cognitively intact patients, and whether these volume reductions correlate with various aspects of memory function. METHODOLOGY: Volumetric MRI measures of thalamus and hippocampus of forty-one patients with MS were performed. The patients were divided in two groups depending on the presence or absence of cognitive impairment, based on their neuropsychological tests scores. RESULTS: Right hippocampal volume was found to be associated with learning, and the left thalamic volume was found to predict performance in verbal memory. Cognitively impaired patients had a tendency to have a reduced left thalamic volume compared to cognitively intact patients. CONCLUSIONS: This study does not support a direct relationship between hippocampal atrophy and verbal memory. These results add to the growing evidence of the involvement of thalamus in cognitive impairment in MS and its association with verbal memory deficits.

Altered resting-state functional connectivity in cognitively preserved pediatric-onset MS patients and relationship to structural damage and cognitive performance.

OBJECTIVE: To evaluate resting-state functional connectivity (FC) and relationship to brain volumes and cognition in a sample of cognitively preserved pediatric-onset multiple sclerosis (MS) patients. METHODS: Sixteen cognitively intact pediatric-onset MS patients and 15 healthy age- and sex-matched controls underwent cognitive testing and 3T anatomical and functional MRI. Resting-state FC patterns were examined using region-of-interest-based timeseries correlations. RESULTS: Compared to controls, pediatric-onset MS patients demonstrated higher FC of the precuneus, particularly with the anterior cingulate cortex (z=4.21, p<.001), frontal medial cortex (z=3.48, p<.001), and cerebellum (z=3.72, p<.001). Greater T2 lesion volume and lower normalized thalamic volume were associated with reduced FC of the thalamus, especially for FC with the right superior occipital region (t=-2.87, p=.0123 and t=2.27, p=.04 respectively). FC of the left frontal medial cortex was negatively correlated with composite cognitive z-score in the pediatric-onset MS group (p<.05). CONCLUSIONS: Greater resting-state FC between posterior and anterior brain regions is present in pediatric-onset MS. With greater disease-related structural pathology, there is a disruption of thalamo-cortical FC. In the absence of actual cognitive impairment, heightened FC of the frontal medial cortex was associated with lower cognitive performance, suggesting that greater functional resources are recruited during resting-state in patients with reduced cognitive efficiency.

Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume.

OBJECTIVE: Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. METHODS: Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. RESULTS: Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. SIGNIFICANCE: Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.

Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy.

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.