Microscopic fractional anisotropy outperforms multiple sclerosis lesion assessment and clinical outcome associations over standard fractional anisotropy tensor.

We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

Diffusion tensor imaging metrics associated with future disability in multiple sclerosis.

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

[Thymectomy in thymomatous and non-thymomatous myasthenia gravis: analysis of a cohort of 46 patients]. / Timectomía en miastenia grave timomatosa y no timomatosa: análisis de una cohorte de 46 pacientes.

INTRODUCTION: Factors predicting remission after thymectomy for myasthenia gravis are not well known. AIM: To analyze the clinical evolution of the patients after this intervention and discuss about predictors of response. PATIENTS AND METHODS: We retrospectively reviewed all clinical data of thymectomies in myasthenia gravis patients performed at our hospital between 2006 from 2016. Using the MGFA-PIS classification, «complete stable remission¼, «pharmacologic remission¼, «minimal manifestations¼ and «improved¼ were defined as «good clinical outcome¼, and «unchanged¼, «worse¼, «exacerbation¼ or «died¼, as «poor clinical outcome¼. RESULTS: In 46 consecutive thymectomies for myasthenia gravis, women comprised 71.7%. Median age was 37 years and 10.9% had concomitant autoimmune disorders associated. Thymoma (23.96%) was more frequent in older patients (53 ± 20 vs 33 ± 24 years) and men (54.5% vs 18.8%). A year after thymectomy, 28.2% of patients were in poor clinical outcome group and 54.3% had good clinical outcome. On univariate analysis, thymomatous myasthenia was associated with poor clinical outcome a year after surgical intervention. After ten years of follow-up, 9.8% reached complete stable remission, a total of 32 patients (78%) had a favourable outcome and thymoma was not correlated. CONCLUSION: Thymectomy is considered an effective treatment for myasthenia gravis but the benefit is not immediate. The presence of thymoma may determine a worse initial clinical response following thymectomy in patients with myasthenia gravis.

TITLE: Timectomía en miastenia grave timomatosa y no timomatosa: análisis de una cohorte de 46 pacientes.Introducción. En la actualidad, los factores predictores de remisión de la enfermedad en la miastenia grave tras una timectomía no están claramente establecidos. Objetivo. Analizar la evolución clínica de los pacientes tras esta intervención y abordar los posibles determinantes pronósticos. Pacientes y métodos. Se analizaron retrospectivamente los registros de pacientes con miastenia grave timectomizados en nuestro centro entre 2006 y 2016. Se utilizó la escala Miasthenya Gravis Foundation of America-Post Intervention Status agrupando las categorías «remisión completa estable¼, «remisión farmacológica¼, «manifestaciones mínimas¼ y «mejoría¼ como «buen resultado clínico¼, y las categorías «sin cambios¼, «empeoramiento¼, «exacerbación¼ y «muerte¼, como «mal resultado clínico¼. Resultados. Se analizaron 46 timectomías de pacientes con miastenia grave, un 71,7% mujeres. La mediana de edad era de 37 años y el 10,9% asociaba enfermedades autoinmunes. El timoma (23,9%) fue más frecuentes en los varones (54,5% frente a 18,8%) y a mayor edad (53 ± 20 frente a 33 ± 24 años). Un año después de la timectomía, el 28,2% se encontraba en el grupo de mal resultado clínico, y un 54,3%, en el de buen resultado clínico. En el análisis univariante, el timoma se asoció a peor resultado clínico al año de la intervención. Tras diez años de seguimiento, 32 pacientes (78%) alcanzaron un buen resultado clínico, un 9,8% en remisión completa estable, y el timoma no se correlacionó como factor de mal pronóstico. Conclusión. La timectomía se considera un tratamiento efectivo, pero sin beneficio inmediato. La presencia de timoma podría determinar una respuesta clínica inicial peor tras la realización de una timectomía en pacientes con miastenia grave.

[Antibiotic diffusion to central nervous system]. / Difusión de los antibióticos en el sistema nervioso central.

Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice.