Collateral circulation that determines infarct progression in large vessel occlusion (LVO) is implicitly regarded as stationary. We investigated collateral circulation changes during interfacility transfer for endovascular thrombectomy (EVT) and its association with functional outcome in anterior circulation LVO stroke. Seventy consecutive patients with middle cerebral artery occlusion transferred for EVT from January 2017 to December 2018 within a regional stroke network underwent repeated CTA at the comprehensive center allowing longitudinal assessment of collateral status, quantified by the Tan score, and AI-derived collateral percentage. Demographics, NIHSS, intravenous thrombolysis, blood pressure, stroke-to-reperfusion time, recanalization status, and 90-day mRS were recorded. Ordinal logistic regression was used to identify predictors of outcome. Collateral status was dynamic rather than stationary, with changes observed in 51/70 (73

BackgroundThe role of rituximab in the treatment of myasthenia gravis (MG) remains uncertain due to limited randomized controlled evidence and heterogeneous observational data. While rituximab is often used in refractory MG, its comparative effectiveness against other non-steroidal immunosuppressive therapies (NSISTs) has yet to be fully clarified.ObjectiveTo evaluate the effectiveness of rituximab compared to a second NSIST in achieving a composite clinical outcome in acetylcholine-receptor-antibody (AChR-Ab) positive MG patients using causal inference methods to adjust for confounding.MethodsWe conducted a retrospective cohort study of AChR-Ab positive MG patients treated with rituximab or a second NSIST. The primary outcome was time to achieving a composite clinical endpoint representing a patient acceptable symptom state (PASS): Myasthenia Gravis Composite (MGC) score ≤ 3, daily corticosteroid dose ≤ 5 mg prednisolone equivalent, and no rescue therapy use in the preceding month. To reduce confounding by indication and improve causal comparability between treatment groups, inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline covariates. Cox proportional hazards models were applied to estimate the effect of treatment on time to outcome.Results169 patients entered into the time-to-event analysis, and after IPTW adjustment, baseline characteristics between treatment groups were balanced. There was no statistical difference in the hazard ratio between Rituximab compared to a second NSIST in achieving the composite clinical outcome (HR = 1.27, 95% CI 0.66–2.45, p = 0.48).ConclusionIn this IPTW-adjusted analysis, rituximab did not improve the time-to-improvement compared to a second NSIST in AChR-Ab-positive MG.

INTRODUCTION:Cognitive impairment (CI) is a significant burden for patients with multiple sclerosis (MS). However crucial its assessment is, longitudinal measurement of cognitive performance is susceptible to learning effect, making the results of repeated evaluations difficult to interpret. Reliable change index (RCI) and standardized regression based norms (SRB) are accepted statistical methods to assess the reliability of a difference score between two observations. Thus, our aims were to provide RCIs and SRBs for all three subtests of the Brief International Cognitive Assessment for MS (BICAMS) battery and to measure the prevalence of true cognitive worsening and improvement. METHODS:We retrospectively evaluated the first interim analysis data of the longitudinal follow-up or our BICAMS prevalence study-cohort after 1-year. We analyzed the data of 242 MS patients. RESULTS:We calculated both the RCIs and the SRBs for all three subtests of the BICAMS battery. According to the RCI, 5.4%, 6.9% and 14.6% worsened while 12.3%, 34.3% and 10.6% improved on the SDMT, BVMT-R and CVLT-II respectively. In case of SRB method, 3.8%, 8.3% and 19.7% worsened while 3.8%, 7.6% and 0.0% improved. The κ values revealed a mild-to-moderate agreement (κ=0.391-0.540; p<0.001). In case of the BVMT-R and the CVLT-II assessments the baseline scores influenced this outcome significantly (BVMT-R: OR: 1.068; 90%CI: 1.001-1.138; CVLT-II: OR: 1.096; 90%CI: 1.041-1.153). CONCLUSION:Comparing the methods, RCI seems to be better in cases with already established CI, while SRB, the more complex method, seemingly detects change better in cognitively intact patients.

INTRODUCTION/AIMS:Sex-specific differences in myasthenia gravis (MG) are widely acknowledged, yet data on sex-based outcomes of MG treatment are scarce. In accordance with Sex and Gender Equity in Research guidelines, this post hoc analysis assessed potential sex-specific differences in treatment outcomes in acetylcholine receptor antibody-positive (AChR-Ab+) generalized (g)MG participants in the Phase 3 ADAPT trial (NCT03669588). METHODS:Participants received four once-weekly efgartigimod infusions (10 mg/kg) or placebo per cycle. Endpoints (primary: proportion of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders (Cycle 1); secondary: proportion of Quantitative Myasthenia Gravis (QMG) and early (Cycle 1) MG-ADL responders, and time with clinically meaningful improvements in MG-ADL score; additional: quality of life outcomes, pharmacodynamics) were assessed according to sex. RESULTS:Females were younger (mean age: 42.9 vs. 54.8 years), more likely to have undergone thymectomy (65.1% [56/86] vs. 44.2% [19/43]), and had higher baseline QMG scores (16.3 vs. 14.3) compared with males. Efgartigimod demonstrated homogeneous effects between sexes, with no significant difference in proportions of MG-ADL (p = 0.7014), early (Cycle 1) MG-ADL (p = 1.00), or QMG responders (p = 0.1595). Improvements in quality-of-life assessments, rates of minimal symptom expression, and mean total immunoglobulin G reductions (Cycle 1) were greater with efgartigimod verso placebo in females and males. Efgartigimod was well tolerated, with similar safety profiles across sexes. DISCUSSION:In ADAPT, efgartigimod-treated female and male AChR-Ab+ gMG patients had similar efficacy and safety outcomes. These data provide valuable insight for clinicians, given the established sex differences in MG disease course and treatment responses. TRIAL REGISTRATION:The ADAPT trial is registered on ClinicalTrials.gov (NCT03669588).

Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS). We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18–39 years), transition onset (40–49 years), LOMS (50–59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions. Among 81,236 patients, 5.2

BACKGROUND:Left-truncation is an unrecorded interval between multiple sclerosis (MS) onset and initial data in observational studies. This delay may bias estimates of disease-modifying therapy (DMT) effectiveness, especially when determined by patient or disease characteristics. OBJECTIVES:To examine whether causal effect estimates of DMTs over the full disease course can be reliably derived from left-truncated registry data. METHODS:We analysed data from MSBase (144 centres, 41 countries) to assess the impact of left-truncation on causal treatment effect estimates. Cox marginal structural models (MSMs) estimated hazard ratios (HRs) for relapses, disability worsening and improvement, considering left-truncation at random and not-at-random. Fixed-time truncation and multivariable adjustment were applied to remediate bias. RESULTS:The study included 5588 patients tracked from true MS onset. The null model, without left-truncation, estimated the DMT effect on relapse risk (HR = 0.64; 95% confidence interval (CI) = 0.54-0.77). Left-truncation inflated this estimate. Shorter random truncation (1 year) produced greater bias (HR = 0.34), decreasing with longer durations (3-year HR = 0.48). Truncation not-at-random biased relapse estimates (HR = 0.37). Disability outcomes were less sensitive. CONCLUSION:MSMs can reliably estimate DMT effectiveness in left-truncated MS registry data, although accuracy depends on truncation mechanism and duration. Both random and not-at-random truncation impact relapse estimates. Disability outcomes appear less sensitive. Fixed-time truncation and covariate adjustment mitigated bias.

A myasthenia gravis (MG) a neuromuscularis transzmisszió zavarával jellemzett ellenanyag-mediált autoimmun betegség, klinikailag kóros izomgyengeség, fáradékonyság tüneteivel manifesztálódik, ami jelentkezhet izoláltan a szemizmokban vagy generalizáltan a test egyéb harántcsíkolt izmaiban is (bulbaris, végtagi, légzőizmok). A betegség a becslések szerint hazánkban 1700 beteget érint. Enyhébb esetekben tüneti – kolinészteráz-gátló – kezelés elegendő lehet a betegség kezelésében, de a betegek többsége a kórtörténete során hosszabb-rövidebb időtartamú immunszuppresszív kezelésre szorul. A hagyományos gyógyszerekkel az esetek 60-70%-ában érhető el tünetmentes állapot. A betegek 10-20%-a szenved refrakter myastheniában, ők a hagyományos kezelésre nem reagálnak megfelelően, vagy az alkalmazott kezelés mellett tolerálhatatlan mellékhatásokat tapasztalnak. Az utóbbi években több klinikai vizsgálat zajlott MG-ben új, célzott molekuláris terápiákkal: ma már komplement-, FcRn- és B-sejtgátló szerek szélesítik terápiás arzenálunkat, és ígérnek izgalmas, bizonyítottan hatékony, viszonylag gyors hatású kezelési lehetőségeket, mindenekelőtt refrakter MG-ben. Napjainkban az MG-kezelés célja a teljes remisszió elérése, a légzési elégtelenséggel járó myastheniás krízis kivédése és a betegek életminőségét negatívan befolyásoló tünetek megszüntetése. A kórkép ritka volta, változatos lefolyása indokolttá teszi – különösen a refrakter betegek esetében –, hogy a gondozás az MG kezelésében nagy gyakorlattal rendelkező, a kórkép ellátásának teljes spektrumával bíró neuroimmunológiai centrumokban történjen. A refrakter MG hatékony kezeléséhez elengedhetetlen, hogy a közelmúltban törzskönyvezett új terápiák mielőbb elérhetővé váljanak a magyar betegek számára is.

Early prediction of disability progression in multiple sclerosis (MS) remains challenging despite its critical importance for therapeutic decision-making. We present the first systematic evaluation of personalized federated learning (PFL) for 2-year MS disability progression prediction, leveraging multi-center real-world data from over 26,000 patients. While conventional federated learning (FL) enables privacy-aware collaborative modeling, it remains vulnerable to institutional data heterogeneity. PFL overcomes this challenge by adapting shared models to local data distributions without compromising privacy. We evaluated two personalization strategies: a novel AdaptiveDualBranchNet architecture with selective parameter sharing, and personalized fine-tuning of global models, benchmarked against centralized and client-specific approaches. Baseline FL underperformed relative to personalized methods, whereas personalization significantly improved performance, with personalized FedProx and FedAVG achieving ROC-AUC scores of 0.8398 ± 0.0019 and 0.8384 ± 0.0014, respectively. These findings establish personalization as critical for scalable, privacy-aware clinical prediction models and highlight its potential to inform earlier intervention strategies in MS and beyond.

Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular transmission, presenting with fatigable weakness that is either isolated to ocular muscles only or generalised (limb, bulbar and respiratory muscles can be affected). The disorder is estimated to affect around 1700 patients in our country. In some cases symptomatic treatment with acetylcholinesterase inhibitors may be sufficient, but most patients with MG require immunosuppressive drugs at some point for disease control, which is achieved in about 60-70% of patients. 10-20% of MG cases are refractory; they do not respond adequately to the traditional treatments or suffer from severe side effects. In the past few years, new biological agents against complement, the FcRn receptor, or B-cell antigens have been tested in clinical trials. These new therapies extend the possibilities for targeted immunotherapies and promise exciting new options with a relatively rapid mode of action. The goal of the treatment of MG is achieving remission, avoiding myasthenic crisis and eliminating symptoms which worsen the quality of life of our patients. The disease is rare, the clinical picture is variable, therefore the treatment of MG patients, especially of refractory MG should be conducted in neuroimmunological centres with adequate expertise in MG. For the adequate treatment of refractory MG we need the new drugs to be reimbursed in our country.

BACKGROUND:Prognostic machine learning research in multiple sclerosis has been mainly focusing on black-box models predicting whether a patients' disability will progress in a fixed number of years. However, as this is a binary yes/no question, it cannot take individual disease severity into account. Therefore, in this work we propose to model the time to disease progression instead. Additionally, we use explainable machine learning techniques to make the model outputs more interpretable. METHODS:A preprocessed subset of 29,201 patients of the international data registry MSBase was used. Disability was assessed in terms of the Expanded Disability Status Scale (EDSS). We predict the time to significant and confirmed disability progression using random survival forests, a machine learning model for survival analysis. Performance is evaluated on a time-dependent area under the receiver operating characteristic and the precision-recall curves. Importantly, predictions are then explained using SHAP and Bellatrex, two explainability toolboxes, and lead to both global (population-wide) as well as local (patient visit-specific) insights. RESULTS:On the task of predicting progression in 2 years, the random survival forest achieves state-of-the-art performance, comparable to previous work employing a random forest. However, here the random survival forest has the added advantage of being able to predict progression over a longer time horizon, with AUROC >60% for the first 10 years after baseline. Explainability techniques further validated the model by extracting clinically valid insights from the predictions made by the model. For example, a clear decline in the per-visit probability of progression is observed in more recent years since 2012, likely reflecting globally increasing use of more effective MS therapies. CONCLUSION:The binary classification models found in the literature can be extended to a time-to-event setting without loss of performance, thus allowing a more comprehensive prediction of patient prognosis. Furthermore, explainability techniques proved to be key to reach a better understanding of the model and increase validation of its behaviour.

INTRODUCTION/AIMS:Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS:Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS:The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION:Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

Background Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. Methods Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS. Findings Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history. Conclusions Good discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study.

Multiple sclerosis (MS) may impact quality of life, careers and family plans of the affected individuals. The current treatments with disease modifying therapies aim to prevent people with MS (pwMS) from disability accumulation and progression. Different countries have different reimbursement policies resulting in inequalities in patient care among geographical regions. Access to anti-CD20 therapies for relapsing MS is restricted in Hungary because therapy of individual cases only is reimbursed. In the light of the latest research and national guidelines, 17 Hungarian MS experts agreed on 8 recommendations regarding relapsing pwMS using the Delphi round method. Strong agreement (> 80%) was achieved in all except one recommendation after three rounds, which generated a fourth Delphi round. The experts agreed on treatment initiation, switch, follow-up and discontinuation, as well as on special issues such as pregnancy, lactation, elderly population, and vaccination. Well-defined national consensus protocols may facilitate dialogue between policymakers and healthcare professionals and thus contribute to better patient care in the long run.

Background and Objectives Myasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG. Methods In this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II–Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline). CS doses were increased (based on the current CS dose) in patients who worsened. Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required. The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45). The study results and full protocol are available at clinicaltrials.gov/ct2/show/NCT02473965. Results The primary end point (≥50% reduction in CS dose) showed no significant difference between the IGIV-C treatment (60.0% of patients) and placebo (63.3%). There were no significant differences for secondary end points. Safety data indicated that IGIV-C was well tolerated. Discussion In this study, IGIV-C was not more effective than placebo in reducing daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different. Trial Registration Information The trial was registered on clinicaltrialsregister.eu (EudraCT #: 2013-005099-17) and clinicaltrials.gov (identifier NCT02473965). Classification of Evidence This study provides Class II evidence that IVIG infusions in adult patients with MG do not increase the percentage of patients achieving a ≥50% reduction in corticosteroid dose compared with placebo.

Az elülső mediastinum leggyakoribb daganata, a thymoma videotorakoszkópos eltávolítása mára világszerte elterjedőben lévő, de sok tekintetben még vitatott műtéti eljárássá vált. Az egyoldali megközelítéssel végzett műtéteink korai és késői eredményeit elemezzük két magyar mellkassebészeti centrum 17 éves adatai alapján. A thymoma anatómiai helyzetétől függően jobb vagy bal oldal felől, 2 vagy 3 intercostalis porton keresztül, ultrahangos vágóeszköz és elektrokauter segítségével thymomectomiát és thymectomiát végeztünk Masaoka–Koga I–II–III. stádiumban. Nemzetközi standardokat alkalmazva elemeztük a perioperatív szövődményeket, a középtávú onkológiai és a myastheniás klinikai eredményeket. 54 beteg (23 férfi, 31 nő), életkori átlag 58 (26–79) év, közülük 23 myasthenia gravis betegséggel. Konverzió: 7/61 (11,5%). Átlagos műtéti idő: 84 (39–150) perc. Átlagos ápolási idő: 5,5 (3–19) nap. Thymoma átlagos mérete: 46 (18–90) mm. Szövettan: A (2), AB (19), B1/2/3 (11/11/1), vegyes B (10). Reszekciós vonal: R0/1/2 (41/12/1). Masaoka–Koga-stádium: I. (17), IIA. (29), IIB. (1), III. (7). 25 thymomectomia, 29 thymectomia. Hét betegnél kiterjesztés pericardiumra (2), tüdőre (4), rekeszidegre (6), vena anonymára (1). 30 napon túli kórházi halálozás 1 eset (1,85%). Morbiditás: 11/54 (20,4%). Átlagos követési idő 62,6 (5–198) hónap. A myastheniás betegcsoportban a műtét effektivitása 18/21 (85,7%), ezen belül a komplett remisszió 5/21 (23,8%). Postthymectomiás myasthenia gravis 2/31 (6,5%) esetben alakult ki. Az általános 5 éves túlélés 100% volt, a daganatmentes 5 éves túlélés 96%-nak bizonyult. A korai eredményekben a thymomectomia magasabb aránya és a magas konverziós ráta, valamint az alacsonyabb R0-arány összefügghet a sebészek szemléletével, tanulóidejével és az egyoldali műtéti módszer korlátaival. A késői eredmények a követési idő növekedésével reálisabbá és összehasonlíthatóbbá válhatnak. Az egyoldali VATS-technika helyett a kedvezőbb vizuális jellemzők miatt áttértünk a subxyphoid VATS-thymectomiák végzésére.