Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS)

Journal of Neurology Neurosurgery & Psychiatry, Год журнала: 2023, Номер unknown, С. jnnp - 332119

Опубликована: Ноя. 14, 2023

Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension intervals.

Язык: Английский

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Infratentorial and spinal cord lesions: Cumulative predictors of long-term disability?

Multiple Sclerosis Journal, Год журнала: 2019, Номер 26(11), С. 1381 - 1391

Опубликована: Авг. 2, 2019

The objective of the study was to determine whether early infratentorial and/or spinal cord lesions are long-term cumulative predictors disability progression in multiple sclerosis (MS).We selected 153 MS patients from longitudinal Amsterdam cohort. Lesion analysis performed at baseline and year 2. Disability after 6 11 years measured using Expanded Status Scale (EDSS) EDSS-plus (including 25-foot walk 9-hole peg test). Patients with or were compared for risk 6- 11-year without lesions, respectively. Subsequently, on both locations only lesions.Baseline show a higher 6-year EDSS (odds ratio (OR): 3.6, p = 0.007) (OR: 2.5, 0.028) 2.8, 0.047). did not have than lesions.The presence seems be dominant factor progression. Simultaneous undisputedly predict

Язык: Английский

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Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis

Multiple Sclerosis Journal, Год журнала: 2021, Номер 28(1), С. 102 - 110

Опубликована: Апрель 23, 2021

Background: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). Objective: To study serum contactin-1 (sCNTN1) as novel biomarker natalizumab-treated relapsing-remitting MS (RRMS) patients. Methods: Eighty-nine RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last (median 5.2 years) compared to 222 healthy controls (HC) 15 primary progressive (PPMS). Results between progressive, stable, or improved disability according EDSS-plus criteria. Results: Median levels (ng/mL,) (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; follow-up: 9.7) significantly lower HC (12.5; p ⩽ 0.001). It observed that 48% showed during follow-up, 11% improved, 40% remained stable. progressors both 12M non-progressors. A 1 ng/mL decrease consistent an odds ratio 1.23 (95% confidence interval 1.04–1.45) ( = 0.017) follow-up. Conclusion: Lower concentrations associated long-term treatment, making it possible blood-based prognostic RRMS.

Язык: Английский

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Does Ocrelizumab Limit Multiple Sclerosis Progression? Current Evidence from Clinical, MRI, and Fluid Biomarkers

Neurotherapeutics, Год журнала: 2022, Номер 19(4), С. 1216 - 1228

Опубликована: Июнь 6, 2022

Язык: Английский

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Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Neurotherapeutics, Год журнала: 2024, Номер 21(4), С. e00363 - e00363

Опубликована: Май 7, 2024

Язык: Английский

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Effect of impairment on health-related quality of life in people with multiple sclerosis: association of functional systems and EQ-5D-5L index values in a cross-sectional study

Quality of Life Research, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Multiple sclerosis (MS) results in physical and cognitive impairments that negatively affect health-related quality of life (HRQoL). It is unknown to what extent the impact MS-related on HRQoL are reflected association Expanded Disability Status Scale (EDSS) Functional Systems (FS) scores EQ-5D-5L index values. This cross-sectional, single-center cohort study recruited people with MS (pwMS) attending an outpatient clinic at a German university hospital. Impairment was assessed via FS during routine visits. measured The each score values additive effect all modeled multivariate linear regression (MLR). Analyzing 115 participants, unadjusted MLR single revealed brainstem, pyramidal, cerebellar, sensory, cerebral/cognitive dysfunctions were significantly associated lower HRQoL. In adjusted for covariates, one standard deviation decrease function 6% reduction Dysfunctions contribute Cognitive dysfunction identified maintain negative after adjustment routinely appeared useful indicators identify pwMS who may benefit from comprehensive evaluations. adds growing body evidence emphasizing crucial role highlights need effective screening therapeutic strategies.

Язык: Английский

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Smartphone‐derived keystroke dynamics are sensitive to relevant changes in multiple sclerosis

European Journal of Neurology, Год журнала: 2021, Номер 29(2), С. 522 - 534

Опубликована: Окт. 31, 2021

To investigate smartphone keystroke dynamics (KD), derived from regular typing, on sensitivity to relevant change in disease activity, fatigue, and clinical disability multiple sclerosis (MS).Preplanned interim analysis of a cohort study with 102 MS patients assessed at baseline 3-month follow-up for gadolinium-enhancing lesions magnetic resonance imaging, relapses, fatigue outcomes. Keyboard interactions were unobtrusively collected during typing using the Neurokeys App. From these 15 features aggregated 16 summary time series statistics. Responsiveness KD anchor-based was by calculating area under receiver operating characteristic curve (AUC). The optimal cut-point used determine minimal clinically important difference (MCID) compared smallest real (SRC). Commonly measures analyzed comparison.A total 94 completed follow-up. five best performing had AUC-values range 0.72-0.78 lesions, 0.67-0.70 Checklist Individual Strength Fatigue subscale, 0.66-0.79 Expanded Disability Status Scale, 0.69-0.73 Ambulation Functional System, 0.72-0.75 Arm function Questionnaire. MCID exceeded SRC group level. higher than comparative outcomes, aside ambulatory function.Keystroke demonstrated good responsiveness changes MS, detected beyond measurement error better commonly measures.

Язык: Английский

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Assessment of Natural Language Processing Methods for Ascertaining the Expanded Disability Status Scale Score From the Electronic Health Records of Patients With Multiple Sclerosis: Algorithm Development and Validation Study

JMIR Medical Informatics, Год журнала: 2022, Номер 10(1), С. e25157 - e25157

Опубликована: Янв. 12, 2022

The Expanded Disability Status Scale (EDSS) score is a widely used measure to monitor disability progression in people with multiple sclerosis (MS). However, extracting and deriving the EDSS from unstructured electronic health records can be time-consuming.We aimed compare rule-based deep learning natural language processing algorithms for detecting predicting total functional system subscores of patients MS.We studied 17,452 4906 MS followed at one Canada's largest clinics between June 2015 July 2019. We randomly divided into training (80%) test (20%) data sets, compared performance characteristics 3 models. First, we applied approach, sentences containing keyword "EDSS." Next, trained convolutional neural network (CNN) model predict 19 half-step increments score. Finally, combined rule-based-CNN model. For each determined accuracy, precision, recall, F-score reference standard, which was manually labeled scores clinic database.Overall, keyword-CNN demonstrated best performance, an 0.90, 0.83, 0.83 respectively. Respective figures CNN models individually were 0.57, 0.91, 0.65, 0.70, 0.86, 0.70. Because missing data, lower than that Performance improved when considering notes known values subscores.A extract accurately patient records. This approach automated efficient information extraction clinical research settings.

Язык: Английский

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Serum glial fibrillary acidic protein in natalizumab-treated relapsing-remitting multiple sclerosis: An alternative to neurofilament light

Multiple Sclerosis Journal, Год журнала: 2023, Номер 29(10), С. 1229 - 1239

Опубликована: Авг. 2, 2023

There is a need in Relapsing-Remitting Multiple Sclerosis (RRMS) treatment for biomarkers that monitor neuroinflammation, neurodegeneration, response, and disease progression despite treatment.To assess the value of serum glial fibrillary acidic protein (sGFAP) as biomarker clinical brain volume measurements natalizumab-treated RRMS patients.sGFAP neurofilament light (sNfL) were measured an observational cohort patients at baseline, +3, +12, +24 months last sample follow-up (median 5.17 years). sGFAP was compared between significant progressors non-progressors related to magnetic resonance imaging (MRI)-derived volumes whole brain, ventricle, thalamus, lesion. The relationship sNfL assessed.A total 88 included, 47.7% progressed. levels baseline higher with gadolinium enhancement (1.3-fold difference, p = 0.04) decreased 3 (adj. < 0.001). No association found longitudinal progressor status. 12 significantly associated normalized ventricular (positively), thalamic (negatively), lesion (positively). Baseline 12-month predicted annualized ventricle change rate after 1 year treatment. correlated (p 0.001) but stabilized earlier.sGFAP MRI markers neuroinflammation neurodegeneration.

Язык: Английский

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A Combined Radiomics and Machine Learning Approach to Overcome the Clinicoradiologic Paradox in Multiple Sclerosis

American Journal of Neuroradiology, Год журнала: 2021, Номер 42(11), С. 1927 - 1933

Опубликована: Сен. 16, 2021

Conventional MR imaging explains only a fraction of the clinical outcome variance in multiple sclerosis. We aimed to evaluate machine learning models for disability prediction on basis radiomic, volumetric, and connectivity features derived from routine brain images.In this retrospective cross-sectional study, 3T studies patients with sclerosis, including 3D T1-weighted T2-weighted FLAIR sequences, were selected 2 institutions. images processed obtain volume, score (inferred T2 lesion location), texture an atlas-based set GM regions. The site 1 cohort was randomly split into training (n = 400) test 100) sets, while 104) constituted external set. After feature selection clinicodemographic imaging-derived variables, different algorithms predicting as measured Expanded Disability Status Scale trained cross-validated evaluated sets. effect model performance tested using 1-way repeated-measures ANOVA.The procedure identified 9 most informative age secondary-progressive course subset radiomic extracted prefrontal cortex, subcortical GM, cerebellum. predicted high accuracy (r approaching 0.80) excellent intra- intersite generalizability ≥ 0.73). algorithm had no relevant performance.The multidimensional analysis images, data, is highly status representing promising approach bridge gap between conventional disability.

Язык: Английский

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