Clinical Predictors of Neurogenic Lower Urinary Tract Dysfunction in Persons with Multiple Sclerosis

Background: Multiple sclerosis patients often develop neurogenic lower urinary tract dysfunction with a potential risk of upper urinary tract damage. Diagnostic tools are urodynamics, bladder diary, uroflowmetry, and post-void residual, but recommendations for their use are controversial. Objective: We aimed to identify clinical parameters indicative of neurogenic lower urinary tract dysfunction in multiple sclerosis patients. Methods: 207 patients were prospectively assessed independent of the presence of lower urinary tract symptoms. We analyzed Expanded Disability Status Scale scores, uroflowmetry, post-void residual, rate of urinary tract infections, standardized voiding frequency, and voided volume in correlation with urodynamic findings. Results: We found a significant correlation between post-void residual (odds ratio (OR) 4.17, confidence interval (CI) 1.20–22.46), urinary tract infection rate (OR 3.91, CI 1.13–21.0), voided volume (OR 4.53, CI 1.85–11.99), increased standardized voiding frequency (OR 7.40, CI 2.15–39.66), and urodynamic findings indicative of neurogenic lower urinary tract dysfunction. Expanded Disability Status Scale shows no correlation. Those parameters (except post-void residual) are also associated with reduced bladder compliance, as potential risk for kidney damage. Conclusion: Therefore, bladder diary and urinary tract infection rate should be routinely assessed to identify patients who require urodynamics.

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

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

Reliability of televisits for patients with mild relapsing–remitting multiple sclerosis in the COVID-19 era

Background Evidence of the cost-effectiveness of telemedicine (TM) for the management of Multiple Sclerosis (MS) has been provided recently. However, some doubts persist about the accuracy of neurological examinations performed remotely. Objectives This study investigated the reliability of neurological evaluations performed through TM in mild MS patients as compared with standard in-person visits. Methods In total, 76 patients with relapsing–remitting MS and Expanded Disability Status Scale (EDSS) ≤ 3.5 were consecutively recruited. Of them, 40 patients (52.6%) accepted to undergo both in-person and TM evaluations with independent examiners within 48 h. We alternatively asked patients to assure or not the presence of a caregiver during TM visits. A satisfaction questionnaire was administered to all participants. Results The inter-rater agreement attributed by two independent neurologists during TM visit was high (κ > 0.80) for EDSS and Functional Systems (FS) scores. Moderate agreement between TM and in-person evaluations emerged for pyramidal (κ = 0.57; p < 0.001), brainstem (κ = 0.57; p < 0.001), bowel and bladder (κ = 0.54; p < 0.001) and sensory (κ = 0.51; p < 0.001) FS scores, higher in patients providing the support of a caregiver. A good reliability was reported for EDSS scores computed during remote and in-person visits (ICC = 0.83; 95% CI 0.70–0.91; p < 0.001). Conclusions Despite the complexity of neurological examination, TM could be useful in monitoring MS patients with low disability.

Long-term real-world effectiveness and safety of fingolimod over 5 years in Germany

Objective To evaluate the 5-year real-world benefit–risk profile of fingolimod in patients with relapsing–remitting MS (RRMS) in Germany. Methods Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) is a non-interventional real-world study to prospectively assess the effectiveness and safety of fingolimod in routine clinical practice in Germany. The follow-up period comprised 5 years. Patients were included if they had been diagnosed with RRMS and had been prescribed fingolimod as part of clinical routine. There were no exclusion criteria except the contraindications for fingolimod as defined in the European label. The effectiveness and safety analysis set comprised 4032 and 4067 RRMS patients, respectively. Results At the time of the 5-year follow-up of PANGAEA, 66.57% of patients still continued fingolimod therapy. Annualized relapse rates decreased from baseline 1.5 ± 1.15 to 0.42 ± 0.734 at year 1 and 0.21 ± 0.483 at year 5, and the disability status remained stable, as demonstrated by the Expanded Disability Status Scale mean change from baseline (0.1 ± 2.51), the decrease of the Multiple Sclerosis Severity Score from 5.1 ± 2.59 at baseline to 3.9 ± 2.31 at the 60-months follow-up, and the percentage of patients with ‘no change’ in the Clinical Global Impression scale at the 60-months follow-up (78.11%). Adverse events (AE) occurring in 75.04% of patients were in line with the known safety profile of fingolimod and were mostly non-serious AE (33.62%) and non-serious adverse drug reactions (50.59%; serious AE 4.98%; serious ADR 10.82%). Conclusions PANGAEA demonstrated the sustained beneficial effectiveness and safety of fingolimod in the long-term real-world treatment of patients with RRMS.

Associação entre avaliação clínica e autopercepção da deglutição com a escala de incapacidade motora em pacientes com esclerose múltipla

RESUMO Objetivo Investigar a associação entre a avaliação clínica e autopercepção da deglutição com a escala de incapacidade motora em pacientes com Esclerose Múltipla. Método Estudo transversal, prospectivo realizado com indivíduos com Esclerose Múltipla atendidos pelo ambulatório de Neuroimunologia de um hospital do sul do Brasil. Realizamos a revisão dos prontuários eletrônicos dos pacientes para extração do escore da última Expanded Disability Status Scale. Após a análise dos critérios de inclusão, e em consulta clínica, foram aplicados dois protocolos, o de autopercepção para o risco de disfagia, através do instrumento de equivalência brasileira do Eating Assessment Tool e a avaliação clínica da deglutição, com alimentos, através da escala Gugging Swallowing Screen. Os dados foram analisados através de tabelas, estatísticas descritivas e pelos testes: Teste de Associação Exato de Fisher e Teste Qui-quadrado para avaliar a associação entre os resultados das escalas aplicadas. Consideramos um nível de significância máximo de 5% (p<0,05). Resultados Foi possível observar que houve associação significativa entre os escores das escalas Gugging Swallowing Screen com a Expanded Disability Status Scale dos pacientes. Além disso, também se observou relação entre os resultados de ambos protocolos com a Expanded Disability Status Scale. Conclusão Os pacientes com Esclerose Múltipla deste estudo apresentaram disfagia orofaríngea. Houve associação entre os achados da avaliação clínica, do instrumento de autopercepção da deglutição e da escala de incapacidade motora em pacientes com esclerose múltipla.

Coping Strategies and Their Impact on Quality of Life and Physical Disability of People with Multiple Sclerosis

The aim of the study is to investigate the impact of coping strategies on Health-Related Quality of Life (HRQoL) and physical disability assessed with the Expanded Disability Status Scale (EDSS) of people with multiple sclerosis (pwMS). PwMS were asked to focus on “MS diagnosis” as the core stressor. One hundred eight pwMS completed the Coping Responses Inventory-Adult form (CRI-Adult), the Multiple Sclerosis Quality of Life-29 (MSQoL-29), and the Depression Anxiety Stress Scale-21 (DASS-21). Multiple regression analyses (first block: EDSS, disease duration, and DASS-21) revealed that physical MSQoL-29 was positively associated with Alternative Rewards and negatively with Resigned Acceptance of the CRI-Adult. The mental MSQoL-29 was positively associated with Problem-Solving and negatively with Emotional Discharge. The Expanded Disability Status Scale (EDSS; first block: disease duration and general distress) was negatively associated with Positive Reappraisal. The Analysis of covariance (ANCOVA) revealed that pwMS with lower physical disability showed higher scores in Positive Reappraisal and lower scores in Emotional Discharge than pwMS with a higher physical disability. Coping strategies can play a role on HRQoL and physical disability in pwMS above and beyond EDSS, disease duration, and general distress. Psychological interventions should be considered in pwMS since the time of diagnosis to promote engagement in adaptive coping strategies and contrast the maladaptive ones.

Pregnancy in women with MS: Impact on long-term disability accrual in a nationwide Danish Cohort

Background: Pregnancy is considered to influence the disease course in women with multiple sclerosis (MS). Objective: The aim of this study was to investigate the effect of pregnancy on long-term disability accrual in women with MS. Methods: The Danish Multiple Sclerosis Registry (DMSR) was used to identify women diagnosed with clinically isolated syndrome or relapsing-remitting MS. Cox models with pregnancy as a time-dependent exposure and propensity score (PS) models were used to evaluate time to reach confirmed Expanded Disability Status Scale (EDSS) score of 4 and 6. Results: A total of 425 women became parous and 840 remained nulliparous. When including pregnancy as a time-dependent exposure, a non-significant association with time to reach EDSS 4 (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.61–1.20) and EDSS 6 (HR 0.70, 95% CI 0.40–1.20) was found. Correspondingly, the PS model showed no association with pregnancy on time to reach EDSS 4 (HR 0.85, 95% CI 0.56–1.28). Conclusion: This study concludes that pregnancy does not affect long-term disability accumulation.

Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis

<b><i>Introduction:</i></b> We aimed to develop and validate an Expanded Disability Status Scale (EDSS) model through clinical, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) measures. <b><i>Methods:</i></b> Sixty-four multiple sclerosis (MS) patients underwent peripapillary retinal nerve fiber layer and segmented macular layers evaluation through OCT (Spectralis, Heidelberg Engineering). Brain parenchymal fraction was quantified through Freesurfer, while cervical spinal cord (SC) volume was assessed manually guided by Spinal Cord Toolbox software analysis. EDSS, neuroradiological, and OCT assessment were carried out within 3 months. OCT parameters were calculated as the average of both nonoptic neuritis (ON) eyes, and in case the patient had previous ON, the value of the fellow non-ON eye was taken. Brain lesion volume, sex, age, disease duration, and history of disease-modifying treatment (1st or 2nd line disease-modifying treatments) were tested as covariables of the EDSS score. <b><i>Results:</i></b> EDSS values correlated with patient’s age (<i>r</i> = 0.543, <i>p</i> = 0.001), SC volume (<i>r</i> = −0.301, <i>p</i> = 0.034), and ganglion cell layer (GCL, <i>r</i> = −0.354, <i>p</i> = 0.012). Using these correlations, an ordinal regression model to express probability of diverse EDSS scores were designed, the highest of which was the most probable (Nagelkerke <i>R</i>² = 43.3%). Using EDSS cutoff point of 4.0 in a dichotomous model, compared to a cutoff of 2.0, permits the inclusion of GCL as a disability predictor, in addition to age and SC. <b><i>Conclusions:</i></b> MS disability measured through EDSS is an age-dependent magnitude that is partly conditioned by SC and GCL. Further studies assessing paraclinical disability predictors are needed.

Anakinra Treatment for Refractory Cerebral Autoinflammatory Responses

BackgroundRefractory cerebral autoinflammatory-autoimmune diseases are often associated with dysregulated innate immunity, which are targeted by anakinra, an interleukin-1 receptor antagonist. Here, we analyzed the therapeutic effect of anakinra in refractory cerebral autoinflammatory response (CAIR).MethodsWe analyzed single institutional patients treated with anakinra for CAIR from January 2017 to May 2021. Anakinra was sympathetically used for patients with intractable CAIR at 100 mg/day subcutaneously. A good response was defined as any improvement of the modified Rankin Scale, Clinical Assessment Scale in Autoimmune Encephalitis, or Expanded Disability Status Scale.ResultsA total of twelve patients with various diagnostic etiologies were treated with anakinra (mean age=45.1; male=7). Four patients showed good responses, and eight patients had unclear responses. Among the good responders, 75% of the patients had pathologically demonstrated CAIR. The two very good responders had primary progressive multiple sclerosis and cerebral granulomatosis with polyangiitis in each, and microglia/macrophage infiltration was prominent in their brain biopsies. No patient had a serious adverse effect.ConclusionsAnakinra may be a therapeutic option for refractory cerebral autoinflammatory diseases with microglia and macrophage infiltrations.

Progressive resistance power training for gait and balance rehabilitation in multiple sclerosis: a pilot single-arm study.

Aims: The aim of the study was to evaluate the effectiveness of 4-weeks inpatient power training protocol on parameters of gait and balance in pwMS. Materials and methods. 26 subjects aged 18 65 years and Expanded Disability Status Scale (EDSS) score 2.0 to 6.5 Receiving standard rehabilitation with PRT was applied for 30 minutes, 5 days a week for 4 weeks in addition to other rehabilitation methods. The primary endpoint was the time of 6-minute walking test (6MWT) at week 4 (W4) compared to week 1 (W1). Secondary outcomes included the time in Timed 25-foot walking test (T25FW), Timed Up-n-Go test (TUG), 5 times sit-to-stand test (5TSST), Expanded disability status scale score (EDSS), muscle strength. Results. After the 4-week course of rehabilitation a significant improvement was reached in all tests. The most prominent was the improvement in the 6MWT with 20/25 (80%) patients showing the increase in the distance walked above the minimal clinically important difference (MCID). Changes in other tests were less manifest: 3/25 (12%) of patients improved above MCID in both TUG and 5TSST, 6/25 (24%) patients - in T25FW. After a 4-week course of rehabilitation, a significant improvement was acquired in the 6MWT. Changes in other tests were significantly less manifest. Muscle in hip flexors improved significantly on the left side (mean (SD) at W1 - 3,96 (0,67) vs W4 - 4,72 (0,46), p=0,04)) and showed the trend to significance of the right side: W1 - 3,68 (0,8); W4 - 4,52 (0,65), p=0,08. Conclusions: The most significant effect was achieved in the primary outcome that was the distance walked in 6MWT. Less disabled patients can show better improvement in further studies, as was defined by T25FW test. Regular exercise can improve daily activity using a program that patients can easily do at home on their own.