A Retrospective Analysis of Ischemic Stroke Patients Supports That Very Early Mobilization Within 24 Hours After Intravenous Alteplase Is Safe and Possibly Beneficial.

ABSTRACT: BACKGROUND: Stroke care guidelines recommend early mobilization of acute ischemic stroke patients, but there are sparse data regarding early mobilization of stroke patients receiving thrombolytic therapy. We developed the Providence Early Mobility for Stroke (PEMS) protocol to mobilize patients to their highest individual tolerance within 24 hours of stroke admission in 2010, and it has been in continuous use at our primary and comprehensive stroke centers for over a decade. In this study, we evaluated the PEMS protocol in all patients treated with intravenous alteplase without endovascular treatment. METHODS : This retrospective study includes 318 acute ischemic stroke patients treated with alteplase who were admitted to 2 urban stroke centers between January 2013 and December of 2017 and were mobilized with the PEMS protocol within 24 hours of receiving alteplase. Safety of PEMS was assessed by change in National Institutes of Health Stroke Scale at 24 hours by time first mobilized. Using multivariate and logistic regression models, we analyzed time first mobilized and 90-day modified Rankin scale (mRS). RESULTS : Median time first mobilized was 9 hours from administration of alteplase. For every hour delay in mobilization, the odds of being slightly or moderately disabled (mRS, 2-3) at 90 days increased by 7% (adjusted odds ratio, 1.07; P = .004), and the odds of being severely disabled or dead (mRS, 4-6) at 90 days increased by 7% (adjusted odds ratio, 1.07; P = .02). In addition, for every hour delay in mobilization, 24-hour National Institutes of Health Stroke Scale increased by 1.8%. DISCUSSION: Our results support that the PEMS protocol is safe, and possibly beneficial, for acute ischemic stroke patients treated with intravenous alteplase. Our protocol differs from other very early mobility protocols because it does not prescribe a "dose" of activity. Instead, each patient was mobilized to his/her individual highest degree as soon as it was safe to do so.

The natural history of ALS: Baseline characteristics from a multicenter clinical cohort.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare disease with urgent need for improved treatment. Despite the acceleration of research in recent years, there is a need to understand the full natural history of the disease. As only 40% of people living with ALS are eligible for typical clinical trials, clinical trial datasets may not generalize to the full ALS population. While biomarker and cohort studies have more generous inclusion criteria, these too may not represent the full range of phenotypes, particularly if the burden for participation is high. To permit a complete understanding of the heterogeneity of ALS, comprehensive data on the full range of people with ALS is needed. METHODS: The ALS Natural History Consortium (ALS NHC) consists of nine ALS clinics and was created to build a comprehensive dataset reflective of the ALS population. At each clinic, most patients are asked to participate and about 95% do. After obtaining consent, a minimum dataset is abstracted from each participant's electronic health record. Participant burden is therefore minimal. RESULTS: Data on 1925 ALS patients were submitted as of 9 December 2022. ALS NHC participants were more heterogeneous relative to anonymized clinical trial data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. The ALS NHC includes ALS patients of older age of onset and a broader distribution of El Escorial categories, than the PRO-ACT database. CONCLUSIONS: ALS NHC participants had a higher diversity of diagnostic and demographic data compared to ALS clinical trial participants.Key MessagesWhat is already known on this topic: Current knowledge of the natural history of ALS derives largely from regional and national registries that have broad representation of the population of people living with ALS but do not always collect covariates and clinical outcomes. Clinical studies with rich datasets of participant characteristics and validated clinical outcomes have stricter inclusion and exclusion criteria that may not be generalizable to the full ALS population.What this study adds: To bridge this gap, we collected baseline characteristics for a sample of the population of people living with ALS seen at a consortium of ALS clinics that collect extensive, pre-specified participant-level data, including validated outcome measures.How this study might affect research, practice, or policy: A clinic-based longitudinal dataset can improve our understanding of the natural history of ALS and can be used to inform the design and analysis of clinical trials and health economics studies, to help the prediction of clinical course, to find matched controls for open label extension trials and expanded access protocols, and to document real-world evidence of the impact of novel treatments and changes in care practice.

Advancing Care and Outcomes for African American Patients With Multiple Sclerosis.

Multiple sclerosis (MS) has historically been underdiagnosed and undertreated among African Americans. Recent evidence suggests that African Americans with MS have a different clinical presentation, increased disease incidence and burden, and worse long-term outcomes vs their White counterparts. Due to limited data available for African Americans in MS clinical trials, it is difficult to make informed, generalizable conclusions about the natural history, prognosis, and therapeutic response in this population. In this narrative review, we highlight the nature and magnitude of the health disparities experienced by African Americans with MS and underscore the pressing need to increase knowledge about and understanding of MS disease manifestations in this group. In addition, we describe the mission and objectives of the recently established National African Americans with Multiple Sclerosis Registry, which is intended to be a platform to advance the care of African Americans with MS and address health disparities they may experience.

Clinical outcomes of patients with multiple sclerosis treated with ocrelizumab in a US community MS center: an observational study.

BACKGROUND: To monitor long-term outcomes of ocrelizumab treatment. OBJECTIVE: To evaluate safety and treatment outcomes of ocrelizumab in a community-based multiple sclerosis (MS) population. METHODS: Adult patients with MS prescribed ocrelizumab were eligible. Chart reviews were conducted at the start of ocrelizumab treatment and every 6 months thereafter. RESULTS: Of the 355 patients enrolled, 71.9% were female; mean (SD) age was 51.8 (12.5) years; 78.3% had relapsing MS (RMS). Median baseline Expanded Disability Status Scale (EDSS) (IQR) was 3.0 (2.0-4.0) for RMS, 6.5 (6.0-7.5) for secondary progressive MS, and 6.5 (6.0-7.0) for primary progressive MS. Respiratory infections occurred in 40.1% and urinary tract infections in 33.1% of patients. There was no difference in the percentage of infections among patients <55 (68.5%, n=122), and those ≥55 of age (67.5%, n=104) (p=0.94). Twenty-five hospitalisations were due to infections; 69.2% of these patients were ≥55 with a mean EDSS of 5.7 (±1.86). Four patients have died. Serum IgM and IgG levels did not predict infection risk. Annualised relapse rate was 0.34 for the patients with RMS in the preceding 2 years and 0.09 in patients who received ≥2 ocrelizumab 600 mg courses. The first on-treatment MRI was stable in 262 (90.0%) patients, 6.9% had new T2 lesions, 2.7% had enlarging T2 lesions and 1.4% had gadolinium-enhancing lesions. Median EDSS at 12 months was unchanged. CONCLUSION: Ocrelizumab effectively controlled relapse risk and disability worsening. Although only 12.1% of patients have discontinued ocrelizumab, infections resulting in hospitalisation are a concern, especially in older and disabled patients.

Quality of life among injectable and oral disease-modifying therapy users in the Pacific Northwest Multiple Sclerosis Registry.

BACKGROUND: Nine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period. METHODS: Longitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a maximum of 36 months between surveys. Stayers were defined as those who remained on injectable DMTs continuously from Time 1 to Time 2; switchers were those who switched from injectable to either fingolimod, teriflunomide or dimethyl fumarate during the same time interval. Outcomes of interest were physical and psychological QoL, measured by the Multiple Sclerosis Impact Scale (MSIS-29), and disability, measured by the Patient Determined Disease Steps (PDDS). To analyze the effect of switching to oral DMT on outcomes at Time 2, a one-to-two propensity score matching (PSM) was used to match switchers to stayers. Outcomes at Time 2 were analyzed using paired t-test for QoL scores, and Stuart Maxwell test for PDDS as a categorical variable. RESULTS: Among 2385 participants who returned consecutive yearly surveys, 413 met the inclusion criteria for stayers and 66 for switchers. After one-to-two PSM, 124 stayers were matched to 62 switchers. Paired t-test showed no differences between switchers and stayers for physical (mean difference: - 0.41; [95% confidence interval CI: - 3.3-2.4]; p = 0.78) or psychological (mean difference: - 0.23; [95% CI, - 1.6- 1.1]; p = 0.74) QoL. Additionally, no differences were seen between switchers and stayers in self-reported disability status. CONCLUSIONS: MS registry participants who switched to an oral DMT from injectable showed no significant differences in QoL or self-reported disability status compared to those remaining on injectable DMT continuously in the same time period.

Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center.

BACKGROUND: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. OBJECTIVE: To track DMF patients' tolerability, disease progression, and lymphopenia. METHODS: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review. RESULTS: The mean age of patients starting DMF was 49.4 ± 12.0 years and 70% transitioned from a previous disease-modifying therapy (DMT). Of the patients, 38% discontinued DMF, 76% of whom discontinued due to side effects. Clinical relapse and MRI activity were low. Comparing patients who transitioned from interferon-ß (IFN), glatiramer acetate (GA), or natalizumab (NTZ), patients previously on NTZ had higher rates of relapse than those previously on GA (annualized relapse rate p = 0.039, percent relapse p = 0.021). Grade III lymphopenia developed in 11% of patients. Lymphopenia was associated with older age ( p < 0.001) and longer disease duration ( p < 0.001). CONCLUSION: Given the high rates of lymphopenia and discontinuation, it has become our clinical practice to more closely scrutinize older patients and those with a longer disease duration who are potential candidates for initiating DMF therapy.

Telehealth Stroke Dysphagia Evaluation Is Safe and Effective.

BACKGROUND: Rapid evaluation of dysphagia poststroke significantly lowers rates of aspiration pneumonia. Logistical barriers often significantly delay in-person dysphagia evaluation by speech language pathologists (SLPs) in remote and rural hospitals. Clinical swallow evaluations delivered via telehealth have been validated in a number of clinical contexts, yet no one has specifically validated a teleswallow evaluation for in-hospital post-stroke dysphagia assessment. METHODS: A team of 6 SLPs experienced in stroke care and a telestroke neurologist designed, implemented, and tested a teleswallow evaluation for acute stroke patients, in which 100 patients across 2 affiliated, urban certified stroke centers were sequentially evaluated by a bedside and telehealth SLP. Inter-rater reliability was analyzed using percent agreement, Cohen's kappa, Kendall's tau-b, and Wilcoxon matched-pairs signed rank tests. Logistic regression models accounting for age and gender were used to test the impact of stroke severity and stroke location on agreement. RESULTS: We found excellent agreement for both liquid (91% agreement; kappa = 0.808; Kendall's tau-b = 0.813, p < 0.001; Wilcoxon signed rank = -0.818, p = 0.417) and solid (87% agreement; kappa = 0.792; Kendall's tau-b = 0.844, p < 0.001; Wilcoxon signed rank = 0.243, p = 0.808) dietary textures. From regression modeling, there is suggestive but inconclusive evidence that higher National Institute of Health Stroke Scale (NIHSS) scores correlate with lower levels of agreement for liquid diet recommendations (OR [95% CI] 0.895 [0.793-1.01]; p = 0.07). There was no impact of NIHSS score for solid diet recommendations and no impact of stroke location on solid or liquid diet recommendations. Qualitatively, we identified professional, logistical, technical, and patient barriers to implementation, many of which resolved with experience over time. CONCLUSIONS: Dysphagia evaluation by a remote SLP via telehealth is safe and effective following stroke. We plan to implement teleswallow across our multistate telestroke network as standard practice for poststroke dysphagia evaluation.

MRI utility in the detection of disease activity in clinically stable patients with multiple sclerosis: a retrospective analysis of a community based cohort.

BACKGROUND: Since the application of MRI scanning to the diagnosis and treatment of multiple sclerosis, it has been recognized that only a small fraction of lesions seen on MRI scans produce recognizable symptoms or neurological findings. Because new lesions may occur without clinical detection, the recommendation has been made that MRI scanning be performed on a routine scheduled basis, usually yearly, even in patients who are clinically stable. METHODS: A retrospective chart review study was conducted on MS patients who had MRI scans of the central nervous system between 2009 and 2012 at Providence Multiple Sclerosis Center. Inclusion criteria were patients with relapsing MS who had been treated with interferon beta or glatiramer acetate for 6 months or longer. Information on type, indication, and result of MRI and whether a change in disease modifying therapy occurred as a result of the scan was collected. RESULTS: Of the 436 clinically stable patients who had routine MRI, 16.7 % of subjects had scans revealing new, enlarged or active lesions, yet in only 4.4 % patients was there a change in therapy based upon MRI results. Subjects who had MRI changes were found to be younger (50.15 vs 53.43, p = 0.02) but there was no significant difference in other demographic or clinical characteristics when compared with the subjects who did not have MRI changes. Thirty-six percent of patients with MRI changes did not change DMT due to patient request. CONCLUSIONS: This study provides data on the likelihood of detecting MRI-documented disease activity, in patients demonstrating longer term sustained clinical stability while receiving DMTs. These results may materially assist in the decision whether or not to perform yearly MRI scanning of such patients. The potential clinical impact of the results of routine MRI scanning must be weighed against the consideration of considerable expense of frequent MRI scanning, and the yet unknown adverse impact of retained gadolinium in patients repeatedly receiving this contrast agent. The long-term clinical impact of not changing DMTs in patients in whom MRI changes were observed will be addressed in future studies of this cohort.

Results of sustained long-term use of interferon beta-1a in a community-based cohort of patients with relapsing multiple sclerosis.

BACKGROUND: Few studies have evaluated long-term efficacy of interferon beta-1a in large community-based cohorts. OBJECTIVE: Evaluate time to relapse, relapse rate, and disability progression in patients treated with intramuscular interferon beta-1a. METHODS: A retrospective review of medical records from 2000-2010 was performed. Adult patients with relapsing-remitting MS or clinically isolated syndrome treated with interferon beta-1a were included. Primary outcomes were time to relapse, annualized relapse rate, and changes in Expanded Disability Status Scale score. Other outcomes included factors associated with time to first relapse, risk of having a relapse while receiving interferon beta-1a, and discontinuation of therapy. RESULTS: In total, 364 of 696 patients screened were enrolled, with a mean age of 51 ± 12.1 years, disease duration of 9.39 ± 7.02 years, and duration of therapy of 4.03 ± 2.56 years. Mean time to first on-therapy relapse was 5.58 ± 0.26 years, annualized relapse rate was 0.30 ± 0.55 years, and mean increase in sustained Expanded Disability Status Scale score was 0.018. Relapse risk was associated with higher baseline Expanded Disability Status Scale score, age at disease onset, and number of relapses in the 12 months prior to therapy initiation. CONCLUSIONS: This study demonstrates favorable clinical outcomes observed in a large community-based cohort, and serves to emphasize the continued therapeutic importance of interferon beta-1a, despite the development of newer agents with greater convenience of use, but also more potential risk of serious morbidity.