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A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20dimCD8+ T cells with a highly inflammatory and central nervous system (CNS)-homing phenotype, were significantly inversely correlated with pretreatment MRI gadolinium-lesion counts, and also predictive of early disease activity observed after anti-CD20 initiation. Direct removal of pretreatment proinflammatory CD20dimCD8+ T cells had a greater contribution to treatment-associated changes in the CD8+ T cell pool than was the case for CD4+ T cells. Early disease activity following anti-CD20 initiation was not associated with reconstituting CD20dimCD8+ T cells, which were less proinflammatory compared with pretreatment. Similarly, this disease activity did not correlate with early reconstituting B cells, which were predominantly transitional CD19+CD24highCD38high with a more anti-inflammatory profile. We provide insights into the mode-of-action of anti-CD20 and highlight a potential role for CD20dimCD8+ T cells in MS relapse biology; their strong inverse correlation with both pretreatment and early posttreatment disease activity suggests that CD20-expressing CD8+ T cells leaving the circulation (possibly to the CNS) play a particularly early role in the immune cascades involved in relapse development.
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Linfócitos T CD8-Positivos , Esclerose Múltipla , Humanos , Leucócitos Mononucleares , Citometria de Fluxo , Recidiva , Antígenos CD20RESUMO
Introduction: Teleneurology has become widely adopted during severe acute respiratory syndrome coronavirus 2 pandemic. However, provider impressions about the teleneurology experience are not well described. Methods: A novel questionnaire was developed to collect provider impressions about video teleneurology encounters. All providers in the University of Pennsylvania Health System (UPHS) Neurology Department (N = 162) were asked to complete a questionnaire after each video teleneurology patient encounter between April and August 2020. Individual patient and encounter-level data were extracted from the electronic medical record. Results: One thousand six hundred three surveys were completed by 55 providers (response rate of 10.12%). The history obtained and the ability to connect with the patient were considered the same or better than an in-person visit in almost all encounters. The quality of the physician-patient relationship was good or excellent in 93%, while the overall experience was the same as an in-person visit in 73% of visits and better in 12%. Sixty-eight percent of respondents reported that none of the elements of the neurological examination if performed in person would have changed the assessment and plan. Assessment of the visit as the same or better increased from 83% in April to 89% in July and 95% in August. Headache (91%), multiple sclerosis and neuroimmunology (96%), and movement disorder (89%) providers had the highest proportion of ratings of same or better overall experience and neuromuscular providers the lowest (60%). Conclusions: Provider impressions about the teleneurology history, examination, and provider-patient relationship are favorable in the majority of responses. Important differences emerge between provider specialty and visit characteristics groups.
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COVID-19 , Neurologia , Telemedicina , COVID-19/epidemiologia , Humanos , Pandemias , SARS-CoV-2RESUMO
The coronavirus disease-19 (COVID-19) pandemic has compelled health care practices and academic departments to evaluate the suitability of telemedicine for various specialties and attempt rapid implementation to enable continuation of health care that is safe for providers and patients. Many patients with neurological disorders are well suited to evaluations through video. The department of neurology at the University of Pennsylvania (Penn Neurology), with the support of the health system, rapidly expanded telemedicine services to meet the needs of our patient population. This accomplishment required the complex coordination of multiple disciplines and roles within the department and the health care system, including faculty, residents, administrative staff, research and technical staff, information services, and the connected health team. Procedures for provider and patient education were established. Surveys of the provider and patient experience were developed and deployed. The process has demonstrated the vital role telemedicine in neurology (teleneurology) should play in the care of neurological patients beyond the pandemic. We describe our experience as a template for other departments and practices seeking to establish teleneurology programs, as well as an illustration of the challenges and barriers to its implementation.
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COVID-19 , Neurologia , Telemedicina , Humanos , Pandemias , SARS-CoV-2RESUMO
ABSTRACT: Health professions educators are continuing to develop training programs for future health care professionals to understand social determinants of health and address practical needs of their training institutions via service-oriented learning. Although individual U.S. programs have piloted different models, evaluations of programs that have demonstrated longitudinal growth and sustainability in the community are lacking, which is important because these programs can have long-term impacts not only on students but also on the communities they serve. In this article, the authors describe the long-term impacts of the Bridging the Gaps (BTG) program. First established in 1991 as an academic health institution and community organization collaborative, by 2019, the BTG program encompassed 9 academic health institution-based programs, partnering with 96 community organizations and employing 187 health professions students across 15 disciplines. By 2019, the program had 5,648 alumni. Of 3,104 alumni, 2,848 (91.8%) felt that the program broadened their understanding of health issues encountered by vulnerable and/or economically disadvantaged populations, and 2,767 of 3,101 (89.2%) felt that the program increased their interest in working with these populations. A total of 142 of 156 (91.0%) reported an effect on their clinical practice, 169 of 180 (93.9%) reported an effect on their professional role, and 64 of 109 (58.7%) reported an effect on their research careers. Of the community partners, 1,401 of 1,441 (97.2%) felt that the partnership between their organization and the BTG program was beneficial, 955 of 1,423 (67.1%) felt that BTG students brought resources to their organization that had previously been unavailable, and 1,095 of 1,421 (77.1%) felt that the linkages between their agency and other organizations were strengthened. The BTG program demonstrates growth and sustainability in its ongoing efforts to integrate training on social determinants of health via service-oriented learning into health professions education.
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Determinantes Sociais da Saúde , Humanos , Estados Unidos , Ocupações em Saúde/educação , Avaliação de Programas e Projetos de Saúde , Comportamento Cooperativo , CurrículoRESUMO
Multiple sclerosis (MS) has a global prevalence exceeding two million people and is a leading cause of non-traumatic physical disability. MS can be treated with ocrelizumab, an anti-CD20 monoclonal antibody. West Nile virus (WNV) is the most common cause of mosquito-borne viral encephalitis in North America. It can lead to neuroinvasive WNV disease (WNND) affecting the brain and peripheral nervous system, especially in immunocompromised patients, such as those being treated with ocrelizumab for MS. WNND is exceedingly rare and reported in less than 1% of cases of WNV. It has been established that inpatient rehabilitation improves functional outcomes in patients with MS and those with WNND. However, the inpatient rehabilitation outcomes in patients diagnosed with both WNND and MS have not been reported. In this study, we aimed to examine the rehabilitation outcomes of MS patients on ocrelizumab diagnosed with WNND. We performed a retrospective chart review of patients with MS treated with ocrelizumab, who were diagnosed with WNND and admitted to a single facility. Rehabilitation outcomes were assessed using functional independence measure (FIM) scores on admission and discharge. Three patients met the inclusion criteria; two in acute rehab, and one in the long-term acute care hospital (LTACH). Both patients admitted to acute inpatient rehabilitation showed an improvement in FIM scores from admission to discharge, one patient from 9 to 16 and the other from 14 to 54. However, the patient admitted to the LTACH had no improvement in FIM score from admission to discharge. Patients admitted to acute rehab were ultimately discharged home, while the patient admitted to the LTACH required discharge to a subacute rehabilitation facility. Based on our findings, intense and prolonged comprehensive inpatient rehabilitation is associated with improved functional outcomes and increased likelihood of discharge to home in this population suffering from both central and peripheral nervous system involvement due to MS and WNND.
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Purpose of Review: Lack of consistent data and guidance have led to variations between clinicians in the management of pregnancy in women with multiple sclerosis (MS). Pregnant and/or lactating women are often excluded from clinical trials conducted in MS, and thus, the labeling for most disease-modifying therapies (DMTs) excludes use during pregnancy. This has led to heterogeneity in interpretation and labeling regarding the safety of DMTs during pregnancy and lactation and the required preconception washout periods. This review identifies key themes where there is conflicting information surrounding family planning and pregnancy in MS, focusing on the most common discussion points between physicians and patients during preconception planning, pregnancy, postpartum, and lactation. The goal was to inform the patient-physician conversation and provide best practice recommendations based on expert clinical expertise and experience. Recent Findings: We outline the latest evidence-based data for DMT use during pregnancy and lactation, the effect of MS on fertility and fertility treatments, the risk of adverse pregnancy and delivery outcomes, the risk of postpartum relapse, and immunization and clinical imaging safety during pregnancy and breastfeeding. Summary: Management of family planning and pregnancy in patients with MS requires the most current information. Health care providers should discuss family planning early and frequently with patients with MS, and partners where practicable. Because management of pregnant people with MS will often require a risk/benefit analysis of their needs, shared decision-making in family planning discussions is emphasized. Additional data are needed for specific and underrepresented populations with MS (e.g., single parents or those from the LGBTQ+ community) and those at risk of racial and socioeconomic disparities in care. Pregnancy registries and the design and conduct of clinical trials focused on pregnant and lactating patients should provide additional data to guide the ongoing management of patients with MS.
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Background: During the COVID-19 pandemic, SARS-CoV-2 monoclonal antibodies for preexposure prophylaxis (SMA-PrEP) offered patients who were immunocompromised another option for protection. However, SMA-PrEP posed administrative, operational, and ethical challenges for health care facilities, resulting in few patients receiving them. Although the first SMA-PrEP medication, tixagevimab and cilgavimab, had its authorization revoked due to compromised in vitro efficacy, new SMA-PrEP medications are currently completing clinical trials. This article provides an operational framework for administrative organization, patient identification and prioritization, equitable medication allocation, medication ordering and administration, and patient tracking. Methods: A retrospective cohort study evaluating our hospital's SMA-PrEP administration strategy was performed. Multivariable logistic regression was used to examine factors associated with receipt of SMA-PrEP. Results: Despite the barriers in administering this medication and the scarcity of resources, our hospital was able to administer at least 1 dose of SMA-PrEP to 1359 of 5902 (23.0%) eligible patients. Even with the steps taken to promote equitable allocation, multivariable logistic regression demonstrated that there were still differences by race, ethnicity, and socioeconomic status. As compared with patients who identified as Black, patients who identified as White (odds ratio [OR], 1.85; 95% CI, 1.46-2.33), Asian (OR, 1.59; 95% CI, 1.03-2.46), and Hispanic (OR, 1.53; 95% CI, 1.02-2.44) were more likely to receive SMA-PrEP. When compared with patients with low socioeconomic status, patients with high socioeconomic status (OR, 1.37; 95% CI, 1.05-1.78) were more likely to be allocated SMA-PrEP. Conclusions: Despite efforts to mitigate health care disparities, differences by race/ethnicity and socioeconomic status still arose in patients receiving SMA-PrEP.
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BACKGROUND AND OBJECTIVES: Racial disparities exist in both neurologic and obstetric populations, underscoring the importance of evaluating pregnancy outcomes in diverse women with multiple sclerosis (MS). The objective of this multicenter retrospective study was to compare pregnancy care and outcomes between Black and Hispanic (underrepresented) and White women with MS. METHODS: Demographic and clinical data were extracted from medical records of 9 US MS centers for women with MS/clinically isolated syndrome who delivered live births between 2010 and 2021. Sites identified at last 15 consecutive Black/Hispanic women and a matching number of White women. Socioeconomic factors, pregnancy, and MS care/outcomes were compared between groups (underrepresented and White and then Black and Hispanic) using Wilcoxon rank sum (U statistic and effect size r reported), χ2, t tests and logistic regressions as appropriate to data type. Multiple imputation by chained equation was used to account for missing data. RESULTS: Overall, 294 pregnancies resulting in live births were analyzed ( 81 Black, 67 Hispanic, and 146 White mothers). Relative to underrepresented women, White women lived in areas of higher median (interquartile range [IQR]) Child Opportunity Index (79 [45.8] vs 22 [45.8], U = 3,824, r = 0.56, p < 0.0001) and were more often employed (84.9% vs 75%, odds ratio [OR] 2.57, CI 1.46-4.50, p = 0.0008) and privately insured (93.8% vs 56.8%, OR 11.6, CI 5.5-24.5, p < 0.0001) and more received a 14-week ultrasound (98.6% vs 93.9%, OR 4.66, CI 0.99-21.96, p = 0.027). Mode of delivery was significantly different between the three groups (X2(10,294) = 20.38, p = 0.03); notably, Black women had the highest rates of emergency cesarean deliveries, and Hispanic women highest rates of uncomplicated vaginal deliveries. Babies born to underrepresented women had lower median (IQR) birthweights than babies born to White women (3,198 g [435.3 g] vs 3,275 g [412.5 g], U = 9,255, r = 0.12, p = 0.04) and shorter median (IQR) breastfeeding duration (4.5 [3.3] vs 6.0 [4.2] months, U = 8,184, r = 0.21, p = 0.003). While underrepresented women were younger than White women (mean [SD] 30.9 [4.8] vs 33.8 [4.0], t = 1.97, CI 1.96-3.98, p < 0.0001), their median (Q1-Q3, IQR) Expanded Disability Status Scale was higher (1.5 [1-2.5, 1.5] vs 1 [0-1.5, 1.5], U = 7,260, r = 0.29, p < 0.0001) before pregnancy. Finally, medical records were missing more key data for Black women (19.7% missing vs 8.9% missing, OR 2.54, CI 1.25-5.06, p = 0.008). DISCUSSION: In this geographically diverse multicenter cohort, underrepresented women entered pregnancy with higher disability and fewer health care resources. Pregnancy represents a pivotal window where structural factors affect maternal and fetal health and neurologic trajectories; it is a critical period to optimize care and health outcomes.
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Doenças Desmielinizantes , Esclerose Múltipla , Lactente , Gravidez , Criança , Humanos , Feminino , Estudos Retrospectivos , Cuidado Pré-Natal , MãesRESUMO
BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may seek fertility treatment (FT)-including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse. METHODS: Patients with clinically isolated syndrome (CIS) or MS aged 18-45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported. RESULTS: One hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25, p = 0.37), and the IRR was 0.95 (95% CI: 0.52-1.76, p = 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS, p = 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p = 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI. DISCUSSION: In this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.
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Esclerose Múltipla , Gravidez , Feminino , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/etiologia , Estudos Retrospectivos , Fertilização in vitro/efeitos adversos , Indução da Ovulação/métodos , IncidênciaRESUMO
BACKGROUND: B cells can be enriched within meningeal immune-cell aggregates of multiple sclerosis (MS) patients, adjacent to subpial cortical demyelinating lesions now recognized as important contributors to progressive disease. This subpial demyelination is notable for a 'surface-in' gradient of neuronal loss and microglial activation, potentially reflecting the effects of soluble factors secreted into the CSF. We previously demonstrated that MS B-cell secreted products are toxic to oligodendrocytes and neurons. The potential for B-cell-myeloid cell interactions to propagate progressive MS is of considerable interest. METHODS: Secreted products of MS-implicated pro-inflammatory effector B cells or IL-10-expressing B cells with regulatory potential were applied to human brain-derived microglia or monocyte-derived macrophages, with subsequent assessment of myeloid phenotype and function through measurement of their expression of pro-inflammatory, anti-inflammatory and homeostatic/quiescent molecules, and phagocytosis (using flow cytometry, ELISA and fluorescently-labeled myelin). Effects of secreted products of differentially activated microglia on B-cell survival and activation were further studied. FINDINGS: Secreted products of MS-implicated pro-inflammatory B cells (but not IL-10 expressing B cells) substantially induce pro-inflammatory cytokine (IL-12, IL-6, TNFα) expression by both human microglia and macrophage (in a GM-CSF dependent manner), while down-regulating their expression of IL-10 and of quiescence-associated molecules, and suppressing their myelin phagocytosis. In contrast, secreted products of IL-10 expressing B cells upregulate both human microglia and macrophage expression of quiescence-associated molecules and enhance their myelin phagocytosis. Secreted factors from pro-inflammatory microglia enhance B-cell activation. INTERPRETATION: Potential cross-talk between disease-relevant human B-cell subsets and both resident CNS microglia and infiltrating macrophages may propagate CNS-compartmentalized inflammation and injury associated with MS disease progression. These interaction represents an attractive therapeutic target for agents such as Bruton's tyrosine kinase inhibitors (BTKi) that modulate responses of both B cells and myeloid cells. FUNDING: Stated in Acknowledgments section of manuscript.
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OBJECTIVES: The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS). METHODS: This is a case series study. RESULTS: In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ2 p < 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies. DISCUSSION: Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.
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Esclerose Múltipla , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Humanos , Feminino , Masculino , Febre do Nilo Ocidental/complicações , Febre do Nilo Ocidental/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/complicações , Anticorpos Antivirais , Imunoglobulina MRESUMO
OBJECTIVE: Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes. METHODS: Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes. RESULTS: The median average concentration of mAb in breastmilk was low (OCR: 0.08 µg/mL, range 0.05-0.4; RTX: 0.03 µg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse. INTERPRETATION: These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.
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Antineoplásicos , Esclerose Múltipla , Gravidez , Lactente , Criança , Humanos , Feminino , Anticorpos Monoclonais , Rituximab/uso terapêutico , Período Pós-Parto , Esclerose Múltipla/tratamento farmacológico , Imunoglobulina GRESUMO
OBJECTIVE: To report clinical and immunological investigations of contactin-associated protein-like 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC). METHODS: Clinical analysis was performed on patients with encephalitis, PNH, or both. Immunoprecipitation and mass spectrometry were used to identify the antigen and to develop an assay with Caspr2-expressing cells. Immunoabsorption with Caspr2 and comparative immunostaining of brain and peripheral nerve of wild-type and Caspr2-null mice were used to assess antibody specificity. RESULTS: Using Caspr2-expressing cells, antibodies were identified in 8 patients but not in 140 patients with several types of autoimmune or viral encephalitis, PNH, or mutations of the Caspr2-encoding gene. Patients' antibodies reacted with brain and peripheral nerve in a pattern that colocalized with Caspr2. This reactivity was abrogated after immunoabsorption with Caspr2 and was absent in tissues from Caspr2-null mice. Of the 8 patients with Caspr2 antibodies, 7 had encephalopathy or seizures, 5 neuropathy or PNH, and 1 isolated PNH. Three patients also had myasthenia gravis, bulbar weakness, or symptoms that initially suggested motor neuron disease. None of the patients had active cancer; 7 responded to immunotherapy and were healthy or only mildly disabled at last follow-up (median, 8 months; range, 6-84 months). INTERPRETATION: Caspr2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. The occurrence of other autoantibodies may result in a complex syndrome that at presentation could be mistaken for a motor neuron disorder. Recognition of this disorder is important, because it responds to immunotherapy.
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Autoanticorpos/imunologia , Autoantígenos/imunologia , Encefalite/imunologia , Síndrome de Isaacs/imunologia , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Idoso , Animais , Especificidade de Anticorpos/imunologia , Feminino , Humanos , Imuno-Histoquímica , Imunoprecipitação , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Nervos Periféricos/imunologiaRESUMO
BACKGROUND: Patients with multiple sclerosis (MS) were vulnerable to the effects of physical inactivity during the COVID-19 pandemic. As patients returned to in-person visits, providers reported seeing increased weakness, balance issues, falls, worsening pain, and spasticity. Social isolation also contributed to increased stress, depression, and anxiety. This study explored whether attending virtual wellness programs was associated with improvements in standard quality of life questionnaire scores for patients with MS. METHODS: The purposive convenience sample consisted of 43 patients in the treatment group and 28 in the control group. Patients in the treatment group attended 2 monthly programs for 6 months and completed a demographic questionnaire, the 36-Item Short Form Health Survey (SF-36), the Modified Fatigue Impact Scale, and the Medical Outcomes Study Pain Effects Scale (PES). Patients requested additional topics, resulting in 5 additional programs. The control group consisted of patients who chose not to attend the programs but agreed to complete the questionnaires. RESULTS: In comparing questionnaire responses (6 months minus baseline) among the participants in the treatment group, an association was found between higher meeting attendance and improvements in emotional well-being (P = .038), pain on the PES (P = .011), mindfulness on the SF-36 pain scale (P = .0472), and exercise on the PES (P = .0115). CONCLUSIONS: The results of this study suggest that a virtual wellness program may provide beneficial emotional support, physical exercise, and health promotion activities resulting in improved quality of life in people with MS. In addition, mindfulness and exercise programs may be beneficial in pain management.
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BACKGROUND AND PURPOSE: Imaging and autopsy studies show intracranial gadolinium deposition in patients who have undergone serial contrast-enhanced MRIs. This observation has raised concerns when using contrast administration in patients who receive frequent MRIs. To address this, we implemented a contrast-conditional protocol wherein gadolinium is administered only for multiple sclerosis (MS) patients with imaging evidence of new disease activity on precontrast imaging. In this study, we explore the economic impact of our new MRI protocol. METHODS: We compared scanner time and Medicare reimbursement using our contrast-conditional methodology versus that of prior protocols where all patients received gadolinium. RESULTS: For 422 patients over 4 months, the contrast-conditional protocol amounted to 60% decrease in contrast injection and savings of approximately 20% of MRI scanner time. If the extra scanner time was used for performing MS follow-up MRIs in additional patients, the contrast-conditional protocol would amount to net revenue loss of $21,707 (â¼3.7%). CONCLUSIONS: Implementation of a new protocol to limit contrast in MS follow-up MRIs led to a minimal decrease in revenue when controlled for scanner time utilized and is outweighed by other benefits, including substantial decreased gadolinium administration, increased patient comfort, and increased availability of scanner time, which depending on type of studies performed could result in additional financial benefit.
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Gadolínio , Esclerose Múltipla , Idoso , Meios de Contraste , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Medicare , Esclerose Múltipla/diagnóstico por imagem , Estados UnidosRESUMO
Background: The effects of pregnancy on multiple sclerosis (MS) inflammatory activity are not well described in women with moderate to severe disabilities. Objective: To quantify the peripartum annualized relapse rate (ARR) in women with MS with an Expanded Disability Status Scale (EDSS) ≥ 3. Methods: We performed a retrospective cohort study of 85 pregnancies in 74 subjects with preconception EDSS ≥ 3. We quantified peripartum ARR and tested for risk factors predictive of peripartum relapses, postpartum brain magnetic resonance imaging activity (new T2 or gadolinium-enhancing lesions), and disability worsening. Results: There were 74 live births, with a 56% operative delivery rate. In subjects with relapsing-remitting MS, ARR decreased to 0.11 during the third trimester of pregnancy compared to 0.59 in the year preconception and increased to 1.22 in the 3 months postpartum. Women with a higher preconception EDSS had higher odds of postpartum relapses and clinically significant worsening of disability as compared to subjects with a lower EDSS. Conclusions: Moderately to severely disabled women with MS have a lower risk of relapse during pregnancy as compared to preconception, followed by a marked increase postpartum. Further studies are needed to identify ways to reduce peripartum inflammatory activity and disability progression in women with MS with moderate to severe disability.
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BACKGROUND: Immunosenescence (ISC) describes age-related changes in immune-system composition and function. Multiple sclerosis (MS) is a lifelong inflammatory condition involving effector and regulatory T-cell imbalance, yet little is known about T-cell ISC in MS. We examined age-associated changes in circulating T cells in MS compared to normal controls (NC). METHODS: Forty untreated MS (Mean Age 43·3, Range 18-72) and 49 NC (Mean Age 48·6, Range 20-84) without inflammatory conditions were included in cross-sectional design. T-cell subsets were phenotypically and functionally characterized using validated multiparametric flow cytometry. Their aging trajectories, and differences between MS and NC, were determined using linear mixed-effects models. FINDINGS: MS patients demonstrated early and persistent redistribution of naïve and memory CD4 T-cell compartments. While most CD4 and CD8 T-cell aging trajectories were similar between groups, MS patients exhibited abnormal age-associated increases of activated (HLA-DR+CD38+; (P = 0·013) and cytotoxic CD4 T cells, particularly in patients >60 (EOMES: P < 0·001). Aging MS patients also failed to upregulate CTLA-4 expression on both CD4 (P = 0·014) and CD8 (P = 0·009) T cells, coupled with abnormal age-associated increases in frequencies of B cells expressing costimulatory molecules. INTERPRETATION: While many aspects of T-cell aging in MS are conserved, the older MS patients harbour abnormally increased frequencies of CD4 T cells with activated and cytotoxic effector profiles. Age-related decreased expression of T-cell co-inhibitory receptor CTLA-4, and increased B-cell costimulatory molecule expression, may provide a mechanism that drives aberrant activation of effector CD4 T cells that have been implicated in progressive disease. FUNDING: Stated in Acknowledgements section of manuscript.
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Linfócitos T CD4-Positivos , Esclerose Múltipla , Adulto , Envelhecimento , Linfócitos T CD8-Positivos , Antígeno CTLA-4 , Estudos Transversais , Humanos , Ativação Linfocitária , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON). METHODS: Patients underwent OCT measurement of RNFL thickness at baseline and at 6-month intervals during a mean follow-up of 18 months at 3 centers. Low-contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed. RESULTS: Among 299 patients (593 eyes) with >or=6 months follow-up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low-contrast acuity, 2.5%: p < 0.001; VA: p = 0.005). RNFL thinning increased over time, with average losses of 2.9microm at 2 to 3 years and 6.1microm at 3 to 4.5 years (p < 0.001 vs 0.5-1-year follow-up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test-retest variability (>or=6.6microm) increased from 11% at 0 to 1 year to 44% at 3 to 4.5 years (p < 0.001). INTERPRETATION: Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with subclinical axonal loss in the anterior visual pathway in MS, and support the use of OCT and low-contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols.
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Esclerose Múltipla/complicações , Esclerose Múltipla/patologia , Fibras Nervosas/patologia , Neurônios/patologia , Retina/patologia , Transtornos da Visão/etiologia , Adulto , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: Oral disease-modifying therapies, namely dimethyl fumarate, fingolimod and teriflunomide, have become standard treatments for multiple sclerosis. Clinical trials demonstrated a reduction in annual relapse rate, but real-world data is lacking, particularly in older adults. The objective of our study is to evaluate the real-world effectiveness of oral disease-modifying therapies among individuals with multiple sclerosis. METHODS: We used OptumTM ClinformaticsTM Data Mart, a large dataset representative of commercially insured individuals in the United States, to conduct a retrospective cohort study of adult users of three oral disease-modifying therapies from September 2010 through September 2015. The therapies of interest included dimethyl fumarate, teriflunomide, and fingolimod. Hospitalization for multiple sclerosis, an approximation of the clinical trial endpoint for relapse, was the study outcome. Cox proportional hazards models were built to evaluate the association of demographic and clinical factors with multiple sclerosis hospitalization. A subgroup analysis was performed on individuals ages 55 years or older. RESULTS: We identified 1,823, 318, and 1,156 users of dimethyl fumarate, teriflunomide, and fingolimod that met our inclusion criteria, respectively. Rates of hospitalizations for multiple sclerosis were low among these 3,297 persons (1,041 ages 55+): 36/1,000 patient-years for dimethyl fumarate, 43/1,000 for teriflunomide, and 45/1,000 for fingolimod. Multiple sclerosis hospitalization was associated with therapy switching (adjusted hazard ratio 2.21, 95% confidence interval 1.57-2.84), minority (1.44, 1.10-1.89), and history of relapse in the year preceding oral therapy initiation (5.25, 3.89-7.09). CONCLUSION: Oral disease-modifying therapies are comparably effective for the outcome of multiple sclerosis hospitalization, even in older adults.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Idoso , Crotonatos , Fumarato de Dimetilo , Cloridrato de Fingolimode , Hospitalização , Humanos , Imunossupressores , Pessoa de Meia-Idade , Estudos Retrospectivos , Toluidinas , Estados UnidosRESUMO
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.