Practical Considerations for Managing Pregnancy in Patients With Multiple Sclerosis: Dispelling the Myths.

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.

Insights for Healthcare Providers on Shared Decision-Making in Multiple Sclerosis: A Narrative Review.

Shared decision-making (SDM) between the patient and their healthcare provider (HCP) in developing treatment plans is increasingly recognized as central to improving treatment adherence and, ultimately, patient outcomes. In multiple sclerosis (MS), SDM is particularly crucial for optimizing treatment in a landscape that has grown more complex with the availability of newer, high-efficacy MS therapies. However, little direct evidence on the effectiveness of SDM is available to guide practice. Multiple factors, including patient age, ethnic background, perceptions, invisible MS symptoms, and psychological comorbidities can influence a patient's willingness and ability to participate in SDM. HCPs need to appreciate these factors and ask the right questions to break down obstacles to SDM. The HCP has a responsibility to help patients feel adequately informed and comfortable in having an active role in their care. This review identifies potential barriers to SDM and provides a strategy for HCPs to overcome these obstacles through patient (and caregiver) discussions to ensure optimal patient satisfaction with treatment and thus the best possible outcomes for their patients.

Consensus Curriculum for Fellowship Training in Multiple Sclerosis and Neuroimmunology.

Management of multiple sclerosis and neuroimmunologic disorders has become increasingly complex because of the expanding number of recognized neuroimmune disorders, increased number of therapeutic options, and multidisciplinary care management needs of people with multiple sclerosis and neuroimmunologic disorders. More subspecialists are needed to optimize care of these patients, and many fellowship programs have been created or expanded to increase the subspecialty workforce. Consequently, defining the scope and standardizing fellowship training is essential to ensure that trainees receive high-quality training. A workgroup was created to develop a consensus fellowship curriculum to serve as a resource for all current and future training programs. This curriculum may also serve as a basis for future accreditation efforts.

Outcomes and Risk Factors Associated With SARS-CoV-2 Infection in a North American Registry of Patients With Multiple Sclerosis.

Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections. Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS. Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. Health care professionals were asked to report patients after a minimum of 7 days from initial symptom onset and after sufficient time had passed to observe the COVID-19 disease course through resolution of acute illness or death. Data collection began April 1, 2020, and is ongoing. Exposures: Laboratory-positive SARS-CoV-2 infection or highly suspected COVID-19. Main Outcomes and Measures: Clinical outcome with 4 levels of increasing severity: not hospitalized, hospitalization only, admission to the intensive care unit and/or required ventilator support, and death. Results: Of 1626 patients, most had laboratory-positive SARS-CoV-2 infection (1345 [82.7%]), were female (1202 [74.0%]), and had relapsing-remitting MS (1255 [80.4%]). A total of 996 patients (61.5%) were non-Hispanic White, 337 (20.8%) were Black, and 190 (11.7%) were Hispanic/Latinx. The mean (SD) age was 47.7 (13.2) years, and 797 (49.5%) had 1 or more comorbidity. The overall mortality rate was 3.3% (95% CI, 2.5%-4.3%). Ambulatory disability and older age were each independently associated with increased odds of all clinical severity levels compared with those not hospitalized after adjusting for other risk factors (nonambulatory: hospitalization only, odds ratio [OR], 2.8 [95% CI, 1.6-4.8]; intensive care unit/required ventilator support, OR, 3.5 [95% CI, 1.6-7.8]; death, OR, 25.4 [95% CI, 9.3-69.1]; age [every 10 years]: hospitalization only, OR, 1.3 [95% CI, 1.1-1.6]; intensive care unit/required ventilator support, OR, 1.3 [95% CI, 0.99-1.7]; death, OR, 1.8 [95% CI, 1.2-2.6]). Conclusions and Relevance: In this registry-based cross-sectional study, increased disability was independently associated with worse clinical severity including death from COVID-19. Other risk factors for worse outcomes included older age, Black race, cardiovascular comorbidities, and recent treatment with corticosteroids. Knowledge of these risk factors may improve the treatment of patients with MS and COVID-19 by helping clinicians identify patients requiring more intense monitoring or COVID-19 treatment.

Missed Opportunity Encounters for Early Diagnosis of HIV Infection in Adolescents.

BACKGROUND: Early diagnosis of HIV infection improves patient outcomes and reduces transmission. Adolescents make up one-fifth of new HIV diagnoses in the United States. We sought to quantify the number of missed opportunity encounters (MOEs) before HIV diagnosis for adolescents at a pediatric hospital (PediHosp) and a proximate adult hospital which employs universal HIV screening in its emergency department (ED) (CountyHosp). METHODS: An observational study at 2 academic tertiary care hospitals in the United States that included all adolescents 13-20 years old with a new diagnosis of behaviorally-acquired HIV infection from 2006 to 2017. MOE were defined as any encounter at PediHosp or CountyHosp after the latter of the individual's 13th birthday or the date 3 months after the individual's most recent negative HIV screen, and before the encounter of HIV diagnosis. Comparisons were made by site of diagnosis and location of MOE. RESULTS: Two-hundred five subjects met inclusion criteria: 68% male, 76% Black and 81% men who have sex with men. There were 264 MOE, the proportion of adolescent ED encounters that were MOE at the PediHosp ED was 8.3 MOE per 10,000 encounters and the proportion at the CountyHosp ED was 1.2 (relative risk = 6.7; 95% CI: 4.1-11.0; P < 0.001). CONCLUSIONS: MOE for HIV diagnosis in adolescents occur frequently and are greater in number at a PediHosp as compared with a similar adult setting with universal screening. Universal HIV screening protocols at PediHosp may identify HIV-positive adolescents earlier.

Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis: Recommendations of the National Multiple Sclerosis Society.

Importance: Autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis has gained increasing interest in recent years. Despite the availability of many US Food and Drug Administration-approved disease-modifying therapies, some patients do not respond adequately and others may have very early aggressive disease that prompts consideration of alternative, highly effective, long-lasting therapy. The National Medical Advisory Committee of the National Multiple Sclerosis Society has reviewed recent literature on AHSCT for the purpose of making recommendations about its use based on current knowledge, as well as pointing out areas of controversy and issues requiring further research. Observations: Studies on AHSCT have repeatedly demonstrated high efficacy and a durable outcome in people with relapsing multiple sclerosis. Recent studies have shown considerable improvement in the safety of the procedure, with much lower mortality rates than were reported earlier. Consensus is emerging about the characteristics of the best candidates for the procedure. Questions remain about the ideal protocol, particularly about the best conditioning regimen to be used to kill immune cells. Larger randomized clinical trials are needed to address the question of whether AHSCT has advantages over the most efficacious disease-modifying agents currently available. One such trial (Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis [BEAT-MS) is currently in progress. Conclusions and Relevance: The National Multiple Sclerosis Society believes that AHSCT may be a useful treatment option for people with relapsing multiple sclerosis who demonstrate substantial breakthrough disease activity (ie, new inflammatory central nervous system lesions and/or clinical relapses) despite treatment with high-efficacy disease-modifying therapy or have contraindications to high-efficacy disease-modifying therapies. The best candidates are likely people younger than 50 years with shorter durations of disease (<10 years). The procedure should only be performed at centers with substantial experience and expertise. Ideally, recipients of the procedure should be entered into a single database, and further research is needed to establish ideal cell mobilization and immune-conditioning regimens.

Rapid transfer of knowledge for multiple sclerosis clinical care during COVID-19: ECHO MS.

BACKGROUND: Healthcare providers caring for people with multiple sclerosis (MS) have had significant concerns about the intersection of MS and COVID-19. As a result, there has been an urgency to understand and share information about how to best provide MS clinical care during COVID-19. The Project ECHO model is well-suited for this challenge, as it provides a uniquely efficient and effective approach to sharing information in real-time using real cases. We report on the translation of the Project ECHO model for the rapid sharing of knowledge among MS clinical providers during COVID-19. METHODS: The ECHO MS COVID-19 Response Clinic was a videoconference-based education and case consultation program offered to providers in the U.S. who care for individuals with MS. The Response Clinic was offered as four sessions, each delivered by three regional hubs. Data were collected on participation and the self-reported impact of the program. RESULTS: A total of 132 unique providers participated in the Response Clinic, which consisted of 11 didactic modules and 43 case consultations. Participant providers overwhelmingly indicated that the program improved their knowledge, attitude, and skills for providing healthcare for people with MS during the COVID-19 pandemic. DISCUSSION: The Project ECHO model was successfully adapted to serve the needs of the MS community during COVID-19, suggesting the program could be continued or could be expanded to other disease areas for a similar purpose. More research is needed to objectively measure the impact of the program on patient outcomes.

An International Standardized Magnetic Resonance Imaging Protocol for Diagnosis and Follow-up of Patients with Multiple Sclerosis: Advocacy, Dissemination, and Implementation Strategies.

Standardized magnetic resonance imaging (MRI) protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS). The Consortium of Multiple Sclerosis Centers (CMSC) convened an international panel of MRI experts to review and update the current guidelines. The objective was to update the standardized MRI protocol and clinical guidelines for diagnosis and follow-up of MS and develop strategies for advocacy, dissemination, and implementation. Conference attendees included neurologists, radiologists, technologists, and imaging scientists with expertise in MS. Representatives from the CMSC, Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, US Department of Veteran Affairs, National Multiple Sclerosis Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis companies were present. Before the meeting, CMSC members were surveyed about standardized MRI protocols, gadolinium use, need for diffusion-weighted imaging, and the central vein sign. The panel worked to make the CMSC and MAGNIMS MRI protocols similar so that the updated guidelines could ultimately be accepted by international consensus. Advocacy efforts will promote the importance of standardized MS MRI protocols. Dissemination will include publications, meeting abstracts, educational programming, webinars, "meet the expert" teleconferences, and examination cards. Implementation will require comprehensive and coordinated efforts to make the protocol easy to access and use. The ultimate vision, and goal, is for the guidelines to be universally useful, usable, and used as the standard of care for patients with MS.

Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course.

OBJECTIVES: To provide clinicians who treat multiple sclerosis (MS) patients with evidence-based or expert opinion-based recommendations for promoting exercise and lifestyle physical activity across disability levels. METHODS: The National MS Society ("Society") convened clinical and research experts in the fields of MS, exercise, rehabilitation, and physical activity to (1) reach consensus on optimal exercise and lifestyle physical activity recommendations for individuals with MS at disability levels 0-9.0 on the Expanded Disability Status Scale (EDSS) and (2) identify and address barriers/facilitators for participation. RECOMMENDATIONS: Based on current evidence and expert opinion, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers:Healthcare providers should endorse and promote the benefits/safety of exercise and lifestyle physical activity for every person with MS.Early evaluation by a physical or occupational therapist or exercise or sport scientist, experienced in MS (hereafter referred to as "specialists"), is recommended to establish an individualized exercise and/or lifestyle physical activity plan.Taking into account comorbidities and symptom fluctuations, healthcare providers should encourage ⩾150 min/week of exercise and/or ⩾150 min/week of lifestyle physical activity.Progress toward these targets should be gradual, based on the person's abilities, preferences, and safety.If disability increases and exercise/physical activity becomes more challenging, referrals to specialists are essential to ensure safe and appropriate prescriptions.When physical mobility is very limited, exercise should be facilitated by a trained assistant.

World Health Organization Essential Medicines List: Multiple sclerosis disease-modifying therapies application.

INTRODUCTION: The World Health Organization (WHO) publishes a biennial Essential Medicines List (EML) to assist governments in low-resource settings to prioritize their spending on medicines. Currently, no medicines on the EML have a multiple sclerosis (MS) indication. Multiple Sclerosis International Federation (MSIF) prepared an application for inclusion of MS disease-modifying therapies (DMTs) for the 2019 EML together with the regional Committees for Treatment and Research in Multiple Sclerosis (TRIMS) and the World Federation of Neurology. RATIONALE: The MSIF taskforce categorized 15 DMTs according to their efficacy and risk profiles to ensure the ability to treat as many different clinical scenarios as possible. Three DMTs were selected: glatiramer acetate, fingolimod, and ocrelizumab. OUTCOME: The WHO Expert Committee did not recommend the addition of any of the DMTs to the EML. They acknowledged the public health burden of MS, the need for effective and affordable MS medications, and the high volume of letters received in support of the application but requested a revised application. DISCUSSION: Despite the negative outcome, the repeated recognition of MS as a global public health burden is sending a powerful message to governments globally that a range of affordable and good quality medications need to be available to health systems and people affected by MS.

Telemedicine and multiple sclerosis: A comprehensive literature review.

INTRODUCTION: Patients with multiple sclerosis (pwMS) face barriers accessing specialty care for evaluation and treatment. Telemedicine, the practice of clinical care at a distance with the aid of technology, may be a potential bridge to close the access gap for pwMS separated by distance or disability. The objective of this review was to investigate the types of telemedicine being utilized and overall outcomes for pwMS and their providers. METHODS: A Boolean search of the medical literature was conducted between January 2000 and January 31, 2018. PubMed, EMBASE, PsycINFO and the Cochrane databases, were used to identify all relevant citations. Two reviewers independently appraised the articles for meeting study criteria and for study quality using the CASP system. Financial costs of the telemedicine applications were assessed. RESULTS: A total of 28 studies involving 3252 participants met criteria for inclusion. Telemedicine interventions were classified, and outcomes were assessed systematically by the following categories: general MS care; rehabilitation and exercise; and neuropsychology/mental health. Studies showed a range of outcomes with variable quality. Overall, remote clinical examinations, long-term telemedicine management interventions and telerehabilitation were shown to be beneficial, cost-effective and satisfactory for patients and providers. DISCUSSION: Telemedicine is a viable platform for delivering specialty MS care. Remote neurological assessments and several forms of therapy have been shown to be technically feasible. Optimal implementation and barriers to the use of telemedicine in the current healthcare system should be explored.

Computerized neuropsychological assessment devices in multiple sclerosis: A systematic review.

BACKGROUND: The proliferation of computerized neuropsychological assessment devices (CNADs) for screening and monitoring cognitive impairment is increasing exponentially. Previous reviews of computerized tests for multiple sclerosis (MS) were primarily qualitative and did not rigorously compare CNADs on psychometric properties. OBJECTIVE: We aimed to systematically review the literature on the use of CNADs in MS and identify test batteries and single tests with good evidence for reliability and validity. METHOD: A search of four major online databases was conducted for publications related to computerized testing and MS. Test-retest reliability and validity coefficients and effect sizes were recorded for each CNAD test, along with administration characteristics. RESULTS: We identified 11 batteries and 33 individual tests from 120 peer-reviewed articles meeting the inclusion criteria. CNADs with the strongest psychometric support include the CogState Brief Battery, Cognitive Drug Research Battery, NeuroTrax, CNS-Vital Signs, and computer-based administrations of the Symbol Digit Modalities Test. CONCLUSION: We identified several CNADs that are valid to screen for MS-related cognitive impairment, or to supplement full, conventional neuropsychological assessment. The necessity of testing with a technician, and in a controlled clinic/laboratory environment, remains uncertain.

Recommendations for cognitive screening and management in multiple sclerosis care.

PURPOSE: To promote understanding of cognitive impairment in multiple sclerosis (MS), recommend optimal screening, monitoring, and treatment strategies, and address barriers to optimal management. METHODS: The National MS Society ("Society") convened experts in cognitive dysfunction (clinicians, researchers, and lay people with MS) to review the published literature, reach consensus on optimal strategies for screening, monitoring, and treating cognitive changes, and propose strategies to address barriers to optimal care. RECOMMENDATIONS: Based on current evidence, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society: Increased professional and patient awareness/education about the prevalence, impact, and appropriate management of cognitive symptoms. For adults and children (8+ years of age) with clinical or magnetic resonance imaging (MRI) evidence of neurologic damage consistent with MS: As a minimum, early baseline screening with the Symbol Digit Modalities Test (SDMT) or similarly validated test, when the patient is clinically stable; Annual re-assessment with the same instrument, or more often as needed to (1) detect acute disease activity; (2) assess for treatment effects (e.g. starting/changing a disease-modifying therapy) or for relapse recovery; (3) evaluate progression of cognitive impairment; and/or (4) screen for new-onset cognitive problems. For adults (18+ years): more comprehensive assessment for anyone who tests positive on initial cognitive screening or demonstrates significant cognitive decline, especially if there are concerns about comorbidities or the individual is applying for disability due to cognitive impairment. For children (<18 years): neuropsychological evaluation for any unexplained change in school functioning (academic or behavioral). Remedial interventions/accommodations for adults and children to improve functioning at home, work, or school.