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.

Validated, Quantitative, Machine Learning-Generated Neurologic Assessment of Multiple Sclerosis Using a Mobile Application.

BACKGROUND: The BeCare MS Link mobile app collects data as users complete different in-app assessments. It was specifically developed to evaluate the symptomatology and neurologic function of patients with multiple sclerosis (MS) and to become a digital equivalent of the Expanded Disability Status Scale (EDSS) and other standard clinical metrics of MS progression. METHODS: Our research compared EDSS scores derived from the BeCare MS link app to EDSS scores derived from neurologist assessment for the same cohort of 35 patients diagnosed with MS. App-derived data were supplied to 4 different machine learning algorithms (MLAs) with an independent EDSS score prediction generated from each. These scores were compared with the clinically derived EDSS score to assess the similarity of the scores and to determine an accuracy estimate for each. RESULTS: Of the 4 MLAs employed, the most accurate MLA produced 19 EDSS score predictions that exactly matched the clinically derived scores, 21 score predictions within 0.5 EDSS points, and 32 score predictions within 1 EDSS point. The remaining MLAs also provided a relatively high level of accuracy in predicting EDSS scores when compared with clinically derived EDSS, with over 80% of scores predicted within 1 point and a mean squared error with a range of 1.05 to 1.37. CONCLUSIONS: The BeCare MS Link app can replicate the clinically derived EDSS assessment of a patient with MS. The app may also offer a more complete evaluation of disability in 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.

Interim guidelines for the assessment and treatment of pain in children with multiple sclerosis.

Introduction: Pain in multiple sclerosis (MS) is common, but literature on pain in children with MS remains scarce. Pain has physical, psychological, and social implications in MS, and both comprehensive assessment and interdisciplinary management approaches are needed. We sought to develop an interdisciplinary interim guideline for the assessment and management of pain in children with MS. Methods and materials: We convened a modified Delphi panel composed of 13 experts in pediatric and adult MS neurology, physiotherapy, pain, patient lived-experience, advanced practice nursing, psychology, physiatry, and MS research. A survey was sent to panelists for anonymous completion. The panel discussed survey themes extracted by the panel chair. The process was repeated twice. Results: Thirteen assessment and treatment recommendations were produced regarding pain in children with MS. Discussion: Future studies will assess implementation of these pain assessment and treatment guidelines in the clinical setting.

A retrospective evaluation of seroconversion after COVID-19 during the early Omicron wave in fully vaccinated multiple sclerosis patients receiving anti-CD20 therapies.

BACKGROUND: Patients with multiple sclerosis (MS) are commonly treated with anti-CD20 therapies. Reduced seroconversion following COVID-19 vaccination in patients receiving certain anti-CD20 therapies has been reported; however, the immune response following natural infection is poorly characterised. This study aimed to retrospectively evaluate COVID-19 antibody responses after vaccination and natural infection in patients treated with anti-CD20 therapies. METHODS: We performed a retrospective review evaluating COVID-19 seroconversion and anti-spike glycoprotein antibody titres in double-vaccinated patients with MS, or related neuroinflammatory conditions, treated with anti-CD20 therapies (N = 30) with a confirmed history of natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (n = 14) or without infection (control; n = 16). This single-centre study was performed at the Yale Multiple Sclerosis Center, where patients treated with anti-CD20 therapies (ocrelizumab, n = 21; rituximab, n = 5; ofatumumab, n = 4) were systematically checked for SARS-CoV-2 anti-spike antibody levels throughout the pandemic. Data were collected from March 2020 to March 2022. All patients had received at least two doses of a Food and Drug Administration (FDA)-approved COVID-19 vaccine. Qualitative anti-spike antibody seropositivity was determined based on test-specific laboratory reference ranges. For a subset of patients (n = 18), quantitative anti-spike antibody levels were assessed via DiaSorin LIAISON® chemiluminescence immunoassay (positive titre was defined as ≥ 13). Vaccination and infection dates were also recorded, and patients were monitored for adverse COVID-19-related health effects. RESULTS: Overall, 15/30 (50.0%) patients seroconverted following double vaccination. After infection, 13/14 (92.9%) seroconverted, while 6/16 (37.5%) uninfected patients seroconverted after vaccination. For the 18 patients with quantitative anti-spike antibody titres, mean titre post-vaccination was 37.4. Mean antibody titres were significantly higher after infection: 540.3 versus 20.1 in the control group (p < 0.05). Of the 14 infected patients, 13 had mild COVID-19 symptoms and one was asymptomatic. No hospitalisations or deaths were reported. CONCLUSIONS: This study reports that SARS-CoV-2 anti-spike antibody titres in double-vaccinated MS patients treated with anti-CD20 therapies were significantly increased post-infection compared with the control group. Patients treated with anti-CD20 therapy who had confirmed infections displayed mild or asymptomatic infection. These results provide reassurance that anti-CD20 therapies in double-vaccinated patients do not preclude an appropriate SARS-CoV-2 antibody response post-infection.

Seroconversion after COVID-19 vaccination for multiple sclerosis patients on high efficacy disease modifying medications.

The impaired ability to mount an effective immune response to vaccination leaves immunosuppressed patients at higher risk of severe COVID-19 infection. This retrospective study aimed to evaluate COVID-19 seroconversion and antibody titers for patients on immune modulating therapies compared to those not on disease modifying therapy (DMT). As expected, individuals on B-cell depletion therapies (BCDT) and those on sphingosine 1-phosphate (S1P) modulators had an impaired humoral response to mRNA vaccination. We observed variable seroconversion depending on the type of B-cell depleting medication, with a smaller percentage of seroconversion in patients on infused BCDT (iBCDT, ocrelizumab and rituximab) compared to ofatumumab. The humoral response to vaccination was not impaired for individuals on natalizumab or for untreated MS patients. These observations may influence DMT selection during the COVID-19 era.

Validation of claims-based diagnoses of adult and pediatric neuromyelitis optica spectrum disorder and variations in diagnostic evaluation and treatment initiation.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease in need of more studies to determine effective treatment regimens. The rarity of the disorder, however, makes large randomized-controlled trials challenging. Validation of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for NMO could facilitate the use of large healthcare claims data for future research. We aimed 1) to determine the positive predictive value (PPV) of the ICD-9-CM code for NMO as well as evaluate case-finding algorithms for the identification of patients with NMO/NMOSD and 2) to compare the evaluation of and treatment for pediatric versus adult patients. METHODS: This was a multicenter retrospective cohort study of patients with ≥ 1 ICD-9 code for NMO seen at 3 pediatric and 2 adult United States medical centers from 2001-2016. Using a standardized data entry form, pediatric and adult neurologists and rheumatologists reviewed patients' medical records to determine whether patients fulfilled the 2006 criteria for NMO and/or the 2015 criteria for NMOSD in order to determine the positive predictive value (PPV) for the ICD-9-CM code. Demographic and clinical information was abstracted from patient medical records to ascertain variables then evaluated in case-based finding algorithms for further identification of patients with true NMO/NMOSD. We also evaluated differences in clinical characteristics between pediatric and adult patients using chi-squared or Fisher's exact tests, as appropriate, to assess for treatment variation. RESULTS: A single code for NMO had a PPV of 47% across all sites, with significant site variation (0-77%). The best case-finding algorithm included at least 5 codes as well as a documented hospitalization (PPV = =90% for children and PPV = 92% for adults). Children were more likely to be evaluated by a rheumatologist or ophthalmologist, undergo magnetic resonance imaging of the orbits, and receive immunosuppressive and biologic agents than their adult counterparts. Rituximab was administered similarly among the two groups. CONCLUSION: The ICD-9 code for neuromyelitis optica (NMO) is inaccurate for identification of NMO/NMOSD. Using case-finding algorithms increases the PPV. The initial diagnostic evaluation and treatment of NMOSD differs significantly between children and adults.

Severe acute inflammatory demyelinating polyradiculoneuropathy with persistent weakness associated with tumor-like nerve root enlargement.

We report a 23-year-old woman with rapid onset of proximal and distal limb weakness and areflexia, associated with tumor-like spinal nerve root enlargement and markedly elevated cerebrospinal fluid protein. Our patient developed the inability to walk within days, without preceding illness. Within two weeks, she had near-complete bilateral wrist and foot drop. Her cranial nerves and respiratory function remained intact. She received intravenous immunoglobulin early on for suspected Guillain-barre syndrome but remained wheelchair-bound until 6 Plasma exchange sessions were completed. After that, she continued to improve with intravenous immunoglobulin dosed every 3-4 weeks. Prominent demyelinating features were found on NCS, with cerebrospinal fluid protein of 415 mg/dL. Comprehensive infectious work-up was negative. Magnetic resonance imaging of lumbosacral and cervical spine showed tumor-like masses mistaken for neurofibromatosis (axial diameter, 7.5-10 mm). Repeated magnetic resonance imaging 6 months later showed persistent nerve root enlargement, despite the patient's improved functional status.

Muscle activation patterns and patellofemoral pain in cyclists.

INTRODUCTION: Patellofemoral pain syndrome (PFPS) is pervasive and debilitating in the sport of cycling. Currently, little is known about the underlying mechanism causing patellofemoral pain in cyclists. PURPOSE: The purpose of this study was to determine whether temporal differences in the muscle activity of the vastus medialis (VM), vastus lateralis (VL), semitendinosus (ST), and biceps femoris (BF) were correlated to patellofemoral pain in cycling. METHODS: Ten healthy cyclists (six women and four men, height = 1.74 ± 0.10 cm, weight = 71.9 ± 16.5 kg, cycling experience = 199.5 ± 82 miles · wk(-1)) and seven cyclists with PFPS (one woman and six men, height = 1.84 ± 0.08 cm, weight = 89.8 ± 9.4 kg, cycling experience = 228 ± 51 miles · wk(-1)) volunteered to participate in this study. Each participant completed a 10-min cycling trial during which surface EMG was recorded for the VM, VL, ST, and BF muscles. Sagittal plane knee kinematic data were recorded using an electrogoniometer. RESULTS: An ANOVA revealed no significant difference between groups for the differences in onset times of the VM and VL (P = 0.805). There were significant differences between groups for the differences in offset time of the VM and VL (P = 0.032), the differences in onset time of BF and ST (P < 0.001), and the differences in offset time of the ST and BF (P = 0.024). Root mean square values for BF activity were significantly higher in the PFPS group compared with the control (CTL) group (P < 0.01), and ST values were significantly lower in the PFPS group compared with the CTL group (P < 0.01). Root mean square values for BF were significantly greater than ST activity in the PFPS group (P < 0.01) but not in the CTL group (P > 0.05). CONCLUSION: The results of this study indicate that trained cyclists with PFPS exhibit altered temporal characteristics in muscle activation patterns compared with trained cyclists without PFPS.

Use of therapies other than disease-modifying agents, including complementary and alternative medicine, by patients with multiple sclerosis: a survey study.

CONTEXT: Many patients with multiple sclerosis use complementary and alternative medicine (CAM) to supplement their traditional treatment. OBJECTIVE: To identify both the prevalence and frequency of use of therapies other than disease-modifying agents (DMAs), including CAM, among patients with multiple sclerosis. DESIGN: The authors administered a 13-question survey regarding patients' current use of non-DMA therapies-including dietary supplements, exercise, and "true" CAM (eg, acupuncture, chiropractic, massage)-and mainstream treatments, including physical therapy and osteopathic manipulative treatment. Patients rated their level of disability on a scale of 1 to 10 (with 10 being most severe). SETTING: A hospital outpatient clinic in Philadelphia, Pennsylvania. PATIENTS: Inclusion criteria were physician-confirmed multiple sclerosis (either relapsing-remitting or progressive), regardless of sex, duration of disease, age at onset, disability level, or type of disease. Patients were excluded if they were younger than 18 years. MAIN OUTCOME MEASURE: Patient-reported use of non-DMA therapies and perception of disability. RESULTS: A total of 111 patients with multiple sclerosis completed the survey properly. All respondents used non-DMA therapies. Twenty-three patients (20.7%) used these therapies without concomitantly taking a DMA. A plurality (34.8%) of those patients reported a disability score of 7 or 8. Sixty-two of the 88 participants (70.5 %) who used DMAs reported disability scores of 5 or less. Sixty-five patients (58.6.%) reported exercising on a weekly basis. Among those patients, 47 (72.3%) reported a disability score of 5 or less. Sixty-four patients (57.7%) used such CAM therapies as acupuncture and massage, or such other non-DMA treatments as osteopathic manipulative treatment and psychotherapy. Among those patients, 37 (64.9%) reported a disability score of 5 or less. CONCLUSION: Many patients with multiple sclerosis are seeking more than traditional medical treatment. Physicians and other health care professionals must be aware of the extensive use of alternative modalities among these patients, and these professionals must provide guidance and monitoring in use of these therapies to improve outcomes.

Veterinary students as elite performers: preliminary insights.

The KPMG ''Mega Study'' (Brown JP, Silverman JD. The current and future market for veterinarians and veterinary medical services in the United States. J Am Vet Med Assoc 215:161-183, 1999) and other studies (Cron WL, Slocum JV, Goodnight DB, Volk JO. Impact of management practices and business behaviors on small animal veterinarians' incomes. J Am Vet Med Assoc 217:332-338, 1999; Lewis RE. Non-technical Competencies Underlying Career Success as a Veterinarian: A New Model for Selecting and Training Veterinary Students. Minneapolis: Personnel Decisions, 2002) concur that improvement in veterinary practitioner performance is necessary. Improvement in practitioners' non-technical competencies is considered most vital. Little research exists that identifies underlying psychological factors harbored by veterinary students that inhibit ability to achieve sustained maximum professional performance. Left unaddressed, these same characteristics may lead to coping behaviors that disrupt or, in the worst cases, lead to voluntary or involuntary termination of professional careers. Several performance-related characteristics and interpersonal dynamics are investigated in this study that provide preliminary evidence for the long-term shortcomings addressed in previous veterinary practice management literature. Pedagogical recommendations for addressing these student psychological characteristics are submitted for consideration.