Impact of a free medication intervention on seizure recurrence and anxious and depressive symptoms in people living with epilepsy in the Republic of Guinea.

BACKGROUND AND OBJECTIVE: Of ~5 million people living with epilepsy (PLWE) in Sub-Saharan Africa, roughly one-third experience depression and over one third experience anxiety. In Guinea, these issues may be compounded by fewer available resources, such as appropriate anti-seizure medications (ASMs). We aim to quantify seizure frequency, anxiety and depression in PLWE in Guinea, before and after a free ASM intervention and neurologist's consultation. METHODS: Guinean participants >12 years old with ≥2 unprovoked seizure were prospectively recruited. As part of a broader interview, participants reported prior 30-day seizure frequency and screened for depression (PHQ-9) (range 0-27 points) and anxiety (GAD-7) (range 0-21 points) with re-evaluation at 90 days. RESULTS: Of 148 participants enrolled (mean age = 27.3 years, range 12-72; 45% female), 62% were currently taking ASMs. For the 30 days pre-enrolment, average seizure frequency was 3.2 (95%CI 2.3, 4.2); 28% of participants were seizure-free. ASM regimens were modified for 95% of participants, mostly initiating levetiracetam (n = 115, 80% of modifications). 90-day study retention was 76% (n = 113) among whom 87% reported full adherence to the ASM. After 90 days, the average seizure frequency over the prior 30 days was 1.5 (95%CI 0.5, 2.6), significantly lower than at baseline (p = 0.002). 66% were seizure-free. At baseline, average PHQ-9 score was 21.2 (95%CI [20.2, 22.2]), indicating severe depressive symptoms. Average GAD-7 score was 16.5 [15.6, 17.4], indicating severe anxious symptoms. At 90-days, average PHQ-9 score was 17.5[16.4, 18.5] and significantly lower than baseline (p < 0.001). Average GAD-7 score was 14.4 [13.6, 15.3] and significantly lower than baseline (p = 0.002). Seizure frequency was not correlated with PHQ-9 nor GAD-7 scores at baseline but was at 90 days for both PHQ-9 (r = 0.24, p = 0.01) and GAD-7 (r = 0.22, p = 0.02) scores. The prevalence of suicidal ideation dropped from 67% to 47% of participants (p = 0.004). DISCUSSION: ASM management has dual importance for PLWE in resource-limited settings, improving both seizure control and mental health.

E = mc2 : Education (E), medication (m), and conditional cash (c2 ) to improve uptake of antiseizure medications in a low-resource population: Protocol for randomized trial.

OBJECTIVE: Most people with epilepsy (PWE) could live seizure-free if treated with one or more antiseizure medications (ASMs). The World Health Organization (WHO) estimates that 75% of PWE in low-resource settings lack adequate antiseizure treatment. Limited education surrounding epilepsy and the out-of-pocket costs of ASMs in particular pose barriers to managing epilepsy in resource-poor, low-income settings. The aim of this study is to implement and test a novel strategy to improve outcomes across the epilepsy care cascade marked by (1) retention in epilepsy care, (2) adherence to ASMs, and (3) seizure reduction, with the measured goal of seizure freedom. METHODS: A randomized, double-blinded clinical trial will be performed, centered at the Ignace Deen Hospital in Conakry, Republic of Guinea, in Western Sub-Saharan Africa. Two hundred people with clinically diagnosed epilepsy, ages 18 years and above, will receive education on epilepsy and then be randomized to (i) free ASMs versus (ii) conditional cash, conditioned upon return to the epilepsy clinic. Participants will be followed for 360 days with study visits every 90 days following enrollment. SIGNIFICANCE: We design a randomized trial for PWE in Guinea, a low-resource setting with a high proportion of untreated PWE and a nearly completely privatized healthcare system. The trial includes a conditional cash transfer intervention, which has yet to be tested as a targeted means to improve outcomes for people with a chronic neurological disorder. The trial aims to provide an evidence base for the treatment of epilepsy in such settings. PLAIN LANGUAGE SUMMARY: We present a clinical trial protocol for a randomized, blinded study of 200 people with epilepsy in the low-resource African Republic of Guinea, providing an educational intervention (E), and then randomizing in a 1:1 allocation to either free antiseizure medication (m) or conditional cash (c2 ) for 360 days. Measured outcomes include (1) returning to outpatient epilepsy care, (2) adherence to antiseizure medications (ASMs), and (3) reducing the number of seizures. This study is an initial look at giving small amounts of cash for desired results (or "nudges") for improving epilepsy outcomes in the sub-Saharan African and brain disorder contexts.

Improvement in health perception but not quality of life with an antiseizure medication intervention in people with epilepsy in Guinea: A cohort study.

BACKGROUND: This study assesses perceptions of quality of life (QOL) and overall health in people with epilepsy (PWE) in Guinea after a clinical intervention providing modified and new antiseizure medicine (ASM) regimens. METHODS: Participants 12 years and older diagnosed with active epilepsy were prospectively and consecutively enrolled at two health centers in the Republic of Guinea (one urban, one rural) in 2022. 95% of participants were prescribed new/increased ASM doses, and interviewed for QOL and overall health perceptions at enrollment and three- and six-month follow ups. Univariate and linear mixed models were used to evaluate effects on QOL and overall health over time. RESULTS: The mean QOLIE-31 score (±SD) among 148 Guinean PWE (82 male, 66 female; mean age 27.3; 137 with >1 seizure in prior year) was 51.7 ± 12.8 at enrollment, 57.6 ± 16.0 after three months (n = 116), and 52.2 ± 9.9 after six months (n = 87). Overall health scores were 53.1 ± 26.9, 72.6 ± 21.5, and 65.7 ± 20.2 respectively. After three months, PWE had improved overall health and QOLIE-31 scores (p<0.0001, p = 0.003), but these improvements persisted for overall health and not QOLIE-31 after six months (p = 0.001, p = 0.63). Seizure freedom (prior 30 days) was 26% initially, and 62 (42%) of the remaining PWE experiencing seizures achieved seizure freedom at either the first or second follow-ups. CONCLUSIONS: A noticeable discrepancy exists between Guinean PWE's self-rated perceptions of QOL and overall health. Purely clinical interventions may not be sufficient to improve QOL, especially in people that experience severe, previously-untreated epilepsy in lower income settings.

Familial Mediterranean Fever and multiple sclerosis treated with ocrelizumab: Case report.

BACKGROUND: Familial Mediterranean Fever (FMF) is associated with increased risk of multiple sclerosis (MS). Optimal treatment of patients with comorbid FMF and MS remains uncertain. CASE: A 28-year-old woman with FMF, treated with colchicine, had symptomatic onset of relapsing remitting MS following four simultaneous vaccines. MRI brain with a 7-Tesla magnet demonstrated several areas of leptomeningeal enhancement with predominant linear, spread/fill and rare nodular patterns. Central vein signs were present in supratentorial white matter lesions. She received four cycles of ocrelizumab and achieved no evidence of disease activity (NEDA-3) at 20 months' follow up. DISCUSSION: FMF with incident CNS demyelinating disease demonstrated neuroimaging features typical for classic RRMS including the central vein sign and leptomeningeal enhancement. Treatment with B-cell depleting therapy for FMF-MS led to clinical stability and symptomatic improvement at 20 months' follow up. We add to the sparse literature characterizing the course of FMF as a genetic risk factor for CNS demyelinating disease, demonstrating pathognomonic imaging features of MS on 7 T imaging and treatment efficacy with B-cell depletion.

Quantifying the economic burden to patients of relapse events from neuromyelitis optica spectrum disorders: A cross-sectional survey.

We surveyed 103 adults (mean age 46 years; 85% female) with neuromyelitis optica spectrum disorders (NMOSD) through social media about their personal economic burden of NMOSD emergency department visits and hospitalizations ("relapse events"). The average number of relapse events over the prior 3 years was 5.3. Participants reported direct, out-of-pocket costs for 52% of events (mean cost per event 3326 USD, 95% CI [2378,4274]) and indirect costs (e.g., childcare) for 26% (mean cost per event 1907 USD, 95% CI [1159,2655]). Sixty-nine percent reported lost income due to hospital visits. Future work should identify and support subgroups with higher economic burden from NMOSD.

Social determinants of health in multiple sclerosis.

Social determinants of health are the conditions in which people are born, grow, live, work and age. These circumstances are the non-medical factors that influence health outcomes. Evidence indicates that health behaviours, comorbidities and disease-modifying therapies all contribute to multiple sclerosis (MS) outcomes; however, our knowledge of the effects of social determinants - that is, the 'risks of risks' - on health has not yet changed our approach to MS. Assessing and addressing social determinants of health could fundamentally improve health and health care in MS; this approach has already been successful in improving outcomes in other chronic diseases. In this narrative Review, we identify and discuss the body of evidence supporting an effect of many social determinants of health, including racial background, employment and social support, on MS outcomes. It must be noted that many of the published studies were subject to bias, and screening tools and/or practical interventions that address these social determinants are, for the most part, lacking. The existing work does not fully explore the potential bidirectional and complex relationships between social determinants of health and MS, and the interpretation of findings is complicated by the interactions and intersections among many of the identified determinants. On the basis of the reviewed literature, we consider that, if effective interventions targeting social determinants of health were available, they could have substantial effects on MS outcomes. Therefore, funding for and focused design of studies to evaluate and address social determinants of health are urgently needed.

Anti-SARS-CoV-2 monoclonal antibodies for the treatment of active COVID-19 in multiple sclerosis: An observational study.

Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received emergency use authorization for the acute treatment of COVID-19. We are not aware of published data on their use in immunosuppressed people with multiple sclerosis (pwMS). We report 23 pwMS (mean age = 49 years, ocrelizumab (n = 19), fingolimod (n = 2), vaccinated with at least an initial series (n = 19)) who received mAb for acute COVID-19. Following mAb receipt, approximately half recovered in <7 days (48%). There were no adverse events or deaths. Use of mAb for pwMS treated with fingolimod or ocrelizumab was not observed to be harmful and is likely helpful for treatment of acute COVID-19.

A point-of-care diagnostic test for aquaporin-4 antibody seropositive neuromyelitis optica.

BACKGROUND: Given the need for specialized laboratory techniques, diagnostic testing for serum antibodies to aquaporin-4, a protein associated with neuromyelitis optica spectrum disorder (NMOSD), is not globally accessible. We aimed to evaluate a novel point-of-care, filter paper-based test for serum AQP4 antibodies (AQP4-Ab). METHODS: Adults with AQP4-Ab seropositive NMOSD and seronegative controls (with other central nervous system demyelinating diagnoses) used lancets to place blood drops (∼1 mL) on filter paper cards. Samples were analyzed after an average of 9.4 days using transfected AQP4-GFP HEK293 cells, and results were compared to participants' prior serum AQP4-Ab test results by blinded laboratory staff. RESULTS: Of 40 participants (mean age 53.7 years; 83% female), 25 were cases and 15 were controls. The most common diagnosis of controls was multiple sclerosis (73%). The average NMOSD disease duration was 6.3 years. All AQP4-Ab seropositive participants were on disease modifying therapies at the time of participation. The point-of-care test yielded a sensitivity of 80% and specificity of 93% (positive and negative predictive values 95% and 74%). CONCLUSION: This point-of-care AQP4-Ab testing method may become a pragmatic option to diagnose AQP4-Ab seropositive NMOSD in difficult-to-reach settings. This method should be confirmed with other testing parameters and field tested in new populations.

A Mixed-Methods and Prospective Approach to Understanding Coping Behaviors, Depression, Hopelessness, and Acute Stress in a U.S. Convenience Sample During the COVID-19 Pandemic.

The COVID-19 pandemic has led to increases in U.S. residents' stressors while limiting many of the resources previously available to cope with stress. Coping behaviors may contribute to the prevention or proliferation of psychological distress during and after the pandemic. Understanding these coping behaviors and associated psychological outcomes can help health educators develop programs that encourage effective coping and promote mental health. This study used a sequential mixed-methods approach informed by Roth and Cohen's conceptualization of coping to understand the use of approach coping behaviors- which are active and directed toward the perceived threat-and avoidance coping behaviors-which include activity directed away from perceived threat during the COVID-19 pandemic. U.S. residents (N = 2,987) were surveyed online in April 2020 and again in September 2021. Open-ended responses at baseline were thematically analyzed to illustrate coping behaviors in participants' own words. At baseline, more than half (56%) of the sample met criteria for probable depression, 51% for acute stress symptoms, and 42% for moderate to severe hopelessness. At follow-up, 45% meet criteria for probable depression and 23% for acute stress. However, the proportion of the sample who reported moderate to severe hopelessness increased to 48%. We used mixed-effects general linear models to examine changes over time and found that increases in approach coping behaviors were associated with decreases in depressive symptoms and hopelessness; increases in avoidance coping were associated with higher levels of depressive symptoms and higher levels of hopelessness. Increases in both types of coping were associated with increases in acute stress symptoms related to COVID-19. Although there was some attenuation in distress in our sample between April 2020 and September 2021, our findings suggest a need for interventions that encourage the use of approach coping behaviors and that both increase access to and decrease stigma for mental health support.

Efficacy of Fluoxetine for Post-Ischemic Stroke Depression in Tanzania.

OBJECTIVE: Post-stroke fluoxetine trials are primarily conducted in high-income countries. We characterize post-ischemic stroke depression in fluoxetine-treated and -untreated study participants in urban Tanzania. METHODS: Adults (>18 years old) within 14 days of CT-confirmed acute ischemic stroke onset were enrolled at Muhimbili National Hospital, Tanzania. The fluoxetine-treated group took 20mg fluoxetine daily for 90 days in a phase II trial and were compared to fluoxetine-untreated historical controls. The primary outcome was depression at 90 days, measured by the Patient Health Questionnaire-9 (PHQ-9). PHQ-9 scores were compared between fluoxetine-treated and -untreated groups. A score >=9 points was considered to reflect depression. A multivariable linear regression model assessed associations with post-stroke PHQ-9 scores. RESULTS: Of the fluoxetine-treated (n=27) and -untreated (n=32) participants, the average age was 56.8 years old (39% women, 100% Black/African). The average presentation NIHSS score was 12.1 points and modified Rankin Scale (mRS) score was 3.5. The average mRS score at 90-day follow-up was 2.3. There was no significant difference between 90-day PHQ-9 scores in the fluoxetine-treated (mean=4.1 points, standard deviation=3.2; 11% depression) and untreated (mean=4.4, standard deviation=4.8; 19% depression) groups, p=.69. In the multivariable analysis, older age (ß=0.08, p=.03) and higher NIHSS score (ß=0.15, p=.04), but neither fluoxetine (ß=0.57, p=.59) nor sex (ß=-0.51, p=.63), were significantly associated with more depressive symptoms. CONCLUSIONS: Our findings parallel results from trials from higher income settings that fluoxetine does not significantly improve post-ischemic stroke depression, although our sample size was small. More work is needed to depict the longitudinal nature and treatment of post-stroke depression in Sub-Saharan Africa.

COVID-19 vaccine acceptance and hesitancy in N'Djamena, Chad: A cross-sectional study of patients, community members, and healthcare workers.

As of March 2022, the COVID-19 vaccination rate in Chad approximated 1%. There are no published reports of COVID-19 vaccine hesitancy or beliefs in Chad. We aimed to study COVID-19 vaccine acceptance and hesitancy among community members, patients, and health care workers in urban Chad. We recruited a prospective convenience sample of adult patients, community members, and healthcare workers from N'Djamena, Chad between August-October 2021. Participants completed a 15-minute, 25-question survey instrument exploring demographic, social, and clinical variables related to COVID-19 and an adapted WHO SAGE Vaccine Hesitancy Survey. Primary outcomes were vaccine acceptance and vaccine hesitancy. Regression models were fit to assess associations between Vaccine Hesitancy Scale (VHS) scores, ranging from 10 (least hesitant) to 50 (most hesitant) points, and pre-selected variables of interest. An inductive thematic analysis was used to analyze the qualitative vaccine hesitancy responses. Of 508 participants (32% female; mean age 32 years), 162 were patients, 153 were community members, and 193 were healthcare workers. COVID-19 vaccine acceptance was significantly higher among patients (67%) than community members (44%) or healthcare workers (47%), p < .001. The average VHS score was 29 points (patients = 27.0, community members = 28.9, healthcare workers = 29.4), and more than one-third of participants were classified as highly vaccine hesitant (score >30 points). Knowing someone who died from COVID-19, believing local healthcare workers support vaccination, trusting the government, having a higher socioeconomic status (i.e. having electricity), and reporting medical comorbidities were each associated with less vaccine hesitancy (all p < .05). The vaccine concerns most frequently endorsed were: vaccine side effects (48%), efficacy (38%), safety (34%), concerns about the pharmaceutical industry (27%), and lack of government trust (21%). Four main themes arose from qualitative vaccine hesitancy responses (n = 116): education, trust, clinical concerns, and misinformation and false beliefs. Overall, COVID-19 vaccine acceptance was low, including among health care workers, and reasons for vaccine hesitancy were broad. We detail the most commonly reported concerns of urban Chadians for receiving the COVID-19 vaccine; we also identify subgroups most likely to endorse vaccine hesitancy. These analyses may inform future vaccination outreach campaigns in N'Djamena.

Measuring Ambulation, Motor, and Behavioral Outcomes with Post-stroke Fluoxetine in Tanzania: The Phase II MAMBO Trial.

We test the safety of fluoxetine post-ischemic stroke in sub-Saharan Africa. Adults with acute ischemic stroke, seen <14 days since new-onset motor deficits, were enrolled from November 2019 to October 2020 in a single-arm, open-label phase II trial of daily fluoxetine 20 mg for 90 days at Muhimbili National Hospital, Dar es Salaam, Tanzania. The primary outcome was safety with secondary outcomes of medication adherence and tolerability. Thirty-four patients were enrolled (11 were female; mean age 52.2 years, 65% < 60 years old; mean 3.3 days since symptom onset). Participants had hypertension (74%), diabetes (18%), and smoked cigarettes (18%). The median National Institutes of Health Stroke Scale score at enrollment was 10.5. The median Fugl-Meyer Motor Scale score was 28.5 (upper extremity 8, lower extremity 17.5). 32/34 participants (91%) survived to 90 days. There were eight serious and two nonserious adverse events. Deaths occurred due to gastrointestinal illness with low serum sodium (nadir 120 mmol/L) with seizure and gastrointestinal bleed from gastric cancer. The average sodium level at 90 days was 139 mmol/L (range 133-146) and alanine transaminase was 28 U/L (range 10-134). Fluoxetine adherence was 96%. The median modified Rankin Scale score among survivors at 90 days was 2 and Fugl-Meyer Motor Scale score was 66 (upper extremity 40, lower extremity 27). Median 90-day Patient Health Questionnaire-9 and Montgomery-Åsberg scores were 3.5 and 4 (minimal depression). Fluoxetine administration for 90 days poststroke in sub-Saharan Africa was generally safe and well-tolerated, but comorbid illness presentations were fatal in 2/34 cases, even after careful participant selection.

Sociodemographic and clinical factors associated with depression, anxiety, and general mental health in people with multiple sclerosis during the COVID-19 pandemic.

Background People with multiple sclerosis (PwMS) may be at increased risk for psychological distress during COVID-19. We study the self-reported mental health of U.S. PwMS during COVID-19, prior to vaccine rollout. Methods A cross-sectional survey was distributed online to PwMS through iConquerMS (12/18/2020-02/10/2021). Depressive and anxiety symptom burdens and general mental health status were measured via the Patient-Health Questionnaire-9, Generalized Anxiety Disorder-7, and PROMIS Global Mental Health scales. Linear regression models assessed associations between mental health variables and age, sex, disability status, comorbidities, and social determinants of health. Results Of 610 U.S. PwMS (mean age 56 years, standard deviation 11, range 20-85; female, 81%; relapsing remitting disease, 62%; previous depression diagnosis, 40%), the prevalences of moderate-to-severe depressive and anxiety symptom burden were 27.4% and 14.7%, respectively; 55.1% endorsed fair/poor general mental health. PwMS who tested positive for COVID-19 (n = 47, 7.7%) reported higher depressive and anxiety symptom burdens (p < 0.05). Increased disability status score and social determinants of health were each associated with more depressive symptoms and worse general mental health. Younger age was associated with increased depressive and anxiety symptom burdens and worse general mental health. Female sex was associated with greater anxiety symptoms. Conclusion There are specific associations for worse mental health among PwMS during COVID-19 that reflect a combination of clinical, demographic, and social determinants of health. Multidisciplinary care teams and vigilance are important to address the ongoing mental health impacts of COVID-19 in PwMS.

Epilepsy stigma in the Republic of Guinea and its socioeconomic and clinical associations: A cross-sectional analysis.

OBJECTIVE: We aim to quantify the degree of epilepsy stigma perceived by people living with epilepsy (PLWE) in the Republic of Guinea (2019 gross national income per capita, 930 USD) and analyze the demographic, social, and clinical factors associated with epilepsy stigma in this setting. METHODS: A prospective convenience cohort of PLWE was recruited at the Ignace Deen Hospital in Conakry and evaluated by U.S. and Guinean neurology-trained physicians. A survey instrument exploring demographic, social, and clinical variables was designed and administered. The primary outcome measure was the Stigma Scale of Epilepsy (SSE), a 24-item scale with scores ranging from 0 (least stigma)-100 (most). Regression models were fit to assess associations between SSE score and pre-selected demographic, social, and clinical variables of interest. RESULTS: 249 PLWE (112 female; mean age 20.0 years; 22 % from rural locales; 14 % of participants >16 years old with no formal schooling; 11 % seizure-free for >=6 months) had an average SSE score of 46.1 (standard deviation = 14.5) points. Children had an average SSE score of 45.2, and adults had an average score of 47.0. There were no significant differences between self- and guardian-reported SSE scores (means = 45.8 and 46.5, respectively), p = .86. In univariate analyses, higher stigma scores were associated with more seizures (p = .005), more depressive symptoms (p = .01), and lower household wealth (p = .03). In a multivariable model including sex, educational level, household wealth, generalized tonic-clonic seizures, seizure frequency, and seizure-related burns, only higher seizure frequency (ß = -2.34, p = .03) and lower household wealth (ß = 4.05, p = .03) were significantly associated with higher SSE scores. CONCLUSION: In this Guinean cohort of people living with poorly-controlled epilepsy, there was a moderate degree of perceived stigma on average. Stigma was associated with higher seizure frequency and lower household wealth-both potentially modifiable factors.

Electronic pill bottles to monitor and promote medication adherence for people with multiple sclerosis: A randomized, virtual clinical trial.

OBJECTIVE: We perform a randomized trial to test the impact of electronic pill bottles with audiovisual reminders on oral disease modifying therapy (DMT) adherence in people with MS (PwMS). METHODS: Adults with multiple sclerosis (MS) taking an oral DMT were randomized 1:1 for 90 days to remote smartphone app- and pill bottle-based (a) adherence monitoring, or (b) adherence monitoring with audiovisual medication reminders. Optimal adherence was defined as the proportion of doses taken ±3 h of the scheduled time. Numbers of missed pills and pills taken early, on time, late, and extra were recorded. A multivariable regression model tested possible associations between optimal adherence and age, MS duration, cognitive functioning, and number of daily prescription pills. RESULTS: 85 participants (66 female; mean age 44.9 years) took dimethyl/diroximel fumarate (n = 49), fingolimod (n = 26), or teriflunomide (n = 10). Optimal adherence was on average higher in the monitoring with reminders arm (71.4%) than the monitoring only arm (61.6%; p = 0.033). In a multivariable model, optimal adherence was less likely in younger participants (p < 0.001) and those taking more daily prescription pills (p < 0.001). In the monitoring only arm, 4.0% of doses were taken early, 61.6% on time, 5.6% late, 4.4% in excess, and 24.4% were missed. In the reminders arm, these proportions were 3.4%, 71.4%, 3.7%, 8.7%, and 12.8%, respectively. CONCLUSION: We map real-world oral DMT adherence patterns using mHealth technology. PwMS who received medication reminders had higher optimal adherence. Nonadherence was more nuanced than simply missing pills. Developing strategies to improve adherence remains important in longitudinal MS care.

Radiologically isolated syndrome: A single-center, retrospective cohort study.

BACKGROUND: Radiologically Isolated Syndrome (RIS) likely represents the earliest detectable form of multiple sclerosis (MS). There are recognized risk factors for conversion of RIS to clinically definite central nervous system (CNS) demyelinating disease. We aim to characterize a new clinical cohort with RIS and to analyze previously established risk factors for conversion to clinically definite disease. METHODS: A medical records search was performed for patients who were diagnosed with RIS by their treating neurologist at our institution in Boston, USA, from January 2005 to April 2020. Demographic data, clinical outcomes, and treatment courses were analyzed. The time to first clinical event representing a demyelinating disease attack or last follow up without clinically definite disease was calculated for each person. Hazard ratios (HRs) for known risk factors for the conversion of RIS to clinically definite disease were calculated using Cox proportional hazards models. RESULTS: Of 89 patients, the median age at RIS diagnosis was 41.0 years (76% female, 8% with a family history of MS and 16% of any autoimmune disorder, 66% never smokers, 40% BMI >30 kg/m2, 45% with spinal cord MRI lesions). Clinically definite disease was observed in 16 patients (18%) during follow-up (median time to first event 3.4 years; median follow-up duration of full cohort 3.8 years). Median EDSS for those who developed clinically definite disease was 1.25 (range: 0-4) at most recent follow up. Of 84 patients with longitudinal brain imaging, 42 (50%) had new demyelinating lesions. Gadolinium-enhancing lesions were seen in 36 patients (43%) at either baseline (n=24) or follow-up (n=12). Most patients had at least one T1-hypointense lesion (n=70, 83%). Five patients underwent ultra-high field MRI (7 Tesla); all were positive for central vein sign, two demonstrated leptomeningeal enhancement, and one was found to have cortical lesions. Out of 30 patients with susceptibility-weighted imaging acquired during routine clinical care, 8 had at least one paramagnetic rim positive lesion. Previously reported risk factors for conversion to MS were not significant: age ≤37 years HR 1.3 (95% confidence interval (CI), 0.47-3.5), male sex 1.5 (95% CI, 0.41-5.2), and spinal cord lesions 1.3 (0.47-3.4). Nearly one-third of RIS patients (n=26) took a disease modifying therapy (DMT) for MS (median total treatment duration on any DMT=2.7 years). The sub-cohort treated with a DMT had a statistically significantly greater number of recognized risk factors for conversion to clinically definite disease compared with the untreated group (p=0.028). Most patients took a DMT for MRI changes demonstrating new demyelinating disease activity (n=16). Dimethyl fumarate (n=9) and glatiramer acetate (n=7) were the most frequently prescribed DMTs. A second-line DMT was started in 10 patients. CONCLUSION: We characterize a new cohort of RIS patients, demonstrating time to clinically evident demyelinating disease from RIS diagnosis of approximately 3.4 years. Our data suggest that early use of a DMT in RIS may mitigate the impact of recognized risk factors on the occurrence of clinically evident disease and reduce the likelihood of conversion to clinically definite CNS demyelinating disease in high-risk individuals.

CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study.

OBJECTIVE: To study long-term outcomes in patients with CNS demyelinating events exposed to TNFa-inhibitors (TNFai), including subsequent clinical relapse, MRI lesions, and use of disease modifying therapy (DMT) for MS. METHODS: Adult patients evaluated for a CNS demyelinating disease during TNFai use were identified at Mass General Brigham [01/1998-08/2020] and analyzed in clinically-relevant subgroups. Inclusion criteria required a first neurological event while taking a TNFai, MRI lesions consistent with demyelination, and the absence of a more probable alternative diagnosis. RESULTS: 21 cases (mean age 44 years, 20 female, 14 ≥ 2 MS risk factors) had an index neurological event (INE) at a median of 12 months (range 1-176) from onset of TNFai use (adalimumab in 10, etanercept 6, infliximab 5). MRI lesions were most often present in periventricular (16/20, 80%) and spinal zones (10/20, 50%); 37% (7/19) met ≥ 2 Barkhof criteria at onset. CSF testing was abnormal in 64% (7/11). 67% (10/15) with available follow-up MRIs developed new lesions by a median of 29.5 months of MRI surveillance (median MRI surveillance 60 months); 55% (11/20) met ≥ 2 Barkhof criteria. 47% (8/17) suffered a clinical relapse by a median of 40.5 months of clinic follow-up (median clinic follow-up since INE: 26 months). In patients discontinuing TNFai (18/21, 86%) at INE onset, 56% (10/18) had further evidence of CNS demyelination. Six patients (6/21, 29%) started an MS disease modifying therapy (DMT) at INE of whom 50% (3/6) had subsequent disease activity. Continuing or restarting TNFai was followed by relapse in 75% (3/4). 65% (13/20) met 2017 McDonald criteria for MS at INE with another 10% (15/20, 75%) by study conclusion. CONCLUSIONS: With extended follow-up, a majority of patients had a relapsing CNS demyelinating disorder-as evidenced by new MRI lesions or clinical relapses-despite TNFai discontinuation.

Characterizing Health Care Delays and Interruptions in the United States During the COVID-19 Pandemic: Internet-Based, Cross-sectional Survey Study.

BACKGROUND: The COVID-19 pandemic has broader geographic spread and potentially longer lasting effects than those of previous disasters. Necessary preventive precautions for the transmission of COVID-19 has resulted in delays for in-person health care services, especially at the outset of the pandemic. OBJECTIVE: Among a US sample, we examined the rates of delays (defined as cancellations and postponements) in health care at the outset of the pandemic and characterized the reasons for such delays. METHODS: As part of an internet-based survey that was distributed on social media in April 2020, we asked a US-based convenience sample of 2570 participants about delays in their health care resulting from the COVID-19 pandemic. Participant demographics and self-reported worries about general health and the COVID-19 pandemic were explored as potent determinants of health care delays. In addition to all delays, we focused on the following three main types of delays, which were the primary outcomes in this study: dental, preventive, and diagnostic care delays. For each outcome, we used bivariate statistical tests (t tests and chi-square tests) and multiple logistic regression models to determine which factors were associated with health care delays. RESULTS: The top reported barrier to receiving health care was the fear of SARS-CoV-2 infection (126/374, 33.6%). Almost half (1227/2570, 47.7%) of the participants reported experiencing health care delays. Among those who experienced health care delays and further clarified the type of delay they experienced (921/1227, 75.1%), the top three reported types of care that were affected by delays included dental (351/921, 38.1%), preventive (269/921, 29.2%), and diagnostic (151/921, 16.4%) care. The logistic regression models showed that age (P<.001), gender identity (P<.001), education (P=.007), and self-reported worry about general health (P<.001) were significantly associated with experiencing health care delays. Self-reported worry about general health was negatively related to experiencing delays in dental care. However, this predictor was positively associated with delays in diagnostic testing based on the logistic regression model. Additionally, age was positively associated with delays in diagnostic testing. No factors remained significant in the multiple logistic regression for delays in preventive care, and although there was trend between race and delays (people of color experienced fewer delays than White participants), it was not significant (P=.06). CONCLUSIONS: The lessons learned from the initial surge of COVID-19 cases can inform systemic mitigation strategies for potential future disruptions. This study addresses the demand side of health care delays by exploring the determinants of such delays. More research on health care delays during the pandemic is needed, including research on their short- and long-term impacts on patient-level outcomes such as mortality, morbidity, mental health, people's quality of life, and the experience of pain.

Low-field portable brain MRI in CNS demyelinating disease.

A low-field (80 mT), portable MRI scanner has been developed that may address barriers to MRI for people with multiple sclerosis (MS). As a proof of concept study, we imaged two participants with central nervous system demyelinating disease by both a standard 1.5 Tesla MRI and the portable MRI scanner. These images demonstrate the ability to identify a solitary demyelinating lesion in early stage disease and cortical atrophy and chronic white matter changes in late stage disease. In spite of device limitations, including border distortion and lower image quality, the portable device has important implications for addressing barriers to care in people with MS.