Longitudinal evaluation of serum MOG-IgG titers in MOGAD after initiation of maintenance immunoglobulin: A case series.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct demyelinating disease of the central nervous system. Immunoglobulin (Ig) has been used as a maintenance therapy to prevent relapses in MOGAD, but the impact of Ig on serum MOG-IgG titers is unclear. OBJECTIVE: To characterize the variation in serum MOG-IgG titers after initiation of Ig treatment in people with MOGAD. METHODS: We conducted a retrospective study of 10 patients with a diagnosis of MOGAD and available serum MOG-IgG titers before and after initiation of maintenance Ig treatment. RESULTS: We found that most of the patients remained MOG-IgG seropositive while on Ig treatment with a reduced or unchanged titer, despite a lack of disease activity. CONCLUSIONS: This case series suggests that the mechanism of action of Ig therapy in MOGAD is not exclusively dependent on MOG-IgG titer reduction.

Implementation and Evaluation of a Neurology Telemedicine Initiative at a Major Academic Medical Center.

Introduction: The COVID-19 pandemic forced rapid adoption of telemedicine for care of neurology patients. This study contributes to this literature by describing the structure and implementation of telemedicine-based outpatient neurology clinics at the UCLA Medical Center and estimates patient cost savings, before and after the California COVID-19 "Safer at Home" directive, and patient satisfaction. Methods: This was a retrospective, nonrandomized, case series study of telemedicine-based neurological management in an urban academic medical center from October 2018 to June 2020. We estimated roundtrip travel time, roundtrip travel distance, total savings, and surveyed patient and provider satisfaction with telemedicine care. We supported these findings through evaluation of 7,194 patients by telemedicine and conducted 9,189 video visits for neurological care. Results: The median telemedicine patient avoided a roundtrip driving distance of 33 miles and roundtrip travel time of 75 min. Within sample, median hourly earnings were $27/h. The median patient saved $18 on fuel and parking and $36 of time-based opportunity savings, for total savings of $54 per video visit. Eighty-six percent of patients surveyed were satisfied with their video visit experience. Conclusions: Telemedicine reduced travel time and also reduced costs for neurology patients. Patients and providers both reported high levels of satisfaction with telemedicine.

Collagen Fibril Ultrastructure in Mice Lacking Discoidin Domain Receptor 1.

The quantity and quality of collagen fibrils in the extracellular matrix (ECM) have a pivotal role in dictating biological processes. Several collagen-binding proteins (CBPs) are known to modulate collagen deposition and fibril diameter. However, limited studies exist on alterations in the fibril ultrastructure by CBPs. In this study, we elucidate how the collagen receptor, discoidin domain receptor 1 (DDR1) regulates the collagen content and ultrastructure in the adventitia of DDR1 knock-out (KO) mice. DDR1 KO mice exhibit increased collagen deposition as observed using Masson's trichrome. Collagen ultrastructure was evaluated in situ using transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Although the mean fibril diameter was not significantly different, DDR1 KO mice had a higher percentage of fibrils with larger diameter compared with their wild-type littermates. No significant differences were observed in the length of D-periods. In addition, collagen fibrils from DDR1 KO mice exhibited a small, but statistically significant, increase in the depth of the fibril D-periods. Consistent with these observations, a reduction in the depth of D-periods was observed in collagen fibrils reconstituted with recombinant DDR1-Fc. Our results elucidate how DDR1 modulates collagen fibril ultrastructure in vivo, which may have important consequences in the functional role(s) of the underlying ECM.

Associations of erythrocyte ω-3 fatty acids with biomarkers of ω-3 fatty acids and inflammation in breast tissue.

There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LCω-3PUFA with breast tissue LCω-3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross-sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C-reactive protein (CRP), interleukin (IL)-6 and IL-8 in plasma and tissue were measured by ELISA. Multivariable-adjusted regression models were used to estimate associations between erythrocyte LCω-3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LCω-3PUFA tertile had LCω-3PUFA concentrations in the breast 73% (95% CI: 31-128%; p trend < 0.0001) higher than women in the lowest tertile. Associations for each individual LCω-3PUFA were similar in magnitude. No significant association was found for the shorter ω-3 PUFA, α-linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: -23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte ω-3 PUFA and tissue IL-6 or IL-8 concentrations. Our findings provide evidence that erythrocyte ω-3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LCω-3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication.

Expanding clinical profiles and prognostic markers in stiff person syndrome spectrum disorders.

OBJECTIVE: To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future disability. BACKGROUND: There is a need to better understand the full spectrum of clinical and paraclinical features and long-term impact of SPSD. DESIGN/METHODS: Observational study from 1997 to 2022 at Johns Hopkins. Clinical phenotypes included classic SPS, partial SPS (limb or trunk limited), SPS-plus (classic features plus cerebellar/brainstem involvement), and progressive encephalomyelitis with rigidity and myoclonus (PERM). Outcome measures were modified Rankin scale (mRS) and use of assistive device for ambulation. Multivariate logistic regression was used to assess significant predictors of outcomes. RESULTS: Cohort included 227 individuals with SPSD with mean follow-up of 10 years; 154 classic, 48 SPS-plus, 16 PERM, and 9 partial. Mean age at symptom onset was 42.9 ± 14.1 years, majority were white (69.2%) and female (75.8%). Median time to diagnosis was 36.2 months (longest for SPS-plus and PERM) and 61.2% were initially misdiagnosed. Most had systemic co-morbidities and required assistive devices for ambulation. Female sex (OR 2.08; CI 1.06-4.11) and initial brainstem/cerebellar involvement (OR 4.41; CI 1.63-14.33) predicted worse outcome by mRS. Older age at symptom onset (OR 1.04; CI 1.01-1.06), female sex (OR 1.99; CI 1.01-4.01), Black race (OR 4.14; CI 1.79-10.63), and initial brainstem/cerebellar involvement (OR 2.44; CI 1.04-7.19) predicted worse outcome by use of assistive device. Early implementation of immunotherapy was associated with better outcomes by either mRS (OR 0.45; CI 0.22-0.92) or use of assistive device (OR 0.79; CI 0.66-0.94). CONCLUSIONS: We present the expanding phenotypic variability of this rare spectrum of disorders and highlight potential predictors of future disability.

Relapsing Encephalomyelitis After COVID-19 Infection and Vaccination: From the National MS Society Case Conference Proceedings.

Prior case studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines may unmask CNS neuroinflammatory conditions. We present a case of relapsing steroid-responsive encephalomyelitis after SARS-CoV-2 infection and subsequent COVID-19 vaccination. We also characterize the frequency of CNS neuroinflammatory events reported in the literature after both SARS-CoV-2 infection and COVID-19 vaccination.

Impact of COVID-19 on prescribing patterns and treatment selection of disease modifying therapies in multiple sclerosis.

BACKGROUND: Certain classes of multiple sclerosis (MS) disease modifying therapies (DMTs) have been associated with an increased risk of severe COVID-19, resulting in prescribers considering changes in their practice habits during the COVID-19 pandemic. This study assessed for differences in prescribing patterns of DMTs along with the reason(s) for modification of therapy over time. METHODS: A retrospective review of medical records at Johns Hopkins Health System was performed. The timeframe of the study, April 2019 to December 2021, was divided into three subcategories: pre-pandemic (April 2019-March 2020), pre-vaccine availability (April 2020-March 2021), and post-vaccine availability (April 2021-December 2021). Patients were identified through dispense reports from the pharmacy dispensing system, and prescribing report from the health-system electronic health record (EHR). The health-system EHR was also utilized to conduct chart reviews for a subset of patients that had a modification in their therapy during the specified timeframes. The study included adult patients that were prescribed at least one DMT through the Johns Hopkins Pharmacy Services during the study timeframe and those who stayed on their DMT for at least 2 months without tolerability issues. Descriptive statistics were used to compare the prescribing practices during the timeframes with the percentage of prescribing for each type of treatment and to assess the percentage of patients that switched therapies in the different time periods. RESULTS: Based on prescribing report data, 670 patients were prescribed a DMT during the pre-pandemic period with infusion therapies being the most prescribed therapies during this timeframe (38%), followed by oral therapies at 35%. In comparison, a total of 620 patients were prescribed a DMT during pre-vaccine pandemic and the percentage of prescriptions of infusion therapies decreased to 28% (-10%) during this timeframe, whereas oral prescriptions increased to 42% (+7%). These trends continued during the post-vaccine timeframe where infusion therapies decreased to 26% (-12%) and oral therapies increased to 43% (+8%) in reference to the pre-pandemic period. Prescribing patterns of self-injectable therapies remained stable throughout the 3 timeframes. A dispensing report cohort of 500 patients were randomly selected for chart reviews to assess therapy modifications due to COVID-19. The percentage of therapy change due to COVID-19 increased to 45.2% during pre-vaccine period and remained at 38.4% during post-vaccine period when compared to the pre-pandemic reference period. The majority of changes due to COVID-19 were delays in infusion therapies (96% during pre-vaccine, and 94% during post-vaccine), not medication changes. CONCLUSION: Prescribing patterns and therapy modifications of DMTs for MS patients were impacted by COVID-19, with the greatest changes observed for the infusion therapies, including reduction in percentage of infusion prescriptions and delays in infusion therapies. Prescribing patterns of lower efficacy self-injectable therapies (interferon-beta and glatiramer acetate) remained stable. The outcomes of this study provide background for future outcomes-focused research studies in MS.

Therapeutic plasma exchange in the management of stiff person syndrome spectrum disorders: a case series and review of the literature.

Background: Stiff person syndrome spectrum disorders (SPSD) are a rare group of disabling neuroimmunological disorders. SPSD often requires immune therapies, especially in the setting of inadequate response to symptomatic treatments. The safety and efficacy of therapeutic plasma exchange (TPE) in SPSD remains uncertain. Objectives: To describe the safety, tolerability, and efficacy of TPE in patients with SPSD. Design: A retrospective observational study. Methods: A retrospective review of SPSD patients seen at Johns Hopkins Hospital (JHH) from 1997 to 2021 was performed. Patient demographics/history, examination/diagnostic findings, treatment response, and TPE-related complications were recorded. Assessment for any associations between clinical characteristics, including age, sex, clinical phenotype, and time on immunotherapy, and response to TPE 3 months after treatment was performed. A subgroup of 18 patients treated with TPE at JHH and 6 patients treated with TPE at outside institutions were evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment. Literature review of SPSD and TPE was also conducted. Results: Thirty-nine SPSD patients were treated with TPE (21 at JHH and 18 at outside institutions); median age 48 years, 77% female, median modified Rankin Scale 3; mean initial anti-GAD65 antibody titer was 23,508 U/mL. Twenty-four patients (62%) had classic SPS, 10 (26%) had SPS-plus, 2 (5%) had progressive encephalomyelitis with rigidity and myoclonus, and 3 (8%) had pure cerebellar ataxia. All patients were on symptomatic treatments, 30 (77%) previously received IVIg, and 3 (8%) previously received rituximab. Four patients (10%) had a TPE-related adverse event. One developed asymptomatic hypotension, another had both line thrombosis and infection, and two had non-life-threatening bleeding events. Twenty-three (59%) patients reported improvement in symptoms after TPE. Of the subgroup of 24 patients evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment, 14 (58%) required fewer GABAergic symptomatic medications. Literature review identified 57 additional patients with SPSD; 43 (75%) reported temporary improvement after TPE. Conclusion: The majority of patients treated with TPE had improvement. Moreover, most patients evaluated for any change in usage of symptomatic medications after the TPE treatment no longer required as much symptomatic medications months after TPE. TPE appears safe and well-tolerated in SPSD. Further studies are needed to assess the long-term efficacy of TPE in SPSD and identify which patients may benefit the most from TPE.

Fast Neuro: A Care Model to Expedite Access to Neurology Clinic.

Background and Objectives: We set out to improve outpatient neurology access while reducing patient volume in the emergency department (ED) for nonemergent neurologic complaints. Methods: We created a rapid access model, University of California Los Angeles (UCLA) Fast Neuro, for patients referred from affiliated EDs to outpatient neurology, enabling appointments within 1 week of referral. Rapid access appointments were also available to established neurology patients with urgent concerns. Fast Neuro was built to reduce nonemergent neurologic care in the ED, improve outpatient neurology access, and avoid use of inpatient neurology services for nonemergent consults. The volume of referrals and neurology consults from the ED and wait time from referral to appointment were measured. Surveys were conducted at 3 and 6 months to assess satisfaction with the model by all stakeholders. Results: From January 2019 through January 2021, 201 patients were referred to outpatient neurology through UCLA Fast Neuro. Wait time for an outpatient neurology appointment was reduced from the prior period by 82.5% (7.0 ± 5.5 vs 40 ± 4.1 days). The number of nonemergent consults from the ED was reduced by 60% (4.1 ± 1.9/mo vs 10.3 ± 1.7/mo). Surveys showed wide acceptance of the new model with 92% of attending physicians and advanced practice providers and 89% of residents endorsing that UCLA Fast Neuro patients did not detract from their clinic experience. Discussion: UCLA Fast Neuro improved ED throughput, reduced inpatient neurology consults from the ED, and decreased wait times for outpatient neurology appointments without using the inpatient neurology service for nonurgent consults. UCLA Fast Neuro was successful. Exploration of how to scale and implement the model of access more broadly is warranted.

Clinical practice guidelines on image-guided thermal ablation of primary and metastatic lung tumors (2022 edition).

The main contents of the Clinical Practice Guidelines on Image-Guided Thermal Ablation (IGTA) of Primary and Metastatic Lung Tumors (2022 Edition) include the following: epidemiology of primary and metastatic lung tumors; the concepts of the IGTA and common technical features; procedures, indications, contraindications, outcomes evaluation, and related complications of IGTA on primary and metastatic lung tumors; and limitations and future development.