Perception of In-Person Prerounding Amongst Neurology Residents Across Two Academic Centers.

Background and Purpose: In-person prerounding has long been a routine practice for residents in the field of neurology. However, with the emergence of the COVID-19 pandemic, many institutions, including our two academic neurology centers, have shifted to computer rounding. This study aims to assess the effects of computer rounding alone compared to a combination of computer rounding and in-person prerounding from the perspective of neurology residents. Methods: A mixed-methods approach was employed, including a survey administered to 79 neurology residents and a qualitative thematic analysis of their responses. Results: The quantitative analysis revealed that residents who engaged in inperson prerounding spent significantly more time on prerounding and computer rounding compared to those who did not. The majority of residents reported a neutral effect of in-person prerounding on their relationship with patients and bedside time, but a significant impact on personal lives and other tasks. Qualitative analysis identified four key themes: accessibility to team members, learning opportunities gained and lost, inefficiency, and sleep disturbance. Conclusions: Overall, residents perceived in-person prerounding as inefficient and causing sleep disruption for both patients and themselves. While some residents valued the face-to-face interaction and improved accessibility, others felt that computer rounding allowed for thorough review of patient data, improving preparedness and efficiency. The potential elimination of in-person prerounding from residents' routines may enhance their overall wellbeing. Further research is needed to assess the advantages and drawbacks of removing this classic approach to caring for patients from the perspective of residents, attendings and patients.

Disease modifying therapy in the treatment of tumefactive multiple sclerosis: A retrospective cohort study.

Tumefactive multiple sclerosis (TMS) is characterized by large demyelinating brain lesions. This was a retrospective cohort study of 67 patients with TMS between January 2015-2023, examining different disease modifying therapy impact on expanded disability scale score change at follow-up. Median age was 36 with a female predominance. Mean EDSS was 3.3 ± 2.3 at TMS onset, 2.1 ± 1.9 at year one, and 2.1 ± 1.9 at last follow-up. A multilinear regression model found higher presentation EDSS and post-diagnosis non-B-cell high efficacy therapies were each independently associated with higher EDSS at last follow up. Further research is needed to determine the value of B-cell therapy in TMS.

Does GPT-4 have neurophobia? Localization and diagnostic accuracy of an artificial intelligence-powered chatbot in clinical vignettes.

BACKGROUND AND OBJECTIVES: This is an observational study of the performance of an artificial intelligence-powered chatbot tasked with solving unknown neurologic case vignettes. The primary objective of the study is to assess the current capabilities of widely-accessible artificial intelligence within the field of clinical neurology in order to determine how this technology can be deployed in clinical practice, and what insights can be learned from its performance and translated to clinical education. METHODS: This observational study tested the accuracy of GPT-4, an artificial intelligence-powered chatbot, at appropriately localizing and generating a differential diagnosis for a series of 29 clinical case vignettes. The cases were from previously published educational material prepared for learners. No cases required more than text input, a current limitation of GPT-4. The primary outcome measures were ranked accuracy of localization and differential diagnosis based on clinical history and exam alone and after ancillary clinical data was provided. Secondary outcome measures included a comparison of accuracy by case difficulty. RESULTS: GPT-4 identified the correct localization less than 50% of the time and performed worse when provided ancillary testing. GPT-4 was more accurate with localization and diagnosis of easier versus harder cases. Diagnostic accuracy was independent of its ability to localize the lesion. DISCUSSION: GPT-4 did not perform as well on neurology clinical vignettes as compared to reported accuracy when provided other medical clinical vignettes. Incorporation of an AI chatbot into the practice of clinical neurology will require neurology-focused teaching.

MYD88 L265P mutation in neurologic autoimmunity without evidence of malignancy.

MYD88 mutation status is assessed in the evaluation of CNS lymphoma since the mutation MYD88 L265P is highly predictive of this disease. However, whether the MYD88 L265P mutation may lead to other diseases outside of malignancy is not well understood. Here we describe two patients with the MYD88 L265P mutation in the CSF with no additional evidence of neoplastic disease but were found to have two distinct neurologic autoimmune conditions (anti-GFAP astrocytopathy and multiple sclerosis). These cases suggest this activating mutation may predispose certain patients to autoimmune conditions and may have future therapeutic implications.

Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination. Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab. Results: After 2-vax, 8/33 (24.2%) patients in ocrelizumab group, 5/7 (71.4%) in fingolimod group, and 29/29 (100%) in HC group (P = 5.7 × 10-11) seroconverted. After 3-vax, 9/22 (40.9%) patients in ocrelizumab group, 19/21 (90.5%) in fingolimod group, and 7/7 (100%) in HC group seroconverted (P = 0.0003). The percentage of SARS-CoV-2 peptide reactive total CD4+ T cells increased in HC and ocrelizumab group but not in fingolimod group after 2-vax and 3-vax (P < 0.0001). The percentage of IFNγ and TNFα producing total CD4+ and CD8+ T cells increased in fingolimod group as compared to HC and ocrelizumab group after 2-vax and 3-vax (P < 0.0001). Conclusions: MS patients on ocrelizumab and fingolimod had attenuated humoral responses, but preserved cytokine producing T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination. Clinical Trials Registration: NCT05060354.

Neurologic disease activity in people with multiple sclerosis treated with immune checkpoint inhibitors.

BACKGROUND: There is concern that immune checkpoint inhibitors (ICPIs) can provoke relapses in people with multiple sclerosis (pwMS). OBJECTIVE: Analyze outcomes of pwMS who received ICPI treatment for malignancy. METHODS: We electronically identified pwMS who received ICPI treatment at Mass General Brigham hospital system. We retrospectively obtained information about patients' MS, cancer, treatment, and outcomes. RESULTS: Sixteen patients were identified with an average (standard deviation (SD)) age of 67.4 (11.9) years. Eleven (68.8%) had no relapses since MS diagnosis. None had MS relapses after ICPI treatment or new MS lesions. CONCLUSION: ICPI use was not associated with increased clinical disease activity in this cohort of older patients with inactive MS.

Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) on some disease modifying therapies (DMTs), particularly anti-CD20 and sphingosine-1-phosphate (S1P) modulators, are at increased risk of severe Coronavirus Disease 19 (COVID-19) and death. COVID-19 vaccinations are effective in preventing infection and severe disease, but humoral response to vaccination and outcomes of COVID-19 infection after vaccination in MS patients on DMTs remain less understood. METHODS: In this retrospective single-center study, patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital) study and biorepository who had been vaccinated against COVID-19 and had SARS-CoV-2 spike antibody (anti-SARS-CoV-2 S Roche-Elecsys) testing were identified and compared to healthy controls. Demographic data, serum immune profiles including lymphocyte count, B-cell count, and immunoglobulins, and clinical outcome of COVID-19 infection were collected. RESULTS: 254 patients (73.2% female, mean (SD) age 52.9 (11.2) years) were identified. When controlling for age, time since vaccination, and vaccine type, patients on fingolimod, ocrelizumab, rituximab, mycophenolate mofetil, natalizumab and teriflunomide had significantly lower levels of spike antibodies compared to healthy controls (n = 34). Longer duration of treatment was associated with lower spike antibody levels in patients on anti-CD20 therapy (p = 0.016) and S1P modulators (p = 0.016) compared to healthy controls. In patients on anti-CD20 therapy, higher spike antibody levels were associated with higher CD20 cell count (p<0.001), and longer time since last anti-CD20 therapy infusion (p<0.001). 92.8% (13/14) vaccine responders (spike antibody titer >100 ug/dL) on anti-CD20 therapy demonstrated B-cell reconstitution (mean CD20 3.6%). Only 1 out of 86 patients with CD20 of 0% had a measurable spike antibody response to vaccination. During follow-up (mean 270 days), five patients were diagnosed with COVID-19 after vaccination (incidence 1.9%), all of whom had spike antibody < 20 ug/dL. No patients required ICU care or died. CONCLUSIONS: Patients on some DMTs demonstrate reduced humoral immunity after Sars-CoV-2 vaccination. Longer duration of anti-CD20 therapy and reduced CD20 cell count is associated with blunted humoral response to vaccination. CD20 reconstitution >0.1% appears necessary, but not always sufficient, for humoral response to vaccination. Breakthrough COVID-19 infection in our cohort of MS patients on DMT was higher than in population studies. We propose that adjustment of B-cell therapy administration to allow for B-cell reconstitution prior to vaccination should be considered.

Treatment outcomes of first-ever episode of severe optic neuritis.

BACKGROUND: Severe optic neuritis (ON) is an acute inflammatory attack of the optic nerve(s) leading to severe visual loss that may occur in isolation or as part of a relapsing neuroinflammatory disease, such neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD), or more rarely multiple sclerosis (MS). In cases of first-ever severe ON of uncertain etiology best treatment strategies remain unclear. METHODS: We reviewed records of all patients with a documented diagnosis of ON between 2004 and 2019 at Mass General Brigham (MGB) and Johns Hopkins University (JHU) hospitals. Out of 381 patients identified, 90 (23.6%) satisfied the study criteria for severe ON with visual acuity (VA) equal to or worse than 20/200 (logMAR=1) at nadir in the affected eye and had sufficient follow-up data. Treatment strategies with corticosteroids only or treatment escalation with therapeutic plasma exchange (PLEX) after steroids were compared and evaluated for differences in visual outcomes at follow-up. RESULTS: Of the 90 patients with severe optic neuritis, 71(78.9%) received corticosteroids only, and 19 (17.0%) underwent PLEX following corticosteroids. Of the 71 patients who received steroids without escalation to PLEX, 30 patients (42.2%) achieved complete recovery (VA 20/20 on the affected eye), whereas 35 (49.3%) had a partial recovery and 6 (8.4%) had no recovery. Among the 19 corticosteroid non-responders patients who underwent escalation treatment, 13 (68.4%) made complete recovery, 6 (31.6%) had partial visual recoveries (p=0.0434). The median delta logMAR of patients who underwent escalation of care was -1.2 compared with 2.0 for the ones who did not (p=0.0208). A change of delta logmar 2.0 is equivalent of going from hand motion to light perception and the positive delta value refers to intra-attack worsening. Other than not responding to steroids, patients who underwent PLEX tended to have more severe ON with significantly worse nadir visual acuity compared with those who received corticosteroids alone (logMAR 3.12 (min 2.0 - max 5.0) vs. 2.17 (min 1.3 - max 3.0); p=0.004). CONCLUSION: In our cohort of first-ever severe optic neuritis of unknown etiology, patients that did not respond adequately to corticosteroids benefited from treatment escalation to PLEX, followed in most cases by Rituximab, regardless of final etiology. Randomized controlled trials are needed to confirm the best treatment strategies.

COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders.

BACKGROUND: Neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 is not well understood. The objective of this study was to investigate neurologic outcomes in patients with MSRD post-COVID-19. METHODS: This was a retrospective medical records review study of adult patients with MSRD and COVID-19 infection at the Brigham MS Center. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudorelapse, new brain MRI activity, worsening of preexisting MSRD symptoms, or development of other long-term neurologic symptoms. RESULTS: 111 patients, 85 (76.6%) females, with a mean [SD] age of 49.3 [12.2] years and median [range] EDSS of 2.5 [0, 8.5] were identified. 41 patients (36.9%) had neurologic worsening post-COVID-19. Of those, 19 (46.3%) had pseudorelapses, 2 (4.8%) had relapses, and 24 (58.5%) patients reported worsening of preexisting MSRD symptoms, or other new long-term neurologic symptoms. Neurologic worsening was associated with hospitalized (moderate or severe) COVID-19 (p = 0.001), treatment for COVID-19 (p = 0.006), and incomplete COVID-19 recovery (p = 0.0267) but not with age, sex, MS type, race, disease duration, EDSS, vitamin D use, or disease modifying therapy use. CONCLUSIONS: COVID-19 severity and lack of complete systemic recovery were associated with new or worsening neurologic symptoms in 36.9% of MSRD patients.

Disease modifying therapy management of multiple sclerosis after stem cell therapies: A retrospective case series.

BACKGROUND: Stem cell therapies (SCT) have not received formal regulatory approval for the treatment of people with multiple sclerosis (PwMS), but PwMS may seek various options on their own accord. The current literature largely focuses on the efficacy and safety of SCT in PwMS in clinical trials, in particular autologous hematopoietic stem cell transplantation (aHSCT), in carefully selected participants. There is little reported on the MS disease modifying therapy (DMT) management of PwMS who choose to undergo SCT outside of these trials. METHODS: We identified PwMS from two academic centers who had MS diagnosis fulfilling 2017 McDonald criteria and received SCT (methodologies permitted: aHSCT, umbilical-derived mesenchymal stem cells and/or adipose-derived mesenchymal stem cells (AdMSC)), with the goal to treat MS, between 1/1/2015 and 11/30/2021. RESULTS: Nine PwMS (five females; age range at SCT treatment 25-69 years old; MS disease duration 1-12 years; six relapsing-remitting, three secondary progressive, one primary progressive) underwent a total of eleven SCTs (nine aHSCT, two AdMSC, one umbilical-derived MSC) with the goal to treat MS. Two of six PwMS who underwent SCT <10 years from MS diagnosis, and one of three PwMS who underwent stem cell therapies >10 years from MS diagnosis were clinically stable thereafter. An MS DMT was resumed in five PwMS afterwards, including rituximab, ocrelizumab, siponimod, and glatiramer acetate: one remained clinically stable, whereas four clinically progressed. Four PwMS remained off of a DMT: three were clinically stable, whereas one clinically progressed. All nine patients demonstrated radiographic stability by MRI after SCT. Only one met formal criteria to consider aHSCT for MS. CONCLUSIONS: We demonstrate the heterogeneous real-world experience of treating MS after patient-chosen experimental SCTs, detailing the range of DMT management in various patient circumstances. Limitations of our study include its small sample size and the variety of stem cell therapies received.

Acute Neurologic Manifestations of Systemic Immune-Mediated Diseases.

Systemic autoimmune diseases can affect the peripheral and central nervous system. In this review, we outline the common inpatient consultations for patients with neurological symptoms from rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, sarcoidosis, immunoglobulin G4-related disease, Behçet's disease, giant cell arteritis, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis, polyarteritis nodosa, and ankylosing spondylitis. We discuss the symptoms, diagnostic strategies, and treatment options.

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.

Influence of Autoimmune Antibody Testing on the Use of Immunotherapy on an Inpatient Neurology Service.

OBJECTIVE: To determine the frequency of autoimmune antibody testing in an inpatient neurology setting and its influence on immunotherapy use on an inpatient neurology service. METHODS: A retrospective descriptive cohort study of patients admitted to the neurology inpatient service at a large tertiary academic medical center who had autoimmune and/or paraneoplastic antibody testing performed between 10/1/2017 and 10/1/2018. Characteristics of patients' initial clinical presentation, antibody testing results, test timing in relation to initiating immunotherapy, and final diagnosis using consensus criteria were extracted and analyzed. Case reports of patients with positive antibody panels are presented. RESULTS: Of 1,604 patients, 50 patients (3.1%) had an antibody panel sent. Tests resulted after an average of 17 days (range 7-27). The most common clinical presenting symptom in those with a panel sent was encephalopathy. There were 5 (10%) positive serum panels and no positive CSF panels. Only one of these 5 patients had autoimmune encephalitis and was treated with immunotherapy. Of those with negative serum and CSF panels, 15 were treated acutely with empiric immunotherapy and the remainder with supportive care. Of those treated with immunotherapy, 14/15 (93%) were treated before the panel tests resulted. Four patients who had negative panels but were empirically treated met consensus criteria for an autoimmune-mediated neurologic process. CONCLUSION: Our study suggests that the results of antibody testing did not influence inpatient neurologists' decision to treat with immunotherapy as most treatments began prior to final results being available.

Reactivation of SARS-CoV-2 after Rituximab in a Patient with Multiple Sclerosis.

A 32-year-old woman with highly active MS was infected with SARS-CoV-2 while on treatment with rituximab. She recovered and was symptom-free for 21 days before receiving rituximab and IVIg for comorbid hypogammaglobulinemia. Three days after the infusion she redeveloped respiratory symptoms and required admission. Three SARS-CoV-2 nasopharyngeal swabs and antibody testing was negative; however, bronchial alveolar lavage detected SARS-CoV-2. Reactivation of SARS-CoV-2 after rituximab for MS has not been reported but is a known risk in other conditions. The timing of anti-CD20 treatment after SARS-CoV-2 infection requires further investigation and individual consideration to reduce the risk of reactivation.

Serum neurofilament levels and patient-reported outcomes in multiple sclerosis.

OBJECTIVE: Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients. METHODS: MS patients with serum samples and health-outcome measurements collected longitudinally between 2011 and 2016 were analyzed. sNfL values were evaluated across age and gender. Data were analyzed using correlation with log-transformed sNfL values. RESULTS: A total of 304 MS patients with a mean age of 32.9 years, average EDSS of 1.6 (SD = 1.5) and baseline sNfL of 8.8 (range 1.23-78.3) pg/mL were studied. Baseline sNFL values increased with age and were higher in females. Baseline sNfL correlated with baseline Multiple Sclerosis Quality of Life physical composite (mean = 49.4 (9.1), P = 0.035) and baseline EDSS (P = 0.002). Other PRO measures at baseline did not show a significant relationship with baseline sNfL. Average of baseline and follow-up sNfL correlated with MSQoL physical-role limitations (mean = 48.9 (10.8), P = 0.043) and social-functioning (mean = 52.3 (7), P = 0.034) at 24-month follow-up. We found a trend for numerically higher sNfL levels in nonpersistent patients compared to those who were persistent to treatment (11.13 vs. 8.53 pg/mL, P = 0.093) measured as average of baseline and 24-month values. Baseline NfL was associated with number of intravenous steroid infusions (mean = 0.2; SD = 3.0, P = 0.013), whereas the average of baseline and 12 months NfL values related to inpatient stays at 12 months (mean = 0.2; SD = 3.0 P = 0.053). CONCLUSION: Serum NfL is a patient-centric biomarker that correlated with MS patient health-outcomes and healthcare utilization measures in a real-world cohort.

Multiple Sclerosis and Autoimmune Neurology of the Central Nervous System.

Autoimmune disorders of the central nervous system are common and often affect people in the most productive years of their lives. Among primary autoimmune diseases of the central nervous system, multiple sclerosis is most prevalent in the United States. Many other autoantibody-mediated neurologic syndromes have been identified within the past 2 to 3 decades, including neuromyelitis optica and anti-N-methyl-D aspartate receptor encephalitis. Finally, the central nervous system can also be affected by systemic autoimmune diseases such as sarcoidosis. Many of these diseases are treatable when detected early.