Anti-NMDA Receptor Encephalitis Related to Renal Cell Carcinoma: A Case Report.

Anti-NMDA receptor (NMDAR) encephalitis is characterized by a well-defined neuropsychiatric syndrome and CSF antibodies against the GluN1 subunit of the NMDAR. 40% of cases are related to underlying tumors, the vast majority ovarian teratomas (94%). We report a case of anti-NMDAR encephalitis associated with renal cell carcinoma (RCC). A 20-year-old female presented to the ED with behavioral changes, involuntary movements, tachycardia, and alternating obtundation with agitation which progressed over 3 weeks. Involuntary movements were severe, requiring intubation and sedation for control, and were accompanied by rhabdomyolysis. Brain MRI showed bilateral mesiotemporal T2/FLAIR hyperintensities. Anti-NMDAR antibodies were present in the serum (1:640) and CSF (1:320). Malignancy screening revealed a renal mass concerning for RCC, which was confirmed upon resection. She was started on high dose IV methylprednisolone and plasmapheresis, followed by rituximab. Lack of response led to escalating immunotherapy with cyclophosphamide. Clinical course was complicated by prolonged ICU admission, prolonged sedation, severe dysautonomia and bacteremia. Improvement began 2 months after immunotherapy, and she was discharged to rehabilitation 100 days after admission with mild neuropsychiatric symptoms. Repeat malignancy screenings, including whole-body imaging and transvaginal ultrasound were consistently negative. Herein, we describe a case of definite anti-NMDAR encephalitis in the setting of newly diagnosed RCC. This case illustrates how tumors other than ovarian teratomas may act as immunological triggers, as well as the complex and prolonged symptomatic and immunosuppressive therapies required in severe presentations of anti-NMDAR encephalitis.

Seven Strategies to Integrate Equity within Translational Research in Neurology.

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose 7 strategies to integrate equity within translational research in neurology: (1) learn history; (2) learn about upstream forces; (3) diversify and liberate; (4) change narratives and adopt best communication practices; (5) study social drivers of health and lived experiences; (6) leverage health technologies; and (7) build, sustain, and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy. ANN NEUROL 2024;95:432-441.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and Transverse Myelitis Probably Associated With SARS-CoV-2 mRNA Vaccines: Two Case Reports.

Post-vaccination CNS demyelinating syndromes have been reported with a variety of vaccines including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. We report a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) probably associated with the mRNA-1273 (by Moderna) SARS-CoV-2 mRNA vaccine, and a case of acute transverse myelitis (ATM) probably associated with the BNT162b2 (by Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine. A 38-year-old man developed left blurry vision, lower extremity weakness/paresthesia, and bowel/bladder dysfunction three days after receiving the Moderna vaccine. He was diagnosed with left optic neuritis and longitudinally extensive transverse myelitis; he tested positive for the myelin oligodendrocyte glycoprotein antibody. A 39-year-old woman presented with progressive lower extremity weakness/numbness 7 days after receiving the Pfizer vaccine. She was diagnosed with ATM. Both patients improved with intravenous corticosteroids. The association between CNS demyelinating syndromes and vaccination has been reported for many years. We describe two cases of acute CNS demyelinating events probably associated with both mRNA variations of the SARS-CoV-2 vaccines. While the risk of CNS demyelinating events is non-negligible, the incidence is very low and the overall benefits of vaccination outweigh the marginal risk. However, providers should be aware of this potential neurological complication of the SARS-CoV-2 mRNA vaccines.

The Importance of Incorporating Stroke Survivors' Health Perceptions in Addressing Health Care Disparities.

Patient-centered research in determining health care disparities among stroke patients is limited. Several studies have examined patient perceptions in stroke survivors and have utilized the Illness Perceptions Questionnaire-Revised (IPQ-R) and Brief Illness Perceptions Questionnaire (BIPQ), which are validated measures of illness beliefs. Yet, there are several domains these surveys could assess that warrant more investigation, including: perception of medication side effects; acceptance of the stroke diagnosis; consequence and long-term impact of symptoms; the importance of medications in long-term health maintenance; and perception of ease of access to equitable health care. Though these surveys are available, representation of diverse and under-represented groups within stroke surveys utilizing them is low. Also, only a limited number of studies of stroke patients' perceptions have focused on health disparities or specifically beliefs and attitudes of under-represented stroke survivors. Due to insufficient current research, future studies should focus on using these patient perception questionnaires with underrepresented populations. Improvements in this field may allow providers to offer patient-centered care among a diverse population, bridging gaps in health care equity.

Prevalence of multiple sclerosis and treatment utilization in a large, highly diverse population.

BACKGROUND: Despite advances in algorithms for identifying people with MS (PwMS) in large data sets, limited data exists on regional prevalence, or prevalence and care in minority populations. OBJECTIVES: To report the 7-year (01/01/2012-12/31/2018) prevalence and demographics of MS and disease-modifying therapy (DMT) utilization in a large, diverse population. METHODS: This retrospective analysis used the OneFlorida Data Trust, which captures health data from >15 million Floridians across 10 constituent organizations. A validated algorithm identified subjects with MS. DMTs were identified using RxNorm concept unique identifiers and National Drug Codes. Results were stratified across age, sex, race-ethnicity, and location. RESULTS: Of 6,638,649 adults in the database, the algorithm identified 9681 PwMS. Overall prevalence per 100,000 was 145.83. MS prevalence was considerable in women of all races and ethnicities ranging from 138.86 to 253.76 per 100,000. 52.6% of PwMS had one or more DMT prescription. DMT prescription was more likely in Hispanic PwMS. CONCLUSION: Prevalence analysis of the OneFlorida Data Trust revealed a substantial burden of disease in women of all races and ethnicities. Variation in treatment utilization among demographic subgroups underscores the need for additional studies to assess health care disparities in MS at the population level.

Neutralizing antibody responses against SARS-CoV-2 in vaccinated people with multiple sclerosis.

Background: Patients with multiple sclerosis (pwMS) are often treated with disease modifying therapies (DMT) with immunomodulatory effects. This is of particular concern following the development of several vaccines to combat coronavirus disease 19 (COVD-19), a potentially fatal illness caused by SARS-CoV-2. Objectives: To determine the efficacy of SARS-CoV-2 vaccination in pwMS and the impact of disease modifying therapies (DMT) on vaccine response. Methods: This is a prospective longitudinal study in pwMS. Longitudinal serum samples were obtained prior to, and after SARS-CoV-2 mRNA vaccination. A novel neutralizing antibody (nAb) assay was used to determine nAbs titres against SARS-CoV-2 spike. Results: We observed that (1) pwMS on B-cell depleting therapies exhibited reduced response to vaccination compared to other pwMS, correlating with time from last anti-CD20 infusion, (2) prior COVID-19 illness, DMT category, and pyramidal function were significant predictors of vaccine responsiveness, and (3) circulating absolute lymphocyte count (ALC) and IgG levels correlated with nAb levels. Conclusions: We demonstrate that pwMS exhibit reduced nAb response to mRNA vaccination dependent on DMT status and identify predictive biomarkers for vaccine efficacy. We conclude that additional vaccination strategies may be necessary to achieve protective immunity in pwMS.

Anti-MOG associated disorder-Clinical and radiological characteristics compared to AQP4-IgG+ NMOSD-A single-center experience.

BACKGROUND: The discovery of two immunoglobulin G (IgG) antibodies against aquaporin 4 (anti-AQP4) and myelin oligodendrocyte glycoprotein (anti-MOG) has led to the distinction of the disorders anti-AQP4 immunoglobulin G positive neuromyelitis spectrum disorder (AQP4-IgG+ NMOSD) and anti-MOG associated disorder (MOGAD). Different clinical and radiological features have been proposed to distinguish these two demyelinating CNS diseases. METHODS: This is a single-center retrospective review at the University of Florida (UF) including all patients with the diagnostic code ICD G36 ("other acute disseminated demyelination") from October 2015 to January 2020 (n=141) and all charts included in the clinical NMOSD database of the UF Division of Neuroimmunology (n=36). A total of 151 cases were reviewed for presence of anti-MOG and anti-AQP4 antibodies and NMOSD diagnostic criteria. Differences in MOGAD and AQP4-IgG+ NMOSD were compared. RESULTS: Of the 151 reviewed patient charts, 11 were consistent with MOGAD and 43 with AQP4-IgG+ NMOSD. Patients with MOGAD were significantly younger at symptom onset compared to patients with AQP4-IgG+ NMOSD (14 [1-33] years vs. 37 [6-82] years; p=0.005). In comparison with AQP4-IgG+ NMOSD, optic neuritis in MOGAD was more frequently associated with bilateral optic nerve involvement: (6/11 [54.5%] vs. 6/43 [13.9%]; p=0.009) and fundoscopic presence of optic disc edema (5/11 [45.5%] vs. 3/43 [7%]; p=0.006). Perineuritis was a common radiological feature in MOGAD (present in 4 cases). In case of myelitis, there was more frequent involvement of the conus medullaris in MOGAD (4/11 [36.4%] vs. 2/43 [4.7%]; p=0.012). Symptomatic cerebral syndrome with supratentorial white matter lesions was seen in MOGAD patients with pediatric onset (pediatric onset: 4/6 [66.7%] vs. adult onset: 0/5 [0%]. In MOGAD, evidence for combined central and peripheral demyelination and increased intracranial pressure was present in one patient each. A preceding inciting event (illness/postpartum) was more frequently identifiable in MOGAD (4/11 [36.4%] vs. 4/43 [7%]; p=0.045). Disability as calculated on the Expanded Disability Status Scale was less severe in MOGAD compared to AQP-IgG+ NMOSD (most severe presentation: 5 [2-7] vs. 7 [1-10]; p=0.015; most recent assessment: 2 [0-5] vs. 5 [0-10]; p=0.045) and patients were more likely to respond to treatment of acute attacks with corticosteroids and/or plasmapheresis (Clinical Global Impression-Global Change scale: 1 [1-4] vs. 3 [1-6]; p=0.001). INTERPRETATION: The study confirms that simultaneous bilateral optic neuritis, presence of optic disc edema, transverse myelitis with conus involvement and a less severe disease course are distinctive features of MOGAD.

Movement for multiple sclerosis: a multi-site partnership for practice and research.

While dance programs for people with Parkinson's disease (PD) have been developed globally over the past two decades, dance programs for people with multiple sclerosis (MS) are just emerging. This article introduces three dance for MS programs and a multi-site partnership that was developed to evaluate and advance a model for dance for MS programs. The program partners convened over 2 days to share program models, consider current and planned program evaluations, and identify unique challenges and promising practices for delivering safe and effective dance for MS programs. This paper presents the findings of this convening and recommendations for dance for MS programs.Background:While dance programs for people with Parkinson's disease (PD) have been developed globally over the past two decades, dance programs for people with multiple sclerosis (MS) are just emerging. This article introduces three dance for MS programs and a multi-site partnership that was developed to evaluate and advance a model for dance for MS programs.Methods: The program partners convened over 2 days to share program models, consider current and planned program evaluations, and identify unique challenges and promising practices for delivering safe and effective dance for MS programs.Results:A set of promising practices for dance for MS programs, including recommendations for partnership, dance and movement approaches, and environmental, physical and psychosocial considerations, was developed by the program partners.Conclusions: These programs suggest that dance may be a useful modality for people with MS. Recommendations are offered to guide safe and evidence-based dance for MS practices.

Anti-JCV antibody index does not change during ocrelizumab-treatment.

OBJECTIVE: To prospectively assess anti-JCV antibody index (AI) and its relationship to immunoglobulin levels in ocrelizumab-treated MS patients. METHODS: Monocentric prospective observational study over 24 months assessing anti-JCV AI and immunoglobulin levels in MS patients before and after initiation of ocrelizumab. RESULTS: No significant change in anti-JCV AI titers was observed 458 ± 300 days after initiation of ocrelizumab (n = 45, 0.7 ± 2.21 vs. 0.6 ± 2.06, p = 0.8). Seroconversion occurred in 1/20 initially anti-JCV seronegative patients. There was no correlation between changes in anti-JCV AI and immunoglobulins. CONCLUSION: Treatment with ocrelizumab is not associated with an increase in anti-JCV AI titers.

Corticosteroids lead to short-term improvement in cerebral amyloid angiopathy-related inflammation.

BACKGROUND: Cerebral amyloid angiopathy - related inflammation (CAA-ri) is an uncommon manifestation of CAA. METHODS: Single-center, retrospective review of all charts with ICD-code I68.0 (CAA) from 2/2/2016-1/1/2020. RESULTS: Of 152 CAA cases, 13 (8.6%) were consistent with CAA-ri. Corticosteroid-treatment led to short-term reduction in modified Rankin Scale scores (2.6 ± 1.4 vs. 1.6 ± 1.5; p = 0.01) and T2/FLAIR lesion volume (78.1 ± 52.2 cm3 vs. 30 ± 30.9 cm3, p < 0.01) as well as short-term improvement in post-treatment Clinical Global Impression - Global Change scores compared to pre-treatment scores (clinical: 6 ± 1 vs. 2.6 ± 1.3, p = 0.03; radiological: 4.6 ± 1.9 vs. 1.2 ± 0.4, p = 0.03). INTERPRETATION: Corticosteroid-treatment leads to clinical and radiological short-term improvement (class IV evidence).

Ibudilast for the treatment of multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) characterized by inflammatory demyelination and progressive axonal loss. Clinically, this is manifest as relapsing and remitting neurological symptoms and progressive accumulation of disability. Ibudilast is a nonselective phosphodiesterase inhibitor which works by blocking the cleavage of cyclic adenosine monophosphate (cAMP). It has been found to have anti-inflammatory and neuroprotective properties in animal studies and in-vitro studies; it is currently being studied in progressive MS. AREAS COVERED: This article reviews various studies looking at ibudilast as a potential therapy for MS. It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology. EXPERT OPINION: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression. Ibudilast may have a role in the treatment of progressive MS phenotypes.