Double inversion recovery to detect cervical spinal cord multiple sclerosis lesions.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) plays a key role in diagnosing and monitoring multiple sclerosis (MS). Double inversion recovery (DIR) is a pulse sequence that has proven highly effective at detecting cortical lesions but is understudied in the spinal cord. We hypothesize that DIR images obtained during brain MRI can be of value in assessing the upper spinal cord of MS patients. METHODS: We retrospectively examined brain MRI exams of 64 patients with established MS, who had also undergone cervical spine MRI. Two blinded MS expert readers, who assessed the scans for lesion numbers and rated lesion visibility and overall image quality, reviewed brain 3-dimensional DIR sagittal and coronal images. Standardized mean contrast-to-noise ratios (C/N) and standard deviation (SD) were calculated in representative lesions for each patient and compared to those of 3-dimensional FLAIR images. RESULTS: For the analysis of lesions categorized as "definite lesions," the sensitivity was 87%, specificity was 61%, and negative predictive value was 80%. On the other hand, for "definite" plus "probable" lesions, the sensitivity was 91%, the specificity was 54%, and negative predictive value was 86%. DIR demonstrated lesions with an average C/N of 7.56 with an SD of 1.77. FLAIR sequence demonstrated lesions with an average C/N of 0.67 and SD of 1.27. CONCLUSIONS: Sagittally acquired brain DIR can provide useful information on upper spinal cord lesions, with high C/N. In theory, this should facilitate the attainment of McDonald's or the Magnetic Resonance Imaging in MS (MAGNIMS) criteria in some cases, without a dedicated cervical spine MRI exam.

Real-world experience of ocrelizumab initiation in a diverse multiple sclerosis population.

BACKGROUND: Ocrelizumab (OCR) is a humanized monoclonal antibody directed against CD20 positive B-lymphocytes. It was approved for use in 2017 by the U.S. Food and Drug Administration (FDA) for both the relapsing-remitting and primary progressive forms of multiple sclerosis (MS). OBJECTIVE: To provide real-world data for patients with MS treated with OCR in our center and evaluate both the safety and efficacy across different ethnic groups not studied in previous clinical trials. METHODS: We performed a retrospective observational analysis of MS patients who were treated with OCR from March 31, 2017 to April 30, 2020. We collected data on patients who had received at least a one dose infusion of OCR at our MS center. Patient characteristics, including demographics, clinical disease course, and documented side effects, were collected and analyzed. RESULTS: A total of 82 patients were eligible for this study, of which 72% had relapsing-remitting MS (RRMS), 14% had primary progressive MS (PPMS), and 11% active/relapsing secondary progressive MS (SPMS). 22% of our patients were of African American descent, 61% Caucasian, and 17% of Hispanic descent. The mean age of starting OCR was 41 ± 11 years. 47% were treatment naïve when started on OCR, 24% were previously treated with one disease-modifying therapy (DMT), 14% were treated with two DMTs, and 15% were treated with more than two DMTs prior to OCR. 50% of patients had at least one adverse event while on OCR; 4.8% had adverse events requiring to OCR discontinuation, 36% had infusion-related reactions, and 7.3% had viral infections. We found two cases of severe babesiosis along with index cases of re-activation of lichen planus, agranulocytosis, severe lymphopenia, and ectopic pregnancy. There were no cases of malignancy, progressive multifocal leukoencephalopathy, or death within our cohort. The mean time after OCR initiation was 17.3 months in the RRMS group, 22.2 months in the PPMS group, and 28.2 months in SPMS group. The annualized relapse rate reduced from 1.33 to 0.15 in the RRMS group. The mean extended disability status scale (EDSS) scores did not worsen across MS phenotypes and ethnic groups while being treated with OCR. CONCLUSIONS: In a diverse patient population, OCR was well-tolerated without significant adverse events. There were novel cases of severe babesiosis, re-activation of lichen planus, lymphopenia, agranulocytosis, and ectopic pregnancy. It is vital to consider geographic risk factors that may expose patients to Babesia microti (B. microti) when either considering or initiating OCR therapy. There were an additional six cases of severe B. microti cases associated with OCR that were reported to the FDA adverse event reporting system (FAERS) along with multiple babesiosis cases associated with other DMTs, including rituximab. OCR was found in our cohort to be effective by decreasing relapse rates and maintaining EDSS scores. Our study extends the generalizability of OCR from clinical trials to a real-world setting consisting of a diverse population.

Babesia microti infection in a patient with multiple sclerosis treated with ocrelizumab.

Ocrelizumab is a humanized monoclonal anti-CD20 antibody approved for treatment of relapsing-remitting and primary progressive multiple sclerosis (MS). Rare parasitic infections have been reported in patients with lymphoproliferative disorders using rituximab, a chimeric anti-CD20 antibody used off-label for the treatment of MS. Here, we report a patient with MS on ocrelizumab with B-cell depletion who developed severe Babesia microti (B. microti) infection with neutropenia, hemolytic anemia, and thrombocytopenia. He recovered after prompt diagnosis and treatment. This case represents the first published occurrence of babesiosis in a patient with MS on ocrelizumab. It also adds to the accumulating evidence from databases of emergent severe or relapsing B. microti infection in patients receiving anti-CD20 antibodies. This presentation stresses the diagnostic vigilance required by MS neurologists in endemic areas to identify cases of babesiosis in patients on anti-CD20 therapy and to better counsel these individuals on their risks of B. microti infection.

Preventive neurology concepts for training the next-generation and closing gaps in real-world Multiple Sclerosis Care.

The field of Multiple sclerosis (MS) has entered an area of growth in the understanding of the MS immune dysregulation that has led to an impressive therapeutics expansion. However, results of surveys and proceedings of the American Academy of Neurology (AAN) support the notion that US neurology residents have fragmented exposure to MS training during residency, resulting in learning gaps in diagnosis, management and follow up of patients with MS. There are annual educational offerings by MS academic societies but limited and tailored to trainees interested in MS/neuroimmunology subespecialization. Therefore, the acquisition of MS clinical skills by all neurology residents is essential for the practice of unsupervised neurology after board certification. Here, we review the current elements and goals of care that are critical for the learning of trainees. We present these elements in a framework focused on current unmet needs to avoid progression in MS in a real-world setting, tailored to preventive and personalized care: The "Multiple Sclerosis 4-square Educational Matrix". This approach could help training neurologist and patients through the essential steps of care. The trainee side emphasizes a goal-oriented approach to satisfy the educational and management components of MS in four areas: burden of symptoms, burden of disease activity, personalized risk factors and personalized patient education. The patient side is similar but simplified for their benefit. This structured approach is based on the principles of personalized preventive neurology and could be useful to solidify trainees and patient education, promoting proactive participation of patients in vital areas of their care, in an anticipatory, and goal-oriented manner. We aim to improve the unmet needs at an individual level and the value of care of populations at risk for progression and disability in MS.

Mild COVID-19 infection despite chronic B cell depletion in a patient with aquaporin-4-positive neuromyelitis optica spectrum disorder.

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2, which affects the lung and other organs. After an incubation period of 3-14 days, the infection presents with symptoms of variable severity, from mild flu-like disease to severe pneumonia and cytokine storm with increased mortality. Immunosuppressed patients may have higher risk of adverse outcomes; hence, there is an urgent need to evaluate the immune response and clinical outcomes of SARS-CoV-2 infection in these patients. Here, we report a 59-year-old woman with aquaporin-4-positive (AQPR4+) neuromyelitis Optica treated with rituximab who developed mild respiratory symptoms with COVID-19, despite B cell depletion at the time of infection.