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.

Optic Perineuritis in an Asymptomatic SARS-CoV-2 Infection.

INTRODUCTION: Optic perineuritis (OPN) is a previously undescribed sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here we present a case of OPN that developed several weeks after initial confirmation of the presence of novel coronavirus RNA in the nasopharynx by polymerase chain reaction assay and subsequent confirmation of SARS-CoV-2 IgG seropositivity in the absence of other systemic inflammatory or infectious markers. CASE REPORT: An asymptomatic 71-year-old man with noninsulin-dependent diabetes mellitus (NIDDM) tested RNA positive for SARS-CoV-2 during a routine screening of patients at a skilled nursing facility. ~3 weeks after the positive SARS-CoV-2 polymerase chain reaction test, the patient developed subacute ophthalmoparesis of the left eye, horizontal diplopia, retro-orbital pain, and frontal headache. An urgent magnetic resonance imaging of the head and orbits suggested OPN. Cerebrospinal fluid studies were without evidence of other infectious, inflammatory, neoplastic, or paraneoplastic processes. He was started on a 5-day course of high-dose intravenous steroids and later transitioned to oral steroid therapy. Sixteen days after the initiation of steroid therapy, the patient had no headache or retro-orbital pain and demonstrated a marked improvement in horizontal gaze. CONCLUSION: SARS-CoV-2-associated neurological sequelae have been increasingly recognized during the current coronavirus disease 2019 pandemic. The present case suggests that patients with confirmed SARS-CoV-2 positivity, even without pulmonary or other classic manifestations of active infection, may manifest diverse clinical presentations including postinfectious OPN that could be related to an underlying autoimmune reactive inflammatory response.

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.

An Update on the Reversal of Non-Vitamin K Antagonist Oral Anticoagulants.

Non-vitamin K antagonist oral anticoagulants (NOACs) include thrombin inhibitor dabigatran and coagulation factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban. NOACs have several benefits over warfarin, including faster time to the achieve effect, rapid onset of action, fewer documented food and drug interactions, lack of need for routine INR monitoring, and improved patient satisfaction. Local hemostatic measures, supportive care, and withholding the next NOAC dose are usually sufficient to achieve hemostasis among patients presenting with minor bleeding. The administration of reversal agents should be considered in patients on NOAC's with major bleeding manifestations (life-threatening bleeding, or major uncontrolled bleeding), or those who require rapid anticoagulant reversal for an emergent surgical procedure. The Food and Drug Administration (FDA) has approved two reversal agents for NOACs: idarucizumab for dabigatran and andexanet alfa for apixaban and rivaroxaban. The American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) have released an updated guideline for the management of patients with atrial fibrillation that provides indications for the use of these reversal agents. In addition, the final results of the ANNEXA-4 study that evaluated the efficacy and safety of andexanet alfa were recently published. Several agents are in different phases of clinical trials, and among them, ciraparantag has shown promising results. However, their higher cost and limited availability remains a concern. Here, we provide a brief review of the available reversal agents for NOACs (nonspecific and specific), recent updates on reversal strategies, lab parameters (including point-of-care tests), NOAC resumption, and agents in development.