Multiple sclerosis (MS) is a chronic neuroimmunological condition associated with acute relapses. Differentiating between acute symptom development related to autoimmune inflammatory demyelination versus pseudoexacerbation remains challenging. We aimed to evaluate the utility of a commercially available multi-analyte protein assay in (1) assessing acute patient-reported symptoms suggestive of clinical exacerbations by comparing the acquired proteomic results to the corresponding MRI findings, and (2) examining the role in the surveillance of disease in individuals exposed and non-exposed to FDA-approved disease-modifying therapies. A retrospective observational study was conducted within a single academic neuroimmunology clinic among individuals with an existing diagnosis of MS who had paired Octave® Multiple Sclerosis Disease Activity (MSDA) Test and MRI results prior to glucocorticosteroid exposure. Participants were evaluated in two cohorts: (1) individuals with acute clinical symptoms concerning for an exacerbation and (2) individuals seen for routine disease surveillance. The timing of the MSDA Test and MRI studies were quantified along with the association between the MSDA composite score and MRI-confirmed relapses. Sixty-six individuals with relapsing–remitting MS were included, with 33 being evaluated for acute neurological symptoms and 33 for routine disease surveillance. Among symptomatic individuals, MSDA testing preceded MRI in 79

Background Natalizumab is a recombinant humanized monoclonal antibody (mAb) against α4-integrin that is approved for relapsing forms of multiple sclerosis (MS). Natalizumab is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), and with disease reactivation after cessation of treatment that is likely mediated by an accumulation of pro-inflammatory lymphocytes in the blood during therapy. Alemtuzumab is a mAb against CD52 that reduces the number of peripheral lymphocytes. Rationale To determine if treatment with alemtuzumab after natalizumab reduces disease activity in patients with relapsing forms of MS. This review article will outline the rationale and objectives of the sequential natalizumab – alemtuzumab therapy in patients with relapsing forms of multiple sclerosis (SUPPRESS; ClinicalTrials.gov ID: NCT03135249) trial in greater detail than would be feasible in a manuscript that summarizes the study results. Methods The SUPPRESS trial is single arm, open-label, multicenter, efficacy pilot study that aims to establish a disease-free state over a 24-months period in patients who received the natalizumab- alemtuzumab sequential therapy. Participants will be recruited from four different sites. The primary endpoint is the annualized relapse rate (ARR) from the time of cessation of natalizumab treatment. Key secondary endpoint is freedom of relapse at 12-months, the number of new/enlarging T2 lesions on magnetic resonance imaging (MRI), and the number of gadolinium (Gd)-enhancing lesions on MRI. An exploratory endpoint is the Expanded Disability Status Scale (EDSS), retinal nerve fiber layer (RNFL) thickness assessment by optic coherence tomography (OCT) and assessment of quality of life (QoL) measures by a pre-defined, self-administered testing battery. To evaluate immunological effects, blood leukocytes will be collected and immunophenotyped by multi-parameter flow cytometry. Conclusion The SUPPRESS trial will provide clinical, imaging, and biological data to determine whether sequential natalizumab to alemtuzumab combination therapy establish a disease-free state in patients with relapsing forms of MS.

Background We report the development of asymptomatic progressive multifocal leukoencephalopathy in a patient with multiple sclerosis on natalizumab therapy. Progressive multifocal leukoencephalopathy often presents with debilitating neurologic symptoms. Very few cases have documented a completely asymptomatic course of the disease. Case presentation A 26-year-old white woman with multiple sclerosis was treated with natalizumab. She was diagnosed as having progressive multifocal leukoencephalopathy based on characteristic magnetic resonance imaging lesions after 27 infusions of natalizumab. She had no neurologic deficits at the time of diagnosis and John Cunningham virus in cerebrospinal fluid was detected at 15 copies/ml. She was initially treated with mefloquine and mirtazapine and remained asymptomatic for 3 months. She later developed worsening magnetic resonance imaging lesions related to immune reconstitution inflammatory syndrome. At that time, she received intravenously administered immunoglobulin and high-dose intravenously administered methylprednisolone with radiologic improvement of the lesions. Conclusions Our case report illustrates that early detection of asymptomatic progressive multifocal leukoencephalopathy and its subsequent treatment resulted in a benign clinical course. In consideration of the additional small number of cases of asymptomatic progressive multifocal leukoencephalopathy that have been reported, we conclude that routine magnetic resonance imaging surveillance is important for patients with multiple sclerosis who are at high risk for developing natalizumab-associated progressive multifocal leukoencephalopathy.