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Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease with heterogeneous clinical presentations and variable long-term disability accumulation. There are currently no standard criteria to accurately predict disease outcomes. In this study we investigated the cross-sectional relationship between disease phenotype and immune-modulating cytokines and chemokines in cerebrospinal fluid (CSF). We analyzed CSF from 20 DMT-naïve MS patients using Olink Proteomics’ Target 96 Inflammation panel and correlated the resulting analytes with respect to (1) disease subtype, (2) patient age and sex, (3) extent of clinical disability, and (4) MRI segmental brain volumes. We found that intrathecal IL-4 correlated with higher Expanded Disability Status Scale (EDSS) scores and longer 25-foot walk times, and CD8A correlated with decreased thalamic volumes and longer 9-hole peg test times. Male sex was associated with higher FGF-19 expression, and Tumefactive MS with elevated CCL4. Several inflammatory markers were correlated with older age at the time of LP. Finally, higher intrathecal IL-33 correlated with increased MS lesion burden and multi-compartment brain atrophy. This study confirms immune heterogeneity underlying CSF profiles in MS, but also identifies several inflammatory protein biomarkers that may be of use for predicting clinical outcomes in future algorithms.

Despite widespread screening and active management of syphilis infection, the rate of secondary and tertiary syphilis has increased over the past decade in the United States, especially with human immunodeficiency virus co-infection. We report a case of ischemic strokes in the middle cerebral artery (MCA) territory with focal stenosis of the left M1 segment of the MCA resulting from neurosyphilis with manifestation of subacute intermittent right-sided hemi-body numbness and transient word finding difficulties in a young adult with no prior known history of syphilis or significant cerebrovascular risk factors. A diagnostic cerebral angiogram was done which was initially concerning for possibility of reversible cerebral vasoconstriction syndrome (RCVS). The serum Treponema pallidum RPR testing resulted positive (1:32 titer) as well as subsequent reactive cerebrospinal fluid (CSF) VDRL test (ratio, 1:8). The patient was treated with intravenous ceftriaxone as well as verapamil and recovered without any residual deficits. To the best of our knowledge, this is the first reported evidence of possible RCVS in a case of neurosyphilis and related ischemic stroke. This case underscores the importance of evaluation for syphilis in young patients with fewer known vascular risk factors, who present with an ischemic stroke. Given the higher rates of stroke recurrence in neurosyphilis relative to few other stroke risk factors, early diagnosis, and treatment is furthermore essential to prevent disease progression.

Background . Most people with multiple sclerosis (MS) want to be involved in medical decision making about disease-modifying therapies (DMTs), but new approaches are needed to overcome barriers to participation. Objectives . We sought to develop a shared decision-making (SDM) tool for MS DMTs, evaluate patient and provider responses to the tool, and address challenges encountered during development to guide a future trial. Methods . We created a patient-centered design process informed by image theory to develop the MS-SUPPORT SDM tool. Development included semistructured interviews and alpha and beta testing with MS patients and providers. Beta testing assessed dissemination and clinical integration strategies, decision-making processes, communication, and adherence. Patients evaluated the tool before and after a clinic visit. Results . MS-SUPPORT combines self-assessment with tailored feedback to help patients identify their treatment goals and preferences, correct misperceptions, frame decisions, and promote adherence. MS-SUPPORT generates a personal summary of their responses that patients can share with their provider to facilitate communication. Alpha testing (14 patients) identified areas needing improvement, resulting in reorganization and shortening of the tool. MS-SUPPORT was highly rated in beta testing (15 patients, 4 providers) on patient-provider communication, patient preparation, adherence, and other endpoints. Dissemination through both patient and provider networks appeared feasible. All patient testers wanted to share the summary report with their provider, but only 60% did. Limitations . Small sample size, no comparison group. Conclusions . The development process resulted in a patient-centered SDM tool for MS that may facilitate patient involvement in decision making, help providers understand their patients’ preferences, and improve adherence, though further testing is needed. Beta testing in real-world conditions was critical to prepare the tool for future testing and inform the design of future studies.

This article reviews and discusses the approved and emerging therapies for multiple sclerosis (MS). MS is a chronic and disabling immune-mediated disease of the central nervous system (CNS) that affects mainly young adults. MS imposes a huge economic burden on healthcare systems and the society. Although the last 20 years have brought a continuous expansion in therapeutic options, there are still unmet needs in MS management. Available MS drugs have varying degrees of efficacy in reducing relapse risk. The long-term term effects of these treatments are incompletely known. New therapies, along with variations of currently available treatments, may prove more effective and tolerable than the available drugs. Treatments for MS differ with respect to the mode of administration, tolerability and likelihood of treatment adherence, side effects, and risk of major toxicity. The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone). The place of each drug in the therapeutic algorithm is dependent on its specific risk-benefit profile. Patients' clinical and paraclinical phenotypes and biomarker profile may help to elucidate disease subtypes and response to therapy in the future, thus allowing treatment individualization.

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.

Background: West Nile Virus (WNV) is an arthropod-borne flavivirus which causes epidemic spread by mosquito bites and its incidence has been ever increasing. Though less than 1% of infections lead to severe neurological involvement, meningoencephalitis is the major cause of morbidity and mortality. There has been little data on the presentation of seizures or non-convulsive status in WNV. We aim to highlight (1) the presentation of nonconvulsive status in WNV infection and (2) value of electroclinical monitoring in its management. Methods: Literature research was conducted using Medline/Pubmed for identifying presenting symptoms in WNV encephalitis. Common and uncommon presentations are described. We report two cases of WNV encephalitis with status epilepticus and review electroencephalographic changes and discuss complexities in its management. Pertinent literature on the investigative findings, management and the outcomes is presented. Results: Electroclinical monitoring revealed patterns consistent with non convulsive status. Antiepileptic medications effectively aborted seizures resulting in clinical improvement. Both patients recovered with minimal neurological impairment and were discharged to rehabilitation facilities. Conclusions: Neurological complications in the form of seizures due to WNV may be more common than realized. Clinicians should have a high index of clinical suspicion for nonconvulsive status when dealing with WNV infected patients presenting with altered sensorium. Continuous electroencephalographic monitoring is crucial in their management.