Progressive multifocal leukoencephalopathy in anti-CD20 and other monoclonal antibody (mAb) therapies used in multiple sclerosis: A review.

Progressive multifocal leukoencephalopathy (PML) is a subacute CNS inflammatory disease seen primarily among immunocompromised patients. It is caused by the JC virus (JCV), a polyomavirus that otherwise induces an insidious, latent infection in the general population. This reactivated disease is characterized by cognitive and behavioral changes, language disturbances, motor weakness, or visual deficits. Median survival in patients with AIDS is approximately 2-4 months, and mortality is high (around 4% in untreated AIDS). Recent scientific developments indicate that PML can also be associated with the increased utilization of monoclonal antibody (mAb) immunotherapy. In fact, PML has been witnessed with several mAbs, including natalizumab in multiple sclerosis, rituximab for lymphoma or lupus, efalizumab for psoriasis, and ofatumumab in leukemia; this leads us to the risk reassessment of PML due to treatment-induced immunosuppression. The range of clinical presentations of JCV-related disease has transformed over time and can pose significant challenges to the current diagnostic criteria. Most cases with PML suffer from persistent and irreversible neurological conditions, and some with chronic, low-level viral replication in the CNS. With the expanded use of mAbs for various autoimmune and lymphoproliferative disorders, we are now seeing this infection in non-HIV patients on drugs such as natalizumab, rituximab, and other recently approved therapies. This article aims to review the relationship between the incidence of PML and all four mAbs used in the treatment of MS. Currently, at least 18 FDA-approved medications carry label warnings for PML;to this date, no treatment has been convincingly effective.

Seizure Control in Patients with Epilepsy during the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Objective To investigate seizure control in patients with epilepsy during the coronavirus disease 2019 (COVID-19) pandemic. Method A systematic review and meta-analysis was conducted, and the MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases were comprehensively searched for relevant studies. Studies that reported seizure control in patients with epilepsy during the COVID-19 pandemic were included. Pooled proportions with 95% confidence intervals (CIs) of patients with epilepsy who experienced seizure worsening during the COVID-19 pandemic were assessed using a random-effects model. The quality of the assessment for each study, heterogeneity between the studies, and publication bias were also evaluated. Subgroup analyses were performed, excluding studies with reports of seizures worsening from caregivers. Results A total of 24 studies with 6,492 patients/caregivers were included in the meta-analysis. The pooled proportion of seizure worsening was 18.5% (95% CI: 13.9-23.6; I2=96%; p<0.01). The pooled proportion of seizure worsening in the subgroup analysis was 18.9% (95% CI: 13.5-25.0; I2=96%; p<0.01). Conclusion Although the heterogeneity was high, our results showed a relatively high incidence of seizure worsening during the COVID-19 pandemic. During the COVID-19 pandemic, physicians should be aware of the likelihood of worsening seizures in patients with epilepsy.

Single-center experience on progressive multifocal leukoencephalopathy (PML) cases, neuroimaging relevance, and management at West Virginia University (WVU).

Progressive multifocal leukoencephalopathy (PML) is an increasingly common and rapidly fatal demyelinating infection of central nervous system caused by the highly prevalent John Cunningham (JC) virus in immunocompromised individuals belonging to all age groups and genders. Human immunodeficiency virus (HIV) is the most common predisposing factor among other immunodeficient conditions leading to reactivation and multiple neurological symptoms. It has varied findings on magnetic resonance imaging (MRI) and diagnosis is confirmed by positive JC virus in cerebrospinal fluid (CSF). We report 12 confirmed cases of PML from a single academic center. We comprehensively described clinical presentations, risk factors, CSF and neuroimaging findings, treatment and outcome for these cases of PML, a rare disease. The cases were almost equivalently distributed among young and old age groups and both genders. Positive JC virus on CSF was present in the majority of cases along with mild to severe reduction in lymphocyte counts. Significant MRI changes were present in all cases ranging from T2 hypertense signals to white matter lesions in various regions. Treatment with the reversion of immune-modulators, optimization of antiviral therapy (ART), plasmapheresis (PLEX), IVIG, Mirtazapine, oral steroids, and others was started as soon as the diagnosis was made in the majority of the cases. However, PML is a rapidly fatal illness and hence, survival was only seen in 4 cases in our study. The objective of this article is to highlight the importance of early diagnosis of PML with CSF findings and neuroimaging, early reversion of immunosuppressive medications, and careful monitoring and treatment of HIV cases with goals to reduce mortality, long-term morbidity, and deficits.

Neuroimaging and CSF Findings in Patients with Autoimmune Encephalitis: A Report of Eight Cases in a Single Academic Center.

Autoimmune Encephalitis (AIE) is a rare and complex group of disorders wherein the body's immune system attacks and causes inflammatory changes in the central nervous system (CNS). It presents with altered mental status and a diverse range of typical and atypical symptoms and neuroimaging and cerebrospinal fluid (CSF) findings. The objective of this article is to highlight the importance of early identification of neurological symptoms, prompt diagnosis with neuroimaging and CSF findings, and timely management for early and complete resolution of the disease and long-term benefits. We report eight AIE cases from a single academic center confirmed by the presence of specific serum and CSF autoantibodies. The patients were mostly women, with imaging findings showing T2-weighted (T2), fluid-attenuated inversion recovery (FLAIR), hyperintensities/changes in cortical/mesio-temporal regions on a magnetic resonance imaging (MRI), and delta brush wave patterns or epileptogenic patterns on an electroencephalogram (EEG). Among the antibodies, the N-methyl-D-aspartate receptor (NMDA-R) antibody (AB) was most frequently identified, and CSF lymphocytosis and elevated CSF glucose were found in majority of the cases, CSF pleocytosis and elevated protein only in a minority of patients, and oligoclonal bands (OCBs) only in NMDA-R encephalitis. Early treatment with intravenous immune globulin (IVIG), steroids, plasmapheresis (PLEX), and rituximab was started in most cases, and all of them responded well and survived, but some had residual symptoms or relapses.

Hypothetical Rectal Microbicide Acceptability and Factors Influencing It among Men Who Have Sex with Men in Tianjin, China.

OBJECTIVES: To measure potential acceptability of rectal microbicides and to explore factors likely to affect their acceptability among men who have sex with men (MSM). METHODS: Cross-sectional and retrospective surveys were conducted in this study. A questionnaire and a scale were used to measure the acceptability score for physical and functional characteristics of hypothetical rectal microbicides. We also evaluated the involvement of other factors such as sexual behaviors, social context, etc. RESULTS: MSMs we interviewed showed a high acceptability to rectal microbicides, indicated by the mean acceptability score of 2.92 (SD, 0.54, scale of 1-4). The results also suggested that microbicides were preferred in a cream form that can moisten and lubricate the rectum, prevent HIV infection and go unnoticed by their partners. Multivariate analysis showed that the microbicides acceptability varied significantly by education level (ß = 0.135; P = 0.028), having casual partners (ß = 0.174; P = 0.007), frequency of lubricant use (ß = 0.134; P = 0.031), history of HIV test (ß = 0.129; P = 0.036), willingness to use lubricant (ß = 0.126; P = 0.045), locus of control by partners regarding STI infection (ß = 0.168; P = 0.009). CONCLUSIONS: A positive response to rectal microbicides among MSMs was found in our study, suggesting that rectal microbicides might have a potential market in MSMs and they might play an important role in HIV/STIs prevention as a supplement. Further studies may be considered to combine the acceptability study with clinical research together to understand the true feelings of MSMs when they use the products.