Compassionate-use pocapavir and immunoglobulin therapy for treatment of rituximab-associated enterovirus meningoencephalitis.

A 71-year-old woman previously on rituximab treatment for rheumatoid arthritis presented with 2 years of progressive neurologic symptoms. She was found to have persistent hypogammaglobulinemia and B cell depletion despite rituximab discontinuation a year prior. MRI revealed diffuse meningeal enhancement along the entire neuroaxis. LP showed a CSF lymphocytic pleocytosis, elevated protein, and presence of enterovirus by PCR. The patient was hospitalized several times for progressive clinical and radiologic decline, though she had transient improvements following treatment with immunoglobulin therapy. Her CSF remained positive for enterovirus PCR for at least 12 months. Though two brain biopsies were non-diagnostic, pan-Enterovirus was ultimately identified using a high-throughput next-generation sequencing technique. She was treated with compassionate-use pocapavir with clinical stabilization at 4-month follow-up; however, she expired 8 months later from a bacterial pneumonia.

Evaluation of ocrelizumab in older progressive multiple sclerosis patients.

BACKGROUND: Seminal trials evaluating anti-CD20 therapy in progressive MS primarily found benefit in younger, less-disabled patients with more inflammatory disease activity. The risks and benefits of ocrelizumab use in older patients with progressive froms of MS are not known. METHODS: Retrospective chart review was performed for patients older than 55 with primary or secondary progressive MS at the time of ocrelizumab initiation. Clinical endpoints from 2 years prior to anti-CD20 therapy served as a within-subject control. RESULTS: Data was reviewed for 56 patients older than the age of 55 at the time of ocrelizumab initiation. Of 37 patients with 2-years of follow up on ocrelizumab, 40%(n=15) experienced confirmed disability progression (CDP) while 60% (n=22) remained stable or improved. 24 patients had data available for the within-subject control; for these patients, median age was 67, baseline EDSS 6.3, and disease duration 20.5 years. Prior to anti-CD20 therapy, 58% (n=14) of patients remained stable and 42% (n=10) experienced CDP. After ocrelizumab initiation, 71% (n=17) remained stable and 29% (n=7) experienced CDP. There was no difference between CDP (p=0.54) or change in EDSS (p=0.09) between time periods. Ocrelizumab was well tolerated and no difference in infection rate was seen using the within-subject control. CONCLUSIONS: We found no difference in clinical endpoints for patients on ocrelizumab compared to prior to anti-CD20 therapy; however, we could not exclude a modest effect given our sample size. Larger trials are needed to evaluate ocrelizumab use in this understudied MS subpopulation.

Potential Neurologic Manifestations of COVID-19.

PURPOSE OF REVIEW: Neurologic complications are increasingly recognized in the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This coronavirus is related to severe acute respiratory syndrome coronavirus (SARS-CoV) and other human coronavirus-related illnesses that are associated with neurologic symptoms. These symptoms raise the question of a neuroinvasive potential of SARS-CoV-2. RECENT FINDINGS: Potential neurologic symptoms and syndromes of SARS-CoV-2 include headache, fatigue, dizziness, anosmia, ageusia, anorexia, myalgias, meningoencephalitis, hemorrhage, altered consciousness, Guillain-Barré syndrome, syncope, seizure, and stroke. In addition, we discuss neurologic effects of other coronaviruses, special considerations for management of neurologic patients, and possible long-term neurologic and public health sequelae. SUMMARY: As SARS-CoV-2 is projected to infect a large part of the world's population, understanding the potential neurologic implications of COVID-19 will help neurologists and others recognize and intervene in neurologic morbidity during and after the pandemic of 2020.

Central nervous system disease with JC virus infection in adults with congenital HIV.

OBJECTIVE: The aim of this study was to describe the natural history of individuals with congenital HIV who develop JC virus (JCV) infection of the central nervous system (CNS). METHODS: We retrospectively evaluated individuals with congenital HIV who met criteria for progressive multifocal leukoencephalopathy (PML) or JCV granule cell neuronopathy (JCV GCN) at three major healthcare centres in the northeast USA. Data on adherence to combined antiretroviral therapy (cART), neurologic symptoms, serum markers of immunity and HIV infection, cerebrospinal fluid (CSF) analyses, radiographic features, modified Rankin Scale (mRS) scores and survival were collected from the electronic medical record up to a censoring date of 1 August 2020. RESULTS: Among 10 adults with congenitally acquired HIV, nine were diagnosed with definitive PML and one was diagnosed with probable JCV GCN. Individuals presented at the time of their PML or JCV GCN diagnosis with a mean mRS of 2.0 (standard deviation 1.0). A premorbid mRS was documented for six patients and was zero in all cases. The most common risk factor was confirmed cART nonadherence in nine individuals. Five individuals with PML and one with JCV GCN died, with a latency from symptom onset to death of approximately 3 months for three individuals, and approximately 2 years for the remaining two. CONCLUSION: Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals.