Inflammatory vaginitis in four B-cell suppressed women with Multiple Sclerosis.

B-cell depleting therapies are effective in multiple sclerosis (MS) and are widely used (Hauser et al., 2017). Inflammatory vaginitis (IV), characterized by unexplained vaginal symptoms including mucopurulent discharge, pain, irritation, and dyspareunia, has been reported in one MS patient on ocrelizumab (Filikci and Jensen, 2022), and to be present in 3.5 % of women on rituximab for autoimmune diseases (Yockey et al., 2021). We report here four cases of IV in B cell depleted women with MS. B-cell reconstitution was temporally associated with improvement of IV symptoms. Further investigation and vigilance for this potential treatment emergent adverse event affecting sexual and reproductive health of women with MS is needed.

Vaccine-breakthrough SARS-CoV-2 infections in people with multiple sclerosis and related conditions: An observational study by the New York COVID-19 Neuro-Immunology Consortium (NYCNIC-2).

BACKGROUND: People with MS (PwMS) and related conditions treated with anti-CD20 and S1P modulating therapies exhibit attenuated immune responses to SARS-CoV-2 vaccines. It remains unclear whether humoral/T-cell responses are valid surrogates for postvaccine immunity. OBJECTIVE: To characterize COVID-19 vaccine-breakthrough infections in this population. METHODS: We conducted a prospective multicenter cohort study of PwMS and related CNS autoimmune conditions with confirmed breakthrough infections. Postvaccination antibody response, disease-modifying therapies (DMTs) at the time of vaccination, and DMT at the time of infection were assessed. RESULTS: Two hundred nine patients had 211 breakthrough infections. Use of anti-CD20 agents at time of infection was associated with increased infection severity (p = 0.0474, odds ratio (OR) = 5.923) for infections during the Omicron surge and demonstrated a trend among the total cohort (p = 0.0533). However, neither use of anti-CD20 agents at the time of vaccination nor postvaccination antibody response was associated with hospitalization risk. Anti-CD20 therapies were relatively overrepresented compared to a similar prevaccination-era COVID-19 cohort. CONCLUSION: Use of anti-CD20 therapies during vaccine breakthrough COVID-19 infection is associated with higher severity. However, the attenuated postvaccination humoral response associated with anti-CD20 therapy use during vaccination may not drive increased infection severity. Further studies are necessary to determine if this attenuated vaccine response may be associated with an increased likelihood of breakthrough infection.

A 53-year-old woman with a rapidly progressive, non-enhancing left frontotemporal lesion.

Fifty-three-year-old woman presented with chronic, episodic headache.

Hypogonadism in men with multiple sclerosis: Prevalence and clinical associations.

It has been hypothesized that multiple sclerosis (MS) has hormonal influences, and testosterone may have anti-inflammatory functions in this context. Given prior reports of lower testosterone levels in men with MS in archival serum samples, we evaluated the prevalence of hypogonadism in the clinical setting and its association with disability in men with MS. Subjects were screened for symptoms of hypogonadism using a clinical instrument, and those with positive screens had total and free morning testosterone levels checked. Of the 64 subjects who were screened, 50 (78%) had positive results, and 46 (92%) had morning testosterone levels checked. Among the latter, 5 were found to have testosterone levels below lower limit of normal. Other than the expected inverse relation with BMI, testosterone did not correlate with demographic or disease related factors. Baseline testosterone did not predict risk of EDSS or T25-FW progression or future MRI activity.

Successful treatment of progressive multifocal leukoencephalopathy with recombinant interleukin-7 and maraviroc in a patient with idiopathic CD4 lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is a rapidly progressive, often fatal viral infection of the brain without a known treatment. Recently, case reports have demonstrated survival from PML with therapies that improve cell-mediated immunity, including interleukin-7 (IL-7) or the chemokine receptor type 5 (CCR5) antagonist, maraviroc (MVC). We present the first known case of a patient with PML successfully treated with both IL-7 and MVC. A 63-year-old woman presented to our center with a 6-month history of progressive left hemiparesis. Extensive laboratory testing was negative except for a severe CD4 lymphocytopenia (140/µL). Serial brain MRIs done prior to presentation revealed an enlarging, non-enhancing T2-hyperintense lesion in the right fronto-parietal white matter. PML was confirmed through detection of the JC virus by PCR in the cerebrospinal fluid and by brain biopsy, and she was started on mirtazapine and mefloquine. She continued to deteriorate and was then given a course of recombinant IL-7. Though she remained clinically stable after IL-7 treatment and serum JCV PCR decreased from 1000 copies/mL to a nadir of 238 copies/mL, a repeat MRI 3 months later showed lesion enlargement. MVC was then initiated. Now, more than 2 years after initial presentation, she remains stable and serum JCV PCR is undetectable. This case demonstrates successful treatment of PML in a patient with idiopathic CD4 lymphocytopenia and highlights the potential benefits of IL-7 and MVC in the treatment of PML. Treatment with IL-7 and MVC led to clinical stability and improvement in JC virus titers.

Risk of venous thromboembolism in neuromyelitis optica patients hospitalized for acute relapse.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. OBJECTIVE: To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. METHODS: Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. RESULTS: A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 ( p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. CONCLUSION: NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis.