Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline.

BACKGROUND: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. OBJECTIVE: To screen for cognitive impairment early in the course of POMS and analyze predictive factors. METHODS: Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free. RESULTS: At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing (n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT. CONCLUSION: Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.

Protean Neurologic Manifestations of Two Rare Dermatologic Disorders: Sweet Disease and Localized Craniofacial Scleroderma.

PURPOSE OF REVIEW: To describe diverse neurologic and neuroradiologic presentations of two rare, immunologically mediated skin conditions: Sweet disease and localized scleroderma (morphea). RECENT FINDINGS: Core syndromes of neuro-Sweet disease (NSD) are steroid responsiveness, recurrent meningitis, and encephalitis. Focal neurologic, neuro-vascular, and neuro-ophthalmologic syndromes have been reported recently in NSD. A variety of steroid-sparing treatments and biologics have been used for relapsing NSD. Localized craniofacial scleroderma is associated with seizures, headaches, and, less commonly, focal deficits and cognitive decline. Immunosuppressive therapy may be required in patients with disease progression; some refractory cases have responded to IL-6 inhibition. Our review provides an up-to-date reference for neurologists faced with a patient with a history or skin findings consistent with Sweet disease or localized scleroderma. We hope that it will stimulate collaborative studies aimed at unraveling the pathogenesis of these disorders, better characterization of their neurologic manifestations, and discovery of optimal therapeutic solutions.

Antibody response to SARS-CoV-2 vaccination following typical and three-dose dosing schedules in multiple sclerosis patients treated with disease modifying therapies.

BACKGROUND: Immunizations against SARS-CoV-2 virus are now available and recommended, but the effect of additional dosing of the vaccine in immunocompromised MS patients is unknown. METHODS: Part I - A retrospective chart review of MS patients who were vaccinated against SARS-CoV-2 and tested commercially for Sars Covid Spike Protein Antibody between March 1 - June 30, 2021. Part II - Patients on treatment with anti-CD20 infusion medications who received a SARS-CoV-2 third mRNA vaccination dose August 13, 2021 - October 31, 2021 and were subsequently commercially tested for Sars Covid Spike Protein Antibody. RESULTS: Part I - A total of N = 208 MS patients, age range 23-76 were tested, with 49% (102/208) demonstrating a humoral response. Stratified by DMT type, patients treated with interferon, teriflunomide, or a remote history of alemtuzumab (>2 years since last DMT) yielded 100% measurable antibodies; >90% amongst patients treated with natalizumab, fumarates and glatiramer acetate; <50% measurable antibodies following vaccination in S1P modulators and anti-CD20 treated patients. Subsequently, in Part II - N = 40 patients on anti-CD20 treatments (33 ocrelizumab, 7 rituximab) who received 3 mRNA vaccinations yielded 20% humoral response. CONCLUSIONS: MS patients are able to mount a humoral vaccine response to SARS-CoV-2, irrespective of the vaccine type administered; patients treated with S1P modulators and anti-CD20 agents are least likely to mount such a response with a typical dosing schedule. Patients treated with ocrelizumab/rituximab show a similar modest humoral immune system benefit following three doses as with standard dosing.

The presence of SARS-CoV2 antibodies in MS patients.

BACKGROUND: The COVID-19 pandemic has raised novel concerns for people living with MS regarding their safety. METHODS: Observational study of patients at a single comprehensive community MS center. RESULTS: 48 patients with MS were suspected of developing COVID-19 March to May 2020; 2 died. Of the remainder, 17 were tested for COVID-19 antibodies as part of routine care. Average age of this subgroup was 49.8y ± 11.3 (age range 32-67), 76% female. 65% were treated with an anti-CD20 drug, 12% untreated, and 6% each received glatiramer acetate, interferon, natalizumab, or teriflunomide. 59% of patients were antibody negative. CONCLUSIONS: The low incidence of SARS CoV2 antibodies following infection suggests that certain DMTs may alter SARS CoV2-Ab response or persistence.

The impact of medications and medical comorbidities on sexual function in people with epilepsy.

OBJECTIVE: People with epilepsy experience increased rates of sexual dysfunction, often affecting quality of life. Sexual dysfunction may result from the underlying disorder, antiseizure or other medications, or comorbid psychosocial factors. This study evaluated the incidence and clinical associations of sexual dysfunction in adult epilepsy patients. METHODS: 89 epilepsy patients 18 years and older admitted to the New York University Comprehensive Epilepsy Center epilepsy monitoring unit between 2016 and 2018 completed a survey on sexual functioning. The survey included demographic, clinical, and sexual functioning information with a validated measure of sexual function (the Arizona Sexual Experiences Scale (ASEX). RESULTS: Of 89 surveys completed, 15 (16.9 %) patients had discussed sexual functioning with a medical professional and 20 (22.5 %) reported sexual dysfunction. For the group, the mean ASEX score was 13.6 (SD 4.8). 59 (66.3 %) participants reported not being asked about sexual health by their doctor or nurse practitioner in the last year. The two independent predictors of sexual dysfunction were self-identifying as overweight/obese (OR 6.1, CI 1.4-26.5, P = 0.02) or taking strong enzyme-inducing antiseizure medications (OR 7.8, CI 1.4-44.9, P = 0.02). Other factors such as age, relationship status, duration of epilepsy, the presence of depression or anxiety, cardiovascular risk factors, and opioid/stimulant use, did not predict sexual dysfunction. SIGNIFICANCE: Our study showed that sexual dysfunction is common in epilepsy patients but infrequently discussed by medical professionals. Two modifiable risk factors, being overweight or taking strong enzyme-inducing antiseizure medications, were independently associated with sexual dysfunction, suggesting interventions to potentially improve sexual health.

Serious safety events in rituximab-treated multiple sclerosis and related disorders.

INTRODUCTION: Studies investigating rates and risk factors for serious safety events (SSEs) during rituximab treatment of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and related disorders are limited. METHODS: Rituximab-treated patients with MS, NMOSD, or related disorders at the Rocky Mountain and New York University MS Care Centers were included. The follow-up period was defined as the time from the initial dose of rituximab up to 12 months of last dose of rituximab or ocrelizumab (in patients who switched). Clinician-reported and laboratory data were retrospectively collected from electronic medical records. RESULTS: One-thousand patients were included comprising 907 MS, 77 NMOSD, and 16 related disorders. Patients had a mean follow-up of 31.1 months and a mean cumulative rituximab dose of 4012 mg. Of the 169 patients who switched to ocrelizumab, the mean ocrelizumab dose was 1141 mg. Crude incidence rate per 1000 person-years (PY) for lymphopenia was 19.2, neutropenia 5.6, and hypogammaglobulinemia 17.8. Infections resulting in either hospitalization, IV antibiotics, or using antibiotics ≥14 days occurred at a rate of 38.6/1000 PY. Risk factors for infection were duration of therapy, male gender, increased disability, prior exposure to immunosuppression/chemotherapy, lymphopenia, and hypogammaglobulinemia. Particularly, wheelchair-bound patients had 8.56-fold increased odds of infections. Crude incidence rates of malignant cancer were 3.5, new autoimmune disease 2.3, thromboembolic event 3.1, and mortality of 5.4 per 1000 PY. INTERPRETATION: Rates of SSEs in patients with MS, NMOSD, and related disorders were low. Through properly assessing risk:benefit of B-cell depleting therapy in neuroinflammatory disorders and continual monitoring, clinicians may decrease the risk of serious infections.