Multiple Sclerosis, Fatigue, Expanded Disability Status Scale: A Cross-Sectional Exploration of Sleep Efficiency and Quantitative Sleep Parameters.

BACKGROUND: Poor sleep quality and sleep disorders are more prevalent in individuals with multiple sclerosis (MS) than in the general population. Poor sleep has been correlated with worse MS outcomes. Sleep efficiency (SE) is one of the most sensitive markers of sleep quality. There is very little written about SE and other polysomnography (PSG) parameters and MS measures. METHODS: This is a retrospective review of 280 consecutive individuals with MS evaluated by PSGs and other standardized MS measures over 13 years at a comprehensive MS center. In addition, the cohort was assessed with 2 fatigue scales, the Epworth Sleepiness Scale, and the Expanded Disability Status Scale. A comparison of means test (independent t test) and a correlation coefficient (r) were used. RESULTS: The PSG measures of SE and Total Sleep Time were significantly different between a group of individuals with MS with a disease duration of more than 5 years vs a group of individuals with MS with a disease duration less than or equal to 5 years. Prevalence of obstructive sleep apnea was 63%, higher than reported in the literature while the prevalence of moderate to severe obstructive sleep apnea was 33.4%, which was lower than reported. CONCLUSIONS: Longer disease duration and worse disability correlate with sleep quality as measured by SE.

Effectiveness of rituximab versus oral immunosuppressive therapies in neuromyelitis optica spectrum disorder in a racially diverse cohort of subjects: A single-center retrospective study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder characterized by severe relapses and high level of disability. In clinical trials of NMOSD, Black patients are under-represented, < 12%, compared to a relatively high prevalence of NMSOD in this population, 10/100,000. Despite the higher prevalence of NMOSD in Black and Asian patients, there is limited knowledge of the effectiveness of disease modifying treatments across racially diverse groups. OBJECTIVE: To assess the effectiveness of rituximab and oral immunosuppressive agents in a cohort of NMOSD patients, the majority of whom are Black, in a real-world, clinical setting. METHODS: A single-center retrospective study was conducted at the University of Chicago Medical Center. INCLUSION CRITERIA: (1) diagnosis according to the 2015 International Panel for NMO Diagnosis (IPND) Criteria, (2) positive anti-aquaporin-4 antibodies on ELISA or cell-based tests, (3) initiation of immunosuppressant therapy within 5 years of disease onset, (4) first-line treatment with rituximab, mycophenolate (MMF), or azathioprine (AZA). Patients with negative anti-AQP4 titers were excluded. Kaplan-Meier survival analysis was used to estimate proportion of relapse-free patients following initiation of first line immunosuppressive therapy. A Cox proportional hazards regression model assessed the association of risk of relapsing with first-line immunosuppressive treatments with and without adjustments of pre-specified factors (age at disease onset, duration of disease, sex, race, CNS location of relapse). RESULTS: 7 of 29 patients (24%) receiving rituximab experienced a relapse within the first 3 years of treatment vs. 13 of 23 patients (57%) receiving either AZA or MMF. Within the first 6 months of treatment, 2 (6.9%) patients treated with rituximab experienced a relapse vs. 7 (30.4%) patients treated with either MMF or AZA. In the 29 patients treated with rituximab, the 1-year and 3-year proportion of relapse-free patients was 88.8% and 70.9%. For the 23 patients treated with either AZA or MMF, the 1-year and 3-year proportion of relapse-free patients was 69.5% and 38.7%. In the univariate analysis, the risk of relapse was significantly higher in patients treated with AZA or MMF compared to those treated with rituximab (hazard ratio [HR] of 2.48 [0.99 - 6.21]; p = 0.046). CONCLUSION: In this real-world study involving a majority of Black NMOSD patients, rituximab was relatively more effective in preventing relapses within 3 years of therapy initiation than AZA and MMF. Rituximab remains an effective option for treating NMOSD, especially when there are delays in treatment due to access and economic issues associated with newer treatments.

Effectiveness of ocrelizumab on clinical and MRI outcome measures in multiple sclerosis across black and white cohorts: A single-center retrospective study.

OBJECTIVE: To examine differences in the therapeutic response to ocrelizumab in multiple sclerosis (MS) patients who self-identified as either White or Black, assessed longitudinally by expanded disability status scale (EDSS) progression and MRI brain volume loss. METHODS: MS subjects treated with ocrelizumab were retrospectively identified. Clinical data were available for 229 subjects (White 146; Black 83) and MRI data from for 48 subjects (White 31; Black 17). Outcome measures were changes in the EDSS and brain volume over time. EDSS were analyzed as raw scores, ambulatory (EDSS <5.0) vs. ambulatory with assistance (5.5 ≤ EDSS ≤ 6.5) status, and EDSS severity (< 3.0, 3.0-5.0, and > 5.5 ≤ 6.5). General linear mixed model was used for statistical analysis. FreeSurfer was used for volumetric analysis. RESULTS: The Black cohort had overrepresentation of females (78% vs. 62%, p = 0.013), lower age (median, 45 (IQR 39-51) vs. 49 (38-58), p = 0.08), lower Vitamin D levels (33 (21-45) vs. 40 (29-52), p = 0.002), and higher EDSS (4 (2-6) vs. 2.5 (1-6), p = 0.019). There was no progression of EDSS scores over the 2-year observation period. The covariates with significant influence on the baseline EDSS scores were older age, race, longer disease duration, prior MS treatment, and lower vitamin D levels. No differences were observed between the racial groups over time in the cortical, thalamic, caudate, putamen, and brainstem gray matter volumes nor in the cortical thickness or total lesion volume. CONCLUSION: In this real-world clinical and radiological study, ocrelizumab treatment was highly effective in stabilizing clinical and MRI measures of disease progression in Blacks and Whites, despite higher baseline disability in the Black cohort.

Analysis of the extent of limbic system changes in multiple sclerosis using FreeSurfer and voxel-based morphometry approaches.

BACKGROUND AND PURPOSE: The limbic brain is involved in diverse cognitive, emotional, and autonomic functions. Injury of the various parts of the limbic system have been correlated with clinical deficits in MS. The purpose of this study was to comprehensively examine different regions of the subcortical limbic system to assess the extent of damage within this entire system as it may be pertinent in correlating with specific aspects of cognitive and behavioral dysfunction in MS by using a fully automated, unbiased segmentation approach. METHODS: Sixty-seven subjects were included in this study, including 52 with multiple sclerosis (MS) and 15 healthy controls. Only patients with stable MS disease, without any relapses, MRI activity, or disability progression were included. Subcortical limbic system segmentation was performed using the FreeSurfer pipeline ScLimbic, which provides volumes for fornix, mammillary bodies, hypothalamus, septal nuclei, nucleus accumbens, and basal forebrain. Hippocampus and anterior thalamic nuclei were added as additional components of the limbic circuitry, also segmented through FreeSurfer. Whole limbic region mask was generated by combining these structures and used for Voxel-based morphometry (VBM) analysis. RESULTS: The mean [95% confidence interval] of the total limbic system volume was lower (0.22% [0.21-0.23]) in MS compared to healthy controls (0.27%, [0.25-0.29], p < .001). Pairwise comparisons of individual limbic regions between MS and controls was significant in the nucleus accumbens (0.046%, [0.043-0.050] vs. 0.059%, [0.051-0.066], p = .005), hypothalamus (0.062%, [0.059-0.065] vs. 0.074%, [0.068-0.081], p = .001), basal forebrain (0.038%, [0.036-0.040] vs. 0.047%, [0.042-0.051], p = .001), hippocampus (0.47%, [0.45-0.49] vs. 0.53%, [0.49-0.57], p = .004), and anterior thalamus (0.077%, [0.072-0.082] vs. 0.093%, [0.084-0.10], p = .001) after Bonferroni correction. Volume of several limbic regions was significantly correlated with T2 lesion burden and brain parenchymal fraction (BPF). Multiple regression model showed minimal influence of BPF on limbic brain volume and no influence of other demographic and disease state variables. VBM analysis showed cluster differences in the fornix and anterior thalamic nuclei at threshold p < 0.05 after adjusting for covariates but the results were insignificant after family-wise error corrections. CONCLUSIONS: The results show evidence that brain volume loss is fairly extensive in the limbic brain. Given the significance of the limbic system in many disease states including MS, such volumetric analyses can be expanded to studying cognitive and emotional disturbances in larger clinical trials. FreeSurfer ScLimbic pipeline provided an efficient and reliable methodology for examining many of the subcortical structures related to the limbic brain.

Narcolepsy type 1 comorbid with myasthenia gravis: possible immunological link.

Narcolepsy type 1 (NT1) has a probable autoimmune pathophysiology. Myasthenia gravis (MG) is an auto-antibody-mediated neuromuscular junction disorder. In the case report below we describe 2 women who were diagnosed with NT1 at ages 33 and 46 years, respectively. Both have seronegative MG and, although the MG was diagnosed earlier than the NT1, the symptoms of both conditions in both women started simultaneously. We discuss the potential mechanism linking these 2 conditions and the possibility of early detection of NT1 in patients with MG. CITATION: El Sammak S, Cipriani V, Sahni A, Attarian H. Narcolepsy type 1 comorbid with myasthenia gravis: possible immunological link. J Clin Sleep Med. 2022;18(7):1889-1890.

Predictive model for bacterial co-infection in patients hospitalized for COVID-19: a multicenter observational cohort study.

OBJECTIVE: The aim of our study was to build a predictive model able to stratify the risk of bacterial co-infection at hospitalization in patients with COVID-19. METHODS: Multicenter observational study of adult patients hospitalized from February to December 2020 with confirmed COVID-19 diagnosis. Endpoint was microbiologically documented bacterial co-infection diagnosed within 72 h from hospitalization. The cohort was randomly split into derivation and validation cohort. To investigate risk factors for co-infection univariable and multivariable logistic regression analyses were performed. Predictive risk score was obtained assigning a point value corresponding to ß-coefficients to the variables in the multivariable model. ROC analysis in the validation cohort was used to estimate prediction accuracy. RESULTS: Overall, 1733 patients were analyzed: 61.4% males, median age 69 years (IQR 57-80), median Charlson 3 (IQR 2-6). Co-infection was diagnosed in 110 (6.3%) patients. Empirical antibiotics were started in 64.2 and 59.5% of patients with and without co-infection (p = 0.35). At multivariable analysis in the derivation cohort: WBC ≥ 7.7/mm3, PCT ≥ 0.2 ng/mL, and Charlson index ≥ 5 were risk factors for bacterial co-infection. A point was assigned to each variable obtaining a predictive score ranging from 0 to 5. In the validation cohort, ROC analysis showed AUC of 0.83 (95%CI 0.75-0.90). The optimal cut-point was ≥2 with sensitivity 70.0%, specificity 75.9%, positive predictive value 16.0% and negative predictive value 97.5%. According to individual risk score, patients were classified at low (point 0), intermediate (point 1), and high risk (point ≥ 2). CURB-65 ≥ 2 was further proposed to identify patients at intermediate risk who would benefit from early antibiotic coverage. CONCLUSIONS: Our score may be useful in stratifying bacterial co-infection risk in COVID-19 hospitalized patients, optimizing diagnostic testing and antibiotic use.

Clinical Characteristics of Multiple Sclerosis in African-Americans.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that affects nearly 1 million people in the USA and has the potential to profoundly affect physical ability and income potential at a young age. Since a landmark paper was published in 2014, few studies have looked at differences in MS disease characteristics between African-American and Caucasian patients. RECENT FINDINGS: African-American patients often have a more severe MS disease course, as well as biomarker data which can portend a worse prognosis. While the sample sizes are usually quite small, subgroup analyses of African-American patients have been performed to evaluate efficacy of disease-modifying treatments as compared with the entire study population, made up of primarily Caucasians. In an era where we strive for personalized medicine, understanding racial differences in MS may help us better treat African-American patients in the future.

Reduction in ocrelizumab-induced infusion reactions by a modified premedication protocol.

BACKGROUND: Ocrelizumab is a monoclonal antibody directed against CD20+ B cells that is approved for MS. The most common side effect is infusion-associated reactions (IARs). This study examines whether a modified premedication protocol reduces incidence of IARs and further examines predictors of IARs. METHODS: Patients took cetirizine 10 mg, ranitidine 75 mg, and increased hydration the night before the ocrelizumab infusion. This regimen was repeated the next day prior to arrival. Just prior to the infusion, patients were pretreated with IV diphenhydramine 50 mg, IV methylprednisolone 125 mg, and oral acetaminophen 650 mg. Rates of IARs with this modified protocol were compared to patients who had received only pretreatment medications. RESULTS: 207 patients received ocrelizumab. With the modified premedication protocol, we found significant decreased odds of IARs (OR 0.40, p = 0.024, 95% CI (0.18, 0.88). Among the baseline characteristics, there was a significant reduction of IARs with increasing age (OR 0.94, p = 0.001) and male sex (OR 0.34, p = 0.034). Body mass index (BMI) increased the odds of IARs (OR 1.07, p = 0.029). Race and smoking status did not affect IARs. CONCLUSION: The modified premedication protocol described herein significantly decreases rates of IARs by 60% and suggests that the additional premedication regimen is beneficial. Age and male sex are protective for IARs while BMI is a risk factor for IARs.