Search

The authors of the article titled "Exploring the association between weight loss-inducing medications and multiple sclerosis: insights from the FDA adverse event reporting system database" respond to a comment made by Dr. Khouri et al. They clarify that they used the term "inverse association" rather than "inverse causality" to highlight potential relationships that require further investigation, and not to suggest direct protective effects. They acknowledge the limitations of using the FDA adverse event reporting system database and the need for additional sensitivity analyses and controls. The authors also agree that integrating other methodological approaches, such as omics and in vitro testing, can provide more comprehensive insights, but this was beyond the scope of their current report. [Extracted from the article]

Background: Sleep is a central component of brain development. Preterm neonates follow an exclusive sleep-wake rhythm in a way that they can sleep up to 22 hours per day, 70% of which is spent during active sleep. Sleep can create a period of time for the production of active neurotransmitters, which can enhance brain development flexibility. Objectives: It is a matter of controversy whether the widespread use of nonsynchronized nasal intermittent positive pressure ventilation (NIPPV) in neonatal intensive care units and the concerns over the use of nonrespiratory support can affect the quantity and quality of the sleep-wake cycle (SWC). Therefore, the current study aimed to compare two types of intervention, nasal continuous positive airway pressure (nCPAP) and NIPPV, during the SWC. Methods: The present randomized controlled trial crossover study was conducted on neonates with 28 - 32 weeks of gestation receiving nCPAP who had been administered surfactant after being diagnosed with respiratory distress syndrome in Shahid Beheshti hospital in Isfahan, Iran, within March 2018 to August 2020. The SWC was monitored using cerebral function monitoring for all study participants. Results: The present study showed no significant difference between the number of SWCs during nCPAP and NIPPV. The duration of SWCs when participants received nCPAP was significantly higher than when they received NIPPV intervention. Rapid eye movement (REM) sleep duration was significantly longer during nCPAP respiratory support. Furthermore, NonREM sleep duration was significantly longer in nCPAP respiratory support. Conclusions: Noninvasive respiratory support modes can affect the SWC, with nCPAP being the favored in the present study. Nonetheless, further studies are required to be performed in this regard. [ABSTRACT FROM AUTHOR]

The differential diagnosis of suspected multiple sclerosis has been developed using data from North America, northern Europe, and Australasia, with a focus on White populations. People from minority ethnic and racial backgrounds in regions where prevalence of multiple sclerosis is high are more often negatively affected by social determinants of health, compared with White people in these regions. A better understanding of changing demographics, the clinical characteristics of people from minority ethnic or racial backgrounds, and the social challenges they face might facilitate equitable clinical approaches when considering a diagnosis of multiple sclerosis. Neuromyelitis optica, systemic lupus erythematous, neurosarcoidosis, infections, and cerebrovascular conditions (eg, hypertension) should be considered in the differential diagnosis of multiple sclerosis for people from minority ethnic and racial backgrounds in North America, northern Europe, and Australasia. The diagnosis of multiple sclerosis in people from a minority ethnic or racial background in these regions requires a comprehensive approach that considers the complex interplay of immigration, diagnostic inequity, and social determinants of health. [ABSTRACT FROM AUTHOR]

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared. Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug–AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR025) exceeded 1. Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug–AE association for rituximab and ocrelizumab were ear pruritus (ROR025: 47.53) and oral herpes (ROR025: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively). Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies. [ABSTRACT FROM AUTHOR]

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing–remitting MS (RRMS). Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level. Results: Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo. Conclusion: DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age. [ABSTRACT FROM AUTHOR]

Diffusion basis spectrum imaging (DBSI) models diffusion-weighted magnetic resonance imaging (MRI) signals as a combination of discrete anisotropic diffusion tensors and a spectrum of isotropic diffusion tensors. Here, we report the histopathological correlates of DBSI in the biopsied brain tissue of a patient with an inflammatory demyelinating lesion typical of multiple sclerosis (MS). Increased radial diffusivity (marker of demyelination), decreased fiber fraction (apparent axonal density), elevated nonrestricted isotropic fraction (marker of vasogenic edema), but unchanged axial diffusivity (marker of integrity of residual axons) seen in the lesion appeared consistent with histopathological findings of inflammatory demyelination with relative axonal sparing. Our report supports the application of DBSI as a biomarker in human studies of MS. [ABSTRACT FROM AUTHOR]

Byline: Mohammad. Harirchian, Mahdi. Maghbooli, Afsaneh. Shirani Choreoacanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder characterized by progressive onset of hyperkinetic movements and red cell acanthocytosis. The most striking [...]

Objective: To examine disease progression in ‘aggressive’ multiple sclerosis (MS), British Columbia, Canada (1980–2009). Methods: Aggressive (or ‘malignant’) MS was defined as Expanded Disability Status Scale (EDSS) ⩾6 within 5 years from onset. The first EDSS ⩾6 was termed ‘baseline’. Within 2, 3 and 5 years post-baseline, patients were categorized as follows: ‘worsened’ or ‘improved’, relative to baseline EDSS (the remainder exhibited no change or had no new scores). The associations between patient characteristics (sex, relapsing onset/primary progressive, onset age, onset symptoms, disease duration, cumulative prior relapses and baseline EDSS) and worsening in disability were examined longitudinally using logistic regression. Results: Of the 225/4341 (5.2%) aggressive/malignant MS patients, 134 (59.6%) were female, 167 (74.2%) were relapsing onset, 94 (41.8%) had received disease-modifying drugs at some point and the mean follow-up was 8.7 years. The proportion of patients who ‘worsened’ increased from 40.4% to 57.8%, while those who ‘improved’ varied little (range, 8.9%–10.2%). The odds of worsening increased with disease duration (adjusted odds ratio (AOR) = 1.36; 95% confidence interval (CI) = 1.22–1.52) and the presence of primary progressive (vs relapsing-onset) MS (AOR = 1.85; 95% CI = 1.01–3.38). Conclusion: Apart from disease duration and a primary progressive course, no clinically useful associations of subsequent disease worsening in patients with aggressive/malignant MS were identified. [ABSTRACT FROM AUTHOR]

Background Previous studies examining whether changes in the age of multiple sclerosis (MS) onset have occurred over time have yielded inconsistent findings. Objectives We investigated temporal trends in MS age at onset in three Canadian provinces and assessed the effect of controlling for equal observation time between birth year groups. Methods We included 9459 MS patients from MS clinic databases in British Columbia (BC, n=5423), Manitoba (MB, n=1419), and Nova Scotia (NS, n=2617). Birth years were grouped into five-year blocks and analysed via ANOVA and linear regression to assess temporal trends in age at onset. The complete cohort included all MS patients. The restricted cohort allowed comparable observation times for each birth year group and included patients who had reached age 40 and had MS onset at age 40 or younger. Results The complete cohort showed a steep decline in age at onset (averaging 2.0 years between birth year groups), from 37.0±10.8 years (1941-1945 births) to 28.0±6.4 years (1966-1970 births), p<0.001. In the restricted cohort (n=6003), only BC patients showed a significant decrease in the mean age at onset (averaging 0.3 years between birth year groups): 29.6±6.5 years (1941-1945 births) and 27.4±5.8 years (1966-1970 births), p<0.001. No significant decrease in age at onset was evident in the NS or MB restricted cohorts. Conclusions If the age at MS symptom onset has changed in the last four decades, shifts have been small. Temporal changes in age at MS onset between birth cohorts can be inflated without due consideration to comparable observation time. [ABSTRACT FROM AUTHOR]