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Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: For the last 20 years, the amyloid‐beta (Aβ) cascade hypothesis has been dominant in the research of disease‐modifying therapeutics, with spent of financial and clinical resources in potential drugs targeting Aβ peptide production or clearance. (1) In this context, monoclonal antibodies targeting beta‐amyloid (Aβ‐mAbs) are being tested to reduce the amyloid burden in patients with Alzheimer's Disease (AD). (2) However, the cognitive impact of Aβ‐mAbs remains controversial. (3) We aim to evaluate the conflicting results of previous studies using a meta‐analysis. Method: We searched PubMed, Embase, and Cochrane databases, following until April 2021, using the search terms: ''Alzheimer's disease'' OR ''dementia'' cross‐referenced with ''monoclonal antibodies'', considering the synonyms. Eligible articles were randomized clinical trials with Aβ‐mAbs that reported cognitive outcomes. The cognitive function was assessed by Alzheimer's Disease Assessment Scale (ADAS‐cog) and Mini‐Mental State‐Exam (MMSE). We performed a meta‐analysis comparing mAbs and placebo, considering a minimal significant clinical change of 3 points in ADAS‐Cog and 2 points in MMSE. Result: We found 12 eligible studies in 443 identified records, involving 6736 patients, mean age 71.4 ± 2. We found a small benefit in cognitive outcomes in patients treated with Aβ‐mAbs: ADAS‐Cog: mean difference (MD) = ‐ 0.65; 95% CI (‐1.05 to ‐ 0.26); I² = 12%; (p = 0.001) and MMSE: MD = 0.40; 95% CI (0.18 to 0.63); I² = 10%; (p = 0.0004). The Funnel plot and Egger's test did not show publication bias. MD was below the minimal clinically relevant change in both scales. Conclusion: Aβ‐mAbs may have a positive cognitive benefit in AD patients. However, the impact magnitude is small, not reaching minimal clinically relevant change for these scales. References: (1) Panza F, Lozupone M, Seripa D, Imbimbo BP. Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot? Ann Neurol. 2019 Mar;85(3):303–15. (2) Liu J, Yang B, Ke J, Li W, Suen W‐C. Antibody‐Based Drugs and Approaches Against Amyloid‐β Species for Alzheimer's Disease Immunotherapy. Drugs Aging. 2016 Oct;33(10):685–97. (3) Panza F, Lozupone M, Logroscino G, Imbimbo BP. A critical appraisal of amyloid‐β‐targeting therapies for Alzheimer disease. Nat Rev Neurol. 2019 Feb;15(2):73–88. [ABSTRACT FROM AUTHOR]

• We performed an updated systematic review and meta-analysis of randomized controlled trials of vitamin D 3 supplementation to evaluate its efficacy on multiple sclerosis related outcomes. • Vitamin D 3 as an add-on therapy to low-efficacy disease modifying drugs does not confer clinical or radiological benefits on timeframes lasting up to 24 months. • Additional studies are needed to explore outcomes over longer follow-up times. Vitamin D deficiency has been linked to a higher risk of multiple sclerosis (MS) and disease progression. However, the efficacy of vitamin D 3 as an adjuvant therapy for MS remains a controversial topic. To perform a systematic review and meta-analysis of randomized controlled trials to assess the impact of adjunct high-dose vitamin D 3 on clinical and radiological outcomes. PubMed, Embase, and Cochrane Library were searched for trials published until December 18th, 2022. Authors independently selected randomized controlled trials involving patients with MS, with an intervention group receiving high dose (≥ 1000 IU/day) cholecalciferol and reporting clinical or radiological outcomes. Authors independently extracted data and assessed the risk of bias using a standardized, pilot-tested form. The meta-analysis was conducted using RStudio for EDSS at the last follow-up, ARR, and new T2 lesion count. We included 9 studies with 867 participants. No significant reduction of EDSS (MD = 0.02, CI 95 % [–0.37; 0.41], p = 0.91), ARR (MD –0.03, CI 95 % [–0.08; 0.02], p = 0.26), or new T2 lesions (MD –0.59, CI 95 % [-1.24;0.07], p = 0.08) was observed at 6–24 months. We found no evidence of publication bias. The findings of this meta-analysis strengthen current evidence that vitamin D 3 supplementation has no significant impact on clinical outcomes in patients with MS. However, the non-significant reduction of new T2 lesions could precede long-term clinical benefits and should be validated in additional studies. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• The absolute risk of attacks occurring 30 days after vaccination is small. • Attacks occurred after 13 different vaccines, suggesting a broad autoimmune mechanism. • These attacks had a higher frequency of male and negative anti-AQP4 cases. • Nearly two-thirds of these attacks were an initial event of NMOSD. Vaccination in patients with neuromyelitis optica spectrum disorders (NMOSD) is challenging because there is a concern that vaccines can lead to clinical attacks. However, little is known about the risk and the characteristics of attacks occurring after vaccination. We performed a systematic review and meta-analysis using PubMed and Embase databases to estimate a summary frequency of attacks occurring after vaccination and describe the clinical features of theses attacks. We defined attacks occurring after vaccination as typical NMOSD attacks that occurred up to 30 days after vaccine administration. For the frequency of attacks occurring after vaccination, we selected observational studies that reported the number of attacks and total number of patients that received vaccines; for the clinical description of the attacks, case reports and case series were also included. We included 377 participants from 5 studies to estimate the frequency of NMOSD attacks occurring after vaccination. We found a summary frequency of of 2% (95% CI 1–4%, I2 = 0%). We evaluated 17 studies to identify that 13 different vaccines were associated with NMOSD attacks. A higher-than-expected proportion of males, simultaneous optic neuritis and transverse myelitis attacks, and anti-aquaporin 4 antibody negative cases were identified in vaccine-associated attacks from 24 participants from 17 studies. Nearly two-thirds of attacks occurring after vaccination were an initial event of NMOSD. The frequency of NMOSD attacks occurring after vaccination is low and non-specific to different vaccine technologies. Our work reinforces the safety of vaccine recommendations in patients with NMOSD. [ABSTRACT FROM AUTHOR]

• We found similar frequency of visual impairment at 6–12 months in patients with ON treated with 5-day or 7-day duration of 1 g/d intravenous methylprednisolone treatment (IVMPT). • Corticosteroids comprise a genomic and non-genomic effect. • The ceiling effect of IVMP treatment may occur because the genomic effect is already in place at five days and, hence, the non-genomic effect does not provide additional benefit. Optic neuritis (ON), a major cause of visual impairment in young adults, is generally associated with rapid visual recovery when treated with intravenous methylprednisolone treatment (IVMPT). However, the optimal duration of such treatment is unknown, ranging from three to seven days in clinical practice. We aimed to compare the visual recovery in patients treated with 5-day or 7-day duration IVMPT. We performed a retrospective cohort study of consecutive patients with ON in São Paulo, Brazil, from 2016 to 2021. We compared the proportion of participants with visual impairment in 5-day and 7-day treatment schedules at discharge, at 1 month and between 6 and 12 months after the diagnosis of ON. The findings were adjusted to age, severity of the visual impairment, co-intervention with plasma exchange, time from symptom onset to IVMPT and the etiology of the ON to mitigate indication bias. We included 73 patients with ON treated with 5 or 7-day duration of 1 g/d intravenous methylprednisolone therapy. Visual impairment at 6–12 months in the 5-day or the 7-day treatment groups was similar (57% x 59%, p > 0.9, Odds Ratio 1.03 [95% CI 0.59–1.84]). The results were similar after adjusting for prognostic variables and when observed at different time points. Visual recovery is similar in patients treated with 5-day and 7-day duration treatments of 1 g/day intravenous methylprednisolone, suggesting a ceiling effect. Limiting the duration of the treatment can reduce hospital stay and costs, without interfering with clinical benefit. [ABSTRACT FROM AUTHOR]

• The optimal sequencing of DMDs in MS treatment is unknown. • There are two main strategies: escalating (ESC) and early intensive (EIT) strategy. • Treatment choice depends on effectiveness, safety, and cost. • EIT has a higher efficacy in preventing progression and similar safety profile. • EIT may be cost-effective in 5-year time horizon. The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low- to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies. We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost. Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59–0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38–9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model. EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline. [ABSTRACT FROM AUTHOR]

• The estimated prevalence of anti-AQP4 antibody positive neuromyelitis optica spectrum disorder (NMOSD) is relatively high in the city of São Paulo. • The estimated prevalence of MOG antibody associated disease (MOGAD) is relatively low in the city of São Paulo. Numerous studies addressed the prevalence of multiple sclerosis, but prevalence studies of NMOSD and, particularly, MOGAD are scarce. We aimed to estimate the prevalence of NMOSD and MOGAD in the city of São Paulo, based on the known prevalence of MS. In this observational study, we determined the total number of patients with central nervous system demyelinating disease on regular follow-up in a university referral center in São Paulo, from May 2019 to May 2021 according to the diagnosis of multiple sclerosis (MS), NMOSD and MOGAD using the current diagnostic criteria for these diseases. We used the MS: NMOSD and MS: MOGAD ratios to estimate the ratio of these diseases in São Paulo, Brazil. We identified 968 patients with MS, 133 patients with AQP4 positive NMOSD, and 28 patients with MOGAD. We found the MS: NMOSD ratio of 7,28 and the MS: MOGAD ratio of 34,57. We estimated a prevalence of 2,1 per 100,000 inhabitants for NMOSD and of 0,4 per 100,000 inhabitants for MOGAD. The prevalence of NMOSD is high in São Paulo, but the prevalence of MOGAD is low when compared with the prevalence found in most of the studies reported to date. [ABSTRACT FROM AUTHOR]