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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.)

• Rituximab can be prescribed as first-line treatment (early treatment) or after disease activity in patients receiving oral immunosuppressants (escalating therapy) in patients with NMOSD. • Early rituximab treatment may reduce disability progression in NMOSD patients. • Cost-effectiveness analysis supports early rituximab treatment for NMOSD patients. Rituximab, an anti-CD20 monoclonal antibody, has shown effectiveness in reducing disease relapses and disability accrual through relapses in patients with neuromyelitis optica spectrum disorders (NMOSD). However, its higher cost compared to oral immunosuppressants raises questions about its cost-effectiveness, particularly in low and middle-income countries. This study aimed to compare the cost-effectiveness of early rituximab treatment versus escalation treatment in NMOSD patients. We conducted a retrospective study of NMOSD patients treated with rituximab in the first five years of disease at a hospital in São Paulo, Brazil, from 2015 to 2019. The Early Group consisted of NMOSD patients who received rituximab as a first-line treatment. The Escalating Therapy Group included patients who were prescribed rituximab after experiencing disease activity while on oral immunosuppressants, primarily azathioprine. An economic model based on Expanded Disability Status Score (EDSS) transitions was used to assess cost-effectiveness. Cost and utility data were derived from previous studies, and sensitivity analyses for different willingness to pay (WTP) thresholds and percentage of patients upscaling from oral immunossupressants to rituximab were performed. : Thirty NMOSD patients were included. In the Early Group, the proportion of patients reaching the highest EDSS states (6.5 or more) decreased over five years compared to baseline. In contrast, the Escalating Therapy Group experienced an increase in this proportion over the same period. Cost-effectiveness was achieved for willingness to pay (WTP) of €20–80,000 in our main analysis, sustained in our sensitivity analysis. : Early treatment with rituximab has the potential to lower healthcare costs and enhance quality of life for NMOSD patients, supporting its early prescription for preventive treatment. [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.)

Purpose: To compare the visual evoked potentials (VEPs) of optic neuritis (ON) patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and controls. To evaluate correlations between VEP and optical coherence tomography (OCT), contrast sensitivity (CS), and automated perimetry. Methods: Fifty-five eyes with ON from 29 patients (MS = 14 and NMOSD = 15) and 57 eyes from 29 controls were evaluated using VEP, automated perimetry, CS, and optical coherence tomography. Three groups were analyzed: 1) MS eyes with history of ON (ON-MS), 2) NMOSD eyes with ON (ON-NMOSD), and 3) healthy controls. Groups were compared and associations between the parameters were tested. Results: Compared to controls, ON-MS eyes showed significantly delayed N75 and P100 latencies when using a medium-sized stimulus (30'), and delayed P100 latency when using a large stimulus (1.5[degrees]), but similar amplitudes. Compared to controls, ON-NMOSD eyes showed significantly lower N75/P100 amplitudes (both stimulus sizes) and P100/N135 amplitudes (with the 30' stimulus), but latencies did not differ, except for a delayed P100 latency with the 30' stimulus. When comparing the 2 ON groups using the 1.5[degrees] stimulus, there was significant delay in P100 latency in ON-MS eyes and a reduction in N75/P100 amplitude in ON-NMOSD eyes. Peripapillary retinal nerve fiber layer, macular inner retinal layers, and CS measurements were significantly smaller in ON patients than in controls. A strong correlation was found between VEP parameters and inner retinal layer thickness in ON-NMOSD eyes. Conclusions: ON-MS eyes had normal amplitude and delayed VEP latency, whereas ON-NMOSD eyes displayed reduced amplitude and preserved latency when elicited by checkerboard stimulus with large 1.5[degrees] checks. Under such conditions, VEP may help distinguish resolved MS-related ON from resolved NMOSD-related ON. [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.)

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.)

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.)

• 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.)

Background Low-education attainment is associated with worse cognitive performance in multiple sclerosis (MS) patients, and possibly with a lower cognitive reserve and/or increased inflammatory activity. Cognitive reserve refers to the capability of a source of intellectual enrichment in attenuating a negative effect of a disease-related factor; while the inflammatory activity is often related to T2-lesion load (T2-LL) increase. Objective To disentangle the effects of cognitive reserve and an increased T2-LL in MS-patients with low-education levels. Methods The study included 136 MS patients and 65 healthy-controls, divided in low-education (12 years or less of school education without obtaining any technical superior degree) and high-education (more than 12 years of school education with technical or superior degree) groups. An extensive battery of neuropsychological tests was applied examining intelligence quotient and six cognitive domains. Test results were z-scored and subjects with z-scores ≤ −1.5 in two or more domains were considered cognitively impaired. To test the factors associated with worse cognitive performance, regression models were applied using average cognition as target; education level, Expanded Disability Status Scale (EDSS), T2-LL, disease duration, age of disease onset, age and gender as predictors. We also tested the correlation between T2-LL and cognition in the groups. To investigate the role of education level as a source of intellectual enrichment/cognitive reserve in different stages of MS, we sub-divided the MS patients in three groups according to the disease duration (less than 5 years, between 5 and 10 years and more than 10 years). Results Worse average cognition was associated with low-education level, higher T2-LL and male gender. A higher frequency of cognitively impaired patients was observed in MS patients with low-education level, in all stages of the disease. In patients with a disease duration shorter than five years, there was a lower correlation between worse average cognition and T2-LL in the high-education level group, compared to the patients with low-education level; in MS patients with longer disease duration, we observed a stronger correlation between lesion burden and cognitive impairment in both groups. Conclusion Education attainment is a source of intellectual enrichment and can enhance the cognitive reserve in MS patients. The protective effect of a high-education level was stronger in patients with less than five years of disease, suggesting a stronger role of cognitive reserve in short-term disease. In long-term disease we observed a greater impact of increased inflammatory activity on cognition. [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.)

• 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]

• Disability in NMOSD results from relapsing attacks. • Long-standing NMOSD is usually associated with severe disability. • A small proportion of patients remained fully functional in all systems 15 years after disease onset. • ARR 0.4 was the boundary line above which severe disability occurred. • Good prognosis associated with Caucasians, low ARR, and absent myelitis at disease onset. Neuromyelitis optica spectrum disorders (NMOSD) most commonly cause severe disability which is related to disease attacks. However, some patients retain good neurological function for a long time after disease onset. To determine the frequency, demographic and the clinical features of good outcome NMOSD, and analyze their predictive factors. We selected patients who met the 2015 International Panel for NMOSD diagnostic criteria from seven MS Centers. Assessed data included age at disease onset, sex, race, number of attacks within the first and three years from onset, annualized relapsing rate (ARR), total number of attacks, aquaporin-IgG serum status, presence of cerebrospinal fluid (CSF)-specific oligoclonal bands (OCB) and the Expanded Disability Status Scale (EDSS) score at the last follow-up visit. NMOSD was classified as non-benign if patients developed sustained EDSS score >3.0 during the disease course, or benign if patients had EDSS score ≤3.0 after ≥15 years from disease onset. Patients with EDSS <3.0 and disease duration shorter than 15 years were not qualified for classification. We compared the demographic and clinical characteristics of benign and non-benign NMOSD. Logistic regression analysis identified predictive factors of outcome. There were 16 patients with benign NMOSD (3% of the entire cohort; 4.2% of those qualified for classification; and 4.1% of those who tested positive for aquaporin 4-IgG), and 362 (67.7%) with non-benign NMOSD, whereas 157 (29.3%) did not qualify for classification. All patients with benign NMOSD were female, 75% were Caucasian, 75% tested positive for AQP4-IgG, and 28.6% had CSF-specific OCB. Regression analysis showed that female sex, pediatric onset, and optic neuritis, area postrema syndrome, and brainstem symptoms at disease onset, as well as fewer relapses in the first year and three years from onset, and CSF-specific OCB were more commonly found in benign NMOSD, but the difference did not reach statistical significance. Conversely, non-Caucasian race (OR: 0.29, 95% CI: 0.07–0.99; p = 0.038), myelitis at disease presentation (OR: 0.07, 95% CI: 0.01–0.52; p <0.001), and high ARR (OR: 0.07, 95% CI: 0.01–0.67; p = 0.011) were negative risk factors for benign NMOSD. Benign NMOSD is very rare and occurs more frequently in Caucasians, patients with low ARR, and those who do not have myelitis at disease onset. [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]

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.)

• Half of the patients disclosed new or enlarged brain/spinal cord lesions. • 12.5% of patients presented asymptomatic lesions irrespective of clinical attacks. • 31.2% of patients presented asymptomatic brain lesions associated with attack of other topography. • 74.5% of lesions reduced or remained stable or developed atrophy/cavitation. • The presence of asymptomatic lesions did not change clinical outcome or patient management. Around 5% of all Neuromyelitis Optica Spectrum Disorders (NMOSD) cases start before 18 years of age. Clinical and radiological manifestations of AQP4-IgG positive NMOSD were revised in 2015, and the importance of neuroimaging in the diagnosis is well recognized. Neuroimaging findings in pediatric-onset NMOSD were scarcely described, and longitudinal evaluation of NMOSD lesions was only accessed in a few adult-onset cohorts. This study evaluated brain, spinal cord, and optic nerve MRI of sixteen pediatric-onset AQP4-IgG positive NMOSD through a qualitative evaluation of lesion evolution. Lesions were classified as symptomatic or asymptomatic in acute or chronic phase (> 30 days from last attack) MRI. Seventy MRI scans and 54 subsequent exams were evaluated. Most NMOSD lesions (74.5%) reduced, remained stable, or developed atrophy/cavitation. New brain lesions or enlargement of existing brain lesions were found in two patients (12.5%) without any clinical symptom and in five patients (31.2%) in the course of an attack from other topography (optic neuritis or acute myelitis). One patient (6.3%) presented an asymptomatic spinal cord lesion irrespective of clinical manifestation. No asymptomatic lesion was described in optic nerve MRI. In acute phase exams, longitudinally extensive transverse myelitis (13/19 vs 8/24; p = 0.033), cervical myelitis (15/19 vs 10/24, p = 0.028), lumbar myelitis (5/19 vs 0/24; p = 0.012), and a higher number of segments [median 8 (range 4–17) vs 3.5 (range 1–14); p = 0.003] were affected. Asymptomatic brain and spinal cord lesions can occur in pediatric-onset NMOSD, especially in the course of acute optic neuritis or myelitis. More longitudinal studies are necessary to guide recommendations on neuroimaging frequency in pediatric patients with AQP4-IgG NMOSD. [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.)