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Background: The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. Methods: All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. Results: We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty‐nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p =.027). The ventricular shunting was significantly associated with the presence of pseudocysts (p =.005) and hydrocephalus (p =.044). Conclusion: In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue. [ABSTRACT FROM AUTHOR]

Background: The clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta‐analysis of CNS sporotrichosis. Methods: We searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals. Results: We included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty‐six patients were male (88%, 95% CI: 77–95), and the mean age was 39 years (95% CI: 36–43). Close contact with cats was reported in 55% of cases (95% CI: 37–72). Thirty‐two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61–95). Overall mortality was 56% (22/39). The comparison of Kaplan–Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p =.019). Conclusion: CNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions. [ABSTRACT FROM AUTHOR]

Background: The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series. Objectives: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease. Methods: We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non‐CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi‐squared test was used to compare mortality between pairs of antifungal drugs. Results: We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3–71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49–61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14–61), meningitis (29/185, 14%, 95%CI: 7–25), hydrocephalus (41/185, 37%, 95%CI: 7–83) and vasculitis (18/185, 6%, 95%CI: 1–22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole. Conclusion: Central nervous system histoplasmosis usually presents subacute‐to‐chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality. [ABSTRACT FROM AUTHOR]

Background: Advanced neuroimaging demonstrated that neurological involvement occurs in up to 30% of paracoccidioidomycosis (PCM) cases. Current knowledge of neuroparacoccidioidomycosis (NPCM) is based on a 2009 systematic review. However, in the last decade, several new cases have been published, with modern neuroimaging techniques. Objectives: We believe a new systematic review is needed to summarise these advances. Methods: We searched PubMed/MEDLINE, Embase and LILACS for studies from January 2010 to May 2022. Case series and case reports of NPCM were included. We performed a metaproportion to estimate a summary proportion with 95% confidence intervals (CI). Results: Thirty‐four studies including 104 patients were evaluated. We combined our data with the results from the previous review that included 257 cases, totalling 361 patients. We found no new important demographic, clinical or laboratory characteristics. On magnetic resonance imaging (MRI), we found that 72% (95%CI: 38–91) had hyperintensity on T1‐weighted image; 84% (95%CI: 71%–92%) had hypointensity on T2‐weighted image; 80% (95%CI: 66–89) had contrast enhancement with the classical ring‐enhancing pattern. All 8 patients undergoing spectroscopy presented lipid peaks. We found a 16% mortality, lower than in the previous review (44%). Conclusion: NPCM presents a characteristic pattern on MRI that may help to differentiate it from other causes of single or multiple brain lesions. Albeit there is a frequent pattern, it is not specific, as other granulomatous diseases may show similar findings. Advances in neuroimaging with early diagnosis and appropriate management of the disease may have contributed to reducing its mortality. [ABSTRACT FROM AUTHOR]

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]

Ocrelizumab and siponimod are the two on-label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high-efficacy disease-modifying drugs (DMDs). Off-label prescription of other high-efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on-label and off-label high-efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High-efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta-analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on-label and off-label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off-label drugs (CI95% 0.51-2.16) versus ocrelizumab (reference) and off-label drugs (CI 95% 0.53-1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off-label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on-label DMDs in this network meta-analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Our goal was to describe outcomes in a single-center, real-world series of patients with acute basilar artery occlusion in a middle-income country. In addition, we assessed potential outcome predictors., Material and Methods: Data from 28 patients were retrospectively reviewed. The primary outcome was death until last follow-up. Other outcomes were rates of favorable outcome until last follow-up and rates of intracranial hemorrhage. Outcomes were compared in subgroups according to several variables, including reperfusion (REP group) or no reperfusion (NOREP group) interventions, with chi-squared, Fisher's exact test, or Mann-Whitney tests., Results: The rate of overall intrahospital death was 46%. Death until last follow-up occurred in 8/17 (47%) in the REP and in 7/11 (63%) of the NOREP group. Favorable outcomes were observed in 35.7% of the patients: 8/17 (47%) in REP and in 2/11 (18.1%) in NOREP. NIH stroke scale scores were significantly lower in patients with favorable outcomes. Intracranial hemorrhage was observed in 6/28 (21.4%) of the patients (all in REP group). Twenty patients were treated with anticoagulants within the first 24 h. No hemorrhage was observed in those treated with enoxaparin, while three occurred in subjects treated with unfractionated heparin., Conclusion: Together with other series, our results underscore the relevance of NIH stroke scale at admission as a prognostic marker, the importance of reperfusion to improve outcomes, and the need of clinical trials to compare the impact of treatment with anticoagulants within first 24 h in basilar artery occlusion., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)