<b><i>Background:</i></b> Alzheimer disease (AD) is a chronic neurodegenerative disorder with complex pathophysiology that affects over 50 million people worldwide. Most drug therapies, to date, have focused on targeting the amyloid-beta (Aβ) pathway, but clinical outcomes of anti-Aβ antibodies have been unsuccessful and unable to meet their primary endpoints. Similar trends have also been observed in treatments that target the tau pathway. <b><i>Summary:</i></b> This paper reviews recent anti-Aβ passive monotherapies, since Bapineuzumab, that have progressed to phase 3 clinical trials. Specifically, we discuss the 4 clinical trial programs of Solanezumab (targets Aβ monomers), Aducanumab (targets Aβ oligomers and plaques), Crenezumab (targets Aβ oligomers), and Gantenerumab (targets Aβ fibrils) which are all exogenous monoclonal antibodies. We conclude with potential reasons for why they have not met their primary endpoints and discuss lessons learnt from these trials. <b><i>Key Message:</i></b> Future disease-modifying trials (DMTs) for AD should be conducted in asymptomatic, Aβ-positive individuals. Moreover, potential additive and/or synergistic benefits focusing on anti-Aβ and anti-tau drug combinations merit further investigation.

BACKGROUND: Awake craniotomy (AC) enables real-time monitoring of cortical and subcortical functions when lesions are in eloquent brain areas. AC patients are exposed to various preoperative, intraoperative, and postoperative stressors, which might affect their mental health. OBJECTIVE: To conduct a systematic review to better understand stress, anxiety, and depression in AC patients. METHODS: PubMed, Scopus, and Web of Science databases were searched from January 1, 2000, to April 20, 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. RESULTS: Four hundred forty-seven records were identified that fit our inclusion and exclusion criteria for screening. Overall, 24 articles consisting of 1450 patients from 13 countries were included. Sixteen studies (66.7%) were prospective, whereas 8 articles (33.3%) were retrospective. Studies evaluated stress, anxiety, and depression during different phases of AC. Twenty-two studies (91.7%) were conducted on adults, and 2 studies were on pediatrics (8.3 %). Glioma was the most common AC treatment with 615 patients (42.4%). Awake-awakeawake and asleep-awake-asleep were the most common protocols, each used in 4 studies, respectively (16.7%). Anxiety was the most common psychological outcome evaluated in 19 studies (79.2%). The visual analog scale and self-developed questionnaire by the authors (each n = 5, 20.8%) were the most frequently tools used. Twenty-three studies (95.8%) concluded that AC does not increase stress, anxiety, and/or depression in AC patients. One study (4.2%) identified younger age associated with panic attack. CONCLUSION: In experienced hands, AC does not cause an increase in stress, anxiety, and depression; however, the psychiatric impact of AC should not be underestimated.

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Background Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. Methods A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged < 18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. Results A total of 843 nonduplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6,985 individuals were included, where 12.8% of hospitalized patients experienced neurocognitive impairments: MIS-C (24.2%), neuroinflammation (10.1%), and encephalopathy (8.1%) were the most common disorders; headaches (16.8%) and seizures (3.8%) were the most common symptoms. Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Conclusion Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

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Aims This study aimed to systematically review the literature on neuroanatomical predictors of future problematic drinking in adolescents. Methods Using PRISMA guidelines, a systematic review was conducted to evaluate neuroanatomical predictors of problematic drinking in adolescents. Embase, MEDLINE, and PsycINFO databases were searched from inception to January 6th, 2023. Studies were included if they were original, had a prospective design, had a sample size of at least 12, had a follow-up period of at least one year, had at least one structural neuroimaging scan before 18 with no prior alcohol use, and had alcohol use as the primary outcome. Studies were excluded if: had animals only; and were not in English. Risk of bias was conducted using the CASP tool. Results Out of 1,412 studies identified, 19 studies met the criteria, consisting of eleven gray matter (n = 4,040), five white matter (n = 319), and three assessing both (n = 3,608). Neuroanatomical predictors of future problematic drinking in adolescents were reported to be distributed across various brain regions such as the orbitofrontal cortex and paralimbic regions. However, the findings were largely heterogeneous. Conclusions This is the first systematic review to map out the existing literature on neuroanatomical predictors of problematic drinking in adolescents. Future research should focus on the aforementioned regions to determine their role in predicting future problematic drinking with more certainty.

Objective: Cognitive measures are an important primary outcome of pediatric, adolescents, and childhood epilepsy surgery. The purpose of this systematic review and meta-analysis is to assess whether there are long-term alterations (≥ 5 years) in the Full-Scale Intelligence Quotient (FSIQ) of pediatric patients undergoing epilepsy surgery. Methods: Electronic databases (EMBASE, MEDLINE, and Scopus) were searched for English articles from inception to October 2022 that examined intelligence outcomes in pediatric epilepsy surgery patients. Inclusion criteria were defined as the patient sample size of ≥ 5, average follow- up of ≥5 years, and surgeries performed on individuals ≤ 18 years old at the time of surgery. Exclusion criteria consisted of palliative surgery, animal studies, and studies not reporting surgical or FSIQ outcomes. Publication bias was assessed using a funnel plot and the Quality in Prognosis Studies (QUIPS) toolset was used for quality appraisal of the selected articles. A random- effects network meta-analysis was performed to compare FSIQ between surgical patients at baseline and follow-up and Mean Difference (MD) was used to calculate the effect size of each study. Point estimates for effects and 95% confidence intervals for moderation analysis were performed on variables putatively associated with the effect size. Results: 21,408 studies were screened for abstract and title. Of these, 797 fit our inclusion and exclusion criteria and proceeded to full-text screening. Overall, seven studies met our requirements and were selected. Quantitative analysis was performed on these studies (N = 330). The mean long-term difference between pre- and post- operative FSIQ scores across all studies was noted at 3.36 [95% CI: (0.14, 6.57), p = 0.04, I2 = 0%] and heterogeneity was low. Conclusion: To our knowledge, this is the first meta-analysis to measure the long-term impacts of FSIQ in pediatric and adolescent epilepsy patients. Our overall results in this meta-analysis indicate that while most studies do not show long-term FSIQ deterioration in pediatric patients who underwent epilepsy surgery, the observed changes were not clinically significant. Moreover, at the individual patient level analysis, while most children did not show long-term FSIQ deterioration, few had significant decline. These findings indicate the importance of surgery as a viable option for pediatric patients with medically refractory epilepsy.

Aims This study aimed to systematically review the literature on neuroanatomical predictors of future problematic drinking in adolescents. Methods Using PRISMA guidelines, a systematic review was conducted to evaluate neuroanatomical predictors of problematic alcohol consumption in adolescents. EMBASE, MEDLINE, and PsycINFO databases were searched from inception to 6 January 2023. Studies were included if they were original, had a prospective design, had a sample size of at least 12, had a follow-up period of at least 1 year, had at least one structural neuroimaging scan before 18 with no prior alcohol use, and had alcohol use as the primary outcome. Studies were excluded if they had animals only and were not in English. Risk of bias was conducted using the CASP tool. Results Out of 1412 studies identified, 19 studies met the criteria, consisting of 11 gray matter (n = 4040), 5 white matter (n = 319), and 3 assessing both (n = 3608). Neuroanatomical predictors of future problematic drinking in adolescents were reported to be distributed across various brain regions such as the orbitofrontal cortex and paralimbic regions. However, the findings were largely heterogeneous. Conclusions This is the first systematic review to map out the existing literature on neuroanatomical predictors of problematic drinking in adolescents. Future research should focus on the aforementioned regions to determine their role in predicting future problematic drinking with more certainty.