Anxiety and Depression in Pediatric-Onset Traumatic Spinal Cord Injury: A Systematic Review.

BACKGROUND: Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected individuals. We aimed to investigate anxiety and depression in individuals with pediatric-onset TSCI. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to December 20th, 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and studies were included according to the eligibility criteria. RESULTS: A total of 1013 articles were screened, and 18 studies with 4234 individuals were included in the final review. Of these, 1613 individuals (38.1%) had paraplegia, whereas 1658 (39.2%) had tetraplegia. A total of 1831 participants (43.2%) had complete TSCI, whereas 1024 (24.2%) had incomplete TSCI. The most common etiology of TSCI with 1545 people (36.5%) was motor vehicle accidents. The youngest mean age at the time of injury was 5.92 ± 4.92 years, whereas the oldest was 14.6 ± 2.8 years. Patient Health Questionnaire-9 was the most common psychological assessment used in 9 studies (50.0%). Various risk factors, including pain in 4 studies (22.2%), reduced sleep quality, reduced functional independence, illicit drug use, incomplete injury, hospitalization, reduced quality of life, and duration of injury in 2 (11.1%) studies, each, were associated with elevated anxiety and depression. CONCLUSIONS: Different biopsychosocial risk factors contribute to elevated rates of anxiety and depression among individuals with pediatric-onset TSCI. Individuals at risk of developing anxiety and depression should be identified, and targeted support should be provided. Future large-scale studies with long-term follow-up are required to validate and extend these findings.

Association of SARS-CoV-2 infection with neurological impairments in pediatric population: A systematic review.

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. 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. A total of 843 no-duplicate 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 6985 individuals were included, where 12.8% (n = 892) of hospitalized patients experienced neurocognitive impairments which includes: 1) neurological symptoms (n = 294 of 892, 33.0%), 2) neurological syndromes and neuroimaging abnormalities (n = 223 of 892, 25.0%), and 3) other phenomena (n = 233 of 892, 26.1%). 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%). Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

Awake craniotomy during pregnancy: A systematic review of the published literature.

Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.

Neuroanatomical predictors of problematic alcohol consumption in adolescents: a systematic review of longitudinal studies.

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.

Suicidal ideation and attempts in brain tumor patients and survivors: A systematic review.

Background: Subsequent to a diagnosis of a brain tumor, psychological distress has been associated with negative effects on mental health as well as suicidality. The magnitude of such impact has been understudied in the literature. We conducted a systematic review to examine the impact of a brain tumor on suicidality (both ideation and attempts). Methods: In accordance with the PRISMA guidelines, we searched for relevant peer-reviewed journal articles on PubMed, Scopus, and Web of Science databases from inception to October 20, 2022. Studies investigating suicide ideation and/or attempt among patients with brain tumors were included. Results: Our search yielded 1,998 articles which were screened for eligibility. Seven studies consisting of 204,260 patients were included in the final review. Four studies comprising 203,906 patients (99.8%) reported elevated suicidal ideation and suicide attempt incidence compared with the general population. Prevalence of ideation and attempts ranged from 6.0% to 21.5% and 0.03% to 3.33%, respectively. Anxiety, depression, pain severity, physical impairment, glioblastoma diagnosis, male sex, and older age emerged as the primary risk factors associated with increased risk of suicidal ideation and attempts. Conclusion: Suicidal ideation and attempts are increased in patients and survivors of brain tumors compared to the general population. Early identification of patients exhibiting these behaviors is crucial for providing timely psychiatric support in neuro-oncological settings to mitigate potential harm. Future research is required to understand pharmacological, neurobiological, and psychiatric mechanisms that predispose brain tumor patients to suicidality.

Awake Craniotomy in Africa: A Scoping Review of Literature and Proposed Solutions to Tackle Challenges.

BACKGROUND: Awake craniotomy (AC) is a common neurosurgical procedure for the resection of lesions in eloquent brain areas, which has the advantage of avoiding general anesthesia to reduce associated complications and costs. A significant resource limitation in low- and middle-income countries constrains the usage of AC. OBJECTIVE: To review the published literature on AC in African countries, identify challenges, and propose pragmatic solutions by practicing neurosurgeons in Africa. METHODS: We conducted a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Scoping Review guidelines across 3 databases (PubMed, Scopus, and Web of Science). English articles investigating AC in Africa were included. RESULTS: Nineteen studies consisting of 396 patients were included. Egypt was the most represented country with 8 studies (42.1%), followed by Nigeria with 6 records (31.6%). Glioma was the most common lesion type, corresponding to 120 of 396 patients (30.3%), followed by epilepsy in 71 patients (17.9%). Awake-awake-awake was the most common protocol used in 7 studies (36.8%). Sixteen studies (84.2%) contained adult patients. The youngest reported AC patient was 11 years old, whereas the oldest one was 92. Nine studies (47.4%) reported infrastructure limitations for performing AC, including the lack of funding, intraoperative monitoring equipment, imaging, medications, and limited human resources. CONCLUSION: Despite many constraints, AC is being safely performed in low-resource settings. International collaborations among centers are a move forward, but adequate resources and management are essential to make AC an accessible procedure in many more African neurosurgical centers.

Association of SARS-CoV-2 Infection with Neurological Symptoms and Neuroimaging Manifestations in the Pediatric Population: A Systematic Review.

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.

Long-term full-scale intelligent quotient outcomes following pediatric and childhood epilepsy surgery: A systematic review and meta-analysis.

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, there was an increase of 3.36 FSIQ points, however, 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.

Medial temporal tau predicts memory decline in cognitively unimpaired elderly.

Alzheimer's disease can be detected in living people using in vivo biomarkers of amyloid-ß and tau, even in the absence of cognitive impairment during the preclinical phase. [18F]-MK-6420 is a high-affinity PET tracer that quantifies tau neurofibrillary tangles, but its ability to predict cognitive changes associated with early Alzheimer's disease symptoms, such as memory decline, is unclear. Here, we assess the prognostic accuracy of baseline [18F]-MK-6420 tau-PET for predicting longitudinal memory decline in asymptomatic elderly individuals. In a longitudinal observational study, we evaluated a cohort of cognitively normal elderly participants (n = 111) from the translational biomarkers in ageing and dementia study (data collected between October 2017 and July 2020, with a follow-up period of 12 months). All participants underwent tau-PET with [18F]-MK-6420 and amyloid-ß PET with [18F]-AZD-4694. The exclusion criteria included the presence of head trauma, stroke or other neurological disorders. There were 111 eligible participants selected based on the availability of amyloid-ß PET, tau-PET, MRI and APOEɛ4 genotyping. Among these participants, the mean standard deviation age was 70.1 (8.6) years; 20 (18%) were tau-PET-positive and 71 of 111 (63.9%) were women. A significant association between the baseline Braak Stages I-II [18F]-MK-6240 standardized uptake value ratio positivity and change in composite memory score were observed at the 12-month follow-up, after correcting for age, sex and years of education [logical memory and Rey Auditory Verbal Learning Test, standardized beta = -0.52 (-0.82-0.21), P < 0.001, for dichotomized tau-PET and -1.22 (-1.84-(-0.61)], P < 0.0001, for continuous tau-PET]. Moderate cognitive decline was observed for A + T + over the follow-up period, whereas no significant change was observed for A-T+, A + T- and A-T-, although it should be noted that the A-T + group was small. Our results indicate that baseline tau neurofibrillary tangle pathology is associated with longitudinal changes in memory function, supporting the use of [18F]-MK-6420 PET to predict the likelihood of asymptomatic elderly individuals experiencing future memory decline. Overall, [18F]-MK-6420 PET is a promising tool for predicting memory decline in older adults without cognitive impairment at baseline. This is of critical relevance as the field is shifting towards a biological model of Alzheimer's disease defined by the aggregation of pathologic tau. Therefore, early detection of tau pathology using [18F]-MK-6420 PET provides us with hope that living patients with Alzheimer's disease may be diagnosed during the preclinical phase before it is too late.

Stress, Anxiety, and Depression Associated With Awake Craniotomy: A Systematic Review.

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-awake-awake 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.

Augmented and virtual reality usage in awake craniotomy: a systematic review.

Augmented and virtual reality (AR, VR) are becoming promising tools in neurosurgery. AR and VR can reduce challenges associated with conventional approaches via the simulation and mimicry of specific environments of choice for surgeons. Awake craniotomy (AC) enables the resection of lesions from eloquent brain areas while monitoring higher cortical and subcortical functions. Evidence suggests that both surgeons and patients benefit from the various applications of AR and VR in AC. This paper investigates the application of AR and VR in AC and assesses its prospective utility in neurosurgery. A systematic review of the literature was performed using PubMed, Scopus, and Web of Science databases in accordance with the PRISMA guidelines. Our search results yielded 220 articles. A total of six articles consisting of 118 patients have been included in this review. VR was used in four papers, and the other two used AR. Tumour was the most common pathology in 108 patients, followed by vascular lesions in eight patients. VR was used for intraoperative mapping of language, vision, and social cognition, while AR was incorporated in preoperative training of white matter dissection and intraoperative visualisation and navigation. Overall, patients and surgeons were satisfied with the applications of AR and VR in their cases. AR and VR can be safely incorporated during AC to supplement, augment, or even replace conventional approaches in neurosurgery. Future investigations are required to assess the feasibility of AR and VR in various phases of AC.

GBA1 and The Immune System: A Potential Role in Parkinson's Disease?

It is clear that the immune system and inflammation have a role in Parkinson's disease (PD), including sporadic PD and some genetic forms such as LRRK2-associated PD. One of the most important genes associated with PD is GBA1, as variants in this gene are found in 5-20% of PD patients in different populations worldwide. Biallelic variants in GBA1 may cause Gaucher disease, a lysosomal storage disorder with involvement of the immune system, and other lines of evidence link GBA1 to the immune system and inflammation. In this review, we discuss these different pieces of evidence and whether the interplay between GBA1 and the immune system may have a role in PD.

Lessons Learnt from the Second Generation of Anti-Amyloid Monoclonal Antibodies Clinical Trials.

BACKGROUND: 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 (Aß) pathway, but clinical outcomes of anti-Aß antibodies have been unsuccessful and unable to meet their primary endpoints. Similar trends have also been observed in treatments that target the tau pathway. SUMMARY: This paper reviews recent anti-Aß passive monotherapies, since Bapineuzumab, that have progressed to phase 3 clinical trials. Specifically, we discuss the 4 clinical trial programs of Solanezumab (targets Aß monomers), Aducanumab (targets Aß oligomers and plaques), Crenezumab (targets Aß oligomers), and Gantenerumab (targets Aß 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. Key Message: Future disease-modifying trials (DMTs) for AD should be conducted in asymptomatic, Aß-positive individuals. Moreover, potential additive and/or synergistic benefits focusing on anti-Aß and anti-tau drug combinations merit further investigation.

Systemic therapy for brain metastases.

Metastases from cells outside of the central nervous system are the most common cancer found in the brain and are commonly associated with poor prognosis. Although cancer treatment is improving overall, central nervous system metastases are becoming more prevalent and require finesse to properly treat. Physicians must consider the biology of the primary tumor and the complex neurological environment that the metastasis resides in. This can be further complicated by the fact that the practice of cancer management is constantly evolving and therapy that works outside of the blood-brain barrier may not be effective inside of it. Therefore, this review seeks to update the reader on recent advancements made on the three most common sources of brain metastases: lung cancer, breast cancer, and melanoma. Each of these malignancies has been the subject of intriguing and novel avenues of therapy which are reviewed here.

Single STE-MR Acquisition in MR-Based Attenuation Correction of Brain PET Imaging Employing a Fully Automated and Reproducible Level-Set Segmentation Approach.

PURPOSE: The aim of this study is to introduce a fully automatic and reproducible short echo-time (STE) magnetic resonance imaging (MRI) segmentation approach for MR-based attenuation correction of positron emission tomography (PET) data in head region. PROCEDURES: Single STE-MR imaging was followed by generating attenuation correction maps (µ-maps) through exploiting an automated clustering-based level-set segmentation approach to classify head images into three regions of cortical bone, air, and soft tissue. Quantitative assessment was performed by comparing the STE-derived region classes with the corresponding regions extracted from X-ray computed tomography (CT) images. RESULTS: The proposed segmentation method returned accuracy and specificity values of over 90 % for cortical bone, air, and soft tissue regions. The MR- and CT-derived µ-maps were compared by quantitative histogram analysis. CONCLUSIONS: The results suggest that the proposed automated segmentation approach can reliably discriminate bony structures from the proximal air and soft tissue in single STE-MR images, which is suitable for generating MR-based µ-maps for attenuation correction of PET data.