Acta Neuropathologica Research Articles

CNSC-18. A SCOPING REVIEW OF HISTONE 3.3 G34R/V HIGH-GRADE GLIOMA: EPIGENETIC AND MOLECULAR PROFILES, CLINICOPATHOLOGY, AND TREATMENT AVENUES

Abstract Survival of pediatric and young adults with malignant glioma remains poor despite progress in treatment. This is especially true for histone 3.3 G34R/V (H3.3G34R/V) mutated gliomas, which often present in adolescent and young adult patients. While treatments to date delay progression, post 5-year overall survival is exceedingly rare. Historically, there has been limited research on H3G34R/V mutant tumors, which likely contributes to lack of advancements in current treatments. This scoping review fills the current knowledge gap of H3G34R/V mutated gliomas and summarizes future targets and therapeutic options. In October 2023, MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection were searched. Two reviewers screened all articles by title and abstract review and three independent reviewers extracted all studies meeting inclusion criteria relevant to H3G34R/V tumors (preclinical and clinical studies). Of the 2203 articles screened, 200 were deemed eligible. The 200 articles included 68 literature reviews, 9 systematic reviews, 54 preclinical studies, and 69 clinically oriented studies. We found that the United States and ACTA neuropathologica are the top country and journal contributors, respectively, to understanding molecular diagnosis, disease pathology, and potential targeted treatment options of H3.3G34R/V tumors. This literature collectively demonstrates the involvement of numerous oncogenes and tumor suppressor genes involved in RAS/MAPK, MYCN, NOTCH, and LIF/STAT pathways such as ATRX, PDGFRA, and TP53 in influencing the neural characteristics and prognostic outcomes of the tumor. While certain therapeutic modalities, including H3K9 methyltransferase inhibitors and bevacizumab-based therapy have exhibited preclinical efficacy and some indication of positive clinical outcomes, more research on agents that permeate the blood-brain barrier to impair growth are necessary. Additionally, further research into the supportive role of the tumor microenvironment that enables disease progression is warranted. Collectively, these studies will empower intelligent prospective clinical trials using H3.3G34R/V targeted therapies which enhance disease survival.

Development of Potent and Selective Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 2 for the Potential Treatment of Alzheimer’s Disease

AbstractBackgroundThe metabotropic glutamate receptor 2 (mGluR2) is a group II mGluR that binds glutamate and utilizes Gi/o signaling within the central nervous system (CNS) to modulate synaptic transmission and neuronal excitation.1 The alteration of basal glutamate signaling has been implicated in a variety of neurodegenerative diseases including Alzheimer’s disease (AD).2 mGluR2 has been found to be overexpressed in the hippocampal neurons of AD patients and receptor overactivation has been shown to induce plaque formation in in vitro AD models.3, 4 Thus, the utilization of a mGluR2 negative allosteric modulator (NAM) may prevent neurodegeneration. The utility of mGluR2 NAMs for neurodegenerative diseases remains unclear due to the lack of mGluR selectivity of historical compounds.1. Niswender, C.M. and P.J. Conn, Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annual review of pharmacology and toxicology, 2010. 50: p. 295‐322.2. Li, S.H., K.S. Abd‐Elrahman, and S.S.G. Ferguson, Targeting mGluR2/3 for treatment of neurodegenerative and neuropsychiatric diseases. Pharmacology & Therapeutics, 2022. 239: p. 108275.3. Lee, H.‐g., et al., Aberrant expression of metabotropic glutamate receptor 2 in the vulnerable neurons of Alzheimer’s disease. Acta Neuropathologica, 2004. 107(4): p. 365‐371.4. Caraci, F., et al., Targeting group II metabotropic glutamate (mGlu) receptors for the treatment of psychosis associated with Alzheimer’s disease: selective activation of mGlu2 receptors amplifies beta‐amyloid toxicity in cultured neurons, whereas dual activation of mGlu2 and mGlu3 receptors is neuroprotective. Mol Pharmacol, 2011. 79(3): p. 618‐26.MethodNovel mGluR2 NAMs were synthesized using an iterative library synthetic approach to improve potency, selectivity, and provide an overall sufficient drug metabolism/pharmacokinetics (DMPK) profile. Compound potency (IC50) and selectivity were evaluated in an in vitro GIRK cell‐based T1 flux assay expressing mGluR2 or mGluR3 receptors. Lead compounds were tested in in vitro plasma protein binding assays and rat in vitro and in vivo clearance values were obtained.ResultThe successful discovery and development of a potent and selective mGluR2 NAM as an in vivo tool compound to elucidate the biological effects associated with mGluR2 antagonism was achieved.ConclusionmGluR2 NAMs may be useful therapeutic agents for the potential treatment of AD and other neurodegenerative diseases.

White matter changes with cerebrovascular disease and Alzheimer’s disease pathologies

AbstractBackgroundWhite matter (WM) plays an important role in cognitive function and undergoes substantial changes due to aging and increase in AD and AD related dementia (AD/ADRD) pathologies. While recent work proposed measurement of global WM changes from diffusion MRI as biomarkers for Cerebrovascular disease (CVD) such as PSMD and free water, there needs to be a better understanding of WM changes due to AD/ADRD pathologies. The goal of our recent work was to understand white matter changes with CVD and AD – common pathologies in AD/ADRD ‐ utilizing data from Mayo Clinic Study of Aging and Mayo ADRC.MethodUsing diffusion MRI (dMRI) in 718 participants from Mayo Clinic Study of Aging (mean age = 71.1 years, 56% male), we investigated relationships between commonly used dMRI measures and vascular risk as well as global amyloid PET. In a subset of 233 participants who were amyloid‐PET positive and also competed Tau‐PET (flortaucipir) from Mayo Clinic Study of Aging and Mayo ADRC, we investigated associations between regional flortaucipir SUVRs in Braak stages and regional WM changes.ResultsWe found greater frontal lobe WM damage with increasing vascular risk across all dMRI measures. We previously validated the strong relationship between the genu of the corpus callosum (anterior interhemispheric connections) dMRI measurements made on antemortem scans and cerebrovascular pathology observed on postmortem tissue (Nguyen et. al. Acta Neuropathologica 2022) supporting the utility of genu of the corpus callosum dMRI measures as a potential CVD biomarker. Also, we found greater posterior WM damage with increasing amyloid burden. Among the 233 amyloid positive participants, we found spatially dependent WM degeneration associated with regional flortaucipir SUVRs in Braak stages with greater extent of posterior WM damage. Further, dMRI measurements of the WM damage provided complementary information about disease staging and progression of AD in addition to flortaucipir SUVR measurements.ConclusionsAnterior WM measurements may be more specific to CVD and posterior WM changes are seen with increasing AD pathological burden. Our results suggest that WM changes observed with CVD and typical AD may be different and have clinical utility for differential diagnosis and disease staging.

Association between Microenvironment-Related Genes and Prognosis of Primary Central Nervous System Lymphoma

Background: Comprehensive gene mutation profiling of primary central nervous system lymphoma (PCNSL) revealed genomic abnormalities associated with the NFκB signaling pathway and immune escape (Chapuy B, et al. Blood 2016). Although this has led to advances in targeted therapy, there are only a few candidate biomarkers for diagnosis and prediction of survival in PCNSL. Recurrence still occurs at high rate of over 60% and therapeutic resistance is a significant challenge in the management of recurrent PCNSL. Until now, the systemic profiling of tumor micro-environment (TME) was performed through gene expression analysis by whole transcriptome analysis (WTA) and single-cell RNA sequencing analysis (Heming M, et al. Genome medicine 2022), and stratification in PCNSL was attempted by using spatial transcriptome analysis (Xia Y, et al. Leukemia 2023). However, TME of PCNSL and their impact on prognosis remain uncertain. Objective: We performed this study to investigate the prognostic impact on survival and establish novel prognostic biomarkers in PCNSL. Methods: We analyzed the expression levels of 770 neuroinflammation-related (NFR) genes by the NanoString nCounter technology in tumor samples from 30 PNCSL patients. The clinical significance of genes and their association with prognosis were assessed. Genes related to “worse prognosis (WP)” or “better prognosis (BP)” were identified. We performed the univariable analysis using a cox proportional hazards model to evaluate the predictive value of expression of genes related to WP and clinical risk factors, such as age, sex, serum lactate dehydrogenase level, Karnofsky Performance Status (KPS), consciousness levels at diagnosis and lymphoma involvement of the deep brain structure. Gene expression data related to WP were subjected to multivariate analysis with clinical variables with p values less than 0.15 in the univariate analysis. The genes associated with WP were further validated using WTA of an independent PCNSL cohort (n=30, previously published by Fukumura K, et al. Acta neuropathologica 2016). Results: The median age at diagnosis was 69 years old (range, 32-83). The median follow-up period was 25 months (range, 1-110 months), with overall survival (OS) at 3 years of 39.7% and progression free survival at 3 years of 25.4%. Notably, 48 of 770 NFR genes were highly expressed in the WP group (3-year OS, 22.2%), compared with the BP group (3-year OS, 66.7%) (Figure 1). We found that oligodendrocyte and astrocyte-related signatures were enriched in the WP-associated gene set. Among clinical prognostic factors, KPS > 70 (p=0.0293), and consciousness levels at diagnosis (other than JCS 0-1) (p=0.104) were relatively associated with poor OS (p < 0.15) in univariate analysis. Multivariate analysis revealed that high expressions of TUBB4A (p=0.028, HR:3.88), S100B (p=0.046, HR:3.093) and SLC6A1 (p=0.034, HR:3.765) were significantly related to death independent from KPS and consciousness levels at diagnosis. Expression levels of these 3 genes were also significantly associated with poor OS in a validation cohort. Conclusion: Our observations suggest high expression of TUBB4A, S100B and SLC6A1 are the clinical indicators to predict poor prognosis in PCNSL patients. Furthermore, these data suggest that genes related to TME may play a crucial role in the pathogenesis of PCNSL, complementing the well-known involvement of the NF-kB signaling pathway. Therefore it is necessary to continue research focused on TME-targeted therapeutics to encounter drug resistance and refractoriness in PCNSL.

Central neurocytomas: research trends, most cited papers, and scientometrics analysis to date

Central neurocytoma is the most common primary intraventricular tumor in adults being classified by the World Health Organization (WHO) as a benign grade II tumor with a good prognosis. Given the recent advances with regard to this tumor, a bibliometric analysis was due to study the future direction of research for neurocytomas. A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies to date relevant to neurocytoma. A discrete set of validated bibliometric parameters were extracted and analyzed on R v4.1.3. A total of 1002 documents were included in our analysis covering a period between 1910 and 2021 (111 years). Around 98.5% of the documents were multi-author publications with a collaboration index (CI) of 4.21. Acta Neuropathologica, The American Journal of Surgical Pathology, and Cancer were the journals to include the highest number of top ten cited articles (2 out of 10 most cited articles, 20%). Switzerland (4 out of 10, 40%) accounted for the country to have the highest number of top 10 most cited articles with the USA (5588 out of 16,395 citations, 34.1%) having the greatest number of citations. Lastly, our analysis reported an annual growth rate of 6.9% for the number of papers produced by year. This is the first bibliometric analysis to study the top 10 most cited articles with regard to neurocytomas. A shift from histopathologic and clinical symptoms towards the treatment and management of the tumor was observed in our analysis.

The coarse‐grained plaque is an Aβ plaque‐type in APOE Ɛ4+ Alzheimer’s disease that is associated with astrogliosis and p‐tau burden

AbstractBackgroundThe coarse‐grained plaque (CGP) is a divergent plaque‐type recently described in Alzheimer’s disease (AD)1. In the current study, we studied the CGPs distribution over the brain, and its association with APOE, p‐tau, and neuroinflammation.MethodThe cohort (N = 60) was selected from the Mayo Clinic brain bank in Jacksonville, USA. Brain tissue from the frontal ‐, parietal ‐, temporal cortex, and the hippocampus was immunohistochemically stained for Aβ (6F/3D), p‐tau (AT8), CD68, and GFAP. The CGP and classic cored plaque (CCP) were scored as previously described1. Total plaque burden was expressed as the sum of all cortical regions.ResultThe CGP was predominantly located in the neocortex and present in ∼60% of AD cases, who were younger at onset (p<0.05) and had a lower brain weight (p<0.05) than CGP negative cases. When stratified for APOE Ɛ4+ and Ɛ4‐, CGP burden was only in Ɛ4+ positively correlated with p‐tau, Aβ, and GFAP burden in the frontal and parietal cortex (Table 1). CGP burden was not correlated with CD68. The CCP was negatively correlated with p‐tau, and not with GFAP, Aβ or CD68 (Table 1). In APOE Ɛ4+ cases, the burden of CGPs was negatively correlated with the burden of CCPs (Fig.1).ConclusionThe neocortical CGP is correlated with increased p‐tau burden and astrogliosis in APOE Ɛ4+. The CGP is inversely correlated with the common CCP, suggesting an opposite effect of Aβ‐induced tau‐toxicity for the CGP versus the CCP. 1Boon et al., Acta Neuropathologica, 2020

Cerebellar Liponeurocytoma: Publication Trends, Scientometrics Analysis, and Critical Review

The literature on cerebellar liponeurocytoma (CL) has never been systematically assessed using bibliometric analytic methodologies. We quantitatively analyzed the major trends and scientific output regarding CL, highlighting potential avenues for research. Elsevier's Scopus database was used to collect all published studies relevant to cerebellar liponeurocytoma from 1978 to 2021. The specific bibliometric parameters were extracted and analyzed with R v4.1.2. Our search yielded 108 documents published in 67 sources from 1978 to 2021. The annual growth rate of publications regarding CL has been 7.47% per year since 1978. Journals with the most publications on CL include Clinical Neuropathology and Neurology India (n= 5), followed by Acta Neuropathologica and Journal of Neuro-oncology (n= 4). A total of 529 authors have published on CL and they have been cited 598 times. The 10 most influential authors in the field were determined using their total number of citations and the local H-index. Kleihues P has the highest number of citations (n= 177) with a local H index of 3, followed by Chimelli L with 167 citations and a local H index of 4. Davis DG has 149 citations and a local H index of 3. China had the most single country publications followed by India, Italy, and the USA. France and Austria have the most multiple country publications followed by China, Tunisia, Brazil, United Kingdom, Egypt, and Israel. Our study is the first bibliometric analysis evaluating the present literature and publication trends in CL. Generally, the current literature has a few studies regarding CL relative to other neuro-oncological pathologies. This can be due to the low incidence of the disease and highlights a need for high volume database studies that can offer high quality evidence on the subject.

EPID-17. CENTRAL NEUROCYTOMA: RESEARCH TRENDS, MOST CITED PAPERS, AND SCIENTOMETRICS ANALYSIS TO DATE

Abstract INTRODUCTION Central neurocytoma is the most common primary intra-ventricular tumor in adults being classified by the World Health Organization (WHO) as a benign grade II tumor with a good prognosis. Given the recent advances with regards to this tumor, a bibliometric analysis was due to study the change in research interest and patterns to identify the future direction of research for neurocytomas. MATERIALS AND METHODS A comprehensive Elsevier’s Scopus database search was performed to capture all published and indexed studies to date using the keywords "neurocytoma" and "central neurocytoma". A discrete set of validated bibliometric parameters were extracted and analyzed. All statistical analyses were performed on R 4.1.2. RESULTS A total of 1,002 documents were included in our analysis covering a period between 1910-2021 (111 years). Around 98.5% of the documents were multi-author publications with a collaboration index (CI) of 4.21. Acta Neuropathologica, The American Journal of Surgical Pathology, and Cancer were the journals to include the most number of top ten cited articles (2 out of 10 most cited articles, 20%). Switzerland (4 out of 10, 40%) accounted for the country to have the most number of top 10 most cited articles. The United States of America (5588 out of 16395 citations, 34.1%) had the most number of citations. Lastly, our analysis reported an annual growth rate of 6.9% for the number of papers produced by year. CONCLUSION This is the first bibliometric analysis to study the top 10 most cited articles with regard to neurocytomas. A shift from histopathologic and clinical symptoms toward treatment and management of the tumor was observed in our analysis. These findings highlight the need for investigation into treatment modalities for future research.

Editorial introductions.

Editorial introductions.

Stroke Literature Synopsis (Preclinical).

Stroke Literature Synopsis (Preclinical).

RARE-16. Differential expression of miRNAs in adamantinomatous craniopharynngioma reveals dysregulation of pathogenic pathways

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of target mRNAs and can control whole gene networks. ACPs are benign pituitary tumours that can result in significant morbidity and premature mortality. ACPs harbour mutations in CTNNB1 and are driven by the activation of the WNT/beta-catenin pathway. We sought to explore the expression of miRNAS in adamantinomatous craniopharyngioma (ACP) in a cohort of samples previously subjected to RNA-Seq analysis (Apps et al, Acta Neuropathologica, 2018, May;135(5):757-777). Total RNA ACP samples (n=18), non-functioning pituitary adenomas (n=3) and normal foetal pituitaries (n=3) underwent miRNA sequencing using the Qiagen miRNA library prep kit on a NextSeq 500 to a depth of 16 million reads. Differential expression was performed using DESeq2 and functional analysis with mirPath v.3. Expression of miRNAs was correlated with previously published mRNA expression We found that 210 miRNA were upregulated and 275 down regulated in ACP compared with controls (adjusted p-value <0.1). MIR-205-5p was the most upregulated miRNA (619 fold) and its expression correlated with genes expressed within the tumour epithelium (e.g. TP63). miR-375 an inhibitor of the WNT pathway was the most down regulated miRNA (361 fold). KEGG Pathway analysis identified Glycosphingolipid synthesis as the most enriched pathway targeted by upregulated miRNAs. Pathways that were enriched by down regulated miRNAs included: ECM-receptor interaction, fatty acid biosynthesis, Hippo, TGF-beta, WNT, and ErbB pathways. Down regulation of miR-132 has previously been suggested as a marker of aggressiveness in ACP, and was 16 fold down regulated (adjusted p-value<0.001) in this cohort and expression was inversely correlated with genes relating to epithelial development. This data confirms previous studies indicating that miRNA expression is altered in ACP. In silico analysis suggest that the dysregulation of miRNA affects the expression of genes involved in pathogenic pathways in ACP.

Pediatric brain tumors: a bibliometric analysis.

The purpose of this study was to identify tendency and current issues in research on pediatric brain tumors over the past 20years and to help researchers and investors explore new directions for future research in this subject. Web of Science Core Collection was used for article selection and CiteSpace 5.8.R 1 was used for bibliometric analyses with these articles. The overall h-index was found to be 131 in the analysis made in a total of 4019 publications on the subject between the years 2000 and 2021. A total of 16,101 authors have published articles on pediatric brain tumors. The most active author in this field was Michael D. Taylor (h-index: 105). The publication which received the strongest citation burst among publications was published in 2016 by Louis et al. published in Acta Neuropathologica, and its content is the World Health Organization's classification of central nervous system tumors. Considering the country contribution, the USA is seen in the leading position. The most publications on the subject were followed by the Journal of Clinical Oncology. By examining the studies on childhood brain tumors carried out around the world, the subjects that can be determined as the focus were tried to be highlighted. And it has been seen that the scientific and industrial community should work together and the financial support for multidisciplinary studies should increase.

Editorial introductions.

Editorial introductions.

1374International representation of authors, editors and research in neurology journals

Abstract Background Published research informs international healthcare, yet only a few studies have assessed the representation of authors, editors, and research from developing countries in biomedical journals. Methods We reviewed all research articles published in five high-ranking peer-reviewed neurology journals (The Lancet Neurology, Acta Neuropathologica, Nature Reviews Neurology, Brain and Annals of Neurology) in 2010 and 2019 to determine the extent of contributions of authors, editors and research from developing countries, and the degree of international research collaboration between developed and developing countries. Results First authorship was attributed to authors from developing countries in only 2% (11/729) of research articles in 2010 and 3% (19/647) of research articles in 2019. All 144 editorial board members in 2019 were from developed countries. International research collaboration between developing and developed countries accounted for only 4% (30/729) of all research articles in 2010 and 6% (40/647) of all research articles in 2019. Conclusions Representation of authors, editors and research from developing countries is rare in high-ranking peer-reviewed neurology journals, and this has not improved over the past decade. Supporting high quality and contextually appropriate biomedical research now is necessary for developing countries to meet the rising healthcare needs of their populations in the future. Key messages Published research should reflect the diversity of global health. There is an urgent need for strategies to support high quality and contextually appropriate biomedical research in developing countries.

Gliosarcomas: A Rare Case Report at Viet Duc University Hospital and Review of the Literature

Gliosarcoma is a rare biphasic subtype of glioblastoma with the poor prognosis, principally affects adults; males are more frequently affected, with a male-to-female ratio of 1.8/1. Gliosarcomas are usually located in the cerebral hemispheres, involving the temporal, frontal, parietal, and occipital lobes in decreasing order of frequency. Rarely, gliosarcomas occur in the posterior fossa, lateral ventricles, or spinal cord. A case study: A 32-year-old woman presented with persistent nausea and headache. The preoperative diagnosis was Ependymoma in the right lateral ventricle of the brain. The patient underwent surgical resection of the tumor followed by external radiotherapy, and chemotherapy treatment. Histologic description: The tumor was made up of spindle cells with hyperchromic large nuclei and pink cytoplasm intermingled with large cells with markedly pleomorphic nuclei and abundant cytoplasm along with prominent mitotic activity. Tumour cells revealed positive staining for Ki67 (25%), Oligo2 (focal), GFAP (focal), SMA (focal); negative immunoreactivity for EMA, CD34, Bcl-2, TTF1. Pathological diagnosis: Gliosarcoma, grade IV. Conclusions: Gliosarcoma is an extremely rare neoplasm with an aggressive biological behavior. In terms of histopathology, gliosarcomas are characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. &#x0D; Keywords&#x0D; Gliosarcoma, glioblastoma multiforme, brain neoplasm.&#x0D; References&#x0D; [1] World Healh Organization, WHO Classification of Tumors of the Central Nervous System, International Agency for Research on Cancer (IARC) 69372 Lyon Cedex 08, France, 2016. [2] F. A. Hashmi, A. Salim, M. Shamim, M. Bari, Biological Characteristics and Outcomes of Gliosarcoma, The Journal of the Pakistan Medical Association, Vol. 68, No. 8, 2018, pp. 1273-1275. [3] P. Giglio, M. R. Gilbert, Encyclopedia of the Neurological Sciences (Second Edition), MA: Academic Press/Elsevier, Waltham, 2014. [4] R. K. Kevin, M. Anand, S. M. John, Adult Gliosarcoma: Epidemiology, Natural History, and Factors Associated with Outcome, Neuro Oncol, Vol. 11, No. 2, 2009, pp. 183-191, https://doi.org/10.1215/15228517-2008-076. [5] L. Han, X. Zhang, S. Qiu et al., Magnetic Resonance Imaging of Primary Cerebral Gliosarcoma: A Report of 15 Cases, Acta Radiologica, Vol. 49, No.9, 2008, pp. 1058-1067, doi:10.1080/02841850802314796. [6] D. N. Louis, H. Ohgaki, O. D. Wiestler et al., The 2007 WHO Classification of Tumours of the Central Nervous System, Acta Neuropathologica, Vol. 114, No. 2, 2007, pp. 97-109, doi:10.1007/s00401-007-0278-6. [7] L. Seth, P. Arie, I. James et al., Greenfield’s Neuropathology (Ninth Edition), CRC Press, Boca Raton, Florida, 2015. [8] L. Cervoni, P. Celli, Cerebral Gliosarcoma: Prognostic Factors, Neurosurgical Review, Vol. 19, No. 2, 1996, pp. 93-96, https://doi.org/10.1007/bf00418077. [9] J. Pardo, M. Murcia, G. Felip et al., Gliosarcoma: A Rare Primary CNS Tumor. Presentation of Two Cases, Reports of Practical Oncology &amp; Radiotherapy, Vol. 15, No. 4, 2010, pp. 98-102, https://doi.org/10.1016/j.rpor.2010.05.003. [10] J. Lutterbach, R. Guttenberger, A. Pagenstecher, Gliosarcoma: A Clinical Study, Radiotherapy andOncology, Vol. 61, No. 1, 2001, pp. 57-64,https://doi.org/10.1016/S0167-8140(01)00415-7. [11] B. K. Kleinschmidt, T. Tihan, F. Rodriguez, Diagnostic Pathology: Neuropathology (Second Edition), Elsevier, Philadelphia, 2016. [12] H. F. Irwin, W. G. Sidney, Sarcoma Arising in Glioblastoma of the Brain, Am J Pathol, Vol. 31, No. 4, 1955, pp. 633-653. [13] A. S. Awadalla, A. M. A. Essa, H. H. A. Ahmadi et al., Gliosarcoma Case Report and Review of the Literature, The Pan African Medical Journal, Vol. 35, No. 26, 2020, https://doi.org/10.3109/02841869709001353.&#x0D; &#x0D; &#x0D; &#x0D;

International representation of authors, editors and research in neurology journals

BackgroundPublished research informs international healthcare, yet only a few studies have assessed the representation of authors, editors, and research from developing countries in biomedical journals.MethodsWe reviewed all research articles published in five high-ranking peer-reviewed neurology journals (The Lancet Neurology, Acta Neuropathologica, Nature Reviews Neurology, Brain and Annals of Neurology) in 2010 and 2019 to determine the extent of contributions of authors, editors and research from developing countries, and the degree of international research collaboration between developed and developing countries.ResultsFirst authorship was attributed to authors from developing countries in only 2% (11/729) of research articles in 2010 and 3% (19/647) of research articles in 2019. All 144 editorial board members in 2019 were from developed countries. International research collaboration between developing and developed countries accounted for only 4% (30/729) of all research articles in 2010 and 6% (40/647) of all research articles in 2019.ConclusionsThere is urgent need for strategies to support high-quality and contextually appropriate biomedical research in developing countries. Supporting high quality and contextually appropriate biomedical research now is necessary for developing countries to meet the rising healthcare needs of their populations in the future.

Putative dendritic correlates of chronic traumatic encephalopathy: A preliminary quantitative Golgi exploration.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that is associated with repetitive head impacts. Neuropathologically, it is defined by the presence of perivascular hyperphosphorylated tau aggregates in cortical tissue (McKee et al., 2016, Acta Neuropathologica, 131, 75-86). Although many pathological and assumed clinical correlates of CTE have been well characterized, its effects on cortical dendritic arbors are still unknown. Here, we quantified dendrites and dendritic spines of supragranular pyramidal neurons in tissue from human frontal and occipital lobes, in 11 cases with (Mage = 79 ± 7 years) and 5 cases without (Mage = 76 ± 11 years) CTE. Tissue was stained with a modified rapid Golgi technique. Dendritic systems of 20 neurons per region in each brain (N = 640 neurons) were quantified using computer-assisted morphometry. One key finding was that CTE neurons exhibited increased variability and distributional changes across six of the eight dendritic system measures, presumably due to ongoing degeneration and compensatory reorganization of dendritic systems. However, despite heightened variation among CTE neurons, CTE cases exhibited lower mean values than Control cases in seven of the eight dendritic system measures. These dendritic alterations may represent a new pathological marker of CTE, and further examination of dendritic changes could contribute to both mechanistic and functional understandings of the disease.

MISSED OPPORTUNITIES FOR ORGAN DONATION FROM POTENTIAL DONORS WITH PRIMARY BRAIN TUMOURS IN AUSTRALIA; COHORT STUDY 2010-2015

Centre for Organ Donation Excellence. Aims: The critical shortage of donor organs represents a global challenge necessitating consideration of all potential safe donors. Most primary brain tumours (PBTs) are not a contraindication to organ donation as risk of tumour transmission to a transplant recipient is low. However, uncertainty regarding transmission risk and biovigilance may result in some referrals being overlooked due to the presence of PBT. We aimed to describe referrals with PBTs in New South Wales (NSW) Australia, identify any transmission events from PBT donors, and highlight potential missed opportunities for donation among organ donor referrals declined due to the presence of PBT. Methods: We undertook a retrospective population-based cohort study in NSW Australia, utilising the Safety and Biovigilance in Organ Donation (SAFEBOD) public health register linking donors’ and recipients’ records in NSW Organ and Tissue Donation Service datasets, NSW Ministry of Health datasets, and Australian transplant registries. We reviewed referrals 2010-2015, identifying and characterizing referrals and donors with PBTs. Tumours were classified using World Health Organization (WHO) grading and risk-assessed using Transplant Society of Australia and New Zealand (TSANZ) guidelines. Data linkage was used to determine accuracy of risk assessment at time of referral, and identify any PBT transmission events.Results: Of 2957 referrals 2010-2015, 76 (3%) had PBT. 44 (58%) of these PBTs were accurately graded at time of referral. Medical reasons other than PBT meant that 47 (62%) referrals were excluded, while 10 (13%) became donors. The remaining 19 (25%) referrals did not proceed to donate, and may represent missed donor opportunities. These referrals were significantly younger (47.7 vs. 58.6 years, p<0.001) and had fewer comorbidities (0.8 vs. 2.1, p<0.001) than referrals overall. WHO-I tumours were most common among PBT referrals (36, 47%) and PBT donors (8, 80%), but WHO-IV tumours predominated among missed opportunities (12, 68%) including glioblastoma multiforme (GBM) (11, 63%). All PBT donors had tumours categorized as ‘not contraindicated’ by TSANZ. No referrals with GBM or ventriculo-peritoneal shunt donated organs. No transmission events occurred after 860 months total follow up of 23 PBT transplant recipients.Conclusions: There remain opportunities to increase organ donation rates through greater consideration of referrals with PBTs. Risk of PBT transmission must be considered, especially when evaluating referrals with GBM. These risks should be balanced against others in transplantation, including receiving a marginal transplant or remaining on the transplant wait list. New South Wales Organ and Tissue Donation Service. New South Wales Ministry of Health. Reference: 1. Louis DN, Perry A, Reifenberger G et al. The 2016 World Health Organization classification of tumours of the central nervous system: a summary. Acta Neuropathologica. 2016;131(6):803-20

Diagnostic Accuracy of Amyloid versus FDG PET in Patients with Cognitive Impairment and Autopsy

Background: β-Amyloid and Flurodeoxyglucose (FDG) PET are clinically available diagnostic tools in the assessment of neurodegenerative disorders. We compared the diagnostic accuracy of [11C]Pittsburgh Compound B (PIB) and [18F]FDG PET in a large sample of patients with cognitive decline and neuropathology. Methods: 101 individuals underwent PIB and FDG during life and post-mortem neuropathological assessment. PET scans were visually interpreted by three raters blinded to clinical information. PIB scans were rated as positive or negative for cortical retention while FDG scans were read as showing an Alzheimer’s disease (AD) or non-AD metabolic pattern. AD neuropathological changes (ADNC) were measured at autopsy. Majority visual reads were compared to intermediate-high ADNC as the gold standard. Findings: 60 males and 41 females were included (average age: 67·2Y, mean MMSE: 21·9, mean PET-to-autopsy interval: 4·4Y). At autopsy, 32 patients showed pure AD pathology, 13 mixed AD and non-AD and 56 non-AD neuropathology. Compared to FDG, PIB showed higher sensitivity for detecting intermediate-high ADNC (96% [95% confidence interval: 89-100%] vs 80% [68-92%] for FDG, p=0·02) and higher negative predictive value (96% [91-100%] vs 84% [74-93%], p=0·01), but equivalent specificity (86% [76-95%] vs 84% [74-93%], p=0·80) and positive predictive value (84% [74-94%] vs 80% [68-92%], p=0·53). In patients with congruent PIB and FDG reads (77/101), combined sensitivity was 97% [92-100%] and specificity 98% [93-100%]. Nine of 24 patients with incongruent reads were found to have co-occurrence of AD and non-AD pathologies. Interpretation: PIB had higher sensitivity to detect intermediate-high ADNC compared to FDG, particularly at early clinical stages, with similar specificity. When both modalities are congruent, sensitivity and specificity approach 100%, while mixed pathology should be considered when PIB and FDG are incongruent. Funding Statement: National Institute of Health (R01-AG045611, P01-AG1972403, P50-AG023501, P30-AG010129, R01-AG032306, K24-AG053435, R01-AG038791, K08-AG052648, P30-AG010129, K23-AG045289), the Alzheimer’s Association (AARF-16-443577), Bluefield Project to Cure FTD, Tau Consortium. Declaration of Interests: Orit H Lesman-Segev – none, Renaud La Joie – none, Iryna Lobach - none, Howard J Rosen - Dr Rosen has received research support from Biogen Pharmaceuticals, has consulting agreements with Wave Neuroscience and Ionis Pharmaceuticals, and receives research support from NIH. Sang Won Seo - none, Mustafa Janabi - none, Suzanne L Baker - consult for Genentech, Lauren Edwards - none, Julie Pham - none, John Olichney - has received grant funding from Roche/Genentech, Adam Boxer - Dr. Boxer receives research support from NIH, the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer’s Drug Discovery Foundation and the Alzheimer's Association. He has served as a consultant for Aeton, Abbvie, Alector, Amgen, Arkuda, Arvinas, Asceneuron, Ionis, Lundbeck, Novartis, Passage BIO, Sangamo, Samumed, Third Rock, Toyama and UCB, and received research support from Avid, Biogen, BMS, C2N, Cortice, Eli Lilly, Forum, Genentech, Janssen, Novartis, Pfizer, Roche and TauRx. Eric Huang - none, Marilu Gorno-Tempini – none, Ji-Hye L. Hwang - none, Charles DeCarli - none, Mackenzie Hepker - none, Salvatore Spina - none, Bruce L Miller – Dr. Miller receives grants in support of the Memory and Aging Center from the NIH/NIA, the Quest Diagnostics Dementia Pathway Collaboration, Cornell University and The Bluefield Project to Cure Frontotemporal Dementia. He serves as Medical Director for the John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; and Past President of the International Society of Frontotemporal Dementia (ISFTD). Lea T Grinberg - Dr. Grinberg receives research support from Avid Radiopharmaceuticals, Eli Lilly. She has received consulting fees from Simon Foundation and Cura Sen Inc. She serves as associate editor for Frontiers in Aging Neurosciences, Frontiers in Dementia and Journal of Alzheimer Disease William W. Seeley - Dr. Seeley has received consulting fees from Biogen Idec, Third Rock Ventures, and Guidepoint Global Advisors. He serves on the editorial board of Acta Neuropathologica and Neuroimage Clinical. William J Jagust - Dr. Jagust has received honoraria as a consultant to Novartis, Genentech, and Curasen Gil D Rabinovici – Dr. Rabinovici receives research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare and Life Molecular Imaging. He has received honoraria as a consultant for Axon Neurosciences, Eisai and Merck, and speaking honoraria from GE Healthcare. Dr. Rabinovici serves as Associate Editor for JAMA Neurology. Ethics Approval Statement: Informed consent was obtained from all subjects or their surrogate decision makers, and the UCSF, UCD, University of California Berkeley (UCB) and/or Lawrence Berkeley National Laboratory (LBNL) Institutional Review Boards for human research approved the study.

Editorial introductions

Current Opinion in Oncology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of psychiatry is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Marc SansonMarc SansonDr Marc Sanson, MD, PhD is Professor at Sorbonne Université, Paris, France. He is active in clinical neuro-oncology at the Department of Neurology 2, Pitié-Salpêtrière Hospital in Paris. He is also head of the research team ‘experimental neuro-oncology’ at the Institut du Cerveau et de la Moelle (ICM) in Paris. Dr Sanson is the Director of the recently created “CURAMUS” site of Sorbonne-Université which is one of the eight French Sites for Integrated Research on Cancer (SiRIC). Dr Sanson has published many research articles on neuro-oncology, including more than 200 dedicated to gliomas, as well as book chapters, and is a frequently requested lecturer on this topic. His main interest is focused on clinical and translational research on gliomas, including novel targeted therapies, germline and somatic genetic characterisation and development of new biomarkers. He is a reviewer on a number of journals, including the Journal of Clinical Oncology, Lancet, Lancet Oncology, Annals of Oncology, Annals of Neurology, Neurology, Cancer, Clinical Cancer Research, Cancer Research and Acta Neuropathologica. Dr Sanson earned his MD at University R Descartes and his PhD at University D Diderot, both in Paris. He completed a residency in Neurology in Paris, and a post-doctoral stage at McGill University, Canada. Miguel A. SanzMiguel A. SanzDr Miguel A. Sanz is Head at the Department of Oncology, Hematology and Bone Marrow Transplant Unit at the University Hospital La Fe in Valencia, Spain, as well as Professor of Medicine at the University of Valencia. After earning his medical degree at the University of Salamanca in Spain, he was intern, resident and subsequently completed a fellowship in Hematology at the University Hospital La Fe. He was appointed as Head of the Clinical Hematology Section to the University Hospital La Fe in 1977 and then later promoted to Head of the Hematology Department in 2007. Professor Sanz is Chairman of the Spanish PETHEMA Group and leads the Working Parties of Acute Promyelocytic Leukemia and Infections in Neutropenic Patients. He is currently a reviewer for numerous high-profile medical journals, including all top hematology journals, and has authored more than 540 papers, peer-reviewed papers, numerous book chapters, and over 1100 abstracts at national and international meetings. Prof. Sanz has lectured widely in Europe, North, central and South America, as well as in the Middle East and Asia, and also at the American Society of Hematology and European Hematology Association meetings on several occasions.