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Protein Arginine Methyltransferase 5 (PRMT5) is an enzyme that regulates gene expression and protein function through arginine methylation. Its association with isocitrate dehydrogenase (IDH) mutation in Grade-4 astrocytoma was rarely investigated. Our aim was to aim to explore the association between IDH mutation and PRMT5 and its effect on tumor recurrence. A retrospective cohort of 34 patients with Grade 4 astrocytoma has been tested for PRMT5 expression using protein and gene expression arrays. The impact of IDH-mutation and PRMT5 expression on tumor recurrence was explored. IDH-wildtype was detected in 13 tumors. PRMT5 protein was highly expressed in 30 tumors and the expression was low in four tumors. PRMT5 gene expression was upregulated in 33 tumors and downregulated in a single tumor case. Tumors with different PRMT5 gene expressions and IDH mutation were found to have a significant statistical difference in recurrence-free interval (RFI) (p-value<0.001). IDH-wildtype glioblastoma with upregulated PRMT5 gene or protein expression showed earlier tumor recurrence compared to IDH-mutant Grade 4 astrocytoma with upregulated PRMT5 expression. The association between IDH mutation and PRMT5 in IDH-mutant Grade 4 astrocytoma or IDH-wildtype glioblastoma is indirectly bidirectional. PRMT5 upregulation in glioblastoma can lead to increased cell proliferation and tumor regrowth. [ABSTRACT FROM AUTHOR]

Background: Solitary plasmacytoma of the calvarium (SPC), without evidence of multiple myeloma (MM), is extremely rare. We report a case of a long-standing large SPC that was treated successfully by surgical excision and adjuvant radiotherapy with a long follow-up period. Case Description: A 58-year-old male patient presented with a 5-year history of painless skull swelling. On the physical examination, the mass was 6 × 6 cm in size, oval, not tender, and firm in consistency with normal skin color. A brain computed tomography scan showed a destructive skull lesion. A brain magnetic reasoning imaging (MRI) showed a large expansile lytic mass lesion arising from the skull vault in the frontal-parietal region with multiple internal septa. The patient underwent a craniectomy and excision of the lesion, followed by cranioplasty using methyl methacrylate. The final diagnosis was consistent with plasmacytoma based on the histopathological features. One month follow-up brain MRI showed no evidence of residual tumor. The skeletal survey and bone marrow biopsy did not reveal any evidence of MM. The patient was referred to medical oncology for further treatment and received radiation therapy. During nine years of clinical and radiological follow-up, there was no evidence of any metastasis or recurrence. Conclusion: SPC is a rare disease with high rates of misdiagnosis. Careful evaluations are crucial to exclude systemic involvement. Surgical resection followed by radiotherapy may be adequate for the disease control. Close follow-up with regular lifelong examinations is important to avoid a generalized incurable disease. [ABSTRACT FROM AUTHOR]

Introduction: CD8+ T-cells and MHC-I have been detected in brain gliomas with a significant outcome. The effect of chemotherapies on the crosstalk interaction between CD8+ T-cells and MHC-I has never been explored. Material and methods: The protein expression profiling of CD8 cytotoxic T-cells and the gene expression assay of MHC-I in 35 patients diagnosed with WHO grade 4 astrocytoma were performed. The impact of these two factors on tumor recurrence was analyzed. Results: IDH was wildtype in 13 tumors. MHC-I protein expression was absent or low in 34 tumors and dense in a single case. MHC-I gene expression was upregulated in 10 tumors and 25 tumors showed MHC-I gene downregulation. Temozolomide (TMZ) was given to 24 patients and 11 patients received TMZ plus other chemotherapies. No statistically signifi- cant association was observed between IDH mutation and CD8+ T-cells (p = 0.383). However, this association was significant in recurrence-free interval (RFI) (p = 0.012). IDH-wildtype tumors with highly infiltrated CD8+ T-cells or IDH-mutant tumors with low CD8+ T-cells showed late tumor recurrence. There was a statistically significant difference in RFI between tumors with different MHC-I expression and CD8+ T-cell counts after treatment with TMZ or TMZ plus (p = 0.026). Conclusions: No association between IDH mutation and CD8+ cytotoxic T-cell was found. IDH is directly linked to tumor recurrence regardless of CD8+ T-cells infiltration. TMZ plus other adjuvants is proved to be more effective in improving patient survival and delaying tumor recurrence, as compared to using TMZ alone. Nonetheless, none-TMZ adjuvants may increase tumor sensitization to cytotoxic T-cells more than TMZ. [ABSTRACT FROM AUTHOR]

Purpose: IDH1 and IDH2 are hotspot mutations commonly identified in WHO-grade 4 astrocytomas. Their association with TAMs has never been investigated. We aim to explore the crosstalk between the IDH1/2 mutation metabolic effect and TAMs in tumour microenvironment and how this relationship affects the tumour recurrence. Patients and Methods: The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1R132 and IDH2R172 was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry. Results: IDH1R132 and IDH2R172 were symmetrically identified as wildtype in 18/20 tumours (90%) and the remaining 2 tumours (10%) showed synonymous mutations on both codons. Tumours with IDH1/2-wildtype showed high expression of CD204+TAMs in 10 cases and low expression in 8 cases. Typical expression was seen equally in IDH1/2 mutant tumours. There was no significant association between IDH1/2 and CD204+TAM expression (p= 0.999). The association between the two groups was significantly observed among IDH-wildtype tumours (p=0.027). Highly expressed CD204 in IDH-wildtype tumours showed a median recurrence at 10 months compared to low CD204 expression, showed a median recurrence interval at 24 months. Conclusion: IDH1R132 or IDHR172 has the same impact on the classification and prognosis of WHO-grade 4 astrocytoma. There was no crosstalk between IDH1/2 metabolic effect and CD204+TAM. However, IDH-wildtype glioblastomas with dense CD204+TAM are associated with early recurrence. Because the sample size is small, a larger study is recommended to determine the impact of IDH1/2 on TAMs. [ABSTRACT FROM AUTHOR]

Tumors of the pineal region typically present with symptoms and signs of mass effect and increased intracranial pressure. However, although rare and can be overlooked, hearing impairment is a potential clinical finding in these cases. The authors describe a 24-year-old male who presented to the emergency room complaining of bilateral hearing impairment. Brain computed tomography showed a pineal region tumor. Histopathological examination demonstrated features consistent with germinoma. This case reports a rare presentation rarely seen in the literature and in practice as evident by the conducted literature review. Therefore, we highlight the importance of considering hearing impairment as a presenting symptom of pineal region tumors since prompt recognition and intervention, as demonstrated in this case, can lead to successful outcomes. [ABSTRACT FROM AUTHOR]

Aim of the study: Oligodendrocyte transcriptional factor-2 (Olig2) is an essential marker for oligodendrocytes expression. We aimed to explore the expression of Olig2 in different glial neoplasms and to investigate if diffuse Olig2 expression can replace 1p19q co-deletion for the diagnosis of oligodendroglioma. Material and methods: Olig2 was performed on 53 samples of different glial neoplasms using immunohistochemistry (IHC). 1p/19q deletions were investigated using fluorescence in situ hybridization (FISH). Results: Olig2 labelling of different glial neoplasms revealed various expressions, in which 26 tumours showed diffuse expression (≥ 60%) and 23 tumours showed partial focal expression (< 50%). Four tumours showed no expression. Of the 26 tumours, 6 oligodendrogliomas had 1p19q co-deletion and the remaining 3 oligodendrogliomas showed no co-deletion. Three non-oligodendroglial tumours were found to have 19q deletion. The FISH of the remaining tumours (14/26) showed no aberrations. There was no significant difference in the final diagnosis by using 1p19q co-deletion test among glial neoplasms with diffuse Olig2 expression (p = 0.248). Conclusions: Olig2 marker cannot be used as an alternative diagnostic method for 1p19q co-deletion to distinguish oligodendrogliomas from other glial neoplasms. Although some glial tumours showed diffuse Olig2 expression, 1p19q co-deletion testing is the best diagnostic method. [ABSTRACT FROM AUTHOR]

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Objective: Unusual clinical course Background: Chronic subdural hematoma is defined as collection in the subdural space for more than 3 weeks. The incidence ranges from 1 to 20 per 100 000/year, with increased prevalence in the elderly, in males, and with use of anticoagulants or antiplatelets. Chronic myeloid leukemia has been linked to spontaneous subdural hematoma, with the highest reported cases of 39 patients in Korea, but no management is mentioned in that paper. There are few reported cases of patients who are medically free with no use of anticoagulants, diagnosed as having a subdural hematoma and then later discovered to have chronic myelogenous leukemia. Case Report: We report the case of a 45-year-old man, with known hypertension and diabetes mellitus type 2, on aspirin weekly, who was referred from another hospital with a history of sudden-onset severe headache not related to trauma. Computed tomography (CT) of the brain done in the other hospital showed a left-side subdural hematoma with midline shift. He underwent left-sided acute subdural hematoma evacuation and decompressive hemicraniectomy. He was started on hydroxyurea for chronic myelogenous leukemia. Conclusions: A lesson from this rare case is to look for a differential diagnosis and to keep chronic myelogenous leukemia in mind in patients with leukocytosis. Also, we recommend sending a hematology referral in nontraumatic subdural hematoma. There is no specific treatment or algorithm based on previous research, although from observed data and based on information from the American Heart Association, it is reasonable to perform craniectomy in extra-axial collections of more than 1 cm with midline shift to avoid mortality, as reaching a diagnosis would take too much time. [ABSTRACT FROM AUTHOR]

Tumor suppressor (p53) acts to integrate multiple stress signals into diverse antiproliferative responses. Its potential to transactivate or downregulate genes through apoptotic pathway in IDH-wildtype glioblastoma has never been explored. A group of twenty patients diagnosed with IDH-wildtype glioblastoma, were tested for p53 expression and NDRG2/NRF2 genes activity through protein and gene profiling assays. The connotation between these elements has been explored. The mean patients' age was 64-years. All tumors were IDH-wildtype. p53 was expressed in 12 tumors and absent in 8 tumors. The activity of NDRG2 gene was downregulated in all cases. The activity of NRF2 gene was upregulated in 17 tumors and downregulated in 3 tumors. There was a significant statistical difference in PFS among tumors exhibiting different levels of p53 expression and NDRG2 gene activity [p-value= 0.025], in which 12 tumors with downregulated NDRG2 expression and positive p53 expression had earlier tumor recurrence. This statistical difference in PFS was insignificant when we compared p53 expression with NRF2 gene activity [p-value= 0.079]. During cell cycle arrest at G2 phase, p53 expression in IDH-wildtype glioblastoma in elderly individuals, coupled with the downregulation of NDRG2 gene activity, led to an aberrant increase in tumor cell proliferation and accelerated tumor recurrence. However, the influence of p53 on NRF2 gene activity was found to be insignificant. [ABSTRACT FROM AUTHOR]

MHC-I expression is a crucial factor in cancer immunity, and its regulations can impact tumor progression and recurrence. The mechanism through which glioblastoma use MHC-I to avoid immunosurveillance has been rarely investigated. A retrospective cohort of 35 patients with IDH-mutant WHO-Grade 4 astrocytoma and IDH-wildtype glioblastoma were examined for MHC-I using protein and gene expression assays. The association between IDH mutation, TP53 mutation, and MHC-I expression with recurrence-free interval were investigated. The average patients' age was 49.6 year. IDH was wildtype in 13 tumors. MHC-I protein expression was absent in 30 tumors, faint in 4 tumors, and membrane bound dense expression in single tumor. MHC-I expression was upregulated in 10 tumors and 25 tumors showed MHC-I downregulation. P53 was positively expressed in 19 cases and lost in 13 cases. A significant statistical difference was observed in the RFI between tumors with distinct MHC-I expression and IDH-mutation [p-value = 0.008]. IDH-wildtype tumors with upregulated MHC-I expression showed late tumor recurrence compared to IDH-wildtype tumors with downregulated MHC-I expression. There was insignificant statistical difference in RFI among patients with varying degree of MHC-I expression, who received TMZ or TMZ and other chemotherapies [P-value = 0.44] Glioblastoma with upregulated MHC-I showed a delayed tumor recurrence in comparison to those with downregulated MHC-I expression. However, downregulated MHC-I may not necessarily be an indicator of poor problems. [ABSTRACT FROM AUTHOR]

NDRG2 is a tumour suppressor gene involved in tumor growth inhibition. Its effect on tumour recurrence remains controversial. The aim of this study is to explore the dual effect of IDH mutation and NDRG2 dysregulation in WHO-Grade 4 astrocytoma recurrence. A group of 36 patients with WHO-Grade 4 astrocytoma were examined for NDRG2 expression using protein and gene expression assays. The relationship between IDH, NDRG2 protein and gene expressions, and recurrence-free interval [RFI] was explored. The mean patients age in this study was 45-years with 21 males and 15 females. IDH was mutant in 22 tumors. NDRG2 protein expression was low in 23 tumors, and high in 13 tumors. NDRG2 gene expression was upregulated in 4 tumors and 32 tumors showed NDRG2 gene downregulation. The consistency between two tasting methods of NDRG2 expression was 52.8%. There was a significant statistical difference in RFI among tumors with varying NDRG2 gene expression and IDH mutation [p-value= 0.021]. IDH-mutant tumours with downregulated NDRG2 expression showed late recurrence compared to IDH-wildtype glioblastoma. IDH-mutant WHO Grade-4 astrocytoma with downregulated NDRG2 gene are associated with late tumor recurrence. IDH mutations cause excessive accumulation of D-2-hydroxyglutarate, that may inhibit the activity of TET proteins, potentially leading to DNA hypermethylation and gene silencing. [ABSTRACT FROM AUTHOR]

Background: The significance of histological grading and peritumoral edema (PTE) in predicting intracranial meningioma recurrence among Saudis is often neglected. This study aimed to evaluate the impact of these factors over a 10-year follow-up period., Methods: A retrospective cohort of 124 patients with intracranial meningioma was analyzed over the period from 2011 to 2021. All patients underwent gross total resection (GTR) of the tumor. Post-surgical radiotherapy (RT) was offered to patients with grade II-III meningiomas. The impact of histological grading, PTE, and RT on the recurrence-free interval (RFI) was investigated., Results: The mean age of the patients was 49 years (range: 18 - 84), with 87 females (70.2%) and 37 males (29.8%). Most tumors (88.7%, n = 110) were supratentorial, while 11.3% (n = 14) were infratentorial. The World Health Organization (WHO) grading classified 101 tumors (81.5%) as grade I, 17 (13.7%) as grade II, and six (4.8%) patients as grade III. Grading was significantly associated with RFI (P = 0.013), with grade I meningiomas having the slowest recurrence. The overall recurrence rate was 16.9%, with 38.1% (n = 8) of grade I and 61.9% (n = 13) of grade II-III meningiomas recurring within 5 years post-GTR and RT. There was no significant difference in RFI between RT-exposed and non-exposed patients (P = 0.15). PTE was present in 76 cases (61.3%) and absent in 48 (38.7%), significantly affecting RFI (P = 0.014), with shorter RFI in PTE cases. Overall, 95.2% (n = 118) of patients survived, while 4.8% (n = 6) died; five had grade II-III, and one had grade I meningioma., Conclusions: Totally, resected intracranial meningiomas with grade II-III features and PTE were associated with earlier tumor recurrence and poorer patient survival. Post-surgical RT had an insignificant effect on the RFI., Competing Interests: The authors have no relevant conflict of interest to disclose., (Copyright 2025, Alkhotani et al.)

Metabolic reprogramming within tumor cells involves a shift towards either glycolysis or mitochondrial respiration, depending on the stage of tumor progression. Consequently, irreversible dysfunction of the mitochondria is considered a crucial mechanism driving the progression mechanism. While numerous mutations in mitochondrial DNA (mtDNA) have been identified across various tumor types, including glioblastoma, many studies have been limited in the scope, focusing on small segments of mtDNA or utilizing sequencing methods with restricted sensitivity. As a result, several potentially significant mtDNA mutations may have been underestimated, along with their heteroplasmic states, which play a crucial role in determining the phenotypic impact of mtDNA mutation. Although both somatic and germline mtDNA mutations have been observed in different tumor types, research on the mtDNA mutations linked to glioblastoma remains scarce. The mitochondrial genome encodes thirteen protein-coding genes that are essential for the proper functioning of respiratory complex chains. Alterations in mitochondrial function manifest at various levels, including structural and functional changes, impacting mitogenic, hemodynamic, bioenergetic, and apoptotic signaling pathways. These alterations often signify a reduced efficiency of the oxidative phosphorylation system and energy production in tumor cells. As the crucial role of mitochondrial dysfunction in glioma development grows, mitochondria have emerged as promising targets for therapy aimed at overcoming chemoresistance and eliminating cancer cells. This brief review outlines the association between mtDNA alteration and glioblastoma, as well as the current advancements in therapeutic strategies targeting mtDNA alterations., (© 2024 The Author(s). Published by IMR Press.)

Background:  Deep brain stimulation (DBS) is a neurosurgical procedure approved for treating psychiatric and movement disorders, including Parkinson's disease (PD), essential tremor, dystonia, and other neurological conditions. The widespread use of DBS may not be reflected in the medical education curricula in Saudi universities, thus jeopardizing future patients' access to it. This study aims to investigate the knowledge and attitudes of medical students toward DBS as a therapeutic option., Method: A descriptive cross-sectional questionnaire-based study was conducted. The survey was distributed on online platforms to acquire responses from different regions of Saudi Arabia. The target population was medical students in the preclinical and clinical phases of medical education from different regions of Saudi Arabia., Results: A total of 1075 medical students from various medical schools in Saudi Arabia were included. More than half of the students aged 21 to 23 (50.1%) were females (63.2%). More than half of the students have correctly recognized DBS as a Food and Drug Administration (FDA)-approved treatment (59.7%). Only 20.1% of the students stated that they received adequate education/training about DBS. About 53.8% of the students had self-rated their knowledge as poor, whereas 20.6% had rated their knowledge as good. A negative bias was more observed among the older students and students with a family history of DBS treatment. Half of the participants (54.1%) indicated that DBS is associated with severe adverse effects. A significant association between the level of knowledge about DBS and the academic level was observed., Conclusion: Almost half of the medical students had poor knowledge and unfavorable attitude toward DBS in Saudi Arabia. The current medical curricula are incommensurable with the clinical implications of DBS, which may deny future patients from such an effective therapeutic option. We recommend incorporating DBS teaching sessions to enhance future physicians' awareness and understanding of the benefits of this intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Aldharman et al.)

Purpose: IDH1 and IDH2 are hotspot mutations commonly identified in WHO-grade 4 astrocytomas. Their association with TAMs has never been investigated. We aim to explore the crosstalk between the IDH1/2 mutation metabolic effect and TAMs in tumour microenvironment and how this relationship affects the tumour recurrence., Patients and Methods: The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1 R132 and IDH2 R172 was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry., Results: IDH1 R132 and IDH2 R172 were symmetrically identified as wildtype in 18/20 tumours (90%) and the remaining 2 tumours (10%) showed synonymous mutations on both codons. Tumours with IDH1/2-wildtype showed high expression of CD204 + TAMs in 10 cases and low expression in 8 cases. Typical expression was seen equally in IDH1/2 mutant tumours. There was no significant association between IDH1/2 and CD204 + TAM expression (p= 0.999). The association between the two groups was significantly observed among IDH-wildtype tumours (p=0.027). Highly expressed CD204 in IDH-wildtype tumours showed a median recurrence at 10 months compared to low CD204 expression, showed a median recurrence interval at 24 months., Conclusion: IDH1 R132 or IDH R172 has the same impact on the classification and prognosis of WHO-grade 4 astrocytoma. There was no crosstalk between IDH1/2 metabolic effect and CD204 + TAM. However, IDH-wildtype glioblastomas with dense CD204 + TAM are associated with early recurrence. Because the sample size is small, a larger study is recommended to determine the impact of IDH1/2 on TAMs., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Kurdi et al.)

Novel Severe Acute Respiratory Syndrome-Corona Virus-2 infection (SARS-CoV-2) is an acute respiratory and infectious disease. This perspective aims to provide a basic understanding of the inflammation caused by SARS-CoV-2 and its relation to the trigeminal ganglion (TG). The virus enters through the mucous membranes of the orofacial region and reaches the TG, where it resides and takes control of its peptides including Substance P (SP). SP is the main neuropeptide, neuromodulator, and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and, consequently, affects the immune cells and blood vessels to release the mediators for inflammation. Hence, cytokine storm is initiated and causes respiratory distress, bronchoconstriction, and death in complicated cases. Neurokinin-1 Receptor (NK-1R) is the receptor for SP and its antagonists, along with glucocorticoids, may be used to alleviate the symptoms and treat this infection by blocking this nociceptive pathway. SP seems to be the main culprit involved in the triggering of inflammatory pathways in SARS-CoV-2 infection. It may have a direct association with cardio-respiratory rhythm, sleep-wake cycle, nociception, and ventilatory responses and regulates many important physiological and pathological functions. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation. Here, it is further proposed that there is a possibility of latency in SARS-CoV-2 virus infection if it is acting through TG, which is the main site for other viruses that become latent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mehboob, Kurdi, Bamaga, Aldardeir, Nasief, Moshref, Alsinani, Rayes and Jabbad.)