Comparative Analysis of the Prognostic Significance of IDH,TERT, EGFR and MGMT Status in Patients with Adult Non-H3-Altered Grade 4 Gliomas: A Prospective Cohort Study.

INTRODUCTION: Gliomas continue to have a dismal prognosis. A myriad of genetic alterations has been described in this subset of tumors over the last decades. The integrative interpretation of the biomarker constellation for individual patients remains unclear. This study aims to evaluate the impact of some known genetic factors as prognostic biomarkers in grade 4 gliomas. METHODS: Adult non-H3-altered grade 4 gliomas who underwent maximal safe resection accompanied by adjuvant therapy were successively enrolled since January 2019 till January 2021. Patient data were documented preoperatively and during the follow-up visits. The genetic profiling of the tumors included Isocitrate Dehydrogenase (IDH)-1 and IDH-2 mutation, MGMT promoter methylation rate, EGFR gene amplification and telomerase reverse transcriptase gene promoter (TERTp) mutation. RESULTS: Mean Overall survival (OS) and Progression-free survival (PFS) were 14.45 ± 5.13 months (3-24 months) and 10.66 ± 4.87 months respectively. TERTp-mutant group had a significantly lower OS (10.9 vs. 15.9) and PFS (6.9 vs. 12.3) than TERTp wildtype group. In the TERT-mutant group, those with concomitant IDH wildtype tumor had higher OS and PFS, comparable to those with both TERTp and IDH wildtype tumors. In multivariate analysis, IDH mutation and TERTp wildtype status were predictive of longer OS and PFS. While IDH and absence of TERTp mutation were associated with KPS > 80 across the follow-ups, their predictive values were inferior to preoperative KPS scores. CONCLUSIONS: TERTp mutation and IDH-wildtype status were associated with worse OS and PFS and lower follow-up KPS score in surgically resected gliomas, while MGMT and EGFR status did not have considerable prognostic value in this study.

Perioperative seizure in patients undergoing brain mapping under awake craniotomy for language-related eloquent region gliomas: a prospective study.

BACKGROUND: Awake craniotomy (AC) is standard of care for lesions of eloquent brain areas. One important complication during AC is occurrence of intraoperative seizure (IOS), reported to occur among 3.4-20% of the patients. In this study, we report our experience with IOS during AC for resection of gliomas of the language eloquent regions and evaluate the predisposing factors and consequences. METHODS: Patients who underwent AC for language related regions of the dominant hemisphere from August 2018 to June 2021 were enrolled. The rate of IOS during AC and relationship between predisposing factors and IOS were evaluated. RESULTS: Sixty-five patients were enrolled (mean age: 44.4±12.5 years). Among 6 patients with IOS (9.2%), only one needed conversion to general anesthesia (GA) due to repeated seizures; while in the remaining 5, AC accomplished successfully despite one seizure attack in the awake phase. Tumor location (especially premotor cortex lesions, P=0.02, uOR:12.0, CI: 1.20-119.91), higher tumor volume (P=0.008, uOR: 1.9, CI: 1.06-1.12) and a functional tumor margin during surgery (P=0.000, uOR: 3.4, CI: 1.47-12.35) were significantly linked with IOS. CONCLUSIONS: Occurrence of IOS was associated with a longer ICU stay after surgery and worse immediate neurological outcome, but had no impact on the late neurological status. IOS can usually be managed during AC without need to converting to GA. Those with larger tumors, frontal premotor lesions and positive brain mapping are susceptible to IOS. Early neurological deterioration observed after IOS, seems to be transient with no major long-term consequence on the neurological outcome.

Disparity of Primary and Secondary Language Outcomes in Bilingual Patients Undergoing Resection of Glioma of the Speech-Related Regions.

BACKGROUND: The existing data about language recovery in bilingual patients come from few studies on acute lesional deficits like stroke or traumatic injury. Still, little is known about the neuroplasticity potential of bilingual patients who undergo resection of gliomas affecting language-eloquent brain regions. In this study, we prospectively evaluated the pre- and postoperative language functions among bilinguals with eloquent region gliomas. METHODS: We have prospectively collected the preoperative, 3-month and 6-month postoperative data from patients with tumors infiltrating the dominant hemisphere language areas during a 15-month period. Validated Persian/Turkish version of Western Aphasia Battery test and Addenbrooke Cognitive Examination were assessed for main language (L1) and second acquired languages (L2) in each visit. RESULTS: Twenty-two right-handed bilingual patients were enrolled, and language proficiencies were assessed using mixed model analysis. On baseline and postoperative points, L1 had higher scores in all Addenbrooke Cognitive Examination and Western Aphasia Battery subdomains than L2. Both languages had deterioration at 3-month visit; however, L2 was significantly more deteriorated in all domains. At 6-month visit, both L1 and L2 showed recovery; however, L2 recovered to a less extent than L1. The single most parameter affecting the ultimate language outcome in this study was the preoperative functional level of L1. CONCLUSIONS: This study shows L1 is less vulnerable to operative insults and L2 may be damaged even when L1 is preserved. We would suggest the more sensitive L2 be used as the screening tool and L1 be used for confirmation of positive responses during language mapping.

Alteration of anxiety and depression after awake craniotomy: a prospective study on patients with language eloquent high-grade glioma.

BACKGROUND: Awake craniotomy (AC) is considered to achieve maximal safe resection of language eloquent gliomas. Impact of AC on the psychological status of patients (mainly anxiety, and post-traumatic stress disorder [PTSD]) is a potential concern. Despite the studies reporting the early postoperative patient's perception after AC, this study has been performed to quantitatively evaluate the long-term influence of AC on the level of anxiety/depression after surgery. METHODS: Patients who underwent AC for suspected language eloquent high-grade glioma were enrolled in this study. The anxiety, depression and PTSD of the patients were evaluated via hospital anxiety and depression scale (HADS) one week before and 1 and 6 months after the operation. PTSD symptoms were assessed according to the DSM-V checklist and confirmed by a structured clinical interview for DSM-V. RESULTS: Twenty-eight patients (22 men, six women) with the mean age of 39.2 years were enrolled. The mean preoperative depressive and anxiety score was 4.9±5.9 and 7.7±5.8 respectively. One month after surgery they were 6±4.9 and 7.4±6.2 and at 6 months' follow-up 5.5±5.1 and 5.4±4.2 respectively. There was no statistically significant trend for alterations of the anxiety/depression levels before and after surgery. Female patients, those suspected to have glioblastoma and patients presenting with speech disturbance had remarkably higher preoperative anxiety levels. Three patients had PTSD symptoms 3 months after AC while at 6 months there was no indication of PTSD. The decremental trend of PTSD score within 6 months was statistically significant. CONCLUSIONS: Judicious application of AC is not associated with an escalation of the anxiety/depression level among the patients. Even patients with high preoperative anxiety levels could be managed with AC without severe psychological deterioration.

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.

Changes in Cognitive Functioning After Surgical Resection of Language-related, Eloquent-area, High-grade Gliomas Under Awake Craniotomy.

BACKGROUND: Dominant-hemisphere tumors, especially gliomas, as infiltrative tumors, frequently affect cognitive functioning. Establishing a balance between extensive resection, which is proven to result in longer survival, and less extensive resection, in order to maintain more cognitive abilities, is challenging. OBJECTIVE: To evaluate changes in cognitive functioning before and after surgical resection of language-related, eloquent-area, high-grade gliomas under awake craniotomy. METHOD: We provided individuals with newly diagnosed high-grade gliomas of the language-related eloquent areas with the same standard of care, including surgical resection of the glioma using intraoperative sensory-motor and cognitive mapping under awake craniotomy, and the same protocol for chemoradiotherapy. Cognitive functioning was assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R) at four time points (preoperatively, early after surgery, and 3 and 6 months postoperatively). RESULTS: The preoperative evaluation revealed a range of cognitive impairments in 70.7% of the individuals, affecting all of the cognitive subdomains (mostly attention and visuospatial abilities). Overall cognitive functioning (ie, ACE-R score) dropped by 13.5% (P = 0.169) early postoperatively. At the 3-month evaluation, an average of 15.3% (P = 0.182) recovery in cognitive functioning was observed (mostly in verbal fluency: 39.1%). This recovery improved further, reaching 29% (P < 0.001) at the 6-month evaluation. The greatest improvement occurred in verbal fluency: 68.8%, P = 0.001. CONCLUSION: Extensive resection of eloquent-area gliomas with the aid of modern neuroimaging and neuromonitoring techniques under awake craniotomy is possible without significant long-term cognitive sequela.

Meningioma as the host for metastatic breast cancer: A rare occurrence with important therapeutic impact.

BACKGROUND: Tumor-to-tumor metastasis is a rare condition. There are few reports of metastatic tumors within intracranial tumors, including meningiomas. Since some metastatic tumors have osteoblastic imaging pattern, it is not always easy to differentiate them from meningioma on preoperative studies. CASE DESCRIPTION: A 60-year-old female referred to our center complaining about a progressive headache, nausea, and vomiting for the past month. She had a history of breast cancer treated with radical mastectomy (5 years ago) and adjuvant chemotherapy (until 1 year ago). Workups revealed a dural-based mass in the left temporobasal and midline subfrontal regions. Histopathological study showed breast cancer metastasis nests within the primary meningioma. CONCLUSION: As the diagnosis of metastatic nests inside a benign tumor, drastically alters postoperative adjuvant treatments, a high index of suspicion is needed evaluating tumors from patients with a history of systemic neoplasms.

Juvenile Psammomatoid Ossifying Fibroma of the Orbital Roof: A Rare Cause of Proptosis among Children.

INTRODUCTION: Juvenile psammomatoid ossifying fibroma (JPOF) is a rare bone tumor characterized by a predilection for the sinonasal region and a tendency to affect younger patients, with a potential for aggressive growth and high recurrence (30-56%). JPOF warrants complete surgical resection to avoid recurrence. CASE PRESENTATION: In this article, we report a young boy who presented with unilateral prop-tosis with an expansile bony tumor with ground glass appearance involving the left frontal bone and orbital roof on his images. Complete surgical resection was done, and histopathological examination revealed JPOF with abundant psammomatoid bodies. DISCUSSION: This patient is a rare case of neurocranial JOPF and adds new features to the typical features already described for JPOF.

Status of essential elements in autism spectrum disorder: systematic review and meta-analysis.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that imposes heavy financial burden on governments and families of affected children. It is considered a multifactorial condition, where trace elements are among environmental factors that may contribute to ASD. Meanwhile, the between-study variance is high. The present systematic review was designed to investigate the difference in trace element measures between patients with ASD and control subjects. Meta-analyses showed that the hair concentrations of chromium (p=0.024), cobalt (p=0.012), iodine (p=0.000), iron (p=0.017), and magnesium (p=0.007) in ASD patients were significantly lower than those of control subjects, while there were higher magnesium levels in the hair of ASD patients compared to that of controls (p=0.010). Patients with ASD had higher blood levels of copper (p=0.000) and lower levels of zinc compared to controls (p=0.021). Further urinary iodine levels in patients with ASD were decreased in comparison with controls (p=0.026). Sensitivity analyses showed that ASD patients in non-Asian but not in Asian countries had lower hair concentrations of chromium compared to controls. Also, such analyses indicated that ASD patients in Asian countries had lower hair zinc concentrations, whereas ASD patients in non-Asian countries had higher hair zinc concentrations in comparison with control subjects. This study found significant differences in the content of trace elements between patients with ASD compared to controls. The findings help highlighting the role of trace elements as environmental factors in the etiology of ASD.