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.

Design of a multi-epitopic vaccine against Epstein-Barr virus via computer-based methods.

Background: Scientific findings have shown that Epstein-Barr virus (EBV) plays a key role in the development of some tumor diseases. Therefore, this study intends to take a practical step in controlling the pathogenicity of this virus by designing an effective vaccine based on the virus Capsid Envelope and Epstein-Barr nuclear immunogen (EBNA) Proteins Epitopes. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. So, we applied a computer-based strategy to design an epitope vaccine. Results: We designed a powerful multi-epitope peptide vaccine against EBV using in silico analysis. The vaccine is made up of 844 amino acids derived from three different types of proteins (Envelope, Capsid, EBNA) found in two different viral strains. responses. These epitopes have a high immunogenic capacity and are not likely to cause allergies. To enhance the vaccine immunogenicity, we used rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, as an adjuvant and linked it to the vaccine's N and C terminus. The physicochemical and immunological properties of the vaccine structure were evaluated. The proposed vaccine was stable, with a stability index of 33.57 and a pI of 10.10, according to bioinformatic predictions. Docking analysis revealed that the vaccine protein binds correctly with immunological receptors. Conclusion: Our results demonstrated that the multi-epitope vaccine might be potentially immunogenic and induce humoral and cellular immune responses against EBV. This vaccine can interact appropriately with immunological receptors Also, it has a high-quality structure and suitable characteristics such as high stability.

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.

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.

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.

Comparison of Preoperative Hypertonic Saline versus Mannitol for Intraoperative Brain Relaxation and Early Postoperative Outcome among Patients with Cerebral Low-grade Glioma: A Prospective Study.

INTRODUCTION: Hypertonic saline (HS) has an important role in the treatment of raised intracranial pressure after traumatic brain injury. This study evaluates the efficacy and safety of HS and its impact on the postoperative course of patients undergoing craniotomy for low-grade gliomas. MATERIALS AND METHODS: Sixty patients with supratentorial low-grade glioma were enrolled. All patients were anesthetized and operated with the same team and protocol. They successively received either HS or mannitol just before surgery. The amount of brain edema was classified according to the dural tension score (I-III) just after craniotomy and before dural opening. Other intraoperative measurements (such as urine output, need, and dosage of other diuretic agents) and postoperative findings (intensive care unit [ICU] and hospital stay, corticosteroid demand, and confusion period) were also assessed. Pre- and postoperative serum S100B levels were documented in both groups. RESULTS: The dural tension score was not significantly different among the two groups: severe tension in six and five patients in the mannitol and HS groups, respectively. HS group had a significantly lower amount of diuresis (609 vs. 725 ml) during surgery. Patients in the HS group had shorter ICU stay (16.3 vs. 27.9 h) and shorter duration of corticosteroid therapy after surgery (3.4 vs. 5.2 days). CONCLUSION: HS infusion just before the onset of craniotomy is at least as effective as mannitol in controlling intraoperative brain edema in patients with supratentorial glioma. Improved early postoperative course and lower degrees of S100B rise after craniotomy seen in the HS group needs to be explained in more detailed studies.

Total Corpus Callosotomy for Medically Refractory Status Epilepticus Due to Progressive Myoclonic Epilepsy: A Clinically Challenging Case.

BACKGROUND: Progressive myoclonic epilepsy (PME) is a syndrome characterized by development of progressive myoclonus, cognitive impairment, and other neurologic deficits. Despite major advances in medical treatment of epilepsy, some PME patients remain refractory to antiepileptic drugs. This may further accentuate cognitive impairment and deteriorate functional capacity. Corpus callosotomy (CC) is used in patients with drug-resistant epilepsy who are not candidates for either excisional epilepsy surgery or neurostimulation. We report the application of the standard complete callosotomy to control medically refractory status epilepticus in a patient with PME. CASE DESCRIPTION: A 16-year-old boy was referred to the emergency department with generalized tonic-clonic seizures. He was known to have PME since 5 years earlier, with frequent generalized seizures requiring hospitalization and reloading of the drugs. The patient was discussed by the epilepsy surgery working group, and corpus callosotomy was considered as a last resort to control the refractory status epilepticus. The patient experienced no generalized seizures during the 3-month postoperative period (Engel class IIIB). CONCLUSIONS: Inasmuch as surgery was the last resort to control severe disabling status epilepticus, because most of the epileptogenic discharges were originating from the parieto-occipital regions and profound cognitive impairment was present, we decided to perform a complete rather than just an anterior callosotomy. CC may be considered to prevent secondary generalized seizures as the most disabling attacks in patients with certain epilepsy syndromes. Nevertheless, the impact of palliative surgical intervention on the overall disease course of patients with an underlying diffuse pathologic state remains to be determined.