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.

Prognostic Factors of the Primary Central Nervous System Lymphoma: Clinical Experience from a Tertiary Care Center in the Middle East.

Aim Primary central nervous system lymphoma (PCNSL) is a rare extra nodal non-Hodgkin's lymphoma. The optimal treatment for PCNSL is still unclear. In this study, we present our experience with management of PCNSL in a tertiary care center in Iran. Methods In this retrospective study, 58 patients with tissue diagnosis of PCNSL were studied. All patients were treated with chemotherapy including intravenous high-dose methotrexate, rituximab and temozolomide and radiotherapy by the same oncologist. Statistical analysis was performed using SPSS. Results The mean overall survival (OS) in this study was 37.4 ± 13.6 months and the mean progression free survival (PFS) was 35.1 ± 9.8 months. The mean time to progression was 15.2 ± 8.79 months among 8 patients who experienced progression in this series. Finding of a positive CSF cytology was not linked with disease progression, while HIV infection and multifocal involvement at initial presentation were strongly linked to a lower PFS. The single most important factor affecting the OS was the histopathologic type of the PCNSL; two of the three patients who died from their disease in this series had non-B cell PCNSL, whereas only one patient with DLBCL died because of brainstem involvement. Conclusion The results of this study show a lower rate of HIV-infection in patients with PCNSL as compared to the series from the western countries. Non-B cell histopathology and HIV-infection were found to be associated with the dismal prognosis.

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.

Photoacoustic-MR Image Registration Based on a Co-Sparse Analysis Model to Compensate for Brain Shift.

Brain shift is an important obstacle to the application of image guidance during neurosurgical interventions. There has been a growing interest in intra-operative imaging to update the image-guided surgery systems. However, due to the innate limitations of the current imaging modalities, accurate brain shift compensation continues to be a challenging task. In this study, the application of intra-operative photoacoustic imaging and registration of the intra-operative photoacoustic with pre-operative MR images are proposed to compensate for brain deformation. Finding a satisfactory registration method is challenging due to the unpredictable nature of brain deformation. In this study, the co-sparse analysis model is proposed for photoacoustic-MR image registration, which can capture the interdependency of the two modalities. The proposed algorithm works based on the minimization of mapping transform via a pair of analysis operators that are learned by the alternating direction method of multipliers. The method was evaluated using an experimental phantom and ex vivo data obtained from a mouse brain. The results of the phantom data show about 63% improvement in target registration error in comparison with the commonly used normalized mutual information method. The results proved that intra-operative photoacoustic images could become a promising tool when the brain shift invalidates pre-operative MRI.

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.

Adult cerebellopontine angle ependymoma presenting as an isolated cisternal mass: A case report.

INTRODUCTION: Ependymomas represent approximately 2%-8% of all primary intracranial brain tumors. The occurrence of extra-axial posterior fossa ependymomas in adults is rare. CASE AND OUTCOMES: We report a case of extra-axial cerebellopontine (CP) angle ependymoma in an adult patient, managed through gross total resection (GTR) and adjuvant radiotherapy. At her one-year postoperative visit, the patient remained clinically stable without any symptoms or focal neurological deficit and a follow up MRI showed no evidence of tumor recurrence. DISCUSSION: Only six cases of adult cerebellopontine angle ependymomas have been reported in the English literature, with the left side affected more commonly. Including this case, the mean age of the reported cases of adult extra-axial CP angle ependymoma is 44.14 years (range 22-66 years). Men accounted for five out of seven cases (71.4%). Maximal surgical resection is the mainstay of treatment in extra-axial CP angle ependymomas. Among seven reported cases, five received GTR and two had subtotal resection (STR). Patients were followed an average of 13.6 months (range 2-30 months) and only two patients with STR died during the follow-up period (6 weeks and 2 months after surgery). Six of the seven reported cases (including this one) received adjuvant radiotherapy. CONCLUSION: Although rare, extra-axial CP angle ependymomas should be considered as a differential diagnosis to other lesions of the CPA. Radical resection, whenever possible, is usually associated with a good outcome. Adjuvant radiotherapy remains an optional treatment with an unknown impact on overall and progression-free survival.

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.

High-quality photoacoustic image reconstruction based on deep convolutional neural network: towards intra-operative photoacoustic imaging.

The use of intra-operative imaging system as an intervention solution to provide more accurate localization of complicated structures has become a necessity during the neurosurgery. However, due to the limitations of conventional imaging systems, high-quality real-time intra-operative imaging remains as a challenging problem. Meanwhile, photoacoustic imaging has appeared so promising to provide images of crucial structures such as blood vessels and microvasculature of tumors. To achieve high-quality photoacoustic images of vessels regarding the artifacts caused by the incomplete data, we proposed an approach based on the combination of time-reversal (TR) and deep learning methods. The proposed method applies a TR method in the first layer of the network which is followed by the convolutional neural network with weights adjusted to a set of simulated training data for the other layers to estimate artifact-free photoacoustic images. It was evaluated using a generated synthetic database of vessels. The mean of signal to noise ratio (SNR), peak SNR, structural similarity index, and edge preservation index for the test data were reached 14.6 dB, 35.3 dB, 0.97 and 0.90, respectively. As our results proved, by using the lower number of detectors and consequently the lower data acquisition time, our approach outperforms the TR algorithm in all criteria in a computational time compatible with clinical use.

Initial Experience with Diffusion-weighted Imaging to Predict the Tumor Consistency and Surgical Success in Solid Growth Hormone Producing Pituitary Macroadenomas.

BACKGROUND: Tumor consistency is an important factor impeding transsphenoidal resection of some pituitary macroadenomas. Preoperative prediction of the tumor consistency may help neurosurgeons in preparing the patients for other therapeutic options after a subtotally resected growth hormone (GH)-producing macroadenoma. We present the preliminary results of our study about the application of the preoperative diffusion-weighted (DW) magnetic resonance imaging (MRI) to predict the consistency and resection rate of GH-producing pituitary macroadenomas. MATERIALS AND METHODS: Sixteen primary patients with solid GH-producing pituitary macroadenomas were enrolled. Hormonal assays as well as standard and DW-MRI were obtained before surgery. All the patients were operated via an endoscopic transsphenoidal approach. The intraoperative tumor consistencies (suctionable versus nonsuctionable) were documented. The samples were stained for measurement of the collagen content (low, moderate, and high). Postoperative hormonal study and MRI were performed after 8 weeks to evaluate the resection ratio and the hormonal remission. RESULTS: On DW images, the tumor diffusion was enhanced (free) in four, moderate in ten, and restricted in two patients. The tumor was suctionable in 14 cases; gross total resection and hormonal remission were achieved in 12/14 of these. All the 14 suctionable tumors had moderate to enhanced diffusion on DW imaging (DWI). The two patients with a nonsuctionable fibrous tumor had a restricted diffusion in DWI. These were the only ones to have high collagen content in the histopathologic study. CONCLUSION: DWI could help identify the fibrous nonsuctionable GH-producing adenomas from the others.

Application of multi-wavelength technique for photoacoustic imaging to delineate tumor margins during maximum-safe resection of glioma: A preliminary simulation study.

Accurate margin delineation and safe maximal resection of glioma is one of the most challenging problems of neurosurgery, due to its close resemblance to normal brain parenchyma. However, different intraoperative visualization methods have been used for real-time intraoperative investigation of the borders of the resection cavity, each having advantages and limitations. This preliminary study was designed to simulate multi-wavelength photoacoustic imaging for brain tumor margin delineation for maximum safe resection of glioma. Since the photoacoustic signal is directly related to the amount of optical energy absorption by the endogenous tissue chromophores such as hemoglobin; it may be able to illustrate the critical structures such as tumor vessels during surgery. The simulation of the optical and acoustic part was done by using Monte-Carlo and k-wave toolbox, respectively. As our simulation results proved, at different wavelengths and depths, the amount of optical absorption for the blood layer is significantly different from others such as normal and tumoral tissues. Furthermore, experimental validation of our approach confirms that, by using multi-wavelengths proportional to the depth of the tumor margin during surgery, tumor margin can be differented using photoacoustic imaging at various depths. Photoacoustic imaging may be considered as a promising imaging modality which combines the spectral contrast of optical imaging as well as the spatial resolution of ultrasound imaging, and may be able to delineate the vascular-rich glioma margins at different depths of the resection cavity during surgery.

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.

Pituitary Apoplexy during Treatment of Prolactinoma with Cabergoline.

Pituitary apoplexy is a rare clinical presentation caused by infarction of the pituitary gland or adenoma with or without hemorrhage. Although pituitary apoplexy is usually spontaneous, one of the predisposing factors is treatment with dopamine agonists, especially bromocriptine. The occurrence of apoplexy during cabergoline therapy is reported much less frequently. In this article, we report a 34-year-old man with macroprolactinomas who developed sudden visual deterioration due to pituitary apoplexy 1 year after initiation of cabergoline therapy. He was treated via endoscopic trans-sphenoidal surgery and his visual status recovered dramatically.

Bilateral Ischemic Stroke Due to Carotid Artery Compression by Abnormally Elongated Styloid Process at Both Sides: A Case Report.

Abnormal elongation of styloid process (Eagle syndrome) may cause compression of the adjacent structures in the neck, the most important of which is the carotid artery. This condition may cause damage to the wall of carotid artery and result in cerebrovascular ischemic event. Bilateral carotid artery damage and cerebral stroke because of overgrown styloid processes at both sides is a rare condition. In this article, we report a case of bilateral ischemic stroke because of carotid compression by elongated styloid process at both sides treated by surgical resection of both processes.