BACKGROUND:Differentiating radiation necrosis (RN) from tumor progression is challenging despite advanced neuroimaging techniques. We collected a consecutive series of surgically resected RN with presumptive diagnosis of recurrent/refractory brain metastasis (BM) after radiation therapy (RT) and performed a descriptive analysis of characteristics and clinical courses. METHODS:From 107 patients who underwent surgery to remove previously irradiated BM, we retrieved 18 patients with pathologically confirmed pure RN. RESULTS:Sixteen patients (89%) had preoperative MRI suggesting recurrent/refractory BM in accordance with clinical suspicion, and 14 (78%) patients showed radiological response after RT before progression. The median time from RT to surgery was 28.5 months (range 6-94 months). RT doses varied from 1,800 cGy/single fraction to 8,300 cGy/21 fractions. Lobulated/irregular shape, central necrosis, and substantial increase of perilesional edema were dominant MRI features. Neurological symptoms improved or stabilized in 13 patients (72%) after surgery. Five cases of distant recurrences occurred in patients with uncontrolled systemic cancer, except for one patient with controlled small cell lung cancer who recurred as a leptomeningeal metastasis. One patient had multiple enhancing lesions along the surgical cavity, suggesting local recurrence. Median overall survival after surgical removal of RN was 34 months (range 4.3-132 months), and eight out of eleven patients with controlled systemic cancer remained alive at last follow-up. CONCLUSION:RN frequently mimics recurrent BM despite advanced imaging. Surgical resection provides both definitive diagnosis and symptomatic benefit in selected patients. However, distant recurrence of BM could happen in patients with uncontrolled systemic cancer.
MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) syndrome is a multi-systemic genetic disorder characterized by mitochondrial dysfunction, often presenting with diverse clinical phenotypes. We report a rare case of glioblastoma (GBM) in a 60-year-old female whose MELAS manifestations were primarily metabolic and neuro-sensory. Her clinical course began at age 40 with diabetes mellitus, bilateral sensorineural hearing loss, and left ophthalmoplegia. She was diagnosed with MELAS syndrome by molecular genetic testing at age 56 following her son's diagnosis. Despite the absence of previous stroke-like episodes, she presented with an acute 2-day history of headache, vomiting and altered mental status. Brain MRI revealed a mass lesion, and subsequent gross total resection was performed. Histopathological and molecular analysis confirmed a GBM, IDH-wildtype (CNS WHO grade 4). Despite surgical resection, the patient failed to recover neurologically, remaining in a stuporous state with eye opening but inability to follow commands. She subsequently received the Stupp protocol; however, massive local recurrence with increased relative cerebral blood volume was observed within one month of treatment initiation, indicating rapid and aggressive tumor progression. This case underscores that in MELAS patients, primary brain malignancies can arise independently of typical stroke-like episodes. In addition, the unusually aggressive clinical course and rapid recurrence despite standard Stupp protocol therapy raise the possibility that altered mitochondrial metabolism may influence tumor behavior or treatment response in certain patients.
Intracranial epidermoid cysts have high recurrence rates after surgical resection, and alternative strategies are needed when additional surgery is not feasible. We report a 46-year-old woman with a right cerebellopontine angle epidermoid cyst that recurred three times after surgical resections in 2010, 2016, and 2019, complicated by hydrocephalus requiring ventriculoperitoneal shunt placement. At the third recurrence in 2023, the patient refused further surgery, and radiotherapy (RT) to 50.4 Gy in 28 fractions was delivered using a Novalis Tx linear accelerator. During RT, partial neurological improvement was observed. However, approximately one month after RT completion, neurological deterioration occurred, likely attributable to radiation-induced peritumoral edema and tumor swelling, which persisted for approximately two years. Beginning at 2 years post-RT, progressive neurological improvement was observed with radiographic tumor regression. At 3-year post-RT follow-up, the patient continues to improve, with no evidence of malignant transformation. This case uniquely demonstrates the therapeutic effect of standalone RT without concurrent surgical debulking, characterized by a delayed response pattern of transient post-RT worsening followed by gradual improvement.
Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is the most common subtype of autoimmune encephalitis, typically associated with ovarian teratomas, but also reported in men and children. We describe an exceptionally rare case of anti-NMDA receptor encephalitis following glioma resection. A 34-year-old man with no prior medical history presented with severe headache and generalized tonic-clonic seizure. Brain MRI suggested a tumor in the right insular region, and surgical resection confirmed a diffuse astrocytoma, WHO grade II. Postoperatively, the patient developed fever, seizures, confusion, and visual symptoms. Initial cerebrospinal fluid analysis suggested viral encephalitis, but repeated testing revealed marked pleocytosis and elevated protein. Autoimmune antibody panel confirmed anti-NMDA receptor antibody, while other antibodies and viral studies were negative. High-dose methylprednisolone and intravenous immunoglobulin therapy resulted in clinical improvement. The patient subsequently received adjuvant chemotherapy with procarbazine and lomustine for glioma, and no recurrence of encephalitis was observed during a 4-year follow-up. This case highlights the diagnostic challenge of distinguishing glioma-related neuropsychiatric symptoms from anti-NMDA receptor encephalitis, and raises the possibility that surgical manipulation may act as a trigger. Early recognition and appropriate immunotherapy remain essential for favorable outcomes. Further studies are needed to clarify the role of chemotherapy in long-term prognosis of tumor-associated anti-NMDA receptor encephalitis.
Intracranial germinomas are exquisitely radiosensitive, and a tissue diagnosis obtained by minimal biopsy followed by radiotherapy (with or without chemotherapy) provides excellent long-term control; aggressive resection adds morbidity without oncological benefit. We report a 20-year-old man whose sellar and suprasellar mass was preoperatively interpreted as a pituitary adenoma and was treated by aggressive endoscopic endonasal transsphenoidal resection after an intraoperative frozen section suggested adenoma; final histology demonstrated germinoma. The postoperative course was complicated by a persistent skull-base cerebrospinal fluid (CSF) leak, methicillin-resistant Staphylococcus aureus meningitis/ventriculitis, and CSF dissemination documented by repeatedly positive CSF cytology and elevated CSF β-human chorionic gonadotropin. The initial skull-base reconstruction failed, and the resulting persistent CSF rhinorrhea required revision dural repair on postoperative day (POD) 29; proton craniospinal irradiation was delivered from POD 52. The patient achieved remission but, approximately 21 months after completing radiotherapy, developed a destructive germinoma lesion in the midline maxilla, with no recurrence at the primary site and no leptomeningeal disease at that time. In light of the anterior maxillary location and the relatively long interval after radiotherapy, we interpret the lesion as an isolated extracranial metastasis rather than a proven operative-tract event. The principal lesson is that accurate initial diagnosis and approach selection-measurement of tumor markers and minimal or transventricular biopsy in preference to resection-remain essential in young patients with sellar/suprasellar masses in whom germinoma is a diagnostic possibility.
Meningiomas are the most common primary intracranial tumors and exhibit a broad spectrum of clinical behavior, ranging from indolent growth to repeated recurrence and aggressive progression. Over the past decade, genomic, epigenomic, bulk transcriptomic, and single-cell studies have refined meningioma classification and identified molecular features associated with recurrence risk. However, recurrence is increasingly recognized as a dynamic process shaped by tumor-intrinsic plasticity, subtype redistribution, treatment-related selection, and remodeling of the tumor microenvironment. Recent longitudinal single-nucleus RNA sequencing of matched primary and recurrent meningiomas has extended this framework by demonstrating enrichment of proliferative, DNA repair, and extracellular matrix programs in recurrent disease, together with multidirectional transcriptional trajectories rather than simple linear progression. These findings complement earlier methylation- and transcriptome-based risk models, as well as cross-sectional single-cell studies that have highlighted neoplastic heterogeneity, macrophage interactions, and immune-state diversity across meningioma grades. Among recurrence-associated genes, COL6A3 has emerged as a clinically relevant extracellular matrix marker linked to aggressive tumor states and poor relapse-free survival. Nevertheless, the proposed COL6A3-macrophage interaction should be interpreted cautiously because current evidence remains largely correlative and may be influenced by intervening treatment between primary and recurrent sampling. This review synthesizes current evidence on longitudinal evolution, cellular plasticity, molecular subtype shifts, and microenvironmental remodeling in recurrent meningioma, while outlining key limitations and future directions for clinically actionable longitudinal profiling.
Neuronal hyper-excitability in glioma environments has been reported long before and recent research has clarified that glioma cells are inducing the enhanced excitability of surrounding neurons. Furthermore, the direct interaction between neuron and glioma is also found to be a special characteristic within glioma progression. However, neurovascular unit (NVU) consists of various types of cells and are known to modulate the neuronal activity directly and indirectly. Among different cells constituting the NVU, microglia are recently found to be modulating neuronal activity through negative feedback via purinergic signaling while its modulating function is relatively unknown in glioma environment. In this review, we focus on the role of microglia in controlling neuronal activity and its loss-of-function contributing to the neuronal hyper-excitability within glioma environment.
Dural-based lesions are commonly presumed to be meningiomas due to characteristic imaging features. However, rare neoplastic entities may mimic their radiologic appearance, leading to potential diagnostic pitfalls. This report highlights two unusual cases of dural-based tumors with features mimicking meningiomas: metastatic hepatocellular carcinoma (HCC) and Ewing sarcoma (ES). The first case involved a 52-year-old man presenting with a painless parietal scalp swelling. Imaging revealed a dural-based mass with bone erosion and extracranial extension, initially suspected to be a meningioma. Histopathological evaluation confirmed metastatic HCC. The second case described a 22-year-old man with a large frontoparietal mass exhibiting both intra- and extracranial components. Imaging suggested a meningioma; however, histology and immunohistochemistry confirmed the diagnosis of Ewing sarcoma. Both cases underscore the importance of considering differential diagnoses beyond meningioma for dural-based lesions, particularly when clinical or radiologic findings are atypical. While metastatic HCC to the dura is rare and typically managed with palliative intent, ES requires aggressive multimodal therapy including surgery, chemotherapy, and radiotherapy. These cases emphasize that dural-based lesions with meningioma-like features may harbor unexpected pathology. A high index of suspicion, coupled with thorough histopathological evaluation, is essential for accurate diagnosis and appropriate management.
BACKGROUND:Congenital brain tumors (CBTs), defined as intracranial neoplasms initially presented within the first year of life, are rare and biologically heterogeneous, with outcomes largely derived from high-income country data. Evidence from low- and middle-income countries (LMICs) remains sparse, limiting contextual understanding of disease burden and survival. METHODS:We conducted a retrospective single-center cohort study of infants with surgically managed intracranial tumors presenting within the first year of life at a tertiary referral center in Pakistan between January 1, 1988, and July 31, 2025. Vascular and metastatic lesions were excluded. Demographic, clinical, radiological, histopathological, operative, and adjuvant-treatment data were extracted from medical records. Tumors were classified according to WHO 2021 nomenclature where feasible. Overall survival was estimated using Kaplan-Meier methods, and factors associated with survival were explored using Firth-penalized Cox regression because of low event counts. RESULTS:Fifty infants were included; median age at surgery was 420.00 days (interquartile range 198.50-566.00 days), and 26 were male. Supratentorial tumors comprised 20 (40.0%) cases, and 25 (50.0%) were high-grade (WHO grade III-IV). Gross total resection was achieved in 11 (22.0%) patients and subtotal resection in 20 (40.0%). Postoperative complications occurred in 8 (16.0%). Among 33 patients with available survival follow-up, estimated overall survival was 93.9% at 30 days, 82.5% at 6 months, 74.2% at 1 year, and 58.6% at both 5 and 10 years. No clinicopathological variable was independently associated with survival in penalized Cox regression. CONCLUSION:In this single-center LMIC cohort, survival after surgical management of CBTs appeared lower than that generally reported in high-income settings. These findings highlight the need for earlier diagnosis, improved access to specialized pediatric neuro-oncology care, and multicenter collaborative studies to better define prognostic determinants and improve outcomes.
BACKGROUND:Stereotactic radiosurgery (SRS) is an established treatment for vestibular schwannoma (VS), primarily for tumors smaller than 3 cm in diameter. Its role in larger tumors remains controversial and is generally limited to carefully selected patients. This study evaluated long-term outcomes of primary single-session SRS for VS, stratified by tumor size. METHODS:We retrospectively analyzed 160 patients with unilateral sporadic VS treated with SRS between July 2009 and September 2020. SRS was primarily indicated for tumors <3 cm in maximum diameter, while larger tumors were selectively treated in patients without significant brainstem compression or severe neurological deficits. Patients were stratified by Koos grade: Group A (I), Group B (II-III), and Group C (IV). Median follow-up was 96 months. Primary outcomes included progression-free survival (PFS), hearing preservation, and treatment-related complications. RESULTS:The overall tumor control rate was 98.1%. The 10-year PFS rates were 100%, 97.4%, and 96.6% for Groups A, B, and C, respectively, with no significant difference (p=0.739). Among patients with serviceable hearing, 5-year preservation rates were 91.7%, 36.0%, and 53.6% (p=0.002). New-onset trigeminal neuralgia occurred in 0%, 0.9%, and 6.1% of patients in Groups A, B, and C, respectively. Post-SRS hydrocephalus requiring ventriculoperitoneal shunting was observed in 0%, 5.6%, and 27.3%, respectively. CONCLUSION:Within appropriately selected patients, SRS provides excellent tumor control across tumor sizes. However, the risks of trigeminal neuralgia and hydrocephalus requiring shunting increased with tumor size, underscoring the need for individualized treatment strategies.
BACKGROUND:Health-related quality of life (HR-QoL) is a critical consideration in glioma surgery, alongside improving patient survival. Current evidence highlights maximal surgical resection as a key independent prognostic factor for enhancing HR-QoL and survivability. This study aimed to compare the impact on HR-QoL and survival rates in glioma patients before and after surgery with varying degrees of tumor resection (<10%, 10%-90%, >90%) and residual tumor volumes (≤2 cm³, >2 cm³). METHODS:This single-institution prospective study analyzed 117 patients with newly diagnosed gliomas (2009-2015). HR-QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) (global quality of life status [GQLS], physical, emotional, role, cognitive, and social function, as well as insomnia and fatigue). We compared survival rates and HR-QoL outcomes based on extent of resection and residual tumor volume. Clinically meaningful thresholds and statistical significance were used to evaluate HR-QoL changes. RESULTS:In grade 4 gliomas, resections >90% and residual tumor volumes ≤2 cm³ significantly improved median survival compared to lesser resections. For HR-QoL, resections >90% led to clinically and statistically significant improvements in GQLS, emotional, role, and cognitive function, as well as insomnia. Residual volumes ≤2 cm³ significantly enhanced emotional and role function, with statistical improvements in GQLS, cognitive function, social function, insomnia, and fatigue. Lower resection rates and higher residual volumes resulted in significant HR-QoL declines. When stratified by tumor grade, high- and low-grade gliomas showed clinically significant improvements in different HR-QoL domains. CONCLUSION:Resections greater than 90% and residual volumes ≤2 cm³ significantly improve HR-QoL and overall survival. Conversely, partial resections and larger residual tumor volumes are associated with worse HR-QoL outcomes.
BACKGROUND:Cerebellopontine angle (CPA) tumors present surgical challenges due to their proximity to the facial nerve. Despite preservation efforts, facial nerve paresis is a major issue. This study aims to identify key factors affecting facial nerve preservation during microsurgical resection of large CPA tumors in a low- and middle-income countries (LMIC) setting. METHODS:This retrospective cross-sectional study, conducted at Aga Khan University, included patients who underwent microsurgical resection of large (>3 cm) CPA tumors with House-Brackmann (HB) grades 1-4. Postoperative facial nerve function was assessed using the HB grading system. Data was extracted from medical records and analyzed using SPSS 22. RESULTS:This study analyzed 95 patients (M:F=1:1.16, mean age 44.24±13.71 years) with CPA tumors who underwent microsurgical resection. Common presenting complaints included a complete hearing loss (57.9%), headache (52.6%), and abnormal gait (40%). Preoperative facial nerve function was normal (HB grade I) in 75%, with 19%, 7%, and 2% having HB grades II, III, and IV, respectively. Schwannoma (69.5%), meningioma (16.8%), and epidermoid cyst (10.5%) were the most common diagnoses. Postoperative preservation of facial nerve function was achieved in 73.7% of patients. At six months, HB grades I and II were observed in 64% and 11.5%, respectively, while none had complete facial nerve palsy. On univariate analysis, larger tumor size and higher HB grade correlated with worse facial nerve outcomes (p=0.02). Complications were more frequent in patients with worsened outcomes (72% vs. 38.6%, p=0.004). However, in multivariate analysis, only preoperative HB grade was identified as a predictor. CONCLUSION:Facial nerve preservation during CPA tumor resection is influenced by intrinsic tumor characteristics, surgical complexity, and patient-specific factors. Detailed preoperative counseling is crucial to set realistic expectations.
Pediatric low-grade gliomas (pLGGs) are the most common childhood central nervous system tumors and are frequently driven by alterations in the RAS/mitogen-activated protein kinase (RAS/MAPK) signaling pathway. Advances in molecular profiling have revealed key genetic drivers, including BRAF mutations, BRAF fusions, and other kinase gene rearrangements, enabling the development of genotype-guided targeted therapies. First-generation BRAF inhibitors and mitogen-activated protein kinase kinase (MEK) inhibitors have demonstrated significant clinical benefit in molecularly selected patient subgroups, prompting FDA approvals and a paradigm shift away from traditional chemotherapy. However, challenges such as resistance mechanisms, treatment durability, and long-term toxicities persist. This review summarizes the molecular landscape of pLGG, highlights current and emerging targeted therapies, and discusses unresolved issues including optimal treatment duration, toxicity management, and future directions for individualized care.
Cerebral sparganosis is a rare parasitic infection caused by plerocercoid larvae of Spirometra species. Intracranial involvement is uncommon and may mimic other parasitic or neoplastic diseases. We report the case of a 64-year-old man who presented with dysarthria and dizziness, later diagnosed with cerebellar sparganosis. Retrosigmoid craniotomy was performed, and two intact spargana were removed with the surrounding capsule. Histopathology demonstrated granulomatous inflammation with eosinophilic infiltration and characteristic calcareous corpuscles within degenerated parasitic tissue fragments. Postoperatively, dysarthria and dizziness improved, and the patient was able to ambulate independently. Sparganosis has been continuously reported in Korea for nearly a century, though incidence has declined in recent decades. Parasite invasion into the central nervous system is thought to occur through the foramen magnum, with the brain parenchyma particularly vulnerable due to its soft tissue composition. In our case, prior cerebellar infarction may have provided a structural weakness that facilitated parasite invasion. Differentiation from neurocysticercosis is essential, as imaging findings and clinical implications differ. Surgical excision remains the standard treatment, although recent evidence indicates that long-term, high-dose praziquantel may be effective in selected cases. Cerebral sparganosis should be considered in patients with compatible clinical and radiologic features in endemic regions. Complete surgical removal offers definitive therapy, while high-dose praziquantel may serve as a noninvasive alternative for inoperable cases.
BACKGROUND:Parenchymal brain metastasis (BM) and its extended growth into cerebrospinal fluid (CSF) pathways or surgical spillage could result in leptomeningeal metastasis (LM). We defined BM with epipial spread or dural attachment on MRI as BM with CSF space invasion (BM-CSFi), regardless of CSF cytology results, and evaluated its clinical course after BM resection. METHODS:We retrospectively reviewed 297 patients who underwent craniotomy for BM excluding patients followed for <6 months or without follow-up MRI. Primary outcomes were proportion of patients progressing to overt LM and time to progression. We also evaluated clinical and radiologic variables to identify risk factors for LM progression. RESULTS:A total of 91 patients (30.6%) developed overt LM, with median time to progression of 7.9 months during 18.3 months follow-up after the craniotomy. On multivariable analysis, preoperative MRI evidence of dural attachment with enhancement (hazard ratio [HR], 5.59; p=0.002), primary small cell lung cancer (HR, 4.92; p=0.026), infratentorial BM location (HR, 2.14; p=0.019), and postoperative cumulative CSF cytology positive rate ≥50% (HR, 7.13; p=0.012) were independent risk factors for LM progression. The mode of resection and postoperative radiotherapy or systemic chemotherapy were not significantly associated with LM progression. CONCLUSION:BM-CSFi, defined by preoperative MRI findings, may represent a clinically important precursor of LM. Our findings highlight the need for close monitoring of patients with BM-CSFi and the development of management protocols to minimize the risk of LM progression.
The National Comprehensive Cancer Network (NCCN) recommends a regimen of rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) with methotrexate (MTX) given at ≥3 g/m² for stage IV diffuse large B-cell lymphoma with parenchymal involvement. Tumor lysis syndrome (TLS) may occur after initiation of treatment. MTX, though beneficial, may induce toxicity, especially in elderly patients with comorbidities. This paper discusses a case of 74-year-old female with secondary central nervous system lymphoma with multiple comorbidities and high risk for TLS given a modified schedule of R-CHOP and a lower dose of MTX at 2-2.5 g/m² with a good treatment response. This paper aims to contribute additional information on optimal treatment for this disease.
BACKGROUND:Neuronal cell adhesion molecule (NRCAM) has been implicated in glioma biology through splicing alterations reported by prior studies. However, the relative contributions of genomic and epigenetic mechanisms to NRCAM dysregulation in gliomas remain unclear. METHODS:We analyzed data from The Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) cohort using UCSC Xena and cBioPortal. Copy number variation (CNV), DNA methylation (Illumina HumanMethylation450 BeadChip arrays), and mutation profiles were assessed for NRCAM. Kaplan-Meier survival analyses were performed with Xena, stratifying patients by copy number status and methylation state. Correlations between mutation burden and fraction of genome altered (FGA) were evaluated using Spearman and Pearson methods. RESULTS:Somatic mutations in NRCAM were rare in the TCGA-LGG cohort. In contrast, CNV and methylation changes were frequent and clinically relevant. Copy number gains at the NRCAM locus were associated with significantly shorter overall survival, while higher methylation of NRCAM correlated with improved survival outcomes. NRCAM mutation count did not show a linear correlation with FGA, suggesting these alterations are largely independent of overall genomic instability. The findings highlight copy number imbalance and epigenetic regulation as predominant mechanisms of NRCAM dysregulation. CONCLUSION:NRCAM is recurrently dysregulated in lower-grade gliomas through CNVs and DNA methylation, both of which stratify patient survival. Together with previously reported splicing deregulation, these data suggest that NRCAM functions as a multilayered regulator of glioma progression. NRCAM methylation may represent a potential prognostic biomarker, while therapeutic modulation of NRCAM warrants further investigation.
