Genotype and subependymal lesion burden influence volumetric response to everolimus in tuberous sclerosis complex-associated subependymal giant cell astrocytoma: A 10-year real-world study.

To report early neurodevelopmental outcomes in a child with Tuberous Sclerosis Complex (TSC) treated with everolimus and vigabatrin. The authors report a five-year-old girl with Tuberous Sclerosis Complex who was initiated on vigabatrin at seven weeks old to treat infantile spasms and on everolimus at two months of age to treat a subependymal giant cell astrocytoma. Neuropsychological assessments were conducted in this patient at 12, 24, and 36 months using the Bayley-III and Vineland-II. On the Bayley-III, the patient had a high average cognitive composite score at 12 months and a high average language composite score at 36 months. Bayley-III assessments at 12, 24, and 36 months, yielded average cognitive, language, and motor composite scores. On the Vineland-II at 12 months, her standard score fell in the moderately low range on daily living skills and overall adaptive behavior. Vineland-II assessments at 12, 24, and 36 months yielded average range standard scores in the areas of communication, socialization, daily living skills, overall adaptive behavior, and motor skills. This case highlights early neurodevelopmental outcomes in one TSC child treated with everolimus and vigabatrin in infancy. Continued assessment and longitudinal follow-up is required to understand the broader implications of early treatment with mTOR inhibitors and vigabatrin in TSC patients in childhood.

Central Nervous System (CNS) tumors are the leading solid malignancies in children, 50% of CNS tumors in children are glial tumors, with two-thirds of these gliomas being categorized as low-grade gliomas (LGG). We aimed to review the clinical profile, management, and outcomes of pediatric LGG cases. A retrospective cohort study was conducted at Aga Khan University Hospital between 2013 and 2025 including patients aged ≤ 18 years diagnosed with LGG. A total of 191 patients were identified, with a slight preponderance of male patients (51.3%). Median age was 10 years (IQR 6-14) with the larger age group being 10-18 years (50.3%). Median duration of presenting symptoms was 4 months (IQR 1-18). Headaches (n = 112, 58.6%) and vomiting (n = 93, 48.7%) were the primary presenting complaints. Tumors were predominantly supratentorial (n = 115, 60.2%). The most common histopathology was Pilocytic Astrocytoma (n = 119). Upfront surgery was done in 163 (85.3%) patients; Gross Total Resection (GTR) was achieved in 85 patients (52.1%). Twenty-six (13.7%) patients received Chemotherapy while 9 (4.8%) had radiation therapy. Disease didn't progress in 131 (68.6%) patients while progression and relapse occurred in 36 (18.8%) and 7 (3.7%) patients, respectively. Seventeen (8.9%) patients did not have any follow-op scans. The Overall Survival (OS) was 95.3%, with only 9 deaths recorded. Biopsy was deferred to 28 patients (14.7%), a group primarily comprising Subependymal Giant Cell Astrocytomas (SEGA) (n = 17, 60.7%), Tectal Plate Glioma (n = 3, 10.7%), and Optic Path Glioma (n = 5, 17.8%). Kaplan-Meier analysis estimated a median EFS of 84.2 months (95% CI: 70.9-97.5 months). However, this estimate should be interpreted cautiously given the relatively short median follow-up and substantial right-censoring. Despite heterogeneity in histopathology and location, outcomes were comparable to those reported in the literature, underscoring the effectiveness of current practices while highlighting the need for improved follow-up and comprehensive outcome reporting in resource-limited settings.

Subependymal giant cell astrocytoma (SEGA) is a rare pediatric tumor that most commonly occurs in the setting of tuberous sclerosis complex (TSC). The deep anatomical location of these lesions makes the selection of an appropriate neurosurgical approach critical. However, minimally invasive techniques have emerged as a safe and effective alternative for the surgical resection of tumors located in deep regions. A 7-year-old male with a history of TSC presented with a large intraventricular mass located in the frontal horn of the right lateral ventricle, associated with symptoms suggestive of intracranial hypertension. A minimally invasive transcortical approach using a tubular retractor was initially performed, achieving a partial resection of the tumor, then followed by adjuvant targeted therapy and radiotherapy. Due to persistent seizures, the patient underwent a second intervention using a similar transcortical approach and tubular retraction, this time aided by neuronavigation. An estimated extent of resection (EOR) of 90-95% was achieved resulting in improvement of the patient's neurological involvement. The integration of minimally invasive tubular retractor systems with neuronavigation represents an effective and safe strategy for the surgical management of SEGAs located in critical intraventricular regions. In this case, neuronavigation was essential in achieving GTR while minimizing intraoperative bleeding and reducing injury to critical cortical and subcortical structures. Minimally invasive approaches proved to be safe and were associated with a favorable postoperative course.

Subependymal giant cell astrocytomas (SEGA) are low-grade intraventricular tumors generally associated with tuberous sclerosis complex. Although mechanistic target of rapamycin inhibitors are recommended as first-line therapy for progressive SEGA without hydrocephalus, surgery is still relevant because 40% of patients are drug resistant. This study aimed to evaluate surgical outcomes in terms of tumor control, complication rates, and ventriculoperitoneal shunt (VPS) requirement, through a single-center retrospective series and a meta-analysis. We retrospectively analyzed 31 pediatric SEGA resections performed over 2 decades at a tertiary care center. Clinical, radiological, and surgical variables were examined to identify predictors of outcome. In addition, a systematic literature review and meta-analysis were conducted to contextualize our findings. Gross total resection was achieved in 64.5% of cases, with a 19.3% rate of transient postoperative complications and a 6.4% incidence of VPS placement. No permanent morbidity or mortality occurred. Favorable outcome was associated with a smaller tumor volume and absence of preoperative hydrocephalus. The meta-analysis confirmed that preoperative hydrocephalus was the main predictor of postoperative complications (odds ratio 2.30) and shunt dependence (odds ratio 3.45). Five-year progression-free survival was 90.9% in the gross total resection subgroup and 100% in patients with unilateral tumors. Bilateral tumor location was an independent predictor of recurrence (hazard ratio = 17.79, P = .02). Microsurgical resection of SEGA is a safe and effective therapeutic option, particularly in patients without hydrocephalus. Early surgical intervention may reduce the need for VPS and long-term complications, offering a valid alternative or complement to mechanistic target of rapamycin inhibitor therapy, with durable tumor control especially in unilateral cases.

Abstract Focused ultrasound (FUS) is a minimally invasive procedure with recent applications to patients with neurosurgical conditions. To date, most neuro-oncologic applications of FUS have occurred in the adult population to target high-grade gliomas and brain metastases. Its potential applications in pediatric neuro-oncology are only just starting to be realized. In children, high intensity focused ultrasound (HIFU) has been used to treat benign intracranial lesions such as hypothalamic hamartoms and subependymal giant cell astrocytomas. Experience is now accruing with the use of low intensity focused ultrasound (LIFU) in conjunction with systemically administered microbubbles in children to disrupt the blood brain barrier (BBB) using magnetic resonance-guided focused ultrasound (MRgFUS). The pediatric brain tumor for which this application has been used is diffuse intrinsic pontine glioma (DIPG), a typically fatal neoplasm in children ages 5 – 7 years. Here, the history of FUS is reviewed, the principles of FUS therapy are delineated, and a discussion of its applications in neuro-oncology with a focus on pediatric neuro-oncology is provided. Innovations in MRgFUS are ushering a new and exciting era of minimally invasive treatments for children with brain tumors.

Introduction: Supratentorial intraventricular tumors are rare central nervous system neoplasms located deep within the ventricular system. Their proximity to eloquent neural pathways and critical vascular structures makes surgical management technically challenging. Data from low and middle income regions remain limited. This study evaluates the clinical features, histopathological patterns, surgical approaches, and outcomes of patients treated at a tertiary neurosurgical center in Nepal. Material and Method: A retrospective observational study was conducted including 27 consecutive patients who underwent surgical resection of supratentorial intraventricular tumors between September 2020 and August 2025. Demographic, clinical, radiological, histopathological, operative, and postoperative data were collected and analyzed. Statistical analysis included descriptive statistics, chi-square testing, logistic regression modeling, and calculation of confidence intervals. Institutional Review Committee approval was obtained prior to study initiation. Results: The mean age was 24.9 ± 13.2 years, with a male predominance of 21 (77.8%). Headache was the most common presenting symptom, occurring in 14 (51.9%) patients. Colloid cyst was the most frequent histopathological diagnosis, identified in 7 (25.9%) patients, followed by subependymal giant cell astrocytoma in 5 (18.5%) and choroid plexus tumors in 5 (18.5%). The transcortical-transventricular approach was most frequently utilized in 14 (51.8%) cases. Postoperative hydrocephalus requiring cerebrospinal fluid diversion occurred in 5 (18.5%) patients. Overall mortality was observed in 3 (11.1%) patients. No statistically significant association was found between tumor type or surgical approach and postoperative complications. Conclusion: Microsurgical resection remains the cornerstone of management for supratentorial intraventricular tumors in resource-limited settings. Although acceptable surgical outcomes can be achieved, postoperative hydrocephalus continues to be a significant challenge. Larger prospective multicenter studies are needed to optimize surgical strategies and improve patient outcomes.

Tuberous sclerosis complex (TSC) is a rare genetic disease caused by heterozygous loss-of-function variants in TSC1 or TSC2. Patients present with benign tumours known as hamartomas in the brain, eyes, lungs, kidneys, heart and skin. Many hamartomas contain mosaic second hit variants in TSC1 or TSC2. The most disabling features of TSC include epilepsy and TSC-associated neuropsychiatric disorders (TAND) such as intellectual disability and autism spectrum disorder. Remarkable progress has been made both in understanding the pathogenesis of TSC and in its clinical management, largely due to the discovery of the link between TSC1 and TSC2 and the mechanistic target of rapamycin (mTOR) signalling pathway. TSC1 and TSC2 form a protein complex that inhibits mTOR. Naturally occurring inhibitors of mTOR (rapamycin) and its analogues, collectively known as rapalogues, have been used to test various hypotheses in preclinical models and are approved for the treatment of several manifestations of TSC. Approved drug treatments (rapalogues) exist for subependymal giant cell astrocytomas, renal angiomyolipomas, pulmonary lymphangioleiomyomatosis, facial angiofibromas and refractory seizures. However, there is still an unmet need for effective treatment of TAND and refractory epilepsy, despite the available medical and surgical options.

To document the natural progression of fetal cardiac rhabdomyomas and evaluate the impact of prenatal sirolimus (PNS) on tumor size, cardiac complications and brain-tuber size. This was a single-center retrospective cohort study of pregnancies with suspected fetal cardiac rhabdomyoma referred to our centerfrom April 2013 to May 2024. Serial ultrasound and echocardiography reports were reviewed to obtain tumor characteristics, such as diameter and location, and cardiac complications, including inflow or outflow obstruction, arrhythmia and hydrops. The tumor-to-femur length (TFL) ratio was calculated to correct for fetal growth. Prenatal neurosonography reports were collected from clinical records. Pre- and postnatal brain magnetic resonance imaging (MRI) scans were reviewed by two observers who were blinded to PNS treatment. Brain-lesion severity was assessed based on the presence of subependymal nodules, the EPISTOP score, the maximum diameter of the largest subcortical tuber, the maximum diameter of the largest subependymal giant cell astrocytoma (SEGA) and the diameter of the largest lateral ventricle. Prenatal or postnatal genetic testing results were documented when available. Twenty-seven pregnancies were included in the study, seven of which received PNS. Prior to initiation of treatment, the diameter of the largest cardiac tumorat diagnosis was similar between the non-PNS and PNS groups (mean, 15.2 mm vs 14.3 mm; P = 0.72), with the left ventricle the most frequently affected location. Without treatment, rhabdomyomas grew rapidly from 20 + 0 to 27 + 6 weeks' gestation (mean, 2.58 mm/week) but growth slowed after 28 weeks (mean, 0.44 mm/week). Hydrops was reported in four cases and occurred at a mean tumor diameter of 31.7 ± 6.2 mm, mean TFL ratio of 0.68 ± 0.15 and at a mean growth rate of 4.3 ± 1.7 mm/week. In the seven women treated with PNS, treatment for > 7 days (n = 3) resulted in tumor regression and/or resolution of outflow obstruction, and a reduction inTFL ratio; however, prenatal cessation of treatment resulted in rebound growth (n = 2). Treatment for ≤ 7 days (n = 4) did not impact tumor size or resolve existing cardiac complications. Among the 12 cases that underwent prenatal MRI, the median EPISTOP score was 7 (interquartile range (IQR), 1-15) and the median largest lateral ventricle diameter was 8.9 (IQR, 7.0-9.7) mm; subcortical tubers and subependymal nodules were each identified in 67% of cases, and SEGAs were identified in 58%. Among the 13 cases that underwentpostnatal MRI, the median EPISTOP score was 14 (IQR, 3-16) and the median largest lateral ventricle diameter was 7 (IQR, 7-8) mm; brain tubers were identified in 92% of cases. In cases with both pre- and postnatal MRI findings who received PNS for > 7 days (n = 3), on postnatal MRI compared with prenatal MRI, one patient showed no change in findings, one demonstrated a mild increase in the largest subcortical tuber diameter and one had no detectable brain tubers. Early and sustained PNS treatment was associated with reduced cardiac rhabdomyoma size and/or resolution of cardiac complications. Rebound tumor growth was observed after discontinuation of treatment. Brain tubers appeared unchanged with PNS treatment, although the sample size was too small to draw a definitive conclusion. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Abstract Background Lateral intra-ventricular tumors pose significant surgical challenges owing to their deep-seated location and close relationship with eloquent neural structures. The most commonly used surgical corridors include transcortical and transcallosal approaches. Although these techniques differ fundamentally in terms of cortical, callosal, and subcortical disruption, both continue to be widely utilized in the management of lateral ventricular tumors. The present study does not presuppose biological equivalence between these approaches; rather, it examines their practical clinical implications within a real-world surgical context, in which approach selection is influenced by factors such as tumor location and size, ventricular anatomy, and surgeon experience. The objective of this study is to compare postoperative functional outcomes and extent of resection achieved using both approaches. Results The study included 27 cases (16 males and 11 females). Mean age at diagnosis was 25.33 years (range 5–41). Followed-up for 12 months post-operative. Tumors were predominantly located in ventricular body ( n = 23) with fewer cases in frontal horn ( n = 4). Main pathologies were central neurocytomas (12 patients 44.4%), ependymomas (6 patients 22.2%), and subependymal giant cell astrocytoma (SEGA) (4 patients 14.8%). Excision was gross total resection (GTR) n = 15 (transcallosal group n = 8—transcortical group n = 7) and partial resection n = 10 (transcallosal group n = 4—transcortical group n = 6). 2 case mortalities were recorded. Postoperative intra-ventricular hemorrhage n = 17 (transcallosal group n = 10—transcortical group n = 7), Postoperative Glasgow coma Scale (GCS) 11.28 ± 3.59 range from (5–15), postoperative seizures n = 13 (transcallosal group n = 6—transcortical group n = 7), motor deficits ( n = 4), cognitive affection at 12th month postoperative n = 6 (transcallosal group n = 4—transcortical group n = 2), recurrence cases n = 7 (transcallosal group n = 4—transcortical group n = 3). Causes of death included postoperative intraventricular hemorrhage with refractory hydrocephalus ( n = 1), and systemic medical complications unrelated to the surgical procedure ( n = 1). Conclusions In our series, transcallosal approach was associated with a higher incidence of postoperative cognitive impairment compared with transcortical approach. No significant differences were observed between two approaches with respect to postoperative seizures, motor outcomes, GCS, or extent of resection. Additionally, partial tumor resection was associated with increased risk of postoperative hemorrhage and tumor recurrence.

Central nervous system tumors in children represent the second most common group of malignant neoplasms after acute leukemias and are the leading cause of morbidity and mortality in the pediatric oncology population. It is a heterogeneous group of tumors that differ in histological, molecular, and clinical features. The clinical presentation is often nonspecific and depends on the child's age and the localization of the tumor. The most common symptoms include headache, nausea and vomiting, gait and coordination disorders, epileptic seizures, visual disturbances, and cognitive and behavioral dysfunction. In infancy, macrocephaly may be the first and only sign of intracranial pathology. Children with neurocutaneous syndromes, especially neurofibromatosis type 1 and tuberous sclerosis, have a significantly increased risk of developing central nervous system tumors, including optic pathway gliomas and subependymal giant cell astrocytomas. Recognition of these syndromes allows for timely monitoring and early diagnosis of potential complications. Timely recognition of early symptoms and signs is crucial for referring the child for neuroradiological diagnostic work-up. Magnetic resonance imaging is the method of choice in the evaluation of intracranial lesions due to its high resolution and ability to distinguish parenchymal structures. Early diagnosis allows for optimal planning of a multimodal therapeutic approach, including surgical, oncological, and radiotherapy treatment, which significantly improves outcomes and reduces the risk of permanent neurological damage.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the formation of benign tumors in multiple organs. Neuroimaging plays a pivotal role in diagnosis and surveillance of intracranial and extracranial manifestations. To evaluate and compare the diagnostic performance of CT and MRI in detecting intracranial and extracranial lesions associated with TSC. A retrospective analysis was conducted on imaging data from 57 patients diagnosed with TSC. Cranial CT and routine MRI findings were reviewed and compared. In addition, abdominal and thoracic CT findings were evaluated for renal, hepatic, pulmonary, and skeletal involvement. Subependymal calcified nodules were observed in 51/57 (89.5%) patients, with a CT detection rate of 100% (46/46), significantly higher than routine MRI (68.4%, 13/19; P < 0.001). Cortical dysplasia lesions were found in 19/57 (33.3%) patients, with significant difference between CT (10/46, 21.7%) and routine MRI (16/19, 84.2%; P < 0.001). Subependymal giant cell astrocytoma (SEGA) lesions were detected in 11/19 (19.3%) cases with no statistical difference between CT (7/46, 15.2%) and routine MRI (6/19, 31.6%; P = 0.250). Cerebral fissure malformation and cranial bone dysplasia were detected in 3/57 (5.3%) and 2/57 (3.5%) patients, respectively. Extracranially, renal angiomyolipoma (AML) lesions were detected in 12/21 (57.1%) patients, hepatic AMLs in 5/21 (23.8%), multifocal micronodular pneumocyte hyperplasia (MMPH) lesions in 5/15 (33.3%), pulmonary lymphangioleiomyomatosis (LAM) lesions in 3/15 (20.0%), and multifocal bone sclerosis in 13/36 (36.1%) by CT. CT and routine MRI demonstrated lesion-specific, complementary roles in TSC. CT preferentially identified calcified lesions and delineated extracranial multisystem involvement, whereas MRI offered an advantage in the detection of cortical dysplasia and other soft-tissue abnormalities. Integrating intracranial and extracranial imaging within a single cohort, this study supported a practical, modality-tailored CT-MRI approach for comprehensive assessment and risk-adapted surveillance in TSC.

To identify the features of brain involvement and to characterize the genetic causes of tuberous sclerosis (TS) in patients in the Republic of Bashkortostan. A retrospective analysis of data on patients with TS registered with geneticists of the Republican Medical Genetic Center for the period from 2012 to 2025 was performed. The prevalence of TS in the republic was 2.12 per 100.000 population. Subependymal giant cell astrocytoma was detected in 19%, epilepsy in 67%, subependymal hamartomas in 66%, and cortical tubers in 43% of patients. Cognitive deficits were present in 47% of patients, while autism spectrum disorders were found in only 1%. Mutations were identified in the TSC1 gene in 5 patients, the TSC2 gene in 19 patients, and extended deletions of the TSC2 gene in 4 patients. TS prevalence in the region is 5.24 times lower than the global average. The frequencies of cortical tubers, subependymal nodes, cognitive deficits, and autism spectrum disorders are also significantly lower than those reported in international meta-analyses. No data were available on behavioral disorders or attention-deficit hyperactivity disorder. Five TSC1 gene mutations (three de novo) and 19 TSC2 gene mutations (one de novo) were reported. Eight patients received targeted therapy. Raising awareness of TS among physicians in all specialties is essential to ensure comprehensive case reporting. Genetic confirmation of TS enables effective treatment with mTOR inhibitors. All TS patients should consult a psychiatrist and psychologist for the diagnosis and management of intellectual disability, autism spectrum disorders, and behavioral disorders.

Subependymal giant cell astrocytomas (SEGAs) are benign tumors linked to tuberous sclerosis complex. Surgical resection remains the primary treatment, but carries risks of morbidity, particularly in cases of residual or recurrent disease. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative, though evidence of its efficacy is unclear. This study presents a retrospective, multi-institutional analysis of SEGA outcomes after SRS. Fourteen patients with histologically confirmed SEGA underwent Gamma Knife radiosurgery between 1998 and 2023 across seven centers of the International Radiosurgery Research Foundation. Demographics, tumor features, treatment parameters, and outcomes were evaluated. Local control (LC), progression-free survival (PFS), overall survival (OS), quality of life, and toxicity were analyzed. The median age at treatment was 17 years, and all patients had prior surgery. Median radiological and clinical follow-up were 75 and 77.8 months. LC was achieved in 57.1% of cases, while 42.9% showed local failure, including one distant progression. PFS rates were 85.7% at 12 months and 71.4% at 24 months, with corresponding OS rates of 92.9% and 85.7%. No significant predictors of LC were identified. Post-SRS surgery was required in 35.8% due to progression. Treatment-related toxicity occurred in 21.4%, all Grade 1-2 and managed conservatively. SRS appears to be a safe option for patients with residual or recurrent SEGA who are unsuitable for further surgery. Despite modest LC rates, durable stabilization with minimal toxicity was achieved. Larger prospective studies are warranted to confirm these findings, optimize dosing and refine patient selection criteria.

Subependymal giant cell astrocytoma (SEGA) is classified as a WHO grade I tumor. This tumor is often detected in the lateral ventricles and accompanies tuberous sclerosis complex (TSC). Here, we report a patient with SEGA in the fourth ventricle for the first time.

Relevance. Tuberous sclerosis (TS) is a hereditary tumor syndrome with autosomal dominant type of inheritance, occurring with frequency of 1:6000 — 10000 newborns worldwide. The disease is characterized by severe clinical manifestations in the form of astrocytomas of the brain, rhabdomyomas of the heart, angiomyolipomas of the kidneys, pulmonary lymphangioleomyomatosis and angiofibromas of the skin. Since effective treatment with mTOR inhibitors has been developed for TS, timely detection of patients with TS is important. The aim of the study. To determine the frequency and clinical features of TS in the Republic of Bashkortostan to improve organizational and therapeutic and diagnostic approaches in providing medical care to patients with TS. Material and methods. Determination of clinical and epidemiological features of TS in the Republic of Bashkortostan. Results. In the Republic of Bashkortostan, 86 patients with TS from 82 families were registered, the frequency of occurrence was 1:47048 people. The average age of patients was 18.5 years (from 1 year to 61 years). Depigmentation spots were found in 90 % of patients, facial angiofibromas in 56 %, head fibrous plaques in 33 %, shagreen plaques in 36 %, subependymal nodules of the brain in 66 %, and subependymal giant cell astrocytoma in 19 %, renal angiomyolipomas in 43 %, pulmonary lymphangioleiomyomatosis in 1.2 % of patients. Cognitive deficit was found in 47 %, epilepsy in 67 %, and autism in 1 % of patients with TS. Discussion. Comparative analysis of TS clinical manifestations in patients from the Republic of Bashkortostan with global data showed a significantly lower incidence of facial angiofibromas, lungs, kidneys and brain tumors, cognitive impairment and autism. 8 patients with identified mutations in the TSC1/TSC2 genes are treated with an mTOR inhibitor. Conclusion. The obtained results indicate a low frequency of registered cases of TS in the republic compared to world data. Therefore it is necessary to familiarize doctors of all specialties with the need to refer patients with symptoms characteristic of TS for medical genetic consultation. For reliable detection of tumors of the brain and internal organs, dynamic instrumental studies are necessary; assessment of psychological disorders in TS patients is necessary with consultation of psychotherapists, neurologists and psychologists.

Clinical profiles of tuberous sclerosis complex: A regionally based survey.

Abstract Tuberous sclerosis complex (TSC) is a genetic disorder resulting from mutations in the TSC1/TSC2 tumor suppressor genes. It causes benign tumors in multiple organs including the brain with cortical tubers, subependymal nodules, white matter abnormalities, and low-grade subependymal giant cell astrocytomas (SEGAs). Reported cases of malignant gliomas in TSC patients, with two new cases, are presented below. A 49-year-old woman, with TSC, cortical tubers, epilepsy, and taking everolimus for renal angiomyolipoma, presented with new headaches; a glioblastoma was resected. She underwent radiation, temozolomide, and bevacizumab. She is stable 12 months after diagnosis. A 57-year-old male, with a history of TSC, epilepsy, and cortical tubers, presented with new headaches. An enhancing brain mass was resected as a glioblastoma. He experienced mesenteric ischemia and bowel infarction and died three weeks later. A 22-month-old male, with a malignant gemistocytic astrocytoma, diagnosed after presenting with lethargy and vomiting, survived five months after surgery and radiotherapy. A 17-year-old male had upper motor neuron signs, from a glioblastoma, which was resected and radiated. A 26-year-old male developed glioblastoma eight years after radiation and excision of a SEGA. He died four months after surgery and chemotherapy. A 5-year-old male, with TSC2, lived three years following surgery, chemotherapy, radiotherapy, and mTOR inhibition for glioblastoma. A 33-year-old female presented with behavioral changes and hemiparesis; a glioblastoma was resected. A 58-year-old male, with confusion, dysphasia, and hemiparesis, had a glioblastoma and survived one month. An 11-month-old male had a SEGA resected which recurred as a malignant SEGA; he remained recurrence-free five years after chemotherapy. A 54-year-old male, with TSC1, developed visual loss secondary to a glioblastoma. He received surgery, radiotherapy, chemotherapy, bevacizumab, and anti-PD-L1 antibody, surviving 12 months post-surgery. These cases raise the question of whether malignant gliomas, in patients with TSC, may be more frequent and appear earlier.

Abstract TSC1 and TSC2 encode hamartin and tuberin, key regulators of the mTOR pathway that controls cell growth and proliferation. Germline pathogenic variants in these genes cause tuberous sclerosis complex (TSC), a multisystem disorder frequently associated with neurological tumors such as subependymal giant cell astrocytomas (SEGAs) and cortical tubers. However, population-level data on TSC1 and TSC2 variant frequencies remain scarce, particularly in East Asian populations. We analyzed exome sequencing data from 125,748 individuals in the Genome Aggregation Database (gnomAD), including 9,197 East Asians, as well as Korean-specific datasets comprising 5,305 individuals from the Korean Variant Archive (KOVA), 3,617 from Korea4K, and 1,722 from the Korean Reference Genome Database (KRGDB). Variants in TSC1 and TSC2 were annotated and classified according to ACMG/AMP and ClinGen guidelines, focusing on pathogenic and likely pathogenic variants. The global carrier frequency was estimated at 0.005% for TSC1 and 0.007% for TSC2. Among populations, the TSC1 carrier frequency was highest in Ashkenazi Jewish (0.040%) followed by East Asians (0.011%). TSC2 carrier frequency was also elevated in East Asians (0.011%), second only to Latinos (0.012%). In the integrated Korean dataset (n = 12,553), the estimated carrier frequencies were 0.032% for TSC1 and 0.032% for TSC2, indicating a notably higher prevalence in Koreans compared to other East Asian subgroups. This study provides the first comprehensive, population-based estimate of TSC1 and TSC2 pathogenic variant frequencies in Koreans. These findings highlight a potentially elevated burden of hereditary TSC in this population and underscore the need for population-specific genomic data to support accurate risk assessment, early detection, and clinical management of neuro-oncologic manifestations associated with TSC.

Published literature on epidemiological profile of paediatric brain tumours in Zambia is scarce.AimTo present a retrospective analysis of the histological spectrum of 36 paediatric age group central nervous system tumours operated in a single tertiary care hospital in Lusaka, Zambia between June 2021 and December 2024.Methods and MaterialsRetrospective analysis of the data regarding frequencies of various primary brain tumours among 36 paediatric patients (<18 years of age). The tumours were categorised according to the revised 4th edition of World Health Organization (WHO) classification of tumours of the Central Nervous system.ResultsPaediatric CNS constituted 29.2% of total intracranial tumours (35/120) operated in the study period. The mean age of the patients was 10 years, and a male predominance was noted (1.2:1). Posterior fossa tumors (24/35; 68.6%) were more common than supratentorial tumors. (12/35; 34.3%) Of the posterior fossa tumors majority were the pilocytic astrocytoma tumors (15/24; 62.5%), followed by medulloblastomas (9/24; 37.5%). Of the supratentorial tumors 6 pediatric type-high grade gliomas (17.1%) were recorded, 1 pleomorphic xanthoastrocytoma (2.9%) and 1 subependymal giant cell astrocytoma (2.9%) Our series also included 3 meningiomas (3/35; 8.6%) and one germ cell tumor (1/35; 2.9%).ConclusionsPaediatric central nervous system tumours are more common in boys and in the second decade of life. Astrocytomas are the most common paediatric brain tumours followed by medulloblastomas. Pediatric tumours affect the infratentorial compartment more often than the supratentorial compartment. The profile of paediatric brain tumours in our series is similar to that reported from other countries in sub-Saharan Africa as well as most western literature.