Pediatric Diffuse Leptomeningeal Glioneuronal Tumors: Diagnosis, Follow-up, and Treatment Options.

AIM: To highlight the diagnosis, follow-up, and treatment options for diffuse leptomeningeal glioneuronal tumor (DLGNT) by examining pediatric patients diagnosed with DLGNT by molecular pathological evaluation and next generation sequencing at our center. MATERIAL AND METHODS: In this retrospective analysis, patients diagnosed with DLGNT between January 2017 and December 2022 are outlined according to their demographic data, radiological data, pathology results, treatments, and follow-up data. RESULTS: Four patients were diagnosed with DLGNT. All the patients were male. The mean age was 6.5 years. All but one patient had symptoms of increased intracranial pressure. An open biopsy was obtained from all patients for diagnosis. Three patients received radiotherapy and chemotherapy after the diagnosis. Two patients died during their follow-up, one of them in the early postoperative period. Two patients were clinically and radiologically stable in their follow-up after treatment. CONCLUSION: Further work with larger cohorts is required to determine a common algorithm for DLGNT treatment and follow-up. This analysis may keep this entity in mind in patients with pediatric communicating hydrocephalus and may present insight into diagnosis, follow-up, and treatment options.

Preliminary findings of German-sourced ONC201 treatment in H3K27 altered pediatric pontine diffuse midline gliomas.

PURPOSE: H3K27 altered pediatric pontine diffuse midline gliomas (pDMG) have a poor prognosis, and conventional treatments offer limited benefits. However, recent advancements in molecular evaluations and targeted therapies have shown promise. The aim of this retrospective analysis was to evaluate the effectiveness of German-sourced ONC201, a selective antagonist of dopamine receptor DRD2, for the treatment of pediatric H3K27 altered pDMGs. METHODS: Pediatric patients with H3K27 altered pDMG treated between January 2016 and July 2022 were included in this retrospective analysis. Tissue samples were acquired from all patients via stereotactic biopsy for immunohistochemistry and molecular profiling. All patients received radiation treatment with concurrent temozolomide, and those who could acquire GsONC201 received it as a single agent until progression. Patients who could not obtain GsONC201 received other chemotherapy protocols. RESULTS: Among 27 patients with a median age of 5.6 years old (range 3.4-17.9), 18 received GsONC201. During the follow-up period, 16 patients (59.3%) had progression, although not statistically significant, the incidence of progression tended to be lower in the GsONC201 group. The median overall survival (OS) of the GsONC201 group was considerably longer than of the non-GsONC201 group (19.9 vs. 10.9 months). Only two patients receiving GsONC201 experienced fatigue as a side effect. 4 out of 18 patients in the GsONC201 group underwent reirradiation after progression. CONCLUSION: In conclusion, this study suggests that GsONC201 may improve OS in pediatric H3K27-altered pDMG patients without significant side effects. However, caution is warranted due to retrospective design and biases, highlighting the need for further randomized clinical studies to validate these findings.

Treatment of symptomatic sacral arachnoid cysts in the pediatric population.

OBJECTIVE: Symptomatic sacral arachnoid cysts are extremely rare in pediatric patients, resulting in a lack of consensus regarding optimal treatment measures. The current study evaluated the clinical symptoms and surgical indications, techniques, and outcomes of pediatric patients who underwent treatment for sacral arachnoid cysts with the aim of developing recommendations for follow-up and treatment. METHODS: This retrospective study included pediatric patients who underwent surgical treatment for sacral arachnoid cysts between January 2000 and December 2020 at the Department of Pediatric Neurosurgery, Acibadem University Faculty of Medicine. RESULTS: Thirteen patients were included in the study, 9 of whom were girls and 4 were boys. Five patients presented with urinary incontinence, 2 of whom also exhibited constipation. Other chief complaints included recurrent urinary tract infections (UTIs) and low-back pain (n = 4 patients each). Urological evaluation was performed in all patients, followed by urodynamic examination in those with urinary symptoms. Spinal MRI showed extra- and intradural sacral cysts in 12 patients and 1 patient, respectively. The latter patient exhibited recurrence during follow-up and underwent reintervention. Samples from the excised cyst walls were sent for pathological examination. Five patients with urinary incontinence, 2 with constipation, 4 with recurrent UTIs, and 3 with low-back pain exhibited resolution of symptoms after treatment. However, 1 patient with low-back pain did not show any improvement in symptoms. No postoperative complications were observed in the current study. The patients were followed-up regularly after surgery, and the mean follow-up duration was 4 years. CONCLUSIONS: Sacral arachnoid cysts in pediatric patients may be associated with urinary system dysfunction and low-back pain. Surgery is the treatment of choice for symptomatic patients and those with enlarged cysts with radiological evidence of compression, and the morbidity and mortality rates associated with surgery are low.

Hydatid disease of the brain and spine.

Hydatid disease of the central nervous system is relatively rare and comprises about 2-3% of all the hydatid cyst cases reported in the world. Spinal hydatid disease is an even rarer entity. It is endemic in sheep and cattle-raising regions, seen mainly in Mediterranean countries including Turkey and Syria. Pediatric neurosurgeons in non-endemic countries face a challenge when they encounter children with hydatid cysts of the central nervous system, mostly due to lack of awareness and the ensuing diagnostic dilemmas. It is also a significant socioeconomic problem in developing countries, due to improper hygiene and lack of dedicated veterinary practice. The clinical features are largely nonspecific and very according to location and severity of disease. However, with the advent of advances in MR imaging, the diagnostic accuracy of hydatic disease involving the brain and spine has increased. Intact removal of the cyst/s, without causing any spillage, and appropriate antihelminthic therapy is the goal and key to cure and prevention of recurrence. In this manuscript, the current literature on hydatid cyst of the brain and spine is reviewed to better understand the epidemiology, pathophysiology, diagnostic accuracy, and advances in therapeutic options. A heightened clinical suspicion, awareness of MR imaging features, improved surgical strategies, and options for prevention are discussed.

Surgical Approach to Thalamic Tumors.

Thalamic tumors are deep-seated lesions. Recent improvements in therapeutic approaches and surgical techniques have allowed a more accurate approach to these lesions and a reduction in morbidity and mortality. In this article, the various surgical approaches for the resection of thalamic tumors are described. Each of these approaches has its own indications and risk of complications. Resection of thalamic tumors needs specific anatomical knowledge, especially the vascular anatomy of the region and the thalamic peduncles.

Malignant nerve sheath tumor of oculomotor nerve in a pediatric patient.

Malignant nerve sheath tumors are extremely rare pathologies. They tend to occur within peripheral nerves and have close association of neurofibromatosis disease. Here, we present the second case of MNST of oculomotor nerve in literature. The patient was a 2-year-old girl with left sided oculomotor nerve palsy. After resection, the patient immediately had chemotherapy and radiotherapy. One year after surgery disease progressed with extensive intracranial seedings, and she passed away.

Lumbar intervertebral disc degeneration, end-plates and paraspinal muscle changes in children and adolescents with low-back pain.

The prevalence of low-back pain (LBP) in adolescents ranges from 7 to 72%. We aimed to define the radiologic characteristics of the lumbar spine in children and adolescents with LBP with/without leg pain. Two hundred and fourteen children and adolescents, who were born between 2001 and 2009 and had lumbar spine MRI for LBP with/without leg pain, were evaluated in terms of intervertebral disc degeneration (IVDD), end-plates and paraspinal muscle changes on lumbar spine MRIs. Severe IVDD was detected at all lumbar levels except for L2-L3. Modic changes were present in 4.2% of the patients. Modic changes were more common in patients with severe IVDD than in those with mild-to-moderate IVDD. Severe IVDD was significantly associated with Modic changes at the corresponding L1-L2 and L3-L4 disc levels. Girls had significantly more fatty infiltration in the paraspinal muscles when compared to boys. The risk of having severe IVDD concomitant with Modic changes was high [odds ratio (OR), 8.6]. The OR was 20.7 for predicting the presence of severe IVDD at any level if Modic changes presented particularly at the L3-L4 level. The ORs of Modic changes presented at any lumbar level at the background of fat-infiltrated multifidus at L3-L4 and L4-L5 levels were 8.3 and 9.1, respectively. Fatty infiltration in the paraspinal muscles and IVDD were closely associated with Modic changes in children and adolescents with LBP. Lumbar IVDD in children and adolescents could be the result of a mechanical pathology.

Spinal intramedullary H3K27M mutant glioma with vertebral metastasis: a case report.

A new entity of gliomas, named "diffuse midline glioma (DMG), H3K27M mutant (grade IV)," which represents a specific molecular profile, was introduced to the World Health Organization (WHO) classification 2016 of central nervous system tumors. Many midline localizations have been described for this glioma, and mainly the hypothalamus, pons, thalamus, and spinal cord are sites of predilection in pediatric and young adult patients. We report the case of spinal intramedullary DMG, H3K27M mutant (WHO grade IV), that showed an unusual presentation with multiple vertebral metastases.

Is it a new culprit? "TERT promoter mutation" in an aggressive pediatric pilocytic astrocytoma.

Recent advances in the genomic study have revolutionized the discovery of molecular biomarkers in glioma not only to aid in targeted therapy but also to prognosticate character of tumor and outcome of a patient.The usually benign nature of pilocytic astrocytoma (PA) can now be challenged with the discovery of genomic alterations that could promote more aggressive clinical behavior. CDKN2A deletion and ATRX gene inactivation or mutation have been the most common molecular alterations in worse prognosis.We will discuss a case of pilocytic astrocytoma showing the progressive recurrence with pilomyxoid features and the presence of TERT promoter mutation.

Current Clinical Practice About Pediatric Midline Gliomas in the Scope of Molecular Era.

AIM: To share our clinical experience with surgical and adjuvant treatment strategies followed during the treatment of midline gliomas. MATERIAL AND METHODS: Pediatric patients with midline gliomas who underwent surgery in our clinic between March 2016 and November 2019 were included. Tissue samples were obtained through surgical excision, open biopsy, or stereotactic biopsy. All samples were analyzed for ATRX, BRAFV600E, IDH1/2, H3K27M, and H3G34R mutations, EGFR and PGFRA amplifications, and PTEN loss. RESULTS: There were 7 (43.8%) female and 9 (56.2%) male pediatric patients in the study. Eight patients had thalamic, 5 patients had pontine, 2 patients had medulla oblongata and one patient had brachium pontis tumors. Presenting symptoms were headache, disequilibrium, ophthalmoplegia, and panic attack. Eleven tumors showed H3K27M mutation and were diagnosed as diffuse midline gliomas. BRAFV600E, ATRX mutations, PTEN loss, and EGFR amplifications were other molecular alterations detected within tumor samples. Patients with H3K27M mutant tumors had a shorter life span. Five patients were enrolled in an ONC201 trial. CONCLUSION: Although most midline gliomas are not amenable to gross total excision, obtaining tissue samples is mandatory for determining patients? exact diagnoses, tailored treatment plans, and eligibility for clinical trials. Stereotactic biopsy for midline gliomas is a safe and effective method.

Changes in Callosal Angle After Successful Endoscopic Third Ventriculostomy Procedure in Pediatric Patients.

AIM: To determine whether callosal angle (CA) measurement, a diagnostic and prognostic tool used for normal-pressure hydrocephalus in adults, is a reliable radiological parameter for evaluating endoscopic third ventriculostomy (ETV) outcomes in pediatric patients. MATERIAL AND METHODS: Forty-seven pediatric patients with hydrocephalus who underwent successful ETV in our clinic between 2011 and 2015 were included in this study. Preoperative and postoperative three-month CA, lateral ventricle frontal horn (LVFH) width, Evans' index (EI), and frontal-occipital horn ratio (FOR) parameters were recorded, with changes analyzed using a paired-samples t-test. RESULTS: There were 29 male and 18 female patients included within the cohort. For mean preoperative values, LVFH width was 58.8 ± 14.9 mm, EI was 0.43 ± 0.09, FOR was 0.51 ± 0.74, and CA was 78.5° ± 36.4°. Separately, for mean postoperative values, LVFH width was 54 ± 14.2 mm, EI was 0.39 ± 0.09, FOR was 0.47 ± 0.07, and CA was 104.5° ± 32.6°. The CA was increased and the LVFH width, EI, and FOR were decreased in all patients within three months after surgery. The postoperative three-month change in CA was higher than those observed in the other parameters. CONCLUSION: Changes in CA after successful ETV were dramatically higher than those in the other ventricular parameters. For this reason, we suggest CA be used as a radiological criterion during early radiological follow-up of patients after ETV.

Is H3K27me3 status really a strong prognostic indicator for pediatric posterior fossa ependymomas? A single surgeon, single center experience.

PURPOSE: Posterior fossa ependymomas (PFE) are among the most frequently occurring solid tumors in children. Their definitive treatment is surgical excision and adjuvant radio-chemotherapy. This study aimed to investigate prognostic effects of age, H3K27me3 status, extent of resection, radiation treatment (RT), Ki67 index, WHO grade, and ATRX and H3K27M mutations in PFE patients. METHODS: This retrospective study included 42 pediatric patients with PFE who had undergone operation at our institution between 1996 and 2018. Patient demographics and treatment information were obtained from patient notes. Information on radiological location of tumors (median vs paramedian), extent of tumor resection, and recurrence was obtained from preoperative and postoperative magnetic resonance imaging. Formalin-fixed paraffin-embedded tumor samples were evaluated for H3K27me3 immunostaining, Ki67 index, WHO grades, and ATRX and H3K27M mutations. Tumor samples with global reduction in H3K27me3 were grouped as posterior fossa ependymoma group A (PFA) and those with H3K27me3 nuclear immunopositivity as posterior fossa ependymoma group B (PFB). We evaluated the cohort's 5-year progression-free survival (PFS) and overall survival (OS). RESULTS: There were 20 (47.6%) female and 22 (52.4%) male patients in the cohort. The mean age of patients was 4.4 (range, 0.71-14.51) years. Overall, tumors in 31 (73.8%) and 11 (26.2%) patients were found to be PFA and PFB, respectively. There was no statistically significant age or sex difference between PFA and PFB. All patients received chemotherapy, whereas only 28 (66.6%) received RT. The WHO grades of PFA were statistically higher than those of PFB. There was no significant difference between PFA and PFB in terms of extent of resection, disease recurrence, and survival parameters. Nine of 42 tumor samples had ATRX mutations. One patient with PFA showed H3K27M mutation. Age, WHO grade, H3K27me3 status, and RT had no effect on patients' PFS and OS. Patients with total surgical excisions had significantly better PFS and OS rates. Those with Ki67 < 50% also had better OS rates. CONCLUSIONS: Determining H3K27me3 status by immunohistochemistry is a widely accepted method for molecular subgrouping of PFEs. Most of the reports in the literature state that molecular subgroups of PFEs have significantly different clinical outcomes. However, in our present series, we have shown that the extent of surgical excision is still the most important prognostic indicator in PFEs. We also conclude that the prognostic effect of H3K27me3 status-based molecular subgrouping may be minimized with a more aggressive surgical strategy followed in PFAs.

Management of mature pineal region teratomas in pediatric age group.

PURPOSE: Mature pineal region teratomas differ from other pineal tumors in terms of their characteristic radiological appearance and their clinical outcome after gross total excision. Our aim is to share our clinical experience and treatment outcomes in pediatric patients with mature pineal region teratoma. METHODS: In this retrospective study, we reviewed clinical, radiological, and surgical data of ten patients who had radiologically predicted diagnosis of pineal region teratoma and pathologically confirmed diagnosis of mature pineal region teratoma between years 2004 and 2017 in our clinic. Statistical analysis was performed with SPSS 20. RESULTS: All patients were male. Ages of patients ranged between 5 and 17 (median age was 9.5). All of them presented with headache. Magnetic resonance imaging showed characteristic appearance of teratomas with variable degree of hydrocephalus. All patients had negative results for AFP and b-HCG levels. All patients had gross total resection of pineal tumor through occipital transtentorial approach with no permanent neurological deficit. Pathological results of all tumor samples were consistent with mature teratoma. None of them had adjuvant chemotherapy or radiotherapy. Follow-up periods ranged between 3 and 170 months (median follow-up period was 60.5 months). All patients are alive with no tumor recurrence. CONCLUSIONS: Pediatric mature pineal region teratomas are benign tumors with characteristic MRI appearance and negative tumor markers. Their definitive treatment is gross total surgical excision. Occipital transtentorial approach is a safe procedure for treatment of pediatric mature pineal teratomas.

Behavioral functioning of school-aged children with non-syndromic craniosynostosis.

PURPOSE: This study investigated the risk for children with non-syndromic craniosynostosis to develop behavioral problems during school age determined by the type of craniosynostisis, age at first surgery, and number of surgeries. METHOD: Final sample consisted of 43 children aged between 6 years and 8 months and 17 years and 1 month (M = 10 years and 5 months). Behavioral problems were assessed with Child Behavioral Checklist (CBCL). RESULTS: Our sample had higher scores on the CBCL than the general population; specific elevations were observed including somatic complaints, aggressive behavior, social problems, attention problems, and thought problems and rule-breaking behavior. Behavioral functioning varied by number of surgical procedures, type of craniosynostosis, and age at first surgery. CONCLUSION: For school-aged NSC children's behavioral functioning, diagnosis specific patterns especially impacted by the first age of the surgery and number of surgeries.

Postoperative patency assessment of Cystocisternostomy and Cystoventriculostomy stomas in cases with Arachnoidal cyst.

PURPOSE: The goal of this study was to determine stoma and flow patency with 3D SPACE T2 and 3D CISS sequences in cases with cystocisternostomy or cystoventriculostomy. METHODS: A total of sixty three patients (total 106 MRI examinations) with endoscopic cystocisternostomy or cystoventriculostomy of arachnoid cyst underwent 1.5-3 T MRI to determine flow patency between June 2007 and April 2018. Postoperative results, the patients' clinic and arachnoid cyst volume were used to confirm stoma and flow patency in MRI. RESULTS: The stoma was open and functional in forty three patients. Minimal flow was detected in five patients. Fifteen patients with closed stoma (total 17 MR images) were evaluated with the clinician. Patients' clinic, physical examination, and growth (for pediatric patients) were evaluated. Three of fifteen patients were re-operated. Operative findings and postoperative follow-up MR imaging findings were correlated with our preoperative MRI results. The findings were in compliance in both groups (operated-non-operated groups). CONCLUSION: 3D SPACE T2 and 3D CISS are effective sequences in addition to other routine conventional sequences to evaluate stoma and flow patency.

A rare clinical presentation: a pleomorphic xanthoastrocytoma presenting with intracerebral haemorrhage and metastasizing vigorously-case report and review of the literature.

Metastasis of an intracranial tumour is not a common situation in our daily neurosurgical practice. Pleomorphic xanthoastrocytoma is also a rare glial tumour with relatively a favourable prognosis among other CNS pathologies. Here, we present an anaplastic pleomorphic xanthoastrocytoma case which shows both haematogenous and lymphatic metastasis which is described first time in the up-to-date literature. Our case is a 17-year-old male operated for a right occipital intra-axial lesion with a diagnosis of anaplastic pleomorphic xanthoastrocytoma which recurs 5 years later and metastasize vigorously through haematogenous and lymphatic routes. A rare-presenting symptom for this pathology is also intracerebral haemorrhage. This is the ninth case report in the literature which presents initially with this entity.

Significance of H3K27M mutation with specific histomorphological features and associated molecular alterations in pediatric high-grade glial tumors.

PURPOSE: Pediatric high-grade gliomas (pHGGs) constitute almost 15% of all childhood brain tumors. Recurrent mutations such as H3K27M mutation in H3F3A and HIST1H3B genes encoding histone H3 and its variants were identified in approximately 30% of pediatric glioblastomas. This study aimed to ascertain the morphological and molecular characteristics of pHGGs with H3K27M mutation. METHODS: In total, 61 cases of pHGGs (anaplastic astrocytoma, 12; glioblastomas, 49) from four university hospitals were studied. The histomorphological features were examined and immunohistochemistry was performed to evaluate the mutation status of H3K27M, ATRX, IDH1, BRAF V600E, and p53 genes. RESULTS: The study comprised 25 females and 36 males (age range, 1-18 years) with a clinical follow-up of up to 108 months. From the total, 31 patients were positive for H3K27M mutation located in the midline, mostly in the pons and thalamus. H3K27M mutation was commonly associated with ATRX loss (32.3%) and p53 (74.2%) immunoreactivity with a co-expression rate of 25.8%. While IDH1 mutation was not detected in pHGGs with H3K27M mutation, BRAFV600E mutation was rarely observed. Among the various histomorphological features, increased number of mitosis, increased Ki-67 proliferation index, and palisading and geographical necrosis along with small cell patterns were significantly associated with the H3K27M wild-type tumors. Focal infarct-like necrosis and pilomyxoid morphology was significantly associated with these tumors. CONCLUSION: H3K27M mutation occurs exclusively in pHGGs arising from the midline and presents with varied histomorphological features ranging from low-grade pilomyxoid astrocytoma to highly pleomorphic glioblastoma along with ATRX loss and p53 mutations.

Malignant triton tumor of trigeminal nerve-case report.

INTRODUCTION: Here we are presenting a unique case of malignant triton tumor of the trigeminal nerve in a 4-year-old boy who presented with diplopia and ptosis. INTERVENTION: Near total excision of the tumor was performed, and adjuvant chemotherapy and radiotherapy were administered. RESULTS: The patient is in good health and has no evidence of clinical and radiological tumor recurrence for 22  months.

Hypothalamic hamartoma presenting with infantile spasms.

BACKGROUND: Hypothalamic hamartomas (HH) generally present with gelastic seizures. It is very unusual for a pediatric patient with HH to present with infantile spasms (IS). CASE PRESENTATION: Here we present a 6-month-old boy diagnosed with IS whose brain magnetic resonance imaging (MRI) showed an 18 × 18 × 16 mm mass in the hypothalamus. His seizures did not respond to antiepileptic treatment with vigabatrin and valproic acid. He had disconnective surgery for HH. Immediately postoperatively, his seizures subsided and he has now been seizure-free for 2 years. CONCLUSION: Although hypothalamic hamartomas generally present with gelastic seizures, they should also be considered in the differential diagnosis of infantile spasms.

Neuroendoscopic management of suprasellar arachnoid cysts.

BACKGROUND: The first case of an intracranial arachnoid cyst was described by Bright in 1831. In 1935, Barlow published the first case of a suprasellar arachnoid cyst. Fewer than 200 cases of suprasellar-prepontine arachnoid cysts have been reported in the literature as of January 2011. METHODS: Between 1994 and 2010, the senior author operated on 34 cases of suprasellar-prepontine arachnoid cysts. Eighteen female and 16 male patients ranged in age from 6 days to 16 years (mean 5.2 years). Follow-up of the patients ranged from 1 year to 16 years. RESULTS: Outcome may be evaluated according to radiological and clinical follow-up data. Postoperative radiological examinations must reveal: 1) the adequacy of fenestrations and flow through fenestration sites, 2) reduction of the cyst and ventricle size, and 3) reorientation of the chiasma and mammillary bodies to an acceptable anatomical position. In our series, no mortality occurred. Postoperative complication occurred in 3 cases. CONCLUSIONS: Suprasellar arachnoid cysts can be treated with favorable clinical and radiological results with endoscopic interventions when feasible. Results with ventriculocystocisternostomy are believed superior to those of ventriculocystostomy.