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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.

Objective Diffuse Midline Gliomas (DMG), H3 K27M-mutant have the poorest prognosis among all pediatric high-grade gliomas, with a median survival of 9-11 months. Although radiotherapy (RT) is standard treatment for these tumors, unfortunately there has been no approved and effective treatment which completely diminishes the tumor yet. In our clinic, we started an up-to-date approach to manage DMG, which is adjuvant fractionated external beam radiotherapy along with ONC 201 after tissue diagnosis. Methodology Between January 2016 and June 2021, a total of 11 patients with H3 K27M-mutant diffuse midline glioma, diagnosis confirmed by Next-Generation Sequencing (NGS) were enrolled in study. All patients received ONC201 orally once a week following radiotherapy. Safety, and radiological evaluations were regularly assessed every 12 weeks. Results Among the 11 patients, the median age of diagnosis was 5. Seven (63.6%) patients were male and 4 (36.4%) were female. Primary lesions were localized in the pons in 5 (45.5%) patients, unilateral thalamus (2 on the left, 1 on the right) in 3 (27.3%) patients, bilateral thalamus in 2 (18.2%) patients, and temporo-insular in 1 patient (9.1%). Median progression-free interval was 10 months and median overall survival was 16 months. Conclusion Diffuse midline glioma has dismal prognosis. None of the treatment options made any dramatic changes in disease course during last 30 years. In our series, diffuse midline glioma patients who had ONC201 tend to have few months more progression free and overall survival (16 vs 11 months) in comparison to patients who had classical treatment in literature. As a neurooncology team, we strongly advocate to obtain tissue samples from diffuse tumors, to establish definite diagnosis and to perform NGS

Objective Pediatric high grade gliomas(HGG) have dismal prognosis with median survival of 9-15 months after standard radio-chemptherapy. Recent molecular investigations revealed a missmatch repair defect called Constitutional Mismatch Repair Deficiency (CMMRD), which induce pediatric HGG. In CMMRD, there are mutations at least one of the mismatch repair(MMR) genes in both tumoral and non-tumoral DNA. Patients generally have cafe au lait spots resembling the ones in NF-1. Methodology Forty-four pediatric high-grade glioma cases operated in our clinic between 2015-2021 were included in the study. PMS2, MLH1, MSH6, MSH2 immunohistochemical antibodies were applied to the sections prepared from paraffin blocks with tumors of these 44 cases. Next generation Sequencing (NGS) Custom Panel for Brain Tumors was performed with DNA and RNA obtained from neoplastic tissue of 2 cases and germline NGS analysis was performed with DNA obtained from peripheral blood in 1 case. Results MMR protein expression loss was detected in 11 (25%) cases. In 5 (45%) of these 11 cases, MMR protein loss was detected in both neoplastic and non-neoplastic tissue, and these cases were considered as CMMRD. NGS performed in 2 of these 5 cases revealed a hypermutant profile. At least one MMR protein loss was found only in the neoplastic tissue in 6 (55%) of 11 cases, and PMS2 deficiency was the most common. In 1 of these 6 cases, MSH6 deficiency was shown as germline by NGS. Conclusion CMMRD and MMRD, are disorders with close relationship with pediatric high grade gliomas. Since CMMRD cases also may have cafe au lait spots, they should not be misdiagnosed as NF 1. Temozolomide induce more aggressive tumors in CMMRD ve MMRD, therefore its use is not suggested in those cases. Preliminary literature data advocate use of immunotherapy instead. All pediatric HGG cases should be evaluated for CMMRD and MMRD with molecular investigations to understand their biology.

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.

Tumors originating from the midbrain, pons and medulla are collectively named as brainstem tumors. Their prevalence in the pediatric age group is around 10–20%. They may grow as focal or diffuse lesions. Unfortunately, the majority of these lesions have bad prognosis. In general sense, acute onset of symptoms with multiple cranial nerve palsies indicates worse prognosis. The most frequent symptom of a brainstem tumor is pyramidal weakness. Other symptoms are nausea, vomiting, balance problems and cranial nerve palsies. Patients with cranial nerve palsies may have double vision, conjugate gaze palsy, swallowing difficulties, dropped shoulder, and problems with tongue movements. Papilledema is not a usual sign of brainstem tumors because it is generally a late problem in these patients. Less frequently, these patients may have nystagmus and other rare brainstem syndromes involving the pons and the midbrain.

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. Near total excision of the tumor was performed, and adjuvant chemotherapy and radiotherapy were administered. The patient is in good health and has no evidence of clinical and radiological tumor recurrence for 22 months.

BOZKURT, SUHEYLA UYAR uyar/0000-0002-5947-947X WOS: 000419966300020 PubMed: 29063957 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. 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. 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. 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.

Hypothalamic hamartomas (HH) generally present with gelastic seizures. It is very unusual for a pediatric patient with HH to present with infantile spasms (IS). 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. Although hypothalamic hamartomas generally present with gelastic seizures, they should also be considered in the differential diagnosis of infantile spasms.

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. 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). 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

Objectives: Epilepsy surgery is one of the treatment options in pediatric patients with drug-resistant epilepsy. Our aim is to share demographic data, surgical outcome, possible surgical complications, and factors that affect surgical outcome in pediatric patients with drug-resistant epilepsy who were operated in our clinic. Methods: In this retrospective study, 85 patients who were operated in Acibadem Hospital Pediatric Epilepsy Surgery Clinic between years 2005 and 2017 were included. We investigated the influence of sex, age at seizure onset, side and frequency of seizures, time to surgery, type of epilepsy surgery, and histopathology on pediatric epilepsy surgery outcome. Surgical outcome was assessed by Engel classification system. Statistical analysis was performed with SPSS 20.0 software. Results: There were 56 male (66\%) and 29 female (34\%) participants. Median of the age of seizure onset is 2 years (1 day-15 years). Median of age at operation is 6.2 years (3 months-16 years). Median of the duration of seizure until surgery is 3.2 years (3 months-15.5 years). Median follow-up is 5.6 years (3 months-13.5 years). There were permanent motor neurological deficits in 3 patients (3.5\%). The best surgical outcome was achieved in patients with resective surgeries (p

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 EN 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 (El), 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, El was 0.43 +/- 0.09, FOR was 0.51 +/- 0.74, and CA was 78.5 degrees +/- 36.4 degrees. Separately, for mean postoperative values, LVFH width was 54 +/- 14.2 mm, El was 0.39 +/- 0.09, FOR was 0.47 +/- 0.07, and CA was 104.5 degrees +/- 32.6 degrees. The CA was increased and the LVFH width, El, 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 EN 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.

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. 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. 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. 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.

Background: Diffusion tensor imaging (DTI) is a novel magnetic resonance imaging (MRI) technique potentially able to evaluate the microscopic structural organization of white matter fibers. Aim: This study aimed to compare fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values obtained by DTI in stenotic versus nonstenotic cervical spinal segments of patients with clinical and neurological evidence of cervical spondylotic myelopathy (CSM). Materials and Methods: This prospective study included 21 patients with CSM but without T2 changes on conventional MRI. Diffusion tensor (DT) images from the stenotic and nonstenotic segments of the subjects were obtained. FA and ADC values were estimated and compared with stenotic versus nonstenotic segments. Statistical Analysis: Paired t-test was used [Statistical Package for the Social Sciences (SPSS) 12.0]. Results: In the most stenotic segments, the mean FA value was significantly lower (0.4228 ± 0.1090 vs 0.6884 ± 0.0075, P < 0.001) and the mean ADC value was significantly higher (1.312 ± 0.2405 vs 0.9183 ± 0.1477, P < 0.001) when compared to nonstenotic segments. In addition, there was a negative correlation between FA and ADC values (r = 0.63, P = 0.002). Conclusions: DTI of the cervical spine seems to be a promising novel imaging modality in patients with CSM. Advances in Knowledge: DTI may offer increased diagnostic sensitivity as compared to standard MRI and enables earlier detection of the disease.

WOS: 000358382400025, PubMed ID: 26005079, Meningomyelocele is one of the most common and socioeconomically, psychologically, and physically debilitating neurodevelopmental diseases. A few chromosomal locus and genes have been identified as responsible for the disease; however, clear evidence still needs to be produced. This study aimed to show evidence of a strong genetic linkage in a novel chromosomal locus in a family with this neural tube defect. We identified a neural tube defect family in eastern Turkey, where two of six offspring had operations due to thoracolumbar meningomyelocele. The parents were of a consanguineous marriage. We collected venous blood from six offspring of the family. Whole genome linkage analysis was performed in all offspring. A theoretical maximum logarithm of an odds score of 3.16 was identified on chromosome 9q21.12-21.31. This result shows a strong genetic linkage to this locus. Our results identified a novel chromosomal locus related to meningomyelocele and provide a base for further investigations toward the discovery of a new causative gene.

Introduction: Intracranial aneurysms are very rare in children. Although subarachnoidal hemorrhage (SAH) is by far the most common presentation of aneurysms in the majority of the pediatric case series, it is not rare for an unruptured aneurysm to present with a mass effect. Acute hydrocephalus is a common finding following aneurysmal SAH. However, this malady may develop even in the absence of SAH but secondary to direct obstruction by a giant aneurysm. This situation is extremely rare in children, with only a few known case reports in the literature. Case Report: We report the case of a 10-year-old girl who presented with signs and symptoms of acute hydrocephalus; further radiological evaluation revealed obstructive hydrocephalus and a giant posterior cerebral artery aneurysm. Following endovascular treatment of the aneurysm, hydrocephalus was completely resolved, and the patient was symptom free. Conclusion: Although they are very rare, giant intracranial aneurysms must be kept in mind during the differential diagnosis of pediatric acute hydrocephalus cases. Hydrocephalus may resolve spontaneously after the successful treatment of these aneurysms.

Heterotopic redundancies, such as an accessory limb associated with spina bifida, are extremely rare anomalies. There are 12 cases of accessory limb associated with spinal bifida in literature. This report aims a detailed description of the additional case and an analysis of the findings in light. A male baby was born at 40 weeks of gestation and was referred to the neurosurgery clinic with a diagnosis of accessory lower limb. On physical examination, the dorsal meningocele was located at the lumbosacral region and there was accessory lower limb on it. There was no open neural placode. The accessory limb was excised on postnatal day 3. Dysraphic appendages are rare and complicated anomalies. They should be investigated carefully, and all of the lesions must be repaired for babies’ quality of life.

Objectives: To evaluate the presence of upper urinary tractdeterioration (UUTD) and accompanying pathologies in childrentreated with the diagnosis of non-neurogenic bladder-sphincterdysfunction (NNBSD).Patients and Methods: We retrospectively reviewed themedical records of 316 consecutive patients with NNBSDwho were treated. All cohort were grouped into two: Group I(Treatment success; n=284), Group II (Treatment failure with anyform of occult spinal pathology; n=32). Thirty-four children withtreatment-failure and normal magnetic resonance imaging (MRI)findings were excluded. Groups were compared for pre- and posttreatmentpediatric lower urinary tract symptom score (PLUTSS),presence of UUTD and urodynamic findings.Results: The mean PLUTSS was significantly less in Group Icompared with Group II at pre-treatment and 3 months thereafterthe initial treatment (12.20 ± 5.90 and 5.20 ± 4.90 vs 20.3 ± 2.14and 18 ± 3.4, respectively p20 cmH2O and presence of vesicoureteral reflux (VUR)., Amaç: Nörojenik olmayan mesane–sfinkter fonksiyon bozukluğu(NOMSFB) tanısıyla tedavi edilen çocuklarda üst üriner sistemhasarı (ÜÜSH) ve eşlik eden patolojilerin araştırılmasıdır.Hastalar ve Yöntemler: NOMSFB nedeniyle kliniğimizdetedavi edilen 316 çocuğun tıbbi kayıtları retrospektif olarakincelendi. Çocuklar, tedavi yanıtına ve magnetic resonansgörüntüleme (MRG) bulgularına göre iki gruba ayrıldılar: GrupI (Tedaviye yanıt verenler; n=284) ile Grup II (Tedaviye dirençliolup, lomber MRG’sinde gizli spinal disrafizm bulgusu olanlar;n=32). Tedaviye dirençli olup lomber MRG’sinde patolojisaptanmayan 34 çocuk çalışma dışı bırakıldı. Gruplar tedavi öncesive sonrası semptom skoru (SS), ÜÜSH ile ürodinami bulgularıaçısından karşılaştırıldı.Bulgular: Tedavi öncesi dönemde ve tedavi başladıktan üçay sonra, Grup I’in ortalama SS’si Grup II’ye göre anlamlı olarakdüşük saptandı (sırasıyla 12,20 ± 5,90 ve 5,20 ± 4,90 karşın 20,3± 2,14 ve 18 ± 3,4; p

Patterns of cardiovascular risk factors in populations are not static over time. We examined trends in body mass index (BMI), parental smoking and blood pressure over a 15-year period in Turkish children aged 15-17 years. Two cross-sectional studies were performed in secondary schools in Turkey in 1989-1990 and 2004-2005. Study participants were 673 children in 1989-1990 and 640 adolescents in 2004-2005. Main outcome measures were weight, height, BMI, presence and amount of parental smoking, systolic and diastolic blood pressure. Age and sex matched comparisons were performed to assess temporal trends in these measures. Children in 2004-2005 had increased weight, height, BMI and decreased systolic and diastolic blood pressure in all age groups compared with children in 1989-1990. According to the international criteria, 3.4% of children were obese and 15.8% were overweight in 2005, compared to 0.7% obese and 4.2% overweight in 1990 (P

Pantothenate kinase-associated neurodegeneration (PKAN) syndrome is an autosomal-recessive neurodegenerative disease that causes progressive generalized dystonia. Currently, the disorder remains pharmacologically intractable. Herein we report the first case in which deep brain stimulation helped to relieve dystonic storm in a patient with PKAN syndrome who had homozygous c.628 2 T > G mutation of the PANK2 gene. A 10-year-old boy with PKAN disease presented with dystonic storm and was admitted to the emergency department. Examination revealed generalized dystonia and impaired breathing due to involvement of the respiratory muscles. The patient underwent surgery for bilateral globus pallidus internus deep brain stimulation. The patient showed marked response to treatment.

Primary brain stem tumors are a group of diseases that may be located in the mesencephalon, pons, and medulla oblongata. They are generally considered as diseases with a poor prognosis, because surgery nearby such eloquent structures within the brain stem is a great challenge for many neurosurgeons and complete resection can be achieved in only a small number of selected patients.

We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853\_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.

Vertebral column deformities after resection of posterior fossa tumors in children have been well documented. These include mainly postlaminectomy kyphosis and cervical instability. Risk factors for postoperative vertebral column deformities include multiple levels of laminectomies, involvement of C2, cervical region, childhood, adjuvant radiotherapy, lateral extension of decompression, facetectomy, and number of levels resected.

Adeloye-Odeku disease is composed of dermoid cyst over anterior fontanelle, first described in 1971. We present an 11-year-old girl with a soft, fluctuant swelling over bregma. The lesion content was isointense to cerebrospinal fluid on both T2W and FLAIRW images. There was a lytic area under the lesion, seen on CT. The lesion was totally excised. Histopathology confirmed the diagnosis. The case was unique; because a fibrous band was observed extending to superior sagittal sinus and it has never been reported before. Although lesions are sub-aponeurotic, because of this kind of fibrous band, a thorough examination with neuroimaging tools is very important for planning of surgery.

Hemifacial spasm (HFS) is a condition manifested by involunary unilateral contraction of the facial muscles. Most of symptoms ssociated with HFS result from compression of facial nerve at the oot exit zone. Such compression is usually caused by nearby vesels. Hemifacial spasm may also develop from other pathologies hat involve cerebellopontine angle (CPA), such as tumors, arterivenous malformations (AVMs), or aneurysms that impact the root xit zone of the facial nerve. Microvascular decompression (MVD) s preferred surgical treatment for most patients with HFS [1]. We eport a case of HFS caused by an AVM in CPA in which the patient as treated with gamma knife radiosurgery.

Genetic Clues to Meningioma Meningiomas are the most common primary brain tumors in adults. Located within the layer of tissue covering the brain, these tumors are usually slow-growing and benign but can cause serious neurological complications. About half of these tumors have mutations in the neurofibromin 2 gene ( NF2 ). To identify other genes that contribute to meningioma pathogenesis, Clark et al. (p. 1077 , published online 24 January) performed genome sequence analysis on 300 tumors. Meningiomas fell into two general classes: benign tumors located at the skull base—which tend to harbor mutations in the TRAF7, KLF4, AKT1 , and SMO genes—and higher-grade tumors located in the cerebral and cerebellar hemispheres harbor mutations in NF2.