Expression-based decision tree model reveals distinct microRNA expression pattern in pediatric neuronal and mixed neuronal-glial tumors.

BACKGROUND: The understanding of the molecular biology of pediatric neuronal and mixed neuronal-glial brain tumors is still insufficient due to low frequency and heterogeneity of those lesions which comprise several subtypes presenting neuronal and/or neuronal-glial differentiation. Important is that the most frequent ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNET) showed limited number of detectable molecular alterations. In such cases analyses of additional genomic mechanisms seem to be the most promising. The aim of the study was to evaluate microRNA (miRNA) profiles in GGs, DNETs and pilocytic asytrocytomas (PA) and test the hypothesis of plausible miRNA connection with histopathological subtypes of particular pediatric glial and mixed glioneronal tumors. METHODS: The study was designed as the two-stage analysis. Microarray testing was performed with the use of the miRCURY LNA microRNA Array technology in 51 cases. Validation set comprised 107 samples used during confirmation of the profiling results by qPCR bioinformatic analysis. RESULTS: Microarray data was compared between the groups using an analysis of variance with the Benjamini-Hochberg procedure used to estimate false discovery rates. After filtration 782 miRNAs were eligible for further analysis. Based on the results of 10 × 10-fold cross-validation J48 algorithm was identified as the most resilient to overfitting. Pairwise comparison showed the DNETs to be the most divergent with the largest number of miRNAs differing from either of the two comparative groups. Validation of array analysis was performed for miRNAs used in the classification model: miR-155-5p, miR-4754, miR-4530, miR-628-3p, let-7b-3p, miR-4758-3p, miRPlus-A1086 and miR-891a-5p. Model developed on their expression measured by qPCR showed weighted AUC of 0.97 (95% CI for all classes ranging from 0.91 to 1.00). A computational analysis was used to identify mRNA targets for final set of selected miRNAs using miRWalk database. Among genomic targets of selected molecules ZBTB20, LCOR, PFKFB2, SYNJ2BP and TPD52 genes were noted. CONCLUSIONS: Our data showed the existence of miRNAs which expression is specific for different histological types of tumors. miRNA expression analysis may be useful in in-depth molecular diagnostic process of the tumors and could elucidate their origins and molecular background.

Surgical treatment of neuronal-glial tumors of mesial-basal part of temporal lobe: Long term outcome and control of epilepsy in pediatric patients.

BACKGROUND: Neuronal-glial tumors (ganglioglioma and dysembryoplastic neuroepithelial tumor) are a frequent cause of focal, drug-resistant and epilepsy in children and young adults, that is amenable for surgical treatment. AIM OF PAPER: Assessment of late outcome of surgical treatment and degree of seizure control, as well as prognostic significance of selected clinical factors. MATERIAL AND METHOD: 52 Pediatric patients presenting with epilepsy, lesion of mesio-basal temporal lobe and histologically verified neuronal-glial tumor treated at our facility since 2000-2011. RESULTS: After the mean follow-up of 2.94 years, satisfactory treatment outcome (Engel classes I and II) was obtained in 92% of the patients (n=48). Poor outcome (Engel class III) was seen in 8% of patients (n=4). New neurological deficits appeared in 28% of the patients (n=20) but in most of them resolved over time. CONCLUSIONS: In patients with drug-resistant epilepsy and a lesion of mesial-basal part of temporal lobe suggestive of a glial-neuronal tumor, surgical treatment is strongly recommended, aiming at excision of tumor and elimination of seizures. Histological verification of the lesion is a pre-requisite for optimal treatment planning. In most patients, both treatment goals may be reached. Short duration of epilepsy prior to surgery and young age are favorable prognostic factors. Histological diagnosis of GG, co-existence of cortical dysplasia and location of tumor extending beyond mesial-basal temporal structures are associated with a higher risk of postoperative complications. These may out-weight expected benefits of surgery.

Airgun shot wound to the orbit with retention of pellet. Case report and review of the literature.

Shot wounds become a growing clinical concern in the civilian setting, due to increasing popularity of air guns among minors. We present a pediatric case of a shot wound to the orbit with sparing of the eyeball and retention of airgun pellet in the retrobulbar space. The pellet was removed 3 months after injury via lateral orbitotomy. Pathophysiology and ballistics of shot wounds are briefly reviewed and current views on the management strategy of shot wounds with retained projectile are discussed.

Contrast enhancement pattern predicts poor survival for patients with non-WNT/SHH medulloblastoma tumours.

Recent studies revealed the biological heterogeneity of medulloblastoma, with the existence of at least four groups which are associated with several clinical and morphological features. We investigated for further correlations between molecular types, location of tumours, their contrast enhancement pattern and survival of patients. Altogether 76 tumours were analyzed and molecular subtypes were identified by immunohistochemistry using representative antibodies, detection of chromosome 6 monosomy and CTNNB1 mutation. The site of the tumour was assessed on diagnosis using Magnetic Resonance images and intra-operative surgical reports. In addition, the gadolinium enhancement pattern was also investigated in pre-treatment tumours. Cerebellar hemispheric location was associated with SHH tumours (p < 0.001), as opposed to midline location being typical for WNT and non-WNT/SHH tumours. Remarkably, for patients with non-WNT/SHH tumours, the extensive gadolinium enhancement pattern (present in >75% of tumour volume) predicted worse OS and EFS than for those with none/weak or heterogeneous enhancement (>10-75% of tumour volume), (both p < 0.001). Our analysis indicates that distribution of the medulloblastoma tumours location is related to the biological characteristics of tumour. Importantly, the enhancement pattern of the tumour may be a clinically useful prognostic marker for patients with non-WNT/SHH medulloblastomas.

Giant cerebellar cavernous malformation in 4-month-old boy. Case report and review of the literature.

Cavernous malformations (CMs) are rare vascular lesions that affect 0.4-0.9% of the population. The diagnosis of CMs is simple in most typical cases although some lesions may present unusual imaging features: localization, signal intensity, or size. Extremely rare giant CMs can mimic neoplastic lesion because of their size. We report a case of giant cerebellar CM that is more than 6 cm in size, diagnosed in 4-month-old boy. We discuss magnetic resonance findings and histopatholo-gical features of this lesion.

Bacteria and Candida yeasts in inflammations of the oral mucosa in children with secondary immunodeficiency.

BACKGROUND: Oral microbial flora and a damaged oral mucosa may increase the risk of bacteriemia, fungemia and complications in immunocompromised patients. AIM OF THE STUDY: Assessment of presence: bacteria and Candida spp. in different oral lesions, and the incidence of bacteremia in the case of a damaged mucosa in transplant recipients and patients receiving anti-tumour chemotherapy. MATERIAL AND METHOD: Forty-five patients ­ 18 months to 18 years of life, were included (20 ­ organ recipients, 14­ anti-tumour chemotherapy, 11 ­ control group). Clinical, oral mucosa examination focused on the type, severity and site of lesions, and microbiology assessed the presence of bacteria and fungi in the material from lesions. Blood cultures were performed in ten immunocompromised patients with manifestations of systemic infection. The control material consisted of blood cultures made prior to the onset of oral lesions and after 4­6 weeks following their remission in a diagnosed bacteremia. The statistical analysis was performed. RESULTS: In the subjects with secondary immunodeficiency, among other coagulase-negative Staphylococcus (CoNS), Candidia spp. were more frequent. In cancer patients, mucositis was associated with Candida spp., Streptococcus spp. Organ recipients with stomatitis exhibited the presence of CoNS, Streptococcus viridians and other. Oral lesions in the control group contained Haemophilus parainfluenzae, Neisseria spp. and Staphylococcus aureus. In 30% of immunocompromised patients, oral lesions were accompanied by bacteremia. CONCLUSIONS: A correlation has been found between oral lesions and the presence of S. aureus in patients without secondary immunodeficiency, and of CoNS, Enterococcus spp., Candida spp. in immunocompromised patients.

Congenital brain tumors in a series of 56 patients.

INTRODUCTION: Central nervous system tumors diagnosed before the end of the first year of life differ from those found in older children and in adults. The differences include mode of clinical presentation, anatomical distribution, histopathological diagnoses, response to therapy, and outcome. MATERIALS AND METHODS: The material consists of 56 children (23 girls and 33 boys), aged at recognition 32 Hbd-12 months. We reviewed charts and MR exams according to age of the onset of symptoms, location of tumors, treatment, histopathology, and outcomes. Data of the outcome were analyzed using Kaplan-Meier plots and chi-square test. RESULTS: Eleven cases were recognized before 6 weeks of life, 24 before the age of 6 months, and 21 were diagnosed up to the end of 1 year of age. Thirty-eight tumors were located in the supratentorial compartment; 18 were infratentorial. Median age of tumors' recognition was 5.2 months; 4.3 months for supratentorial and 7.2 months for infratentorial tumors. We found 18 glial cell tumors (high and low grade), 15 embryonal tumors, and 12 choroid plexus tumors. CONCLUSIONS: The outcome of congenital CNS tumors depends on the size, location, time of diagnosis, histological type of the tumor, and therapeutic option. Neurosurgical procedures are necessary in most cases. Despite the notable advances in therapy, the outcome remains poor.

Cognitive and social functioning in children and adolescents after the removal of craniopharyngioma.

PURPOSE: The aim of this study is to assess cognitive, emotional and social functioning in children and adolescents after the removal of craniopharyngioma. METHODS: Twenty-seven children operated for craniopharyngioma and their parents participated in the study. Cognitive functions were assessed with WISC-R/WAIS-R-PL and Rey-Osterrieth Complex Figure Test. Parents completed Achenbach's Child Behaviour Checklist (CBCL) questionnaires on problems in functioning and psychopathological symptoms and took part in an interview on children coping in everyday life. RESULTS: Eighty-two percent of patients were diagnosed with an average level of intellectual functioning. No child received results indicating mental disability. In half of the children, effectiveness of visual memory was reduced, despite normal visual-spatial abilities. The results in the CBCL scale indicated more frequent presence of psychopathological symptoms-especially social problems, depression, anxiety and withdrawal. The most frequent problems in children's everyday functioning included inability to control emotions, difficulties in learning, unsatisfactory peer relationships, and unattractive appearance resulting from hormonal disorders (short height and obesity). One third of parents also reported problems with pathological appetite in their children. CONCLUSIONS: Despite normal intellectual abilities and relatively good physical condition, children after removal of craniopharyngioma experience many difficulties in everyday life regarding social relationships, emotion control and learning. The analogy between the above-mentioned symptoms and symptoms observed in patients after infantile damage in the frontal area leads to an observation that, apart from endocrine disorders, damage to the frontal lobe caused by the growth of tumour and operational intervention is of crucial importance to the further development of children with craniopharyngioma.

Challenges for Safe Electrolytes Applied in Lithium-Ion Cells-A Review.

The aspect of safety in electronic devices has turned out to be a huge challenge for the world of science. Thus far, satisfactory power and energy densities, efficiency, and cell capacities have been achieved. Unfortunately, the explosiveness and thermal runaway of the cells prevents them from being used in demanding applications such as electric cars at higher temperatures. The main aim of this review is to highlight different electrolytes used in lithium-ion cells as well as the flammability aspect. In the paper, the authors present liquid inorganic electrolytes, composite polymer-ceramic electrolytes, ionic liquids (IL), polymeric ionic liquids, polymer electrolytes (solvent-free polymer electrolytes (SPEs), gel polymer electrolytes (GPEs), and composite polymer electrolytes (CPEs)), and different flame retardants used to prevent the thermal runaway and combustion of lithium-ion batteries (LIBs). Additionally, various flame tests used for electrolytes in LIBs have been adopted. Aside from a detailed description of the electrolytes consumed in LIBs. Last section in this work discusses hydrogen as a source of fuel cell operation and its practical application as a global trend that supports green chemistry.

Ganglioglioma associated with alterations of NBN gene. A case report.

We report a case of a 13-year-old girl with a tumour of the right fronto-parietal region of the brain. The tumour consisted of two components: a well-differentiated astroglial component with Rosenthal fibres and a neoplastic neuronal component. The final histopathology established diagnosis of ganglioglioma WHO grade I. The patient was selected from a group of children with central nervous system (CNS) tumours screened for the most common molecular variants in the NBN gene (exons 5 and 6). Molecular analysis revealed the presence of c.511A>G (p.Ile171Val) substitution on one allele. This is the first patient with ganglioglioma and confirmed mutation in the NBN gene.

Long-term functional outcome of surgical treatment of juvenile pilocytic astrocytoma of the cerebellum in children.

PURPOSE: Increasing incidence of pediatric brain tumors and improving survival rates encouraged us to assess long-term functional outcome of patients with cerebellar juvenile pilocytic astrocytoma (JPA). MATERIALS AND METHODS: Our study encompassed 105 children treated since 1980-2005 and consisted in analysis of mailed, custom-designed questionnaires. RESULTS: Mean follow-up time was 8.3 years. Sixty out of 104 patients presented permanent neurological deficits and 47/104 presented significant behavioral disorders. Eighty-nine children continued their education at primary, secondary or high school level. Most patients and their parents were satisfied with treatment outcome. Patients' and parents' notes were usually concordant. CONCLUSIONS: Long-term functional treatment outcome of cerebellar JPA is relatively favorable, in spite of permanent neurological deficits and emotional disorders in over half of the patients. Vermian tumors are associated with worse long-term functional outcome. Neurological deficits and emotional disorders do not preclude further education and independent functioning.

Germinoma Mimicking Brain Inflammation: A Case Report.

The authors report a case of a germinoma of the brain in the child with symptoms restricted to central nervous system. Ten-year-old girl presented initially with sight deterioration, learning difficulties, abnormal behavior, polydipsia, and polyuria. Brain magnetic resonance examination revealed T2 hyperintensity of the corpus callosum, anterior commissure, and caudate nuclei. Brain biopsy revealed extensive macrophage infiltration. Given these results and positive antinuclear antibodies in the blood, immunosuppressive and immunomodulatory treatment was implemented but it was not effective. The patient developed progressive quadriparesis, sleep disturbances, and dementia. Second brain biopsy was performed and it revealed germinoma cells. Chemotherapy was administered, but the girl died due to disseminated intravascular coagulation syndrome. The reported case shows an unusual coexistence of germinoma with prominent inflammation in the brain and highlights the importance of brain biopsy in such complex cases.

Symptomatic Rathke cleft cyst in paediatric patients - clinical presentations, surgical treatment and postoperative outcomes - an analysis of 38 cases.

BACKGROUND: Rathke cleft cysts (RCC) are benign, epithelium-lined intrasellar and/or suprasellar cysts believed to originate from the remnants of the Rathke pouch. The aim of this study was to analyse the symptoms and surgical outcome of patients with the diagnosis of RCC verified in a histopathological examination of the postoperative material. METHODS: The study is a retrospective analysis of 38 cases of children who underwent a neurosurgical treatment due to RCC at the Children's Memorial Health Institute in Warsaw, Poland, between 1994 and 2015. RESULTS: At diagnosis, the mean age was 13 years and 8 months (6 years and 11 months-17 years and 10 months, sex ratio was 1:0.9 with a female prevalence). The most common symptoms were the following: headache (50%), hypothyroidism (50%), short stature and/or decreased growth velocity (47%), delayed puberty and menstrual abnormalities (37%), diabetes insipidus or polydipsia and polyuria (26%), adrenal dysfunction (26%), sleepiness and general weakness (13%) and visual disturbances (11%). Due to the gravity of symptoms and size of the lesion, all the patients underwent a surgical treatment. All but one were successful (one patient died due to postoperative neurosurgical complications). The most common postoperative complications were the following: adenohypopituitarism (67%) and diabetes insipidus (45%). CONCLUSIONS: RCC can present with serious symptoms that significantly deteriorate patients' quality of life. Despite a successful neurosurgical treatment in most of the analysed cases, patients required long-term pharmacological treatment.

Multiple shunt system revisions in patients with hydrocephalus - causes, effects, regularities and prognostic factors.

BACKGROUND AND PURPOSE: Hydrocephalus in its various forms constitutes one of the major problems in neurosurgery. All neurosurgeons struggle with shunt malfunctions and their complications. Clinical experience suggests that there may exist a definite constellation of clinical features associated with higher risk of shunt malfunction. The aim of this study was to elucidate this issue based on our clinical experience. MATERIAL AND METHODS: Retrospective analysis of the clinical database was used to assess shunt procedures performed between 1980 and 2005 in 1860 children and adolescents with active hydrocephalus as the main or associated problem at admission. Overall, 2197 procedures were performed and the analysis included only patients who were treated surgically at least 3 times (n=106). Patients' age ranged from one day to 22 years. RESULTS: Recurrent shunt malfunctions were mostly associated with non-modifiable parameters (e.g. age <1 year, porencephaly, benign tectal mass and slit ventricle syndrome). Modifiable parameters (e.g. type of shunt or surgical technique) had no significant influence on treatment outcome. CONCLUSIONS: 1. The proportion of patients who require multiple (> or = 3) shunt revisions is small. 2. Higher risk of shunt malfunction and its subsequent revisions is associated with age below 1 year at first shunt insertion and aetiology of hydrocephalus resulting in severe shunt dependence. 3. Time interval between consecutive shunt revisions does not exceed 1 year in most cases.

Palliative procedures in the management of brain tumours in children. Change of therapeutic strategy over the last 25 years--an institutional experience Department of Neurosurgery of the Children's Memorial Health Institute in Warsaw.

BACKGROUND AND PURPOSE: The growing incidence of paediatric brain tumours and improved treatment outcome result in longer survival time. In this context, the issue of palliative treatment is becoming increasingly important. THE AIM of this paper is to assess the role of palliative procedures in the treatment of paediatric brain tumours and to analyze changes in therapeutic strategy concerning palliative procedures that have taken place within the last 25 years in one institution. MATERIAL AND METHODS: During the last 25 years (between 1980 and 2005), at the Department of Neurosurgery of the Children's Memorial Health Institute we have treated a total of 3279 children with the principal diagnosis of "CNS tumour", who underwent 611 palliative procedures. In 36 cases we performed a combined therapeutic-diagnostic procedure. This is a retrospective study, based on a review of medical records and search of our clinical database. RESULTS: There were significant differences in the frequency of palliative procedures depending on particular tumour location. There was also a significant linear increase of both the numbers and proportion of palliative procedures in consecutive years. Morbidity associated with palliative procedures was 1.8% and there was 1 perioperative death. CONCLUSIONS: 1. There are significant differences in the frequency of palliative procedures performed in the treatment of paediatric brain tumours depending on their location. 2. There was a quantitative and proportional linear growth of frequency of palliative procedures performed over the last 25 years; a wider spectrum of available therapeutic options increased the scope of neurosurgical interventions. 3. Combination of stereotactic, endoscopic and neuronavigational techniques is of considerable benefit in the treatment of brain tumours in children.

Currarino syndrome in a teenage girl--a case report.

We present a case of Currarino syndrome in a teenage girl, diagnosed relatively late but successfully treated surgically. Discussion focuses on the Currarino syndrome as a form of dysraphic condition, where dysontogenetic tumours may coexist. Emphasis is placed on precise diagnostic evaluation and optimal planning of therapeutic strategy in patients with multiorgan congenital malformations. Another issue is differentiation of a "teratoma" (neoplasm) from a "teratomatous cyst" (a congenital malformation).

Tethered cord syndrome in children - impact of surgical treatment on functional neurological and urological outcome.

BACKGROUND AND PURPOSE: Tethered cord syndrome (TCS) consists of solid adhesion of the distal spinal cord to adjacent structures, resulting in repetitive spinal cord traction during truncal movements. The condition is usually a sequel of lumbosacral dysraphism, spinal cord injury or surgical procedure. Clinical signs of TCS include sphincter disturbances, lumbosacral pain, sensorimotor deficits and orthopaedic deformity. The aim of this study was to assess long-term results of surgical treatment of TCS in children and to define any prognostic factors associated with long- -term outcome. MATERIAL AND METHODS: Between 1980 and 2005, we treated 59 children with TCS. The group included 22 boys and 37 girls (mean age at surgery: 7.7 years). In total, 75 surgical procedures were performed. Mean follow-up time was 4.4 years. RESULTS: Meaningful clinical improvement was obtained in 19 children (32.2%) and was more pronounced in lower extremities than in sphincters. Degree of untethering was the only factor significantly influencing outcome. Neither age at surgery nor severity of spinal cord traction had any prognostic value. Significant correlations were found between severity of pre-existing myelopathy and development of neurogenic bladder, independently of treatment instituted. There was no permanent morbidity and perioperative mortality was nil. CONCLUSIONS: Late results of surgical treatment of TCS in children are generally unsatisfactory - worthwhile improvement was obtained in about 1/3 of patients only. Improvement was more pronounced in lower extremities than in sphincters. The sole factor contributing to good functional outcome was complete untethering of the cord. The decision whether to operate on a child with TCS must be based on coherent clinical, radiological and urological premises; surgery should be performed before irreversible deficits appear.

Accuracy of intraoperative registration during electromagnetic neuronavigation in intracranial procedures performed in children.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate registration accuracy in an electromagnetic navigation system applied to image-guided intracranial procedures in children. MATERIAL AND METHODS: In a group of 34 children aged from 2 weeks to 17 years, 38 procedures were performed using electromagnetic navigation, including 24 neuroendoscopic procedures, 10 craniotomies, and 4 shunting or drainage procedures. Thirty-three registrations based on 7 to 10 anatomical landmarks were digitised, and three-dimensional models of patients' heads were constructed using magnetic resonance images (MRI) (23 cases) or computed tomography scans (CT) (10 cases) and used for further analysis. Registration error calculated by the system was used as a measure of registration accuracy. RESULTS: Registration error in the study group ranged from 0.7 mm to 4.4 mm (median 2.1 mm, mean 2.24 +/- 0.7 mm). It was shown that registration accuracy increased with patients' age. Differences between mean registration errors in procedures based on MRI or CT studies were not significant. There was no correlation between the number of landmarks registered and registration accuracy. CONCLUSIONS: Electromagnetic neuronavigation, which does not require firm head fixation, can be used in the youngest age group. Nevertheless, registration accuracy is lower in newborns and infants. Neither imaging modality (MRI or CT) used for creation of a three-dimensional model of the patient's head nor registration of more than 6 landmarks have an impact on registration accuracy.

Teratoma or enterogenous cyst? The histopathological and clinical dilemma in co-existing occult neural tube dysraphism.

BACKGROUND: Better understanding of embryology, histopathology and genetics of dysraphic conditions have lead to an expansion of this concept to entities with a similar microscopic appearance (e.g. enterogenous cysts, colloid cyst of the III-rd ventricle) or rated among neoplasms (e.g. mature teratoma), creating a certain conceptual confusion. Currently the diagnosis of "teratoma" is being substituted by "enterogenous cyst" or "teratomatous cyst". AIM OF PAPER: Clarification of concepts in this field and presentation of the experience of the Department of Neurosurgery of the Children's Memorial Health Institute associated therewith. MATERIAL AND METHOD: Since January 1990 through April 2005 we had treated 7 children with the final diagnosis of "an enterogenous cyst". The mean age of the children was 10.5 years and the mean follow-up time was 4.1 years. The study was performed by a retrospective analysis of medical records, imaging studies and histological preparations. RESULTS: the study group included: 3 cases of type I enterogenous cyst, 1 case of type II cyst and 3 cases of type III cyst (in 2 cases a former diagnosis of "mature teratoma" has been revised). Within this follow-up time, a good outcome was obtained in 3 cases, moderate disability - in 3 cases and severe disability - in 1 case. CONCLUSIONS: (1) Enterogenous cyst often co-exists with other dysraphic features; (2) Clinical signs of an enterogenous cyst are non-typical and depend on location of the lesion. The presence of secreting gastric mucosa may lead to chemical myelitis; (3) Severity of the postoperative neurological deficit is due to the developmental nature of the lesion and common vascular supply; (4) Late results of treatment are satisfactory, provided the lesion is excised radically; (5) Enterogenous cyst may be diagnosed in the case of a tumor composed of tissues originating from 1, 2 or 3 embryonic layers coexisting with dysraphic stigmata, congenital vertebral abnormalities or a mediastinal tumor of the same type. Types II and III of enterogenous cyst were historically diagnosed as "adult teratoma".

[Osteoblastoma of the dens axis in a 14-year-old boy. A case report]. / Guz zeba kregu obrotowego (osteoblastoma) u 14-letniego chlopca. Opis przypadku.

We present a case of osteoblastoma of C1 in a 14-year-old boy. The case deserves attention because it is a conglomerate of issues important from the point of view of clinical practice. Key issues associated with this interdisciplinary pathology are discussed, such as diagnostic problems, stabilisation of the cervical spine and extensive surgery associated with the risk of severe bleeding in a Jehovah Witness. A short review of pertinent literature is included.