[Supratentorial neuroepithelial tumor with PLAGL1 gene fusion - a new type of morphologically variable pediatric brain neoplasm defined by a distinct DNA methylation class. A case report and literature review]. / Supratentorial'naya neiroepitelial'naya opukhol' so sliyaniem gena PLAGL1 u detei ­ novyi tip opukholi mozga s raznoobraznoi morfologicheskoi kartinoi i otlichitel'nym metilyatsionnym profilem(sluchai iz praktiki i obzor literatury).

BACKGROUND: Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types. OBJECTIVE: To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion. MATERIAL AND METHODS: We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma. RESULTS: Methylation analysis of tumor DNA confirmed a new type of a recently discovered neoplasm - neuroepithelial tumor with PLAGL1 fusion (NET PLAGL1). PCR confirmed fusion of PLAGL1 and EWSR1 genes. No seizures were observed throughout the follow-up period. There was no tumor relapse a year after surgery. CONCLUSION: Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.

[Autologous bone implant for reconstructive surgery after decompressive craniectomy in children]. / Sposob khraneniya i pogotovki kostnogo autotransplantata dlya zakrytiya defektov svoda cherepa u detei posle dekompressivnoi trepanatsii cherepa.

The concept of post-traumatic skull defect closure is based on restoration of anatomical relationships for the maximum possible recovery of brain function, i.e. it is considered as a stage of surgical rehabilitation. The choice of implants in pediatric patients is limited. In this regard, the «gold standard¼ is still autologous bone implant. MATERIAL AND METHODS: We propose a method for storage and sterilization of autologous bone implant. The last one implies keeping at a temperature of -80 ˚C with sterilization in a vacuum chamber filled with hydrogen peroxide vapors of biocidal plasma medium. Sterilization is provided by 45-minute cycle immediately before surgery. We report skull defect closure using autologous bone implants in 79 patients. Evaluation of effectiveness of storage and sterilization of autologous bone implant included analysis of mechanical properties of bone after sterilization, intra-operative microbiological monitoring, incidence of infections in early postoperative period, follow-up with assessment of resorption. RESULTS: Early infectious complications occurred in 2 patients (2.5%). Complete resorption with redo surgery occurred in 6 (10.1%) cases. Sterilization in low-temperature plasma of hydrogen peroxide changes mechanical properties of the bone, increases durability under compressive stresses and decreases durability under tensile conditions. This does not affect functional tasks of autologous bone. The proposed method of storage and sterilization is accompanied by low risk of infections and resorption. Storage of autologous bone implant at a temperature of -80 ˚C with subsequent sterilization in low-temperature plasma of hydrogen peroxide can be considered as a safe and effective method for skull defect closure in children after decompressive surgery.

[Selective neurotization of the median nerve in young patients with CV-CVIIcomplicated spinal cord injury]. / Selektivnaya nevrotizatsiya sredinnogo nerva u molodykh patsientov s oslozhnennoi pozvonochno-spinnomozgovoi travmoi na urovne CV­CVII.

BACKGROUND: Complicated spinal cord injury occurs in 1-5 cases per 100.000. In children, cervical trauma makes up 72% of all spinal trauma. Spinal cord injury complicates vertebral trauma in 25-50% of cases that usually results severe disability. Rehabilitation of these patients is usually ineffective or results a little improvement. Restoration of even minimal movements is essential in these patients. There are reports devoted to surgical rehabilitation of important hand functions after cervical spinal cord injury. OBJECTIVE: To demonstrate the restoration of key hand functions in patients with CV-CVII complicated spinal cord injury using selective neurotization of the median nerve. MATERIAL AND METHODS: Three patients aged 17-19 years with complicated CV-CVII spinal cord injury and ASIA class A have been selected for surgery for 2 years. Mean period after rehabilitation was 11.3 months. Prior to surgery, all patients recovered flexion/extension in the elbow joints, forearm rotation, flexion and extension of hands. However, there were no active movements in distal phalanges of the fingers, and initial signs of flexor contracture were observed. RESULTS: Surgical strategy included selective neurotization of the median nerve with a motor branch of musculocutaneous nerve. In one case, we used additional neurotization of posterior interosseous nerve. Two patients recovered cylindrical grip up to M4 and pinch grip up to M3 within 15 months. In the third patient, postoperative data were not assessed due to short-term follow-up. CONCLUSION: Selective neurotization of anterior interosseous nerve may be considered as a stage or independent surgery for restoration of key hand functions. This approach improves the quality of life in patients with complicated spinal cord injury.

[APOΕ gene polymorphism and markers of brain damage in the outcomes of severe traumatic brain injury in children]. / Polimorfizm gena APOΕ i markery povrezhdeniya mozga v iskhodakh tyazheloi cherepno-mozgovoi travmy u detei.

OBJECTIVE: To compare apolipoprotein E (APOE) genotypes with outcomes and levels of neuromarkers in children with severe traumatic brain injury (TBI). MATERIAL AND METHODS: APOE polymorphisms were genotyped in 69 children with severe TBI. The following markers of brain damage were identified: neuron-specific enolase (NSE), glial protein S100b, content of autoantibodies (aAB) to glutamate receptors (to the NR2 subunit of NMDA receptors), aAB to S100b and brain-derived neurotrophic factor (BDNF). RESULTS AND CONCLUSION: There was no association between APOE 3/3, 3/4, 3/2 genotypes and outcomes assessed by the Glasgow Outcome Scale (GOS). The greatest number of favorable outcomes was noted in the group of APOE 3/3 genotype carriers (60%). The ratio of favorable outcomes to unfavorable outcomes was equal (50%:50%) in groups with APOE 3/4 and APOE 3/2 genotypes. An association between APOE polymorphism and BDNF was found: there were normal BDNF levels in the APOE 3/3 group and reduced levels in the APOE 3/2 group. The correlation between neuromarkers and GOS scores was shown for BDNF and aAB to S100b. In children with favorable TBI outcomes, normal BDNF levels and a lower level of aAB to S100b were observed. Regardless of APOE genotypes, almost all children with severe TBI (95%) showed a significant increase in aAB to glutamate receptors in the remote period and most children had an increase in aAB to S100b in the blood. This fact can be explained by the presence of cerebral hypoxia, activation of autoimmune processes and increased BBB permeability, which may be enhanced by increased NO content and intensification of oxidative processes in children with severe TBI.

Infrascanner in the diagnosis of intracranial lesions in children with traumatic brain injuries.

BACKGROUND: The number of traumatic injuries among children is increasing. However, so-called mild TBI might result in unfavourable outcomes. Early diagnosis of intracranial haematomas prior to development of serious complications may be a decisive factor for a favourable outcome. InfraScan company developed and brought to the market the Infrascanner model 1000, which is a portable detector of blood collections that operates in the near infrared (NIR) band. OBJECTIVE: To estimate the efficiency of the Infrascanner model 1000 for detection of intracranial haematomas among children with mild TBI. MATERIALS AND METHODS: Ninety-five patients with mild TBI were examined. An indication for cerebral CT after mild TBI was the presence of risk factors of intracranial lesions. The Infrascanner was used by a neurosurgeon during primary examination. CT was performed in 43 patients (45%), while 52 patients (55%) with a low risk of intracranial lesions were under observation. RESULTS: The results of examination of patients using CT and infrared scanning coincided in 39 cases and intracranial haematomas were detected in eight patients. False-positive results were obtained in three cases. The sensitivity of the procedure used in this group of patients with a medium and high risk of development of intracranial haemorrhages was 1.00 (0.66; 1.00). The specificity was 0.91 (0.81; 1.00)--the proportions and a 95% CI. The false-positive risk is 0.27 (0.00; 0.58). During infrared scanning in patients with low risk of intracranial lesions, false-positive results were obtained in four cases and false-negative results were absent. CONCLUSION: Infra-scanning might be viewed as a screening technique for intracranial haemorrhages in ambulances and outpatient trauma centres in order to decide on hospitalization, CT scanning and referral to a neurosurgeon. Infra-scanning combined with evaluation of risk factors of intracranial damage might reduce the number of unnecessary radiological examinations.

[Peripheral Blood Lymphocytes Mitochondrial Function in Children with Traumatic Brain Injury].

BACKGRAUND: It is known that mitochondria play an important role in the mechanisms of brain cells damage and death following traumatic brain injury (TBI). However, the relationship between the severity of brain damage following TBI and mitochondrial dysfunction are not well defined. AIM: to study activities of NADN- and succinate dehydrogenases, a key enzyme of mitochondrial oxidative phosphorylation in children with TBI of varying severity and different outcomes; to detect ATP content in lymphocytes; the level of NOx and 3-nitrotyrosine in serum and plasma. Methods: all parameters were determined in the dynamics of one month following TBI, and in some cases up to the death ofpatients. The severity of TBI was scored by Glasgow Coma Scale (GCS), the outcome of TBI-Glasgow Outcome Scale (GOS). Based on the clinical examination children with TBI were divided into 3 groups: (1) mild TBI; (2) severe TBI and (3) severe TBI with fatal outcome. RESULTS: we found that activity of dehydrogenases is significantly reduced only in patients with the poor neurologic outcome. The greatest decrease in these parameters was observed in patients with severe traumatic brain injury and fatal outcome. A direct correlation was found between the indices of dehydrogenases activity and A TP content in lymphocytes (r = 0.97, p = 0.005). The levels of NOx metabolites and 3-nitrotyrosine were significantly increased in children with severe TBI. CONCLUSION: obtained results suggest that mitochondrial dysfunction, impaired cerebral energy metabolism and oxidative stress contribute to cell death in the brain and thus represent therapeutic targets for the treatment of TBI.

[Transsphenoidal surgery of craniopharyngioma: form palliative surgery to radical removal].

The paper presents basic principles of transsphenoidal craniopharyngioma surgery. Stages of methodology development. Steps of methodology development of such operations in the Institute are described--from palliative interventions to the high-tech modern radical surgery with the use of anterior extended approach. Additional stereotactic irradiation provides reliable control of the disease for a long period. The article mainly describes operative technique and contains preliminary analysis of the surgical results showing effectiveness and safety of endoscopic removal of craniopharyngioma.

[Autoantibodies to α7-subunit of neuronal acetylcholine receptor in children with traumatic brain injury].

An objective of the study was to search for new biologically significant markers of brain damage. Levels of blood serum autoantibodies (aAB) to different fragments of α7-subunit of acetylcholine receptor (ACR) were studied in children with traumatic brain injury of different severity. The more severe was trauma, the higher was the level of aAB to fragments of α7-subunit of ACR in the first week after trauma. The data obtained suggest that α7-subunits of ACR and aAB to them are involved in the pathogenesis of traumatic brain lesions and, probably, play a significant role in the course of post traumatic period.

[S100B protein and autoantibodies to S100B protein in diagnostics of brain damage in craniocerebral trauma in children].

Levels of antibodies AB (AB) to S100B and S100B protein were studied in the blood serum of children with different severity and outcomes of traumatic brain injury (TBI) from the 1st to 15-75th days after TBI. Severity and outcomes were assessed using the Glasgow Coma Scale (GCS). Patients were stratified by outcomes into the following groups: complete recovery (group 1), moderate disability (group 2), high disability (group 3), vegetative state (group 4) and fatal outcome (group 5). In patients of groups 1-3, the changes of S100B in the blood serum didn't depend on the severity of brain's damage; the significant increase of S100B protein levels in the 1st day was accompanied by the decrease to the normal range in the following 2-3 days. On the contrary, the levels of nAB in these groups increased starting from 3-5 days corresponding to the severity of brain's damage. The development of vegetative state was accompanied by low S100B and high AB to S100B levels in the blood serum. The maximal level of S100B protein and increased levels of AB were observed in patients with fatal outcome. In most patients with combined TBI, the levels of both parameters were higher compared to those with separate TBI.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.

Autoantibodies to glutamate receptors and products of nitric oxide metabolism in serum in children in the acute phase of craniocerebral trauma.

Levels of serum autoantibodies (aAb) to glutamate receptors and products of nitric oxide (NO) metabolism, i.e., nitrates and nitrites, were assayed in children with recent craniocerebral trauma (CCT) of different levels of severity. All the children showed increases in serum aAb to both AMPA and NMDA receptor subtypes from day 1 to day 10 after trauma. The highest levels of serum aAb were to the NMDA subtype of glutamate receptor, which was characteristic of children with mild CCT (MCCT), with Glasgow Coma Scale (GCS) scores of 14-15 points. Levels of aAb to NMDA (NR2A) receptors in children with severe CCT (SCCT, GCS < 9 points) were lower than in children with MCCT, the lowest levels being seen in the group of children with lethal CCT (SCCT-2). Serum concentrations of NO metabolites increased by large factors in the group of children with SCCT, indicating marked brain hypoxia.

[Autoantibodies to glutamate receptors and metabolic products of nitric oxide in blood serum of children in the acute period of brain trauma].

Autoantibodies (AB) to glutamate receptors of AMPA (Glur1) and NMDA (NR2A) types and nitric oxide metabolites, nitrates and nitrites (NOx), were studied in the blood serum of children with brain trauma of different severity. The level of both AB types increased from the 1st to the 10th day after trauma. The level of NMDA (NR2A) AB was higher comparing to AMPA (Glur1). Patients with mild brain trauma, scoring 14-15 on the Coma Glasgow Scale, had the highest AB concentration while patients with severe brain trauma (scores <9), had the lower level of NMDA (NR2A) AB. The lowest level of AB and the highest level of NOx in the blood serum were found in a group of children with the fatal outcome of severe brain trauma. The many-fold increase of NOx concentration in this group points to marked hypoxia after severe brain trauma.

Glutamate receptor autoantibody concentrations in children with chronic post-traumatic headache.

We report here studies on the levels of autoantibodies (aAb) to AMPA glutamate receptors (GluR1 subunit) and NMDA glutamate receptors (NR2A subunit) in serum from 60 children aged 7-16 years with chronic posttraumatic headache (CPTHA) following mild craniocerebral trauma (CCT). The first group consisted of 48 children who had sustained cerebral concussion (CC), of which 34 had single-episode CC (subgroup 1a) and 14 had repeated CC (subgroup 1). The second group included 12 children with mild cerebral contusions (MCC). Serum glutamate receptor aAb levels were measured six months and one year after trauma. Increased aAb levels were expressed as percentages and were regarded as significant when increases were to 120% of the level seen in healthy children of the same age. The highest levels of aAb to NMDA receptors were seen in children with MCC (165 +/- 34%) and single CC (145 +/- 12.6%). Children with repeated CC had NMDA receptor aAb at normal levels (108 +/- 12.4%). Increases in NMDA receptor aAb were seen during the first year after trauma. Increases in AMPA receptor aAb were seen in children with repeated CC and MCC (150 +/- 16.8% and 167 +/- 31.3%). EEG studies showed that 18% of these children had nonspecific paroxysmal changes and 6% showed epileptiform activity. These results provide evidence that children with post-traumatic headache demonstrated hyperstimulation of glutamate receptors and overdevelopment of the autoimmune process. Increases in serum levels of aAb to NMDA glutamate receptors reflected hypoxic-ischemic brain lesions in children with CPTHA and dictate the need for these children to receive metabolic therapy.

[Autoantibodies to glutamate receptors in children with chronic posttraumatic headache].

Autoantibodies (aAB) to AMPA (Glu R1 subunit) and NMDA (NR 2A subunit) glutamate receptors were studied in blood serum of 60 children, aged 7-16 years, with chronic posttraumatic headache after mild skull injury. All the children were divided into 2 groups: group 1 included 48 children with concussion of the brain, group 2--12 children with brain contusion. Group 1 was divided into 2 subgroups: subgroup 1a comprised 34 children with single concussion and subgroup 1b--14 children with repeated concussion. The aAB level was determined 6 months and 1 year after skull injury. The aAB concentration was expressed in percents to the control level being considered significant if the increase was higher than 120%. The increased NMDA aAB level was observed during the first year after skull injury. In the la subgroup, the NR2 aAB level in blood serum was 145 +/- 12,6%, in the 1b one--108 +/- 12,4%, in group 2--165 +/- 34%. The content of aAB to AMPA receptors was elevated only in children of lb subgroup and group 2 (150 +/- 16,8% and 167 +/- 31,3%, respectively). The EEG examination of this group revealed the nonspecific paroxysmal discharges in 18% of cases and epileptiform activity in 6% of children. The results obtained suggest that children with posttraumatic headache have elevated levels of aAB to glutamate receptors, hyperstimulation of which reflects hypoxic processes in the brain, and are in need of metabolic therapy.

Morphofunctional study of the therapeutic effect of autologous mesenchymal stem cells in experimental diffuse brain injury in rats.

Effects of systemic transplantation of mesenchymal stem cells obtained by culturing of autologous bone marrow on proliferative activity of cells and functional morphology of neurons after diffuse brain injury were studied in Wistar rats. Comparative analysis of the results indicated that systemic injection of mesenchymal stem cells in a syngeneic organism produced proliferotropic, angiogenic, and, presumably, neurotrophic effects. The therapeutic effect visually manifested on day 2 after intravenous injection of mesenchymal stem cells during the early period of reparative regeneration of ischemic cell and tissue structures of the brain. The neuroprotective effect of mesenchymal stem cells was more pronounced against the background of basic therapy.

[Concurrence of Fahr's disease with cerebellar tumors]. / Sochetanie bolezni Fara s opukholiami mozzhechka.

Fara's disease or idiopathic calcification of the basal ganglia is a rare disease that is characterized by multiple petrificates in the area of the basal ganglia, caudate nucleus, and dentate nuclei of the cerebellum. As of now, only two cases of a concurrence of Fara's disease and brain tumors have been described. The authors present two more cases. Both cases are unique since the tumors occurred in the presence of Fara's disease symmetrically, as in the mirror, in the cerebellar hemispheres at the periphery of petrificates. This may be confirmed by the fact that astrocytic proliferation and hyperplasia around the calcified vessels are a cause of neoplasms.

[Lipid peroxidation in the cyst fluid of craniopharyngiomas]. / Perekisnoe okislenie lipidov v kistoznoi zhidkosti kraniofaringiom.

Comparing of the craniopharyngiomas cyst fluid, collected during the surgery, with blood plasma revealed significantly enhanced lipid peroxidation and lactate accumulation in tumour cysts contents. These processes were usually more prominent in endosuprasellar than in suprasellar craniopharyngiomas. The maximum of free radical formation in conjunction with the lowest level of malondialdehyde (MDA) was observed in primary tumours with relatively high proliferation rate. Controversial parameters ratio characterised the recurrent craniopharyngiomas, and in cyst fluids of the primary tumours with low proliferation rate the medium parameter's values were observed. Thus, the estimation of free radical formation level and MDA concentration in cyst fluid of craniopharyngioma seems to be prognostic for the tumour recurrence.

[Single-photon emission-computed tomography of the brain in craniopharyngiomas in the late postoperative period]. / Odnofotonnaia émissionnaia komp'iuternaia tomografiia golovnogo mozga pri kraniofaringiomakh v otdalennom posleoperatsionnom periode.

The paper analyzes tomographic scanning images of 32 patients with craniopharyngiomas in the late postoperative period. Computed tomographic data allowed the patients to be divided into 3 groups: 1) 10 patients without signs of tumor recurrence or hydrocephalus; 2) 14 patients with recurrent cystic craniopharyngiomas; 3) 8 patients with severe hydrocephalus. Single photon emission computed tomography (SPECT) of the brain indicated regional disturbances of brain tissue blood supply in the frontobasal or frontobasotemporal regions of the right hemisphere (the area of an surgical access and of the removed tumor) and revealed them in the distal areas (frontobasotemporal regions of the left hemisphere, parietal and occipital cortices of the cerebral hemisphere or cerebellar tissue). The compensatory reserves of cerebral circulation were assessed by the foci of relative physiological hyperemia of brain tissue (the cerebellum and the medial portions of the occipital regions of the brain). The findings provide evidence for that the vascular factor is involved in the late postoperative pathological picture in patients with craniopharyngiomas.

[Clinical-neuropsychological aspects of the adaptation of patients after the excision of craniopharyngioma in childhood]. / Kliniko-neiropsikhologicheskie aspekty adaptatsii bol'nykh, perenesshikh operatsiiu udaleniia kraniofaringiomy v detskov vozraste.

40 patients aged 9-36 years were followed-up for at least 10 years after craniopharyngiomectomy. A combined neuropsychologic study according to A.R. Luria was carried out both for determination of the degree of psychic defects and for comparison with possibilities of adaptation. Symptoms of a damage of medio-basal regions of the frontal lobes and dyencephalic region were observed in all the patients. The frontal symptoms were decisive for social adaptation after the operation. The adaptation was worse in patients with more pronounced manifestations of frontal symptoms in involvement of medio-basal regions of the left frontal lobe accompanied by poor motivation and inertness. Patients with infact motivation and activity in the presence of dominant dysfunction of the medio-basal regions of the right frontal lobe appeared to be more adapted, even when there were pronounced disorders of vision and memory. The defects were compensated worse in patients operated early in childhood, with features of side cerebral dysfunction and in left-handers.