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Four and two male sibs of two separate families who had biopsy-proven membranoproliferative glomerulonephritis (MPGN) are presented. In the first family four sibs of the first-degree consanguineous marriage showed the clinical picture of nephrotic syndrome without hypocomplementaemia at initial laboratory findings. In the second family two affected sibs showed nephrotic and nephritic syndromes on admission. Family investigations showed normal serum complement, immunoglobulins, T-cell subsets, urine analysis, and serum biochemistry. HLA typing in the two families revealed a common antigen HLA A2 in all affected sibs. Some other reports give suggestive evidence of MPGN in siblings but this is the first report that showed the occurrence of MPGN in four sibs. Our data strengthened the concept that genetic factors are involved in the development of MPGN but additional immunogenetic studies will shed light on the genetic aspects of the disease. [ABSTRACT FROM PUBLISHER]

Objective: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme., Methods: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients., Results: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases., Significance: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: Intracranial germ cell tumors (ICGCTs) comprise approximately 0.4%-3% of all brain tumors. In this study, we aim to evaluate clinical characteristics, treatment and outcomes of patients with ICGCT., Patients and Methods: All patients with ICGCT diagnosed in Hacettepe University's Pediatric Oncology Department between January 1980 and January 2016 were evaluated, retrospectively., Results: We identified 52 patients (male/female: 2.46) diagnosed with ICGT. Median age was 140 months. The median duration of symptoms was 3 months. Patients with endocrine symptoms were diagnosed later than others (P = 0.028). The primary site was pineal region in 20 patients, nonpineal region in 32 which included six bifocal involvements. Pineal location was more common in boys than girls (P = 0.02). Histopathological diagnosis was germinoma in 28 patients, nongerminomatous malignant germ cell tumors in 14 and immature teratoma in 4. The mean age for germinoma was higher than that of nongerminomatous tumors (P = 0.032). Patients treated with surgery and radiotherapy and chemotherapy. Median follow-up time was 52.5 months. Thirty-six patients were alive for 12-228 months. Relapsed/progressive disease was observed in 11 patients. Nongerminomatous tumors more frequently showed relapse/progression than germinoma (P = 0.06). Five-year overall and event-free survival rates for the whole group were 72.6% and 57.2%, respectively. Overall and event-free survival rates for germinoma were better than malignant nongerminomatous tumors., Conclusion: Although the ratio of ICGCTs to central nervous system tumors in our series was similar to western countries, some clinical features such as tumor location were similar to cases from East Asian countries. Although similar protocols were used survival rates lower than developed western and eastern developed countries., Competing Interests: None

The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.

Purpose: Adult-onset asthma with periocular xanthogranuloma and adult-onset xanthogranuloma are 2 rare subtypes of non-Langerhans cell histiocytic disorder and much remains unknown regarding optimal treatment. The authors describe their experience in the management of these 2 disease subtypes., Methods: This is a retrospective case series with histopathologically proven orbital xanthogranuloma over a period of 12 years. Clinical, imaging, and histopathologic features; associated systemic conditions; treatment modality; and outcome during follow-up of 6 adult patients who had adult-onset asthma with periocular xanthogranuloma and adult-onset xanthogranuloma were reviewed., Results: The age range was 29-75 years (median 56 years). The duration of symptoms and signs varied from 10 months to 9 years. All patients had bilateral and asymmetric involvement. Palpebral swelling with yellow discoloration and upper eyelid ptosis were the most common signs. Adult-onset asthma was present in 2 patients. Imaging studies demonstrated ill-defined infiltrative lesions involving the preseptal area, lacrimal glands, extraocular muscles, retrobulbar fat, and optic nerves. The median follow-up was 50 months. Complete regression of all clinical signs was obtained at 8 months, whereas imaging findings disappeared at 18 months with treatment. No recurrence was observed., Conclusions: Treatment consisting of debulking as much affected soft tissue as possible followed by a 3-day course of intravenous pulse methylprednisolone administration and then by oral prednisone for at least 6 months may provide adequate regression of the granulomas without recurrence and satisfactory cosmesis in patients with adult orbital xanthogranuloma with and without asthma.

Introduction: Thalamic tumors are rare tumors which are usually diagnosed in the pediatric age group. Although recent developments in neurosurgical practice allow more radical treatments, information about outcome is scarce for these deep-seated challenging tumors., Methods: Medical records of 45 pediatric patients who presented with thalamic tumors between 1999 and 2012 were reviewed., Discussion: Prognostic implication of tumor characteristics and patient variables are discussed. Although challenging, recent innovations in the field of neurosurgery and refinements in technique may prolong survival in some cases.

Purpose: The management of Langerhans cell histiocytosis is controversial. This study evaluated our clinical experience and therapeutic results in orbital Langerhans cell histiocytosis., Methods: This is a retrospective, noncomparative interventional case series involving 17 consecutive patients with biopsy-proven orbital Langerhans cell histiocytosis. Response to surgery and chemotherapy and development of diabetes insipidus were the main outcome measures., Results: Thirteen (76.5%) of the patients were male and the mean age at diagnosis was 10.7 years (range 2-39 years). The most frequent presenting sign was proptosis (8 patients) and upper eyelid edema (4 patients). Pain was present in 5 cases and periocular redness in 6. No patient reported a history of trauma. The frontal bone was involved in 16 patients followed by the zygomatic in 9 cases. Five patients also had lesions in the calvarium, femur, facial, temporal, and parietal bones. No patients had systemic disease. Ten patients were managed with vinblastine (0.2 mg/kg, 6-12 months) chemotherapy because of major residual tumor burden (5 cases) and multi-bone involvement (5 cases). Four patients were observed following macroscopically complete tumor removal. Three patients with limited anterior orbital soft tissue tumors and single bone involvement received systemic corticosteroids (40 mg/m2/d, 6-10 weeks). No patients developed diabetes insipidus after a median follow-up of 46 months., Conclusions: Macroscopically complete excision of the unifocal tumors may not necessitate any further treatment. Vinblastine chemotherapy following incomplete tumor removal and in patients with multifocal bone disease resulted in recurrence-free survival at 3 years in 90% of patients.

This study evaluated the expression profile of hepatocyte growth factor (HGF), c-Met, epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), and vitreal and serum EGF, HGF, IGF-1 levels in patients with uveal melanoma and assessed their correlation with the clinicopathological parameters. Forty patients with uveal melanoma were included in the study. Clinicopathological parameters were evaluated with hematoxylin-eosin staining. HGF, c-Met, EGFR, and IGF-1R expressions were evaluated immunohistochemically. HGF, EGF, and IGF-1 levels were measured with enzyme-linked immunosorbent assay in vitreous and serum specimens taken at enucleation and 6 months after the enucleation. HGF, c-Met, IGF-1R, and EGFR expressions were detected in 57.5, 20, 20, and 12.5% of cases, respectively. IGF-1R expression was significantly correlated with the degree of pigmentation, necrosis, and lymphocyte infiltration (P=0.013, 0.04, and 0.017). EGFR expression was significantly correlated with the mitosis rate (P=0.02). Vitreal EGF and serum IGF-1 levels were significantly higher in patients with scleral invasion (15.72+/-29.13, 199.01+/-154.01 pg/ml, respectively) when compared with the patients without invasion (0.56+/-1.05, 33.01+/-36.52 pg/ml) (P=0.03 and 0.015). When the preoperative and postoperative serum growth factor levels were compared, the serum EGF level was found to be lower (125.93+/-62.84, 100.02+/-31.19 pg/ml, P=0.007) and the serum IGF-1 level (165.81+/-153.6, 301.35+/-131.24 pg/ml, P<0.001) was found to be higher in the postoperative 6-month specimens. Uveal melanomas express HGF, c-Met, EGFR, and IGF-1R. Vitreal growth factor levels and expression of EGFR and IGF-1R are correlated with some clinicopathological parameters. IGF-1 and EGF may have a role in the development and progression of uveal melanoma.

We retrospectively evaluated 203 patients newly diagnosed with medulloblastoma between 1975 and 2006. All patients underwent surgical resection and after surgery were treated with a combination of radiotherapy and chemotherapy. CCNU-based protocols were used in the early years, with CDDP+VP16 being used more recently. Radiotherapy was used in patients older than three years of age according to the protocols. One hundred fifteen patients had total surgical resection, 78 had subtotal resection, and 4 patients had only a biopsy. Every patient received chemotherapy: 124 with the CCNU-based protocol, 75 with CDDP+VP16, and 4 with other protocols. Overall (OS) and event free-survival (EFS) rates were 43.1 and 41.9% in the whole group, with a median follow-up time of 8 years. OS rates for patients with and without spinal seeding were 30 and 63.1% (P = 0.0002). OS rates for males and females were 36.2 and 54.7% (P = 0.03). OS rates for patients receiving the CCNU and CDDP+VP16 protocols were 41.1 and 45%.

Transpupillary thermotherapy (TTT) used as either an adjunct to plaque brachytherapy or a primary treatment for choroidal melanoma can cause several intraocular complications, particularly in the retina. A 61-year-old woman had a macular choroidal melanoma measuring 8 x 7.5 X 3.6 mm and received TTT in three sessions, each 6 months apart. After the second treatment, pigmented material began to accumulate on the peripheral retina with an increasing pace. The tumor gradually regressed for 16 months, followed by a sudden regrowth. Enucleation of the eye revealed that the peripheral subretinal pigmented deposits consisted of pigment-laden macrophages and retinal pigment epithelial cells without viable tumor cells. The rare complication of peripheral subretinal pigment dispersion following TTT should not be alarming, but close monitoring is recommended.

Objective: The aims of this study are to evaluate the patients with astrocytomas and to investigate survival rates and prognosis., Patients and Methods: Five hundred fourteen patients diagnosed with brain tumor between 1972 and 2003 were retrospectively analyzed. Three different chemotherapy regimens were used according to years. CCNU-based protocols were used in the early years; COPP (cyclophosphamide, oncovin, procarbazine, prednisolone) and CDDP+VP16 (cisplatinum + etoposide) were the other protocols used in the following years. Radiotherapy was used after 3 years of age according to protocols., Results: Ninety-eight (19%) out of 514 patients have astrocytic histopathology. The histopathologic distribution was as follows: low grade, 55 patients; high grade, 43 patients. COPP regimen was given to 24 patients, CCNU-based regimen to 13, and CDDP+VP16 to 10 patients. We did not use any chemotherapy in 51 patients. Overall survival (OS) and event free-survival rates were 59.2 and 45.7% in whole group. OS rates were 93.3 and 22.4% for low-grade and high-grade histopathology, respectively (p=0.0001). OS for CCNU, CDDP+VP16, and COPP were 35.9, 22.8, and 30.4%, respectively., Conclusion: Low-grade astrocytomas are highly responsive to the surgery, and they do not need any further treatment unless the patient has relapse or recurrence. Still, the treatment of the high-grade tumors is a problem, and it needs new treatment approaches.

Objective: Mitoxantrone (MTZ) has potent in vitro activity against malignant glioma cell lines, but it cannot be used effectively as a systemic agent for the treatment of brain tumors because of its poor central nervous system penetration. However, MTZ-loaded poly(lactide-co-glycolide) (PLGA) microspheres may be injected into the peritumoral area and into tumor tissue to provide effective and sustained local drug concentrations without causing systemic side effects., Methods: Fisher rats were randomized into three groups. The first group (n = 9) was concomitantly implanted with rat glioma (RG2) cells and blank PLGA microspheres. The second group (n = 6) was implanted with RG2 cells and MTZ-loaded PLGA microspheres. The third group (n = 9) was implanted with RG2 cells, and MTZ-loaded PLGA microspheres were injected into the same area after 7 days. Animals were sacrificed on Day 15 or 35. Tumor volumes were measured after hematoxylin and eosin staining. Distribution kinetics of MTZ in the brain was determined by high-performance liquid chromatography in nine rats injected with MTZ-loaded microspheres., Results: The tumor volumes were 76 +/- 11 and 107 +/- 11 mm (mean +/- standard error) on Days 15 (n = 6) and 35 (n = 3), respectively, in the control group. In rats treated with MTZ-loaded microspheres on Day 7, tumor volumes were significantly reduced to 17 +/- 4 and 23 +/- 2 mm on Days 15 (n = 6) and 35 (n = 3), respectively. No tumor formation was observed when glioma cells and MTZ-loaded PLGA microspheres were implanted concomitantly (n = 6). No systemic side effects or parenchymal inflammatory infiltration were observed in either group of rats. Brain MTZ concentration was highest at the injection site and declined with time and distance from the injection site and with time., Conclusion: These data demonstrate that MTZ-loaded PLGA microspheres can deliver therapeutic concentrations of drug to the tumor and prevent glioma growth without causing side effects. This treatment method may increase the efficiency of antineoplastic therapy and positively impact survival.

Although controversial, protective and therapeutic effects of valproic acid in various types of cellular injury suggest a potential role for this agent in hypoxic-ischemic brain injury. We therefore investigated the effects of valproic acid in an experimental model of neonatal hypoxic-ischemic brain injury. To examine the effect of valproic acid in this condition, hypoxic-ischemic brain injury was induced in 7-day-old rat pups by ligation of the right common carotid and then the pups were exposed to 1 hour of hypoxia in 8% oxygen. Low (200 mg/kg/day) and high (400 mg/kg/day) doses of valproic acid were administered in a 5-day regimen. Neuropathologic evaluation was performed using the hippocampus, cerebral cortex, and basal ganglia in the coronal plane. The 5-day regimen of valproic acid administration resulted in some protective and therapeutic effects on the brain damage and neuronal apoptosis in both hemispheres in a dose-dependent manner. Administration of valproic acid also decreased the percentage of apoptotic neurons in the contralateral hemisphere (P < .05). These results suggest that valproic acid can have therapeutic and protective effects in hypoxic-ischemic brain injury.

A 6-year-old boy who had been in remission from acute lymphoblastic leukemia for 2.5 years presented with seizures, hemiparesis, visual loss, and white- and gray-matter lesions on cranial magnetic resonance imaging. The diagnosis of progressive multifocal leukoencephalopathy was established on the detection of JC virus DNA by polymerase chain reaction in brain tissue. The patient was administered several anticonvulsants, amantadine, acyclovir, and ganciclovir. He showed partial recovery. This case illustrates the possibility of long-term survival in progressive multifocal leukoencephalopathy with normal immunologic parameters.

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or beta-catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.

Background: Granular cell tumors in the central nervous system are quite rare. To date, only 6 cases of granular cell tumor arising from cranial nerves have been reported in the literature. To the best of our knowledge, we present the first case of a predominant intracavernous granular-cell tumor arising from oculomotor nerve., Case Presentation: A 42-year-old man presented with third-nerve paresis and decreased visual acuity on the left side. Magnetic resonance imaging showed a mainly intracavernous mass partially extending to the superior orbital fissure and entrance of the optic canal. Using a pterional craniotomy, the tumor was removed from within the cavernous sinus via combined superior and lateral intradural approach, and optic nerve was also decompressed. Histologically, the tumor was diagnosed as a granular cell tumor., Conclusions: Although it is quite rare, granular cell tumor should be included into the differential diagnosis of intracavernous masses because surgical treatment is curative.

Hypoxic-ischemic brain damage has significant mortality and morbidity in newborns. Although the role of magnesium in neonatal hypoxic-ischemic brain injury related to N-methyl-D-aspartate receptors has been widely studied; the effects of magnesium on neuronal apoptosis have not been known exactly in hypoxia-ischemia. The aim of this study was to investigate the effects of magnesium on neuronal apoptosis in the 7-day-old rat hypoxia-ischemia model. Seven-day-old rats were administered magnesium sulfate (group 1; n=9) or saline (group 2; n=9) intraperitoneally before hypoxia-ischemia. Additionally 18 seven-day-old rats were given magnesium sulfate (group 3; n=9) or saline (group 4; n=9) after hypoxic-ischemic insult. Neuronal apoptosis was investigated by the dUDP-biotin nick end-labeling (TUNEL) method following 3-day recovery in all subjects. In evaluating TUNEL-positive cells, we firstly calculated the areas (mm(2)) of brain regions, hippocampus, striatum, cortex, in right and left hemispheres in subjects by IMAGE analysis. The numerical density was calculated as the number of cells per square millimeter by counting all TUNEL-positive cells. Afterwards, the ratio of right side numeric density to sum of right and left side numeric densities (right Apoptosis Index) was calculated for every brain region in rats receiving magnesium and compared to vehicle groups. The right Apoptosis Index of the hippocampus in magnesium pre-treated rats (mean+/-S.D.; 36.6+/-22.1) was significantly lower than vehicle (61.0+/-16.0; P<0.05); whereas right apoptosis indices were not changed by magnesium pre-treatment in striatum and cortex. Additionally, magnesium sulfate administration following hypoxic-ischemic insult also had no effect on right apoptosis indices in all three brain regions. It is concluded that magnesium might have a role in preventing neuronal apoptosis due to neonatal hypoxic-ischemic brain injury.

Purpose: The rate of apoptosis in retinoblastoma (Rb) and the factors that may influence this rate, such as therapy prior to surgery, amount of necrosis in tumour tissue, differentiation and laterality of the tumour, were investigated., Methods: Thirty-one specimens (25 enucleation, six exenteration) with Rb were studied. Prior to final surgery, three patients received systemic chemotherapy, one intravitreal chemotherapy, one transpupillary thermotherapy, one external beam radiotherapy and one high-dose oral methylprednisolone therapy. The apoptotic index (AI,%) was calculated by counting at least 1000 cells under light microscopy (x 100) using TUNEL (terminal deoxynu-cleotidyl transferase-mediated dUTP nick-end labelling) method., Results: The mean AI was 2.75 plus minus 1.2. No statistically significant association was observed between rate of apoptosis and the presurgical treatment, extent of necrosis, tumour differentiation and laterality., Conclusion: Apoptosis is an important mechanism of cell death, and may be a limiting factor for tumour progression. In this study, the rate of apoptosis was not affected by any of the studied parameters.

Brief cerebral ischemia is reported to cause selective neuronal necrosis, apoptotic cell death, silent infarcts and, when recurrent, cognitive decline. Acute administration of selegiline and EGb 761 have been shown to have anti-apoptotic and neuroprotective effects in experimental ischemia. Their daily use is currently advised to slow down cognitive decline in patients with vascular dementia. Hence, unlike previous studies, we studied the neuroprotective action of chronic daily administration of these drugs in Swiss mice subjected to 30-min middle cerebral artery occlusion and 72 h of reperfusion since this model was reported to induce a slowly evolving infarct with profuse apoptotic cell death. Infarct area was evaluated by H&E staining on coronal brain sections and, apoptotic cells were identified by histological criteria, terminal transferase-mediated d-UTP nick-end labeling (TUNEL) and by immunohistochemical detection of caspase-cleaved actin fragments (fractin). Fifty-one mice received daily intraperitoneal injections of 10 mg/kg selegiline (n=18) or 50 mg/kg EGb 761 (n=17) or equal volume of saline (n=16) for 10-14 days before but not on the day of insult. The infarct volume, number of TUNEL- and fractin-positive cells were significantly reduced in treatment groups by 30, 42 and 51% (selegiline) and, 27, 27 and 29% (EGb 761), respectively. These data suggest that prophylactic use of selegiline and EGb 761 could increase the brain's resistance to mild ischemic injury.

Background: Infantile myofibromatosis is a proliferative disorder of infancy and early childhood characterized by the development of single or multiple nodular lesions arising from cutaneous or subcutaneous tissue, muscle, bone or visceral organs. In approximately one-third of cases, this myofibroblastic proliferation involves the head and neck region., Case Report: In this paper we report on three cases of cranial infantile myofibromatosis in infants. The clinical presentation and the deceptive histopathological features can make diagnosis difficult., Conclusion: The significance of recognizing this entity is stressed, since its indolent clinical behavior might prevent diagnosis.

Atypical teratoid rhabdoid tumor is a distinctive brain tumor appearing in infancy and early childhood. Leptomeningeal dissemination is common, both at presentation and relapse. Extracranial metastases of the central nervous system tumors are rarely seen. To our knowledge there is only one report with an atypical teratoid rhabdoid tumor metastasizing via a ventriculoperitoneal shunt. We describe the first case of atypical teratoid rhabdoid tumor of the central nervous system who developed lung metastasis without the presence of a shunt.

Colloid cysts appear most commonly in the third ventricle; the occurrence of a colloid cyst in the brainstem is very unusual. The authors report on a patient with an intrapontomesencephalic colloid cyst. This 15-year-old girl complained of a headache associated with diplopia. Her neurological examination revealed right-sided sixth nerve paresis and a mild left hemiparesis. Radiological investigations revealed an intraparenchymal pontomesencephalic cystic mass. Surgical removal of the lesion was achieved via the pterional transsylvian approach and the patient experienced an excellent recovery. Histopathological examination revealed that the lesion was a typical colloid cyst. To the best of the authors' knowledge, this is the first case in which an intraparenchymal upper brainstem colloid cyst was surgically excised totally. In addition to describing this case, the authors also review other brainstem neuroepithelial cysts described in the literature and briefly discuss the concept of their origin.

Nitric oxide can promote or inhibit apoptosis depending on the cell type and coexisting metabolic or experimental conditions. We examined the impact of nitric oxide on development of apoptosis 6, 24, and 72 h after permanent middle cerebral artery occlusion in mutant mice that lack the ability to generate nitric oxide from neuronal nitric oxide synthase. Adjacent coronal sections passing through the anterior commissure were stained with hematoxylin and eosin or terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Immunoblotting was used to identify changes in the anti- and proapoptotic proteins Bcl-2 and Bax, respectively. Activation of caspases was assessed by appearance of actin cleavage products using a novel antiserum directed against 32-kDa actin fragment (fractin). In the neuronal nitric oxide synthase mutant mouse, infarct size and TUNEL positive apoptotic neurons were reduced compared to the wild-type controls. At 6 h, Bcl-2 levels in the ischemic hemisphere were increased in mutants but decreased in the wild-type strain. Bax levels did not change significantly. Caspase-mediated actin cleavage appeared in the ischemic hemisphere at this time point, and was significantly less in mutant brains at 72 h compared to the wild-type. The reduction in the number of TUNEL and fractin positive apoptotic cells appears far greater than anticipated based on the smaller lesion size in mutant mice.Hence, from these data we suggest that a deficiency in neuronal nitric oxide production slows the development of apoptotic cell death after ischemic injury and is associated with preserved Bcl-2 levels and delayed activation of effector caspases.

A 6-year old Turkish boy with a recently defined entity: "leukoencephalopathy with vanishing white matter" is described. He was born to consanguinous parents. His psychomotor development was normal till he first presented with fever and generalized tonic-clonic seizures at the age of 2.5, followed by rapid motor and mental deterioration. Decerebrate posture and marked spasticity subsequently developed. The initial MRI examination showed diffuse involvement of white matter, including subcortical U-fibers, with signal intensity parallel to CSF on all sequences. The white matter appeared swollen. The ventricles were slightly enlarged and there was cavum septi pellucidi et vergae. The posterior crus of the internal capsule, external and extreme capsules were affected. Cerebellar hemispheres and vermis showed atrophy. The involvement pattern of brainstem was noteworthy in that pontine tegmentum and cruri cerebri were affected. Follow-up MRI obtained after three years did not show any interval change. Brain biopsy showed thinned cortex with relatively preserved cortical layering and neuronal structure. There was rarefaction of the white matter with cystic degeneration. Fibrillary gliosis and increased number of oligodendroglial cells were observed within the cerebral white matter.

We report unusual MR serial imaging and electron microscopy findings in a 3-year-old boy who had Leigh syndrome with cytochrome-c oxidase (cox) deficiency. The MR imaging findings included periventricular white matter involvement, posteroanterior progression, and extension through the corpus callosum and internal capsule; however, no basal ganglia or brain stem abnormality was found, which was suggestive of leukodystrophy. The most noteworthy findings were the cystic foci with contrast enhancement in the affected white matter.

Spinal extradural angiolipomas are distinct, benign, and rare lesions composed of mature lipocytes admixed with abnormal blood vessels. They account for 0.14% of all spinal axis tumors. The case described here was a 72-year-old patient presenting with a history of paraparesis, hypoesthesia under the T2 level, hyperreflexia, and urinary overflow incontinence that appeared within 7 days after the administration of a coronary vasodilator drug regimen. The spinal magnetic resonance scan showed a lipomatous mass with signal void lesions, suggesting a vascular component of the tumor. The patient improved rapidly after surgical resection of the epidural tumor and decompression of the cord. According to the present literature, the duration of neurological symptoms ranges from 1 to 180 months (mean 28 months). But this patient's neurological deterioration took place 4 days before hospitalization. We believe that this can be explained by the increased tumor blood volume caused by vasodilator drugs, which in turn exerted a pulsatile compressive effect on the cord.

Six patients admitted to the Department of Pediatric Neurology at Hacettepe University Children's Hospital between 1992 and 1997 with a clinical diagnosis of Rasmussen encephalitis received surgical treatment for their intractable epilepsy. MRI, SPECT and WADA tests were performed in patients with an epileptic focus demonstrated on routine or long-term video EEG monitoring. Viral studies using the PCR methodology were performed in cases with histopathological evidence of Rasmussen encephalitis. The ages of these patients ranged between 7 and 16 years, and the mean age at onset of seizures was 7.1+/-2.2 years. In four patients seizures presented as epilepsia partialis continua and were refractory to anticonvulsive drug therapy. In three cases intravenous immunoglobulin therapy yielded temporary and partial improvement in seizure control. The mean presurgical follow-up duration was 2.04+1.74 years, and early surgical intervention for epilepsy was performed in one case. The surgical approach selected for the treatment of epilepsy was resective surgery with electrocorticography. The mean postoperative follow-up duration was 32.3+17.2 months. Seizures were fully controlled in one patient, in whom surgery was performed 3 months after the seizures first started. Early surgical intervention may provide histopathological evidence for diagnosis as well as effective seizure control.

The proliferative potential of central neurocytomas was determined in a biopsy series of 36 cases and compared with clinical outcome. The mean size of the growth fraction, as determined by MIB-1 labeling index (MIB-1 LI) at first biopsy, was 2.8 +/- 2.5 with a range of 0.1 to 8.6%. Neurocytomas with an MIB-1 LI > 2% comprised 39% of cases and showed a close correlation with the presence of vascular proliferation (p = 0.0006). The Kaplan-Meier analysis showed a highly significant difference in disease-free survival between the 2 groups (p = 0.0068). Over an observation time of 150 months, there was a 22% relapse among patients with an MIB-1 LI less than 2% and a 63% chance of relapse among those with an MIB-1 LI greater than 2%. We propose the term "atypical central neurocytoma" for the latter subset, corresponding to WHO grade II.

Two cases of Wernicke's encephalopathy with the rare phenomenon of ballooned neurons in the mamillary bodies are reported. Both patients suffered from acute Wernicke's symptoms starting approximately two weeks before death. The mamillary bodies contained grossly enlarged, ballooned neurons, in one case associated with focal necrosis. The affected neurons were immunoreactive for phosphorylated neurofilament (160 and 200 kDa), and synaptophysin. Ubiquitin and alpha beta-crystallin expression were not detected. The mamillo-thalamic tract appeared normal in both cases. There was a marked associated microglial reaction, as shown by the antibody Ki-MIP. It is concluded that the ballooning of mamillary neurons reflects an acute retrograde reaction to primarily axonal damage. Rather than being a rare manifestation of the disease, these cases may constitute a typical intermediate early stage (10-15 days) in the development of Wernicke's encephalopathy).

The central neurocytoma is a supratentorial, often calcified brain tumour affecting young adults and is typically located in the lateral ventricles in the region of the foramen of Monro. Clinically, the tumour causes signs of increased intracranial pressure, visual and mental disturbances and, occasionally, pyramidal or endocrine symptoms. By light microscopy, the tumour is composed of small round cells in a delicate fibrillary matrix. Tumour cells consistently show features of neuronal differentiation by electron microscopy (synapses, dense-core vesicles, presynaptic clear vesicles, specialized synaptic junctions) and immunoreactivity for synaptophysin and other neuronal marker proteins. The tumour can be totally removed in nearly half of the cases. After incomplete surgical resection neurocytomas may recur but because of their low proliferation potential, radio- or chemotherapy are not generally recommended. Postoperative recurrence-free survival times of up to 19 years have been reported. Neurocytomas constitute nearly one half of supratentorial intraventricular tumours in adults but amount to less than 1% of all tumours of the central nervous system and its coverings.