Hamilton Matushita

Leptomeningeal dissemination of pilocytic astrocytoma at diagnosis in childhood: two cases report

Pilocytic astrocytoma (PA) is a benign tumor that rarely spread along the neuraxis. At the moment there are no more than five cases of leptomeningeal dissemination (LD) from PA at diagnosis described in the literature. Different patterns of presentation or recurrence may be noted: local recurrence, malignant transformation, multicentric disease or metastatic disease. LD and multicentric disease can be distinct pathological entities. We report two cases and analyse literature, emphasizing leptomeningeal spread at presentation. Hydrocephalus, biopsy and parcial ressection are likely to be favorable factors to the occurrence of LD. Otherwise, LD may be part of natural history of PA, as evidenced by its ocurrence in non-treated cases.

Hydrocephalus in neurocysticercosis

IntroductionCysticercosis (CC) is the most important of the parasitic diseases of the central nervous system due to its high incidence in the world. CC is the infection with the larval cysts of Taenia solium. It is the most common helminthic infection of the nervous system and is endemic in most underdeveloped countries as well as in industrialized nations. It is estimated that approximately 50,000 people die every year from neurocysticercosis (NCC) worldwide.DiscussionHumans with CC are incidental intermediate hosts, which replace the pig in the life cycle of the T. solium. Children are more frequently affected by parenchyma infestation of cysticercus, of which the main clinical manifestation is epilepsy. Hydrocephalus is more common in adults and is caused by cerebrospinal fluid blockage by ventricular cysts and inflammatory reactions (ependimitis/arachnoiditis). Treatment should be individualized based on clinical presentation, degree of infestation, location and viability of cysticercus, and host response. Hydrocephalus can be controlled only by removal of obstructive intraventricular cysts or associated with either ventriculoperitoneal shunt or endoscopic third ventriculostomy. The degree of infestation and complications related to the shunt represents the most important prognostic factors in the outcome of NCC.

CSF markers for diagnosis of bacterial meningitis in neurosurgical postoperative patients

OBJECTIVE To evaluate the diagnostic usefulness of cerebral spinal fluid (CSF) cellularity, protein, neutrophils, glucose and lactate for detection of postoperative bacterial meningitis. METHOD This prospective study was conducted in 28 postoperative neurosurgical patients from 2002 to 2005 at University of São Paulo. The CSF markers were plotted in a receiver operating characteristic (ROC) curve to evaluate their accuracy. RESULTS Based on the area under ROC curve CSF glucose, cellularity, and lactate were considered good tests. Polymorphonuclear and protein did not achieve enough accuracy to be used clinically. CONCLUSION The CSF glucose, lactate, and cellularity can be used for the diagnosis of bacterial meningitis. Moreover, it can be helpful to differentiate bacterial from aseptic meningitis.

Idiopathic distal lenticulostriate artery aneurysm in a child

The authors describe a rare case of idiopathic distal lenticulostriate artery (LSA) aneurysm in a 5-year-old boy who presented in the emergency department with a sudden onset of headache. Admission computed tomography scans revealed an intracerebral hemorrhage in the left caudate nucleus with intraventricular extension. Angiographic studies demonstrated a left medial LSA aneurysm. The patient underwent a left parasagittal frontal craniotomy, the lateral ventricle was accessed via the anterior transcallosal approach, and the aneurysm was removed after sectioning of the parent vessel. The child left the hospital after 5 days; at that time he was asymptomatic and without motor impairment. The optimum treatment of aneurysms involving small perforating arteries is controversial and depends mainly on the causative factors. The pathogenesis and treatment of these unusual aneurysms are discussed.

Brain tumors in the first two years of life: a review of forty cases

From 1962 to 1989, 40 infants with brain tumors and less than 2 years old were treated at the Department of Neurology of the Clinical Hospital of the University of São Paulo Medical School. The clinical and neuropathological findings were reviewed as to histological diagnosis, age, sex, signs and symptoms, therapy and outcome. Medulloblastoma was the most common histological type (n = 11), followed by ependymoma (n = 9), choroid plexus tumor (n = 6), astrocytoma (n = 3) and primitive neuroectodermal tumor (n = 2). The tumor was infratentorial in 21 infants, supratentorial in 18 and disseminated in 1.

PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without β-catenin mutations

INTRODUCTION: Activating mutations in exon 3 of the β-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between β-catenin and PROP1 has been shown to be responsible for pituitary cell lineage determination. We hypothesized that dysregulated PROP1 expression could also be involved in the pathogenesis of craniopharyngiomas. OBJECTIVES: To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the β-catenin gene was screened for mutations, and the expression of the β-catenin gene and PROP1 was evaluated. METHODS: The β-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and β-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and β-catenin immunohistochemistry was performed on 11 samples. RESULTS: Mutations in the β-catenin gene were identified in 64% of the adamantinomatous craniopharyngiomas samples. Evidence of β-catenin gene overexpression was found in 71% of the tumors with β-catenin mutations and in 40% of the tumors without mutations, and β-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples. CONCLUSION: We found evidence of β-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear β-catenin staining pattern regardless of the presence of a β-catenin gene mutation. These results suggest that WNT signaling activation plays an important role in the pathogenesis of adamantinomatous craniopharyngiomas. Additionally, this study was the first to evaluate PROP1 expression in adamantinomatous craniopharyngiomas, and the absence of PROP1 expression indicates that this gene is not involved in the pathogenesis of this tumor, at least in this cohort.

Surgical Treatment of Myelomeningocele Carried Out at ‘Time Zero’ Immediately after Birth

Background/Aims: To present a protocol of immediate surgical repair of myelomeningocele (MMC) after birth (‘time zero’) and compare this surgical outcome with the surgery performed after the newborn’s admission to the nursery before the operation. Methods: Data from the medical files of 31 patients with MMC that underwent surgery after birth and after admission at the nursery (group I) were compared with a group of 23 patients with MMC admitted and prospectively followed, who underwent surgery immediately after birth – ‘at time zero’ (group II). Results: The preoperative rupture of the MMC occurred more frequently in group I (67 vs. 39%, p < 0.05). The need for ventriculoperitoneal shunt was 84% in group I and 65% in group II and 4 of them were performed during the same anesthetic time as the immediate MMC repair, with no statistically significant difference. Group I had a higher incidence of small dehiscences when compared to group II (29 vs. 13%, p < 0.05); however, there was no statistically significant difference regarding infections. After 1 year of follow-up, 61% of group I showed neurodevelopmental delay, whereas only 35% of group II showed it. Conclusions: The surgical intervention carried out immediately after the birth showed benefits regarding a lower incidence of preoperative rupture of the MMC, postoperative dehiscences and lower incidence of neurodevelopmental delay 1 year after birth.

Cerebral abscess caused by Serratia marcescens in a premature neonate

BACKGROUND Cerebral abscesses are extremely rare in neonates. Serratia marcescens is an unusual cause of sepsis and neurological spread is especially ominous. PURPOSE To report the case of a 34-week neonate who developed this rare condition and to discuss diagnostic and therapeutic measures. CASE REPORT A 34-week male neonate sequentially developed respiratory distress syndrome, early sepsis and necrotizing enterocolitis; later cultures revealed S. marcescens. After deterioration, a cerebral abscess became evident, which revealed S. marcescens. Clinical improvement ensued after high-dose amikacin and meropenem. CONCLUSION Clinical signs are often non-specific. Proper diagnostic measures, neurosurgical consultation and aggressive antibiotic therapy are essential for these high-risk neonates.

Meningiomas of pineal region in children

Meningiomas are uncommon tumors in children and either more rarely encountered in the pineal region. We report two cases of meningioma of the pineal region in children. One of these cases was a five years-old girl and the other a one year-old boy. No specific clinical presentation or tomographic examinations findings was identified before treatment, suggestive of a diagnosis of meningioma. The clinical and laboratory features were very similar to the most common tumors of the pineal region. Prior to the surgery, the histology of these tumors was not suspected. Both patients underwent direct surgery and complete removal was achieved by a suboccipital transtentorial approach. The tumors originated from velum interpositum in both cases. At the follow up, one case presented with recurrence six years later, and she underwent a reoperation with total resection without morbidity. Long-term follow up presented no other recurrences.

Novel Molecular Pathways Elicited by Mutant FGFR2 May Account for Brain Abnormalities in Apert Syndrome

Apert syndrome (AS), the most severe form craniosynostosis, is characterized by premature fusion of coronal sutures. Approximately 70% of AS patients carry S252W gain-of-function mutation in FGFR2. Besides the cranial phenotype, brain dysmorphologies are present and are not seen in other FGFR2-asociated craniosynostosis, such as Crouzon syndrome (CS). Here, we hypothesized that S252W mutation leads not only to overstimulation of FGFR2 downstream pathway, but likewise induces novel pathological signaling. First, we profiled global gene expression of wild-type and S252W periosteal fibroblasts stimulated with FGF2 to activate FGFR2. The great majority (92%) of the differentially expressed genes (DEGs) were divergent between each group of cell populations and they were regulated by different transcription factors. We than compared gene expression profiles between AS and CS cell populations and did not observe correlations. Therefore, we show for the first time that S252W mutation in FGFR2 causes a unique cell response to FGF2 stimulation. Since our gene expression results suggested that novel signaling elicited by mutant FGFR2 might be associated with central nervous system (CNS) development and maintenance, we next investigated if DEGs found in AS cells were also altered in the CNS of an AS mouse model. Strikingly, we validated Strc (stereocilin) in newborn Fgfr2S252W/+ mouse brain. Moreover, immunostaining experiments suggest a role for endothelial cells and cerebral vasculature in the establishment of characteristic CNS dysmorphologies in AS that has not been proposed by previous literature. Our approach thus led to the identification of new target genes directly or indirectly associated with FGFR2 which are contributing to the pathophysiology of AS.