Sergio Cavalheiro

Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study.

The treatment of central nervous system (CNS) germ cell tumors (GCT) remains controversial. The purpose of this study was to demonstrate efficacy of a chemotherapy only strategy, with less morbidity, when compared to regimens with irradiation.

Microcephaly and Zika virus: neonatal neuroradiological aspects

PurposeThe aim of this study is to describe some radiological features in the newborns with microcephaly caused by Zika virus infection during pregnancy.MethodsWe radiologically analyzed 13 cases of newborns with microcephaly born to mothers who were infected by the Zika virus in the early stage of pregnancy.ResultsThe most frequently observed radiological findings were microcephaly and decreased brain parenchymal volume associated with lissencephaly, ventriculomegaly secondary to the lack of brain tissue (not hypertensive), and coarse and anarchic calcifications mainly involving the subcortical cortical transition, and the basal ganglia.ConclusionsAlthough it cannot be concluded that there is a definitive pathognomonic radiographic pattern of microcephaly caused by Zika virus, gross calcifications and anarchic distribution involving the subcortical cortical transition and the basal ganglia, in association with lissencephaly and in the absence of hypertensive ventriculomegaly, are characteristic of this type of infection.

Apoptosis in alpha interferon (IFN-α) intratumoral chemotherapy for cystic craniopharyngiomas

ObjectivesThe aim of this study was to verify whether intracystic injections of alpha-Interferon (IFN-α) in cystic craniopharyngiomas were able to reduce the tumor by activating the Fas apoptotic pathway.Materials and methodsTwenty-one patients with cystic craniopharyngiomas treated at the Pediatric Oncology Institute (IOP/GRAACC) of Federal University of São Paulo were submitted to intracystic chemotherapy with IFN-α. The tumor sizes of all patients were monitored and the apoptotic factor soluble FasL (sFasL) concentration was determined by ELISA (enzyme-linked immunosorbent assay) in tumor fluid samples from eight patients.ResultsThere was a complete reduction in 11 patients, a partial response in seven, and a minor response in three patients. The concentration of sFasL was increased in all the eight patients examined concomitantly with the tumor size reduction.ConclusionsOur data demonstrated that the IFN-α was able to induce Fas-mediated apoptosis together with a reduction in the tumor size; such an observation may suggest the importance to investigate still unexplored mechanisms to be exploited in craniopharyngioma therapy.

Pre-surgical evaluation and surgical treatment in children with extratemporal epilepsy.

IntroductionThis review summarizes some patterns of pre-surgical evaluation and surgical treatment of extratemporal epilepsy in pediatric patients with medically refractory seizures, whose ictal behavior is variable. The most effective treatment for intractable partial epilepsy is a focal cortical resection with excision of the epileptogenic zone (the area of ictal onset and initial seizure propagation). This might be risky, though, in the case of a widespread lesion, sometimes encroaching one or more lobes, given the risk to the functional cerebral cortex. An anterior temporal lobectomy might prove more effective then in preventing seizures with fewer potential complications. If partial extratemporal epilepsy is associated with pharmaco-resistant seizures, the preoperative evaluation and operative strategy are determined according to the epileptogenic zone and to the relationship between a substrate-directed disorder and eloquent areas. The pediatric treatment of extratemporal epilepsy is aimed at controlling the seizures, avoiding morbidity, and improving the patient’s quality of life through psychosocial integration. Since the immature brain is more plastic than when mature, the recovery of functions after surgery is greater in children than in adults.RecommendationEarly surgery is recommended for children with intractable epilepsy, and is now accepted as an important therapeutic modality also for children with chronic epilepsy.ConclusionTechnological advances in the last two decades, mainly in neuroimaging, have led many medical centers to consider surgical treatment of epilepsy, accuracy being granted by MRI-based neuronavigation systems—an interface between the lesion seen in the preoperative magnetic resonance imaging (MRI) and the operative field, often invisible to the surgeon.

Quality assessment of a new surgical simulator for neuroendoscopic training

OBJECT Ideal surgical training models should be entirely reliable, atoxic, easy to handle, and, if possible, low cost. All available models have their advantages and disadvantages. The choice of one or another will depend on the type of surgery to be performed. The authors created an anatomical model called the S.I.M.O.N.T. (Sinus Model Oto-Rhino Neuro Trainer) Neurosurgical Endotrainer, which can provide reliable neuroendoscopic training. The aim in the present study was to assess both the quality of the model and the development of surgical skills by trainees. METHODS The S.I.M.O.N.T. is built of a synthetic thermoretractable, thermosensible rubber called Neoderma, which, combined with different polymers, produces more than 30 different formulas. Quality assessment of the model was based on qualitative and quantitative data obtained from training sessions with 9 experienced and 13 inexperienced neurosurgeons. The techniques used for evaluation were face validation, retest and interrater reliability, and construct validation. RESULTS The experts considered the S.I.M.O.N.T. capable of reproducing surgical situations as if they were real and presenting great similarity with the human brain. Surgical results of serial training showed that the model could be considered precise. Finally, development and improvement in surgical skills by the trainees were observed and considered relevant to further training. It was also observed that the probability of any single error was dramatically decreased after each training session, with a mean reduction of 41.65% (range 38.7%-45.6%). CONCLUSIONS Neuroendoscopic training has some specific requirements. A unique set of instruments is required, as is a model that can resemble real-life situations. The S.I.M.O.N.T. is a new alternative model specially designed for this purpose. Validation techniques followed by precision assessments attested to the models feasibility.

Endoscopic approach to fourth ventricle cysticercosis

Neurocysticercosis is the most frequently observed parasitosis of the central nervous system worldwide. The fourth ventricle is the most frequent site of intraventricular infestation, a location that carries a higher risk for CSF blockage and intracranial hypertension due to CSF blockage. A great number of patients become shunt dependent which carries a poorer prognosis. We report on a case of a patient with symptomatic obstructive hydrocephalus due to cysticercus in the fourth ventricle where an endoscopic approach via a frontal burr hole was performed. Although there is no consensus in the literature for the optimal treatment of this disease, this method seemed adequate for treatment of fourth ventricle cysticercosis in patients with hydrocephalus, aqueductal and foramen of Monro dilatations.

In vitro analysis of neurospheres derived from glioblastoma primary culture: a novel methodology paradigm

Glioblastomas are the most lethal primary brain tumor that frequently relapse or progress as focal masses after radiation, suggesting that a fraction of tumor cells are responsible for the tumor regrowth. The identification of a brain tumor cell subpopulation with potent tumorigenic activity supports the cancer stem cell hypothesis in solid tumors. The goal of this study is to determine a methodology for the establishment of primary human glioblastoma cell lines. Our aim is achieved by taking the following approaches: (i) the establishment of primary glioblastoma cell culture; (ii) isolation of neurospheres derived from glioblastoma primary cultures; (iii) selection of CD133 cells from neurospheres, (iv) formation of subspheres in the CD133-positive population, (v) study of the expression level of GFAP, CD133, Nestin, Nanog, CD34, Sox2, CD44, and CD90 markers on tumor subspheres. Hence, we described a successful method for isolation of CD133-positive cell population and establishment of glioblastoma neurospheres from this primary culture, which are more robust than the ones derived straight from the tumor. Pointed out that the neurospheres derived from glioblastoma primary culture showed 29% more cells expressing CD133 then the ones straight tumor-derived, denoting a higher concentration of CD133-positive cells in the neurospheres derived from glioblastoma primary culture. These CD133-positive fractions were able to further generate subspheres. The subspheres derived from glioblastoma primary culture presented a well-defined morphology while the ones derived from the fresh tumor were sparce and less robust. And the negative fraction of CD133 cells was unable to generate subspheres. The tumor subspheres expressed GFAP, CD133, Nestin, Nanog, CD44, and CD90. Also, the present study describes an optimization of neurospheres/subspheres isolation from glioblastoma primary culture by selection of CD133-positive adherent stem cell.

A data mining system for providing analytical information on brain tumors to public health decision makers

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. Malignant brain neoplasms are among the most devastating and incurable forms of cancer, and their treatment may be excessively complex and costly. Public health decision makers require significant amounts of analytical information to manage public treatment programs for these patients. Data mining, a technology that is used to produce analytically useful information, has been employed successfully with medical data. However, the large-scale adoption of this technique has been limited thus far because it is difficult to use, especially for non-expert users. One way to facilitate data mining by non-expert users is to automate the process. Our aim is to present an automated data mining system that allows public health decision makers to access analytical information regarding brain tumors. The emphasis in this study is the use of ontology in an automated data mining process. The non-experts who tried the system obtained useful information about the treatment of brain tumors. These results suggest that future work should be conducted in this area.

Pediatric central nervous system tumors: a single-center experience from 1989 to 2009.

The objective of this study was to determine the epidemiology of primary tumors of the central nervous system (CNS) in pediatric patients from a Brazilian oncology institute. We retrospectively analyzed 741 charts (415 males and 326 females) of patients under 21 years of age who were diagnosed with a CNS tumor. The analysis included patients from 1989 to 2009 and was performed using the World Health Organization criteria. We evaluated the distribution of age, sex, topography, clinical symptoms, symptom intervals, and classification of the tumors. Patients with clinical/radiologic diagnoses were included. Seven hundred forty-one patients with tumors in the CNS were reviewed, and 83% of the patients presented a histologic diagnosis. Males (56%) were more prevalent than females. In children under the age of 1 year, the supratentorial compartment was the predominant region involved (62.0%). Astrocytoma was the most frequent tumor type (37.0%), followed by medulloblastoma (13.6%), craniopharyngioma (10.5%), and ependymoma (6.8%). Headaches were the most common symptom, and the symptom intervals varied from 1 to 5010 days. Approximately 4% of the patients had associated genetic syndromes. Although it was not a population study and selection bias may have occurred, this study supplies important epidemiologic data from an emerging country in which population studies are rare.

Cystic craniopharyngioma: intratumoral chemotherapy with alpha interferon

OBJECTIVE To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.