SOMATIC DEFICIENT MISMATCH REPAIR ASSESSED BY IMMUNOHISTOCHEMISTRY AND CLINICAL FEATURES IN BRAZILIAN GLIOBLASTOMA PATIENTS.

BACKGROUND: Glioblastoma (GBM) is the most frequent primary malignant CNS tumor. Deficient mismatch repair (dMMR) is associated with better prognosis and is a biomarker for immunotherapy. Evaluation of MMR by immunohistochemistry (IHC) is accessible, cost effective, sensitive, and specific. AIM: Our objective was to investigate MMR proteins in adult GBM patients. MATERIALS AND METHODS: We retrospectively analyzed 68 GBM samples to evaluate the proficiency of MMR genes expression assessed by IHC. Clinicopathologic and molecular features were compared in proficient (pMMR) or dMMR. RESULTS: 10 (14.7%) samples showed dMMR, and the most frequent was MSH6 (100%) followed by MSH2, PMS2, and MLH1. We observed heterogeneous expression of dMMR in 5 GBMs. The median overall survival did not differ between pMMR (19.8 months; 0.2-30) and dMMR (16.9 months; 6.4-27.5) (p = 0.31). We observed a significantly higher overall survival associated with gross total resection compared to subtotal resection or biopsy (30.7 vs. 13.6 months, p = 0.02) and MGMT methylated status (29.6 vs. 19.8 months, p = 0.049). At the analysis time, 10 patients were still alive, all in the pMMR group. CONCLUSIONS: Our data demonstrated dMMR phenotype assessed by IHC in an expressive portion of GBM patients, however without significant impact on overall survival.

Association of EGFR c.2073A>T polymorphism with decreased risk of diffusely infiltrating astrocytoma in a Brazilian case-control study.

Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c.-191C>A and c.-216G>T) and the c.2073A>T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A>T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26-0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A>T polymorphism could play a role in future therapeutic approaches to astrocytoma.

[Secretory meningioma. Report of two cases]. / Meningioma secretório. Relato de dois casos.

Two surgically removed meningotheliomatous meningiomas with hyaline inclusions or pseudopsammoma bodies were studied. Both meningiomas showed expression of carcinoembryonic antigen and cytokeratin in the cells surrounding the hyaline bodies. There was widespread vimentin and epithelial membrane antigen except in the cells with hyaline inclusions. Clinically both had a severe cerebral edema. One of the cases showed multiple tumors, probably meningiomas. It is important not to misinterpret this variant of meningioma as metastatic neoplasm which may result in palliative treatment of a potentially curable tumor.

Dengue. Muscle biopsy findings in 15 patients.

Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, serologically confirmed, during the brazilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

[Normative data on the verbal fluency test in the animal category in our milieu]. / Dados normativos para o teste de fluência verbal categoria animais em nosso meio.

OBJECTIVE: Evaluate the performance on verbal fluency (VF) in our population in a Brazilian sample checking the influence of age and literacy. METHODS: 336 people without neurological or psychiatric complaints evaluated through Mini-Mental State Examination and VF (animals). For comparison, and to determine cut-off points, 65 people with cognitive loss followed at our clinic were also evaluated. RESULTS: We found a mean of 13.8 animals in 1 minute, with the following distribution: illiterates, 11.9; up 4 years of education, 12.8; 4 to 7 years, 13.4; 8 years or more, 15.8 (p = 0.0001). In relation to age the means were: up to 64 years, 13.7; 65 years or more, 13.9. There was no difference between the two groups. The cut-off points were 9 for people under 8 years of education with a sensitivity of 75% for illiterates, 100% for low educational level (up 4 years), and 87% for middle level (4 to 7 years). The specificity was respectively 79%, 84%, and 88%. For the high educational level the mean was 13 with a sensitivity of 86% and specificity of 67%. CONCLUSIONS: In the VF (animals) there is a significant influence of schooling and different cut-off points should be used.

Hemorrhagic cerebral metastasis as a first manifestation of a hepatocellular carcinoma. Case report.

We report herein a rare instance in which a patient presented with a hemorrhagic cerebral metastasis as the initial manifestation of a hepatocellular carcinoma (HCC). A few cases of cerebral metastasis from HCC have been reported in the literature, mainly from eastern countries. This is the first report from South America of a cerebral metastasis from hepatocellular carcinoma.

[Germinoma of the basal ganglia and thalamus with brain stem invasion: case report]. / Germinoma localizado nos núcleos da base e tálamo com invasão do tronco cerebral. Relato de caso.

We report an unusual case of germinoma arising from the basal ganglia and thalamus with brain stem invasion, with emphasis on computed tomography and magnetic resonance findings. Diagnosis was confirmed by histopathologic examination. Early detection of this tumor is important due to its potential response to treatment.

[Fraction of gemistocytic astrocytes and immunoexpression of p53 protein in astrocytomas grade II and III (WHO)]. / Indice de astrócitos gemistocíticos e imuno-expressão da proteína p53 em astrocitomas, grau II e III OMS.

Twenty-two patients with astrocytomas, grade II or III WHO, were studied from 1990 to 1998. In all cases, histopathology showed that the astrocytomas had a gemistocytic component. The aims of this study were to establish the fraction of gemistocytic astrocytes, to investigate p53 protein immunoexpression and to evaluate correlations between these two parameters with the tumour outcome. Tumor cells were quantified at high-power magnification (x400). At least 1000 neoplastic cells (small neoplastic astrocytes plus gemistocytes) were counted in each specimen. The percentage of gemistocytes was defined as the gemistocytic index. Nuclear expression of p53 protein was evaluated in neoplastic astrocytes and gemistocytes. Both the frequency (7/22) as well the p53 immunoexpression indices in gemistocytes, regardless of the grade of the astrocytomas, were inferior from those reported in the literature. No correlation was found between the gemistocytic indices and the p53 immunoexpression.

[Orbital phlebography evaluation in 8 cases of Tolosa-Hunt syndrome]. / Avaliação da flebografia orbitária em oito casos de síndrome de Tolosa-Hunt.

Tolosa-Hunt syndrome (THS), or painful ophthalmoplegia is associated to a non-specific granulomatosis of unknown etiology, that involves the superior orbital fissure and its nervous and vascular structures. The clinical picture that responds to steroid therapy, is variable and is always associated with pain. Inflammatory conditions, tumors and aneurysms can produce similar symptoms. Computed tomography, cerebral angiography and orbital phlebography are the imaging methods of choice for making the diagnosis. We revised the results of these radiological examinations of eight patients seen at the Hospital São Paulo from 1989 to 1991, with the diagnosis of THS according to Hunt and Hannerz criteria. The analysis of orbital phlebographic changes based upon Hannerz et al. systematization showed non-specific features, but those were able to help the diagnosis.

[Multiple gliomas. Illustrative cases of 4 different presentations]. / Gliomas múltiplos: casos ilustrativos de quatro formas de apresentação.

Multiple gliomas are uncommon and may be classified according to: a) the time of presentation in early (at diagnosis) or late (during treatment); b) the characteristics of computed tomography or magnetic resonance imaging (CT/MRI) in multifocal (with evidence of spread) and multicentric (without evidence of spread). From 212 patients with histopathologic diagnosis of glioma evaluated from March/90 to September/99, 15 (7%) had multiple lesions. We describe 4 patients: early multicentric, late multicentric, early multifocal and late multifocal, with emphasis on characteristics of CT/MRI and possible differential diagnosis. The differential diagnosis of multiple lesions in the central nervous system includes mainly infectious/inflammatory diseases and metastasis, however multiple gliomas should always be considered, even in patients with known systemic cancer, as described by others. Considering that CT/MRI features are not definite, the diagnosis should always be confirmed by histopathologic examination.

[Actinomycosis of the central nervous system: a rare complication of cervicofacial actinomycosis]. / Actinomicose do sistema nervoso central. Uma rara complicação da actinomicose cervicofacial.

Central nervous system actinomycosis is a rare but treatable chronic suppurative bacterial infection. The case of a young immunocompetent male with actinomycosis of the CNS is presented. The abscess originated from a primary cervico-facial infection and was located in the left parasellar region. After excision of the mass, that showed Actinomyces colonies, the patient was treated with intravenous Penicillin for 42 days followed by oral administration of the drug for 30 days. After surgery the patient was left with mild sequelae that had improved by the last follow-up, 7 months later. A new CT scan at that time revealed no residual disease or recurrence. The early diagnosis of cerebral actinomycosis relies essentially on a clinical suspicion. Hence it is imperative to be aware of the natural history of this infection and its various modes of presentation.

Is the number of microembolic signals related to neurologic outcome in coronary bypass surgery?

Coronary artery bypass surgery (CABG) without cardiopulmonary bypass (CPB) may potentially reduce the number of microembolic signals (MES) associated with aortic manipulation or generated by the pump circuit, resulting in a better neurologic outcome after surgery. Our aim was to compare the frequency of MES and neurologic complications in CABG with and without CPB. Twenty patients eligible to routine CABG without CPB were randomized to surgery with CPB and without CPB and continuously monitored by transcranial Doppler. Neurologic examination was performed in all patients before and after surgery. The two groups were similar with respect to demographics, risk factors, grade of aortic atheromatous disease and number of grafts. The frequency of MES in the nonCPB group was considerably lower than in CPB patients, however, we did not observe any change in the neurologic examination during the early postoperative period. Neurologic complications after CABG may be related to the size and composition of MES rather than to their absolute numbers. A large prospective multicentric randomized trial may help to elucidate this complex issue.

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.

[Diffuse bone marrow metastasis in cerebellar high-grade astrocytoma. A case report]. / Metastasis difusa de la medula osea en un astrocitoma cerebeloso de alto grado. Un caso clinico.

INTRODUCTION: Cerebellar high-grade astrocytoma is uncommon. Although more prone to present cerebrospinal fluid dissemination, the cerebellar location is not particularly related to the occurrence of extra-cranial metastases, which are also unusual in supratentorial malignant gliomas. CASE REPORT: A 46 year-old man with cerebellar anaplastic astrocytoma who developed pancytopenia due to extensive bone marrow metastases. CONCLUSION: Extraneural metastases of brain gliomas are rare and the spread to the bone marrow confers an extremely poor prognosis for these patients. The expected improvement in glioma patients' survival due to the combination of more efficient therapies may lead to an increased incidence of this uncommon presentation, justifying a more rigorous follow-up of systemic manifestations.

Transcranial Doppler assessment of cerebral blood flow: effect of cardiac transplantation.

The authors prospectively studied transcranial Doppler changes in patients with refractory congestive heart failure before and after cardiac transplantation. They evaluated 22 patients preoperatively and 14 patients after transplantation. Mean postoperative flow velocity increased by 53.3% (p < 0.0001). Preoperative waveform changes became normal after transplantation.

Neurological outcome in coronary artery surgery with and without cardiopulmonary bypass.

INTRODUCTION: The neurological complications of coronary artery surgery with cardiopulmonary bypass (CPB) have been extensively studied, but to our knowledge those without CPB (NCPB) have not been defined. PATIENTS & METHODS: We prospectively examined 81 patients, before and up to seven days after surgery, to compare the neurological morbidity between patients subjected to coronary artery bypass graft (CABG) surgery with and without CPB. We analyzed demographic variables, risk factors and neurological examination including neuropsychological (NPS) tests using chi-square and non-parametric analysis (Mann-Whitney and Kruskal-Wallis). RESULTS: Forty-eight patients (34M; median age = 62 yrs; median number of grafts = 3 and median total surgery duration = 300 min) operated with CPB and 33 without CPB (23M; median age = 64 yrs; median number of grafts = 2 and median total surgery duration = 240 min) differed only in relation to number of grafts (p = 0.0001) and surgery duration (p = 0.0001). CONCLUSION: We found no difference in early neurological outcome in patients subjected to CABG with or without CPB.

Neurologic outcome after heart transplantation in Chagas' disease. Preliminary results.

OBJECTIVE: To evaluate the neurologic morbidity after orthotopic heart transplantation (OHT), we examined consecutive Chagas' (Ch) and non-Chagas' (NCh) patients, before and after surgery. MATERIAL AND METHODS: We undertook neurological and neuropsychological evaluations in Ch and NCh patients with end-stage cardiac failure, from September 1993 to September 1995. RESULTS: Of 10 Ch patients (mean age = 33.6 years; 7 male; mean follow-up = 10.8 months) and 13 NCh patients (mean age = 50.9 years; 12 male; mean follow-up = 15 months) 3 died (rejection and sepsis) without neurologic symptoms. Neurologic complications occurred in 4 Ch and 5 NCh patients. Two Ch patients had skin and myocardial Chagas' reactivation successfully treated, without CNS involvement. NPS performance and return to work rates were similar in both groups. CONCLUSION: Although Ch patients are potentially at a higher risk of Trypanosoma cruzi reactivation, in addition to all known neurologic complications of OHT, early neurologic complications detected in this sample were similar in Ch and NCh patients and could not be specifically related to Chagas' disease.

MRI of medulloblastoma in adults.

Medulloblastoma has variable appearances on MRI in both children and adults. Adults are more likely to have heterogeneous cerebellar hemisphere tumours, and this is thought to be related to the greater prevalence of desmoplastic tumours in adulthood. Few studies have addressed the MRI features of adult medulloblastoma and the specific characteristics of desmoplastic and classic tumours have not been analysed. Our aim was to analyse the imaging characteristics of desmoplastic (DM) and classic (CM) medulloblastomas in adult. We retrospectively studied preoperative MRI of six men and three women, median age 33 years, range 23-53 years, with pathologically proved medulloblastomas. There were six (67%) with DM. The tumour was in the cerebellar hemisphere in eight patients (89%), including the three with CM, one of which was bilateral. All tumours were heterogeneous, giving predominantly low or isointense signal on T1- and isointense signal on T2-weighted images. Cystic or necrotic areas in all patients were particularly visible on T2-weighted images. Contrast enhancement was absent in one DM and varied from slight to intense in eight (three CM), homogeneous in one DM and patchy in seven. All tumours extended to the surface of the cerebellum and two had well-defined margins. MRI does not allow a clear distinction between DM and CM in adults.