Paulo Henrique Aguiar

Acute Neurogenic Pulmonary Edema: Case Reports and Literature Review

Neurogenic pulmonary edema (NPE) is an underdiagnosed clinical entity. Its pathophysiology is multifactorial but largely unknown. We report two cases of NPE and review the literature on NPE cases reported since 1990. A 21-year-old man had a seizure episode following cranioplasty. He became increasingly dyspneic, and clinical and laboratory signs of respiratory failure were evident. Chest radiography and computed tomography showed bilateral diffuse infiltrates. After supportive measures were taken, complete respiratory recovery occurred in 72 hours. A 52-year-old woman had several seizure episodes following subarachnoid hemorrhage due to a cavernoma. She became increasingly dyspneic upon arrival at the hospital. After tracheostomy and oxygen support were established, chest radiography showed bilateral diffuse infiltrates. Respiratory recovery was excellent, and the patient was eupneic with normal results of chest radiography 48 hours later. Fourteen reports (21 cases) were found. Thirteen patients were female, and the mean age of the patients was 31.6 years. The most frequent underlying factor was subarachnoid hemorrhage (42.9%). Symptom onset occurred <4 hours after the neurologic event in 71.4% of cases. One third of the patients presented with pink frothy sputum. Chest radiography showed bilateral diffuse infiltrates in 90.5% of cases. Supportive measures included oxygen support and vasoactive drugs. Recovery was usually very rapid: 52.4% of patients recovered in <72 hours. Almost 10% of patients died of NPE. Our two cases had clinical and laboratory features in common with most NPE cases. Physicians should remember NPE when neurologic patients suddenly become dyspneic. The mortality rate is high, but surviving patients usually recover very quickly.

Transient mutism following a posterior fossa approach to cerebellar tumors in children: a critical review of the literature

Transient mutism has been known as a rare complication following a posterior fossa approach to cerebellar tumors and its cause has not been clearly elucidated. The cerebellar mutism is not accompanied by cranial nerve deficits and disorders of consciousness. Since 1985 only 23 cases of mutism following removal of a cerebellar tumor in children have been reported in the literature. Two additional cases have been operated upon in our department. Extensive injury to the vermian and paravermian cerebellar area, involving the hemispheric cortex, cerebellar peduncles, fibers from the dentato-thalamocortical pathway, and dentate and interpositum nuclei may be the most important anatomical substrate of mutism. The mechanism of such transient mutism seems to be a complex of two or more factors (vascular disturbances due to manipulation or retraction of the cerebellar region around the IV ventricle and emotional factors). On the basis of these 25 cases the major features of the cerebellar mutism are discussed.

Evaluation of Onyx HD-500 embolic system in the treatment of 84 wide-neck intracranial aneurysms.

OBJECTIVEWe report our results using Onyx HD-500 (Micro Therapeutics, Inc., Irvine, CA) in the endovascular treatment of wide-neck intracranial aneurysms, which have a high rate of incomplete occlusion and recanalization with platinum coils. METHODSSixty-nine patients with 84 aneurysms were treated. Most of the aneurysms were located in the anterior circulation (80 of 84 aneurysms), were unruptured (74 of 84 aneurysms), and were incidental. Ten presented with subarachnoid hemorrhage, and 15 were symptomatic. All aneurysms had wide necks (neck >4 mm and/or dome-to-neck ratio <1.5). Fifty aneurysms were small (<12 mm), 30 were large (12 to <25 mm) and 4 were giant. Angiographic follow-up was available for 65 of the 84 aneurysms at 6 months, for 31 of the 84 aneurysms at 18 months, and for 5 of the 84 aneurysms at 36 months. RESULTSComplete aneurysm occlusion was seen in 65.5% of aneurysms on immediate control, in 84.6% at 6 months, and in 90.3% at 18 months. The rates of complete occlusion were 74%, 95.1%, and 95.2% for small aneurysms and 53.3%, 70%, and 80% for large aneurysms at the same follow-up periods. Progression from incomplete to complete occlusion was seen in 68.2% of all aneurysms, with a higher percentage in small aneurysms (90.9%). Aneurysm recanalization was observed in 3 patients (4.6%), with retreatment in 2 patients (3.3%). Procedural mortality was 2.9%. Overall morbidity was 7.2%. CONCLUSIONOnyx embolization of intracranial wide-neck aneurysms is safe and effective. Morbidity and mortality rates are similar to those of other current endovascular techniques. Larger samples and longer follow-up periods are necessary.

Expression of cell adhesion proteins and proteins related to angiogenesis and fatty acid metabolism in benign, atypical, and anaplastic meningiomas

Most meningiomas are benign tumours of arachnoidal origin, although a small number have high proliferative rates and invasive properties which complicate complete surgical resection and are associated with increased recurrence rates. Few prognostic indicators exist for meningiomas and further research is necessary to identify factors that influence tumour invasion, oedema and recurrence. Paraffin sections from 25 intracranial meningiomas were analysed for expression of the proteins vascular endothelial growth factor (VEGF), VEGF receptors Flt1 and Flk1, E-cadherin, metalloproteinases 2 and 9 (MMP2, MMP9), CD44, receptor for hyaluronic acid-mediated motility (RHAMM), hyaluronic acid (HA), CD45, cyclooxygenase 2 (COX2), brain fatty acid binding protein (BFABP), Ki67, and proliferating cell nuclear antigen (PCNA). Correlations among protein expression were found for several markers of proliferation (Ki67, PCNA, MI) and microvessel density (MVD). COX2 expression increased with increasing with tumour grade and correlated with Ki67, PCNA, MI, MVD, and BFABP. BFABP expression also correlated with Ki67 and PCNA expression. Relationships were also identified among angiogenic factors (VEGF, Flt1, Flk1) and proliferation markers. Oedema was found to correlate with MMP9 expression and MMP9 also correlated with proliferation markers. No correlations were found for MMP2, E-cadherin, or CD44 in meningiomas. In conclusion Ki67, PCNA, MI, MVD, BFABP, and COX2 were significantly correlated with meningioma tumour grade and with each other. These findings, by correlating both intracellular fatty acid transport and eicosanoid metabolism with tumour proliferation, as determined by Ki67 labelling and mitotic index, suggest fatty acids are involved in the progression of meningiomas.

Peritumoral brain edema in benign meningiomas: correlation with clinical, radiologic, and surgical factors and possible role on recurrence

BACKGROUND Approximately 60% of meningiomas are associated with peritumoral edema. Various causative factors have been discussed in the literature. The objective of this study was to investigate the correlation of PTBE with clinical, radiologic, and surgical aspects and recurrence of meningiomas. METHODS Sixty-one patients with benign meningiomas were chosen for surgical treatment by the Group of Brain Tumors and Metastasis of the Department of Neurosurgery. All patients underwent complete surgical resection (Simpson grades 1 and 2), and those with atypical and malignant histopathologic grades were excluded. Tumors located in the cavernous sinus, tuberculum sellae, foramen magnum, ventricles, and petroclival region were excluded. RESULTS Edema extension had a positive correlation with the higher recurrence rates (P = .042) and with the presence of irregular margins (P < .011) on bivariate analysis. Meningiomas with larger edema sizes also showed correlation with large meningiomas (P = .035), and the ones with smaller edema sizes correlated with the tentorial location (P = .032). Multivariate analysis showed an association between PTBE and the presence of seizures (odds ratio, 3.469), large meningiomas (odds ratio, 15.977), and for each cubic centimeter added to its size, the risk of edema increased 1.082 times (odds ratio). CONCLUSION Peritumoral brain edema may be related to the invading potential of meningiomas and may play a role in the recurrence potential of the tumor. As a consequence, it is reasonable to consider the presence of edema as an additional factor to be taken into account when mapping out strategies for the treatment of meningiomas.

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

Unusual brain metastases from papillary thyroid carcinoma: case report.

OBJECTIVE AND IMPORTANCE Brain metastases from papillary carcinoma of the thyroid gland are unusual. No consensus regarding management has yet been reached. We report a case, review the current literature, and explain our approach on the basis of clinical, pathological, and radiological data. CLINICAL PRESENTATION A 33-year-old woman presented with signs of intracranial hypertension. The diagnostic evaluation included chest tomography, head computed tomography, brain magnetic resonance imaging with and without contrast enhancement, total-body scanning, and cerebral scintigraphy. Multiple supratentorial lesions and one right cerebellopontine angle lesion were observed. Histopathological analysis of the surgical specimen confirmed papillary carcinoma of the thyroid gland. INTERVENTIONA ventriculoperitoneal shunt was placed and a right suboccipital craniotomy was performed, with complete removal of the cerebellopontine angle tumor. Total-brain irradiation with 40 Gy/lesion followed the initial operation. One year after surgery, the patient presented with signs of increased intracranial pressure. A new left frontal lobe lesion with massive peritumoral edema was identified on magnetic resonance imaging scans. The edema was treated clinically and a left frontal craniotomy was performed, with complete resection of the tumor. The patient is currently faring well, with residual expressive aphasia. CONCLUSIONSurgery followed by radiotherapy seems to be a good alternative for the treatment of this specific type of metastasis. Thorough clinical and radiological evaluation, followed by genetic analysis of the surgical specimen, particularly with respect to the potential for tumor invasion under specific conditions, is recommended. The information obtained contributes to better management and better overall long-term outcomes for these patients.

Galectin-3 as an Immunohistochemical Tool to Distinguish Pilocytic Astrocytomas from Diffuse Astrocytomas, and Glioblastomas from Anaplastic Oligodendrogliomas

The distinction of astrocytomas and oligodendrogliomas, mainly pilocytic astrocytomas (PILOs) from infiltrating astrocytomas and oligodendrogliomas (ODs), and high‐grade oligodendrogliomas from glioblastomas (GBMs), poses a serious clinical problem. There is no useful immunohistochemical (IHC) marker to differentiate these gliomas, and sometimes the differential diagnosis between them is arbitrary. We identified galectin‐3 (Gal‐3) as a possible tool to differentiate them based on gene expression profiles of GBMs. We confirmed the differential expression in 45 surgical samples (thirteen GBMs; seven PILOs; 5 grade II ODs; 5 anaplastic oligodendrogliomas [AODs], including 2 Oligo‐astrocytomas; 8 diffuse astrocytomas [ASTs], and 7 non‐neoplastic samples) by quantification of Gal‐3 gene expression by real‐time quantitative PCR (rt‐PCR). Higher expression of Gal‐3 was observed in GBMs and PILOs than in OD, AODs and ASTs. The IHC expression of Gal‐3 was evaluated in 90 specimens (fifteen PILOs, fourteen ASTs, 10 anaplastic astrocytomas, fifteen GBMs, eleven ODs, fifteen AODs, and 10 dysembryoplastic neuroepithelial tumors). The mean labeling score for Gal‐3 determined according to the percentage of labeled cells in the tumor bulk was significantly different in GBMs versus AODs and in PILOs versus ASTs. Hence, Gal‐3 is differentially expressed in central nervous system tumors, making IHC detection of Gal‐3 a useful tool in distinguishing between these gliomas.

MR AND CT IMAGING IN THE DYKE-DAVIDOFF-MASSON SYNDROME : REPORT OF THREE CASES AND CONTRIBUTION TO PATHOGENESIS AND DIFFERENTIAL DIAGNOSIS

Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis, and mental retardation. These findings are due to cerebral injury that may occur early in life or in utero. The radiological features are unilateral loss of cerebral volume and associated compensatory bone alterations in the calvarium, like thickening, hyperpneumatization of the paranasal sinuses and mastoid cells and elevation of the petrous ridge. The authors describe three cases. Classical findings of the syndrome are present in variable degrees according to the extent of the brain injury. Pathogenesis is commented.

Labeling index in pituitary adenomas evaluated by means of MIB-1: is there a prognostic role? A critical review

Abstract Objective: The present article presents an overview of the literature, and analyses the methods and the primary questions related to assessment of proliferation index using the Ki-67/MIB-1 labeling index in pituitary adenomas. Although atypical adenomas are characterized by their atypical morphological features by an elevated mitotic index, a Ki-67 (MIB-1) labeling index greater than 3% and extensive nuclear staining for p53, use of the proliferation index (LI) of pituitary adenomas in assessing the degree of tumor aggressiveness is a controversial topic in the literature, and there are disparate results involving many studies. Methods: A review of literature was carried out to correlate the role of Ki-67 LI and its correlation with clinical findings, tumor size, invasiveness, recurrence, adenoma subtype, adenoma doubling time, and pituitary carcinomas is addressed. Results: The prognosis cannot be predicted on the basis of the Ki-67 LI alone. Although there is no direct relation between Ki-67 LI and some of these variables and controversial data were found regarding some topics, our review justify the use of Ki-67 in the analysis of pituitary adenomas as an additional information for clinical decision. Conclusion: Although assessment of proliferative may be helpful in predicting subsequent tumor recurrence or invasiveness, there are many other important and as yet unidentified factors pituitary tumors. It is clear that further research is needed to clarify these molecular mechanisms to predict those with a potentially poor clinical outcome.