Cerebral apoptosis in severe traumatic brain injury patients: an in vitro, in vivo, and postmortem study.

One of the most important recent observations in traumatic brain injury (TBI) relates to the potential role of apoptosis in secondary brain injury. We aimed to analyze the presence of apoptosis and the expression of apoptosis-related proteins in brain samples from patients with TBI. We also tried to find any association between the in situ results and the in vitro observations in a neuronal model of induced-apoptosis. Brain tissue from the pericontusional zone (PCZ) of patients with traumatic contusions and from post-mortem samples was analyzed. Immunohistochemical analyses of apoptosis-related proteins and the terminal deoxynucleotide transferase-mediated nick end labeling (TUNEL) method to determine the presence of apoptotic cells were performed. Apoptotic rates on neuronal cells induced by jugular bulb vein sera was determined by flow cytometry. TUNEL-positive cells were detected in all PCZ of traumatic contusions and in most of PCZ in post-mortem specimens (none in control; p = 0.026). In vivo samples showed higher expression of antiapoptotic proteins Bcl-2 (p = 0.027) and Bcl-XL (p = 0.014) than post-mortem samples. In autopsies, the expression of Fas and Bim (p < 0.05) were higher in PCZ than in the zone distal from the contusion. In vitro studies showed that apoptotic rate was an independent factor associated with mortality at 6 months (p = 0.014). In the receiving operator curve (ROC) curve, a cut-off point of 66.5% showed a sensitivity of 89.5% and specificity of 66.7% in the prediction of patients' death. Cerebral apoptosis is a prominent form of cell death in the PCZ of human traumatic cerebral contusions, and high rates of in vitro apoptosis are associated with a poorer prognosis after TBI.

Spinal muscular atrophy type I mimicking critical illness neuropathy in a paediatric intensive care neonate: electrophysiological features.

We report the case of a neonate with spinal muscular atrophy type I (SMA type I or Werdnig-Hoffman disease) who was initially misdiagnosis as having critical illness neuropathy. Electromyography (EMG) showed a moderate loss of voluntary and motor unit potentials of both neurogenic and myopathic appearance. Nerve conduction studies revealed the presence of a severe sensory-motor axonal neuropathy. Finally, a biopsy of quadriceps was compatible with the diagnosis of SMA type I. A genetic study confirmed the existence of a homozygous absence of exons 7 and 8 of the telomeric supervival motoneuron gene (SMN1 gene).

First study on the peptidergic innervation of the brain superior sagittal sinus in humans.

The superior sagittal sinus (SSS) of the mammalian brain is a pain-sensitive intracranial vessel thought to play a role in the pathogenesis of migraine headaches. Here, we aimed to investigate the presence and the potential co-localization of some neurotransmitters in the human SSS. Immunohistochemical and double-labeling immunofluorescence analyses were applied to paraformaldehyde-fixed, paraffin-embedded, coronal sections of the SSS. Protein extraction and Western blotting technique were performed on the same material to confirm the morphological data. Our results showed nerve fibers clustered mainly in large bundles tracking parallel to the longitudinal axis of the sinus, close in proximity to the vascular endothelium. Smaller fascicles of fibers encircled the vascular lumen in a spiral fashion, extending through the subendothelial connective tissue. Isolated nerve fibers were observed around the openings of bridging veins in the sinus or around small vessels extending into the perisinusal dura. The neurotransmitters calcitonin gene related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY) were found in parietal nerve structures, distributed all along the length of the SSS. Overall, CGRP- and TH-containing nerve fibers were the most abundant. Neurotransmitters co-localized in the same fibers in the following pairs: CGRP/SP, CGRP/NOS, CGRP/VIP, and TH/NPY. Western blotting analysis confirmed the presence of such neurosubstances in the SSS wall. Overall our data provide the first evidence of the presence and co-localization of critical neurotransmitters in the SSS of the human brain, thus contributing to a better understanding of the sinus functional role.

Incidental localized (solitary) epithelial mesothelioma of the pericardium: case report and literature review.

Primary mesotheliomas of the pericardium are rare tumors. They may occur in diffuse, multiple, and localized forms. Most of the pericardial mesotheliomas are multiple or diffuse growths encasing the heart, localized forms being distinctly uncommon. We report a localized mesothelioma of the pericardium found incidentally at the autopsy of a 76-year-old woman. The neoplasm measured 3.6 x 2.4 x 2.5 cm., was well circumscribed, and affected the entire thickness of the myocardium extending from the epicardium to the endocardium of the anterior wall of the right ventricle. The tumor was epithelial in type, showed an immunohistochemical profile compatible with mesothelioma, and was DNA aneuploid. A review of the literature yielded four cases of localized pericardial mesothelioma, including the present. Most cases are seen in women and are of the epithelial variant. There is a wide age range at presentation. Localized mesotheliomas are capable of aggressive behavior. Nevertheless, in contrast to diffuse tumors, complete surgical excision may be curative. Differential diagnosis includes solitary fibrous tumor, synovial sarcoma, epithelioid angiosarcoma, and adenomatoid tumor of the pericardium.

GFAP and alpha1a-AR staining and nuclear morphometry of oligodendrogliomas by confocal microscopy and image analysis: useful parameters for predicting survival in oligodendrogliomas.

OBJECTIVE: This study attempts to evaluate the GFAP and alpha1a-AR staining and morphometrical nuclear features of oligodendrogliomas and their prognostic implications as compared to present histopathology classification and their survival outcome. STUDY DESIGN: Surgical specimens from 24 patients with oligodendrogliomas during the period 1981-2000 were included. These cases were classified into two groups defined by the grade of the neoplasm: Group I: oligodendrogliomas grade II; Group II: oligodendrogliomas grade III and two groups based on the outcome status: Group of the alive cases and group of the death cases. Death rate for the groups were obtained by patients' charts. Descriptive statistics were used to examine the groups with respect to the morphometrical nuclear variables; area, perimeter, aspect, axes (major and minor), diameters (max, mean and min.), radius (max. and min.) margination, ratio of perimeter-area, roundness and sizes (length and width). In addition, an immunofluorescence method for GFAP and 1a-AR were performed and their area, density and intensity of staining were analyzed. RESULTS: Semiautomated quantitative morphometrical results showed that the variables of nuclear area (GII 48.87 microm2 vs. GIII 43.45 microm2 p-value = 0.02), aspect (GII 1.39 vs. GIII 1.55 p-value = 0.03), axis minor (GII 6.66 microm vs. GIII 6.01 microm p-value = 0.003), diameter minor (GII 5.93 microm vs. GIII 5.27 microm p-value = 0.002), radius minor (GII 2.64 microm vs. GIII 2.25 microm p-value = 0,003), perimeter-area (GII 0.0007 vs. GIII 0.0006 p-value = 0.04), size width (GII 6.60 microm vs. GIII 5.96 microm p-value = 0,003), and density of alpha1a-AR staining (GII 121.38 vs. GIII 146.03 p-value = 0.05) were statistically significant in regard of grade; and that the sum of density of GFAP (p-value = 0.01) and the intensity of alpha1a-AR (p-value = 0.01) were statistically significant in predicting survival. CONCLUSION: These results suggest that some nuclear morphometrical features and the GFAP and alpha1a-AR immunofluorescence staining may be useful parameters for predicting survival in oligodendrogliomas.

Divergent ependymal tumor (ependymoblastoma/anaplastic ependymoma) of the posterior fossa: an uncommon case observed in a child.

We report a divergent ependymal tumor of the posterior fossa (ependymoblastoma/anaplastic ependymoma) observed in an 8-year-old boy. The tumor showed the histological pattern typical of an ependymoblastoma (tubular-papillary fetaloid architecture with stratification of the tumor cells) next to areas in which findings typical of an anaplastic ependymoma were detected. The immunohistochemical study confirmed our diagnostic suspicion, allowing us to establish a differential diagnosis with other entities such as medulloblastoma, medulloepithelioma, atypical rhabdoid/teratoid tumor, or metastases.

Radiological and pathological assessment of hepatocellular carcinoma response to radiofrequency. A study on removed liver after transplantation.

BACKGROUND: The real efficacy of radiofrequency ablation (RFA) in destroying hepatocellular carcinoma is not completely known, nor is the ability of computed tomography (CT) to precisely assess response. Our aims were to analyze pathological response, tumor size influence, and CT response evaluation. MATERIALS AND METHODS: This was a retrospective study of 30 hepatocellular carcinoma nodules treated by RFA before liver transplant (LT) in 28 patients. Pathological study of the whole removed liver was then performed and the tumor response was classified as complete, incomplete, or absent. The biggest nodule diameter was estimated by CT or ultrasound. The procedure was carried out percutaneously in all but 3 patients, and in those 3 it was done surgically. RESULTS: The pathological response was complete in 14 nodules (46.7%) and incomplete in 16 (53.3%). The differences in mean preoperative diameter between cases with complete and incomplete response were not significant (p = 0.3). We found that small tumors were not always completely destroyed, whereas bigger tumors could be successfully deleted. There was no clear association between any location and better or poorer response. The detection of RFA incomplete response by means of CT scan had 50% sensitivity and 100% specificity. CONCLUSIONS: In our experience, RFA can achieve some degree of tumor destruction in every treated case of hepatocellular carcinoma, the complete response rate being slightly lower than half. We have not found any association of response with tumor size or interval RFA-transplant. Second, CT had not enough sensitivity to assess RFA response of hepatocellular carcinoma.

Epilepsia partialis continua in progressive multifocal leukoencephalopathy: a motor cortex isolation syndrome.

We describe the clinical and neuropathological features in a patient aged 45 years with progressive multifocal leukoencephalopathy with epilepsia partialis continua. The motor cortex and basal ganglia were preserved. Our findings lend support to the notion of isolation of the motor cortex as the cause of this particular type of focal status epilepticus.