Papillary Tumor of the Pineal Gland: Series of Four Clinical Cases.

The papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor originating from specialized ependymocytes. It primarily affects structures within the pineal region, including the pineal gland, epithalamus, quadrigeminal cistern, and posterior wall of the third ventricle. Here, we present a series of four cases characterized by symptoms associated with obstructive hydrocephalus such as headaches, seizures, visual disturbances, gait disturbances, and Parinaud syndrome. Imaging studies revealed lesions in the pineal region, prompting surgical intervention. Histopathological examination, including biopsy and intraoperative analysis, confirmed the diagnosis of PTPR. Despite advancements, the etiology and pathogenesis of PTPR remain incompletely understood, warranting further research to refine management strategies.

Comparative genomic analysis of uropathogenic Escherichia coli strains from women with recurrent urinary tract infection.

Introduction: Recurrent urinary tract infections (RUTIs) caused by uropathogenic Escherichia coli are costly public health problems impacting patients' quality of life. Aim: In this work, a comparative genomics analysis of three clinical RUTI strains isolated from bladder biopsy specimens was performed. Materials and methods: One hundred seventy-two whole genomes of urinary tract E. coli strains were selected from the NCBI database. The search for virulence factors, fitness genes, regions of interest, and genetic elements associated with resistance was manually carried out. The phenotypic characterization of antibiotic resistance, haemolysis, motility, and biofilm formation was performed. Moreover, adherence and invasion assays with human bladder HTB-5 cells, and transmission electron microscopy (TEM) were performed. Results: The UTI-1_774U and UTI-3_455U/ST1193 strains were associated with the extraintestinal pathotypes, and the UTI-2_245U/ST295 strain was associated with the intestinal pathotype, according to a phylogenetic analysis of 172 E. coli urinary strains. The three RUTI strains were of clinical, epidemiological, and zoonotic relevance. Several resistance genes were found within the plasmids of these strains, and a multidrug resistance phenotype was revealed. Other virulence genes associated with CFT073 were not identified in the three RUTI strains (genes for type 1 and P fimbriae, haemolysin hlyA, and sat toxin). Quantitative adherence analysis showed that UTI-1_774U was significantly (p < 0.0001) more adherent to human bladder HTB-5 cells. Quantitative invasion analysis showed that UTI-2_245U was significantly more invasive than the control strains. No haemolysis or biofilm activity was detected in the three RUTI strains. The TEM micrographs showed the presence of short and thin fimbriae only in the UTI-2_245U strain. Conclusion: The high variability and genetic diversity of the RUTI strains indicate that are a mosaic of virulence, resistance, and fitness genes that could promote recurrence in susceptible patients.

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.

Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas.

Pituitary adenomas (PAs) can be unpredictable and aggressive tumors. No reliable markers of their biological behavior have been found. Here, a proteomic analysis was applied to identify proteins in the expression profile between invasive and non-invasive PAs to search for possible biomarkers. A histopathological and immunohistochemical (adenohypophyseal hormones, Ki-67, p53, CD34, VEGF, Flk1 antibodies) analysis was done; a proteomic map was evaluated in 64 out of 128 tumors. There were 107 (84%) invasive and 21 (16%) non-invasive PAs; 80.5% belonged to III and IV grades of the Hardy-Vezina classification. Invasive PAs (n = 56) showed 105 ± 43 spots; 86 ± 32 spots in non-invasive PAs (n = 8) were observed. The 13 most prominent spots were selected and 11 proteins related to neoplastic process in different types of tumors were identified. Hint1 (Histidine triad nucleotide-binding protein 1) high expression in invasive PA was found (11.8 ± 1.4, p = 0.005), especially at high index (>10; p = 0.0002). High Hint1 expression was found in invasive VEGF positive PA (13.8 ± 2.3, p = 0.005) and in Flk1 positive PA (14.04 ± 2.28, p = 0.006). Hint1 is related to human tumorigenesis by its interaction with signaling pathways and transcription factors. It could be related to invasive behavior in PAs. This is the first report on Hint expression in PAs. More analysis is needed to find out the possible role of Hint in these tumors.

Chronic consumption of cassava juice induces cellular stress in rat substantia nigra.

OBJECTIVES: Cassava (Manihot esculenta Crantz) contains cyanogenic glycosides (linamarin and lotaustralin) that have been associated with neurological disorders in humans and rats. In basal ganglia, the dopaminergic neurons of substantia nigra pars compacta (SNpc) show high cytotoxic susceptibility; therefore, the chronic consumption of cassava (CCC) could induce neurodegeneration in SNpc. In this study we examine the impact of CCC on the integrity of the nigrostriatal system, including apoptosis and microgliosis. MATERIALS AND METHODS: Male Wistar rats were administered cassava juice daily (3.57 g/kg and 28.56 g/kg, per os) or linamarin (0.15 mg/ml, IP), and its effects were evaluated in rota-rod and swim tests at days 7, 14, 21, 28, and 35 of administration. In SNpc, oxidative/nitrosative stress was determined by malondialdehyde/4-hydroxyalkenals (MDA-4-HAD) and nitrite contents. Tyrosine hydroxylase immunoreactivity (TH-IR) was evaluated in SNpc, neostriatum (NE), and nucleus accumbens (NA). Apoptosis and microgliosis were determined by active-caspase-3 (C3) and CD11b/c (OX42) expression in the medial region of SNpc. RESULTS: Chronic administration of cassava juice, or linamarin, increased motor impairment. The rats that received 28.56 g/kg cassava showed increased MDA-4-HAD content in SNpc and nitrite levels in NE with respect to controls. Significant loss of TH-IR in SNpc, NE, and NA was not found. The 28.56 g/kg cassava administration produced dopaminergic atrophy and microgliosis, whereas linamarin induced hypertrophy and C3-related apoptosis in SNpc. CONCLUSION: CCC induces cellular stress on dopaminergic neurons, which could contribute to motor impairment in the rat.

Lipopolysaccharide-based endotoxemia produce toxicity in peripheral organs and microglia migration in a dose-dependent manner in rat substantia nigra.

The peripheral inflammatory stimulus could induce cell damage in peripheral organs and activate microglial cells in the brain. One such stimulus was given to adult male Wistar rats by injecting different concentrations of lipopolysaccharide (LPS; 50, 300, 500 g/kg and 5 mg/kg i.p.). To verify the systemic effect of the LPS administration, the serum content of C-reactive protein (CRP), the variation of body weight and cellular changes in the spleen, liver and kidney were determined. Motor impairment was evaluated by rotarod and open field tests. Microglia activation and dopaminergic degeneration was confirmed by immunolabelling for CD11b/c (microglia) and tyrosine hydroxylase (TH), respectively. The cell counting was performed in substantia nigra pars compacta (SNpc), microglial activation was explored in SNpc, substantia nigra pars reticulata (SNpr), substantia nigra pars compacta dorsal (SNcd) and the ventral tegmental area (VTA). For the statistical analysis, one-way ANOVA followed by Tukey post hoc test (p ≤ 0.05) was used. On day 7 post intraperitoneal administration of LPS, cellular atrophy was detected in the liver, kidney and spleen at 5 mg/kg, without significant changes in CRP levels. Body weight loss and motor impairment was present only on day 1 post LPS administration. The dosage of 500 g/kg and 5 mg/kg of LPS caused the loss of dopaminergic neurons (40%) in SNpc and microglia migration in a dose-dependent manner in SNcd, SNpc and SNpr. LPS-induced endotoxemia favours damage to the peripheral organs and microglial migration in a dose-dependent manner in rat substantia nigra.

Role of Epstein-Barr Virus in Glioblastoma.

Gliomas are the most common and most lethal primary malignant adult brain tumors, and glioblastomas are the most frequent. Several risk factors are involved in their pathogenesis; these include environmental factors as well as host factors. The etiology of most gliomas remains unknown. Epstein-Barr Virus (EBV), a member of the Herpesviridae family, was the first tumoral virus to be described, and several viruses in connection with cancer were discovered thereafter. During the complex interaction between host and EBV, several events take place. In the context of survival, EBV can drive its host cells with subsequent disruption of the cellular machinery, leading to tumorigenesis as the final outcome. Thus, the EBV infection has been associated with different tumors. In this review, we discuss EBV and cancer. We have analyzed previously published papers and have conducted a critical analysis on the role of the viral infection in glioblastoma. Several works have described the presence of the virus, but none have shown a conclusive association. Thus, there is need to continue analyzing the interaction between host and virus to determine whether the viral presence is incidental or has some association with glioblastoma.

Bilateral Simultaneous Temporal Relapses of Medulloblastoma.

Supratentorial relapses are a common component of medulloblastoma after failure of treatment. Craniospinal irradiation (CSI) to cerebrospinal fluid-bearing areas is an essential part of the management of these tumors both in adults and children. Failure of treatment in specific anatomical regions can be attributable to technical inaccuracies in CSI technique leading to radiation underdosing in such areas. We present two cases of patients with bilateral simultaneous metastasis of a primary medulloblastoma treated, in both cases, four years before the recurrence. In both patients the tumors were mirror images, at the right and left temporal pole. Radiotherapeutic plans were analyzed in both cases, and a possible mechanism determining the pattern of relapse is discussed. We consider, in agreement with the literature, that a prone position during treatment, shielding blocks at the cribiform/subfrontal region, and anatomic inadequacies in the CSI fields could have contributed to the presented pattern of relapse.

Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors.

The endocannabinoid system (ECS), and agonists acting on cannabinoid receptors (CBr), are known to regulate several physiological events in the brain, including modulatory actions on excitatory events probably through N-methyl-D-aspartate receptor (NMDAr) activity. Actually, CBr agonists can be neuroprotective. The synthetic CBr agonist WIN55,212-2 acts mainly on CB1 receptor. In turn, the mitochondrial toxin 3-nitropropionic acid (3-NP) produces striatal alterations in rats similar to those observed in the brain of Huntington's disease patients. Herein, the effects of WIN55,212-2 were tested on different endpoints of the 3-NP-induced toxicity in rat brain synaptosomes and striatal tissue. Motor activity was also evaluated. The 3-NP (1 mM)-induced mitochondrial dysfunction and lipid peroxidation was attenuated by WIN55,212-2 (1 µM) in synaptosomal fractions. The intrastriatal bilateral injection of 3-NP (500 nmol/µL) to rats increased lipid peroxidation and locomotor activity, augmented the rate of cell damage, and decreased the striatal density of neuronal cells. These alterations were accompanied by transcriptional changes in the NMDA (NR1 subunit) content. The administration of WIN55212-2 (1 mg/kg, i.p.) to rats for six consecutive days, before the 3-NP injection, exerted preventive effects on all alterations elicited by the toxin. The prevention of the 3-NP-induced NR1 transcriptional alterations by the CBr agonist together with the increase of CB1 content suggest an early reduction of the excitotoxic process via CBr activation. Our results demonstrate a protective role of WIN55,212-2 on the 3-NP-induced striatal neurotoxicity that could be partially related to the ECS stimulation and induction of NMDAr hypofunction, representing an effective therapeutic strategy at the experimental level for further studies.

Lipomatous/Extensively Vacuolated Ependymoma with Signet-Ring Cell-Like Appearance: Analysis of a Case with Extensive Literature Review.

"Lipomatous" and "extensively vacuolated" are descriptive captions that have been used to portray a curious subset of ependymomas distinctively bearing cells with a large vacuole pushing the nucleus to the periphery and, thus, simulating a signet-ring cell appearance. Here, we would like to report the first ependymoma of this kind in a Latin American institution. A 16-year-old boy experienced cephalea during three months. Magnetic resonance imaging scans showed a left paraventricular tumour which corresponded to anaplastic ependymoma. Intriguingly, it was also composed of cells with single or multiple hollow cytoplasmic vacuoles sometimes giving a signet-ring cell-like configuration. Immunolabeling of these showed membrane positivity for GFAP, PS100, and CD99, while Ki-67 expression was null. Ultrastructural examination of retrieved paraffin-embedded tissue showed the presence of scarce microlumina filled with microvilli but failed to demonstrate any content in such optically empty vacuoles as only scant granulofibrillary debris was observed. A schism prevails at present regarding these unusual morphological variants, being either "lipomatous" or "vacuolated" based mainly on the EMA immunoprofile. This, however, is a misappropriate approaching. Could it be that perhaps we are dealing with the same histopathological entity or it may simply happen that fixation and artefacts cannot allow for their proper identification?

An overview of the infection of CMV, HSV 1/2 and EBV in Mexican patients with glioblastoma multiforme.

Several risk factors are involved in glioblastoma, including cytomegalovirus (CMV). This research was carried out to determine the rate of CMV infection, as well as HSV 1/2 and EBV in brain tissue, in patients with glioblastomamultiforme (GBM). The tissues were tested using immunohistochemistry, PCR, in situ hybridization and real-time PCR. At least, one HHV was detected in 21/29 (72%) patients as follows: single infections with HSV-1/2 in 4/21 (19%), EBV in 6/21 (28.6%) and CMV in 1/21 (4.8%). Mixed viral infection, HSV-1/2 and EBV were detected in 4/21 patients (19%), CMV and EBV in 5/21 (23.8%), and HSV-1/2, EBV, and CMV in 1/21. The CMV viral load ranged from 3×102 to 4.33×105 genome/100ng of tissue. Genotype based on CMV gB was 3/7 where 2/3 was gB1 and 1/3 gB4. HSV, EBV and CMV were frequently found in brain tissues, more in mix in a population reported as highly seropositive.

Intraventricular Neurilemmoma (Schwannoma): Shall GFAP Immunostaining Be Regarded as a Histogenetical Tag or as a Mere Histomimetical Trait?

Neurilemmomas are benign neoplasms presumedly derived from Schwann cells which rarely originate within the central nervous system. Moreover, their intraventricular location has been seldom noticed with less than 30 cases reported worldwide. Here, we add another case study to the record as well as the fifth one in Latin American population. A 16-year-old boy without significant past clinical data debuted with headache and progressive left eye blindness during six months. Neuroimaging scans showed a bulky, multiloculated, intraventricular tumour emerging from the posterior horn of the left lateral ventricle. Microscopically, the lesion put on view the classical schwannian histology: spindle cells arranged in both compact and loosely textured areas. Verocay bodies were not present but vessel hyalinisation, pericellular reticulin, and senescent atypia were observed. The immunoperoxidase reactions were also consistent with neurilemmal differentiation; however, glial fibrillary acidic protein expression was widespread and unexpectedly seen. Traditionally conceived as "nerve sheath tumours" the dual immunophenotype herein demonstrated points to a different histogenetical pathway other than sheer Schwann cell derivation. As previously advised by some authors, neoplastic transformation from a multipotent stem cell may explain the occasional finding of these tumours in unconventional intracranial compartments.

Crush intraoperatory analysis in craniopharyngioma.

Intraoperative smear cytology provides a rapid and reliable intraoperative diagnosis and guidance to the neurosurgeon during surgical resection and lesion targeting. It also helps the surgeon to monitor and modify the approach at surgery. The aim of this article was a clinicopathological and cytomorphological intraoperative crush smear correlation in craniopharyngioma. Thirty craniopharyngiomas were included in this study. Twenty-seven cases were adaCP and only three cases were papCP. This series included 16 (53%) males and 14 (47%) females adult patients, aged from 15 to 86 years (median, 49 year). Two cases were frank errors, 12 cases showed partial correlation, 5 cases showed incomplete typing of the cell type, and 7 cases discrepancy in type of tumors. The percent error was 14%. Correlations with clinical details and radiological findings were helpful in improving the accuracy rate. Smear technique is a fairly accurate, relatively safe, rapid, simple, easily reproducible, and cost-effective tool to diagnose brain tumors. Smear cytology is of great value in intraoperative consultation of central nervous system pathology. The cytological aspects and smear patterns disclose important complementary diagnostic information for the histopathological examination.

Inguinal lymph nodal metastasis of myxopapillary ependymoma confirmed by fine-needle aspiration cytology, biopsy, and immunohistochemistry: case report.

Ependymoma (EP) rarely metastasizes outside the central nervous system. Inguinal nodule metastasis of EP more than 10 years after surgical resection and radiotherapy is extremely rare. We report a man aged 38 years who underwent surgery for lumbosacral myxopapillary EP at the age of 22 years and was treated with several cycles of radiotherapy. The patient was reoperated for residual tumor and received two complete cycles of radiotherapy for 11 years. Biopsies were always diagnosed as myxopapillary EP. Five years after the last surgical excision, the patient developed abdominal pain and inguinal lymphadenopathy. Biopsy was performed by fine-needle aspiration and was proven malignant epithelial neoplasm with a myxoid background, was diagnosed as metastasis of EP. Biopsy showed an anaplastic EP grade III. EP is often recurrent at the primary site but can seed on the entire cerebrospinal axis. We describe the clinical features of this rare lesion and particularly emphasize the need for long-term follow-up, for more than 10 years after the initial treatment, in patients with EP and malignant transformation after radiotherapy.

Coexistence between meningioma and tuberculosis: case report.

Intracranial tuberculoma generally presents as either solitary or multiple lesions in the brain parenchyma. These are characterized by a ring-enhancing area on either computerized tomography scans or magnetic resonance images. A 66 year-old female with a history of breast carcinoma at 41 years, treated with radical mastectomy and radio and chemotherapy, and rheumatoid arthritis, treated in the last 10 years, presented two months ago with occipital headache, nausea, cerebellar syndrome, alterations of speech, and memory loss. The TC scan showed occipital enhancement by contrast and surrounded by oedema, suggesting metastasis. Histology showed a benign meningioma with many multinuclear giant cells, granulomas, and central caseating necrosis. In addition, some classic plasma cells, mastocytes, and lymphocytes were also detected. The authors describe the unusual case of coexistence between an occipital meningioma and tuberculosis in the same area that resembled metastasis.

Chordoid meningioma: a report of ten cases.

Chordoid meningioma is a rare variant of meningioma with histological features resembling those of chordoma. This tumor has a great risk of recurrence and aggressive growth (WHO grade II). This study was done to document the clinical and pathological features of ten patients with chordoid meningioma who submitted to surgery at the National Institute of Neurology and Neurosurgery in Mexico City. Clinical, histological and immunohistochemical features were examined. The age range was from 30 to 67 years old (mean, 34.2 years). Seven patients were female and three male. The duration of symptoms varied from 3.5 months to 5 years (mean, 14.1 months). No systemic symptoms were noted. The tumor was localized in eight cases in the supratentorial compartments. Histologically, the tumors were characterized by strands and cords of meningothelial cells arranged in a mucinous stroma. Two of the ten tumors showed metaplasic changes, and seven showed brain invasion. Tumor cells demonstrated CK7, EMA and focal S-100 protein and Ep-CAM. Cytokeratin AE1/AE3, GFAP and synaptophysin were negative. The MIB-1 proliferative index was from 6 to 9% (mean 7.8). PCNA Li was 6 to 20% (mean, 14), and microvascular density was 6-16 (mean, 14.5). The mean rate of the MIB-1 labeling index in recurrences was 7.1% versus 6.33% for no tumor recurrence. Chordoid meningioma, World Health Organization grade II, is an uncommon variant of meningioma with a propensity for aggressive behavior and increased likelihood of recurrence. Chordoid meningiomas are predominantly tumors of young adults with a predilection for the supratentorial location. Intraventricular location and absence of systemic manifestations, despite the presence of abundant B-lymphocytes, mast cells and low MIB-1 LI, are some of the interesting findings in the present series that need further study. Hence, a larger number of cases with adequate follow-up data need to be studied further to establish the clinical relevance of this variant.

Clinicopathologic and immunohistochemical study of choroid plexus tumors: single-institution experience in Mexican population.

In recent years, few studies have specifically focused on only histological features in choroid plexus tumors. We retrospectively reviewed the clinicopathologic and histological features in 37 patients with choroid plexus tumors and correlated these with glial fibrillary acidic protein (GFAP) expression and proliferation cell nuclear antigen (PCNA), p53, p21, and Rb labeling indexes, with special attention to tumor recurrence/regrowth. The study included 24 choroid plexus papillomas (CPPs), 4 atypical choroid plexus papillomas (ACPPs), and 9 choroid plexus carcinomas (CPCs). Patient age ranged from 15 to 70 years (mean 44 years). Most of the choroid plexus tumors were located in the IV ventricle. Recurrence was observed in 21 (52%) cases, 14 of which were CPP and 7 of which were CPC (P = 0.032). Histologic findings included major necrosis, fibrosis and psammoma bodies, amyloid deposits, inflammation, and thick vessels in recurrent tumors. The PCNA labeling index was 52.04 + or - 13.92 in CPPs, 76.50 + or - 17 in ACPPs, and 95.22 + or - 21.34 in CPCs (P = 0.009), and 67.43 + or - 28 in recurrent tumors. Similar values were found for p53, p21, and Rb. Furthermore, we observed that these presented more histological changes, adding, than nonrecurrent tumors, as well as a higher proliferation index of cell-cycle markers, and these were dependent predictor factors of survival. Recurrent tumors showed a different biological behavior than nonrecurrent tumors, but histological observations showed no mitotic features in order to consider them as grade II.

Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.

It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage.