Geographical evaluation of Neuroparacoccidioidomycosis and Paracoccidioidomycosis in Southern Brazil.

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis among immunocompetent patients in Latin America. This study aimed to describe the expansion over time and the geographical distribution of confirmed Neuroparacoccidioidomycosis (NPCM) and PCM cases, and relate it to environmental characteristics such as climate, soil types and coffee crops. This was a retrospective study of autopsy and biopsy reports between 1951 and 2014 from the Medical Pathology Section of the Hospital de Clinicas, Universidade Federal do Paraná (UFPR), Curitiba, Southern Brazil. PCM was predominant in male agricultural workers. PCM cases predominated in areas with subtropical climate with hot summers in North West Parana state. NPCM cases were distributed statewide more frequent in rural than metropolitan area. There was no association with climate, soil type, or coffee crop culture. Most of the PCM cases were in the metropolitan area of the capital, chiefly due to migration fluxes. Even though the history is predominantly agricultural, PCM cases were distributed mainly in the metropolitan area of the state capital, there was no association with climate and soil. NPCM cases were numerically more frequent in rural than metropolitan area.

Overexpression of mTOR and p(240-244)S6 in IDH1 Wild-Type Human Glioblastomas Is Predictive of Low Survival.

PI3K/Akt/mTOR pathway activation is a hallmark of high-grade gliomas, which prompted clinical trials for the use of PI3K and mTOR inhibitors. However, the poor results in the original trials suggested that better patient profiling was needed for such drugs. Thus, accurate and reproducible monitoring of mTOR complexes can lead to improved therapeutic strategies. In this work, we evaluated the expression and phosphorylation of mTOR, RAPTOR, and rpS6 in 195 human astrocytomas and 30 normal brain tissue samples. The expression of mTOR increased in glioblastomas, whereas mTOR phosphorylation, expression of RAPTOR, and expression and phosphorylation of rpS6 were similar between grades. Interestingly, the overexpression of total and phosphorylated mTOR as well as phosphorylated rpS6 (residues 240-244) were associated with wild-type IDH1 only glioblastomas. The expression and phosphorylation of mTOR and phosphorylation of rpS6 at residues 240-244 were associated with a worse prognosis in glioblastomas. Our results suggest that mTOR and rpS6 could be used as markers of overactivation of the PI3K-mTOR pathway and are predictive factors for overall survival in glioblastomas. Our study thus suggests that patients who harbor IDH1 wild-type glioblastomas might have increased benefit from targeted therapy against mTOR.

Autopsy and biopsy study of paracoccidioidomycosis and neuroparacoccidioidomycosis with and without HIV co-infection.

Paracoccidioidomycosis (PCM) is a systemic mycosis prevalent among immunocompetent patients in Latin America. This study aimed to describe the frequency, demographics and clinical characteristics of central nervous system PCM (NPCM) and PCM in an endemic region, and the impact of human immunosuppression virus (HIV) co-infection. This was a retrospective study of autopsy and biopsy reports from the Medical Pathology Section of the Hospital de Clinicas, UFPR, Curitiba, Southern Brazil, between 1951 and 2014. PCM was present in 0.1% of 378,323 cases examined, with 5.7% being NPCM. Infection was prevalent in working-age men, agricultural workers and rural residents. Numbers of HIV autopsy cases increased over time, while those of PCM cases decreased. Prevalence of co-infection of HIV/PCM and HIV/NPCM was 1.6%, and 0.4%, respectively. Adrenals were affected more frequently in the NPCM group compared with the PCM group. Mortality was higher on NPCM group. The clinical course of PCM in HIV patients resembles an acute/sub-acute infection. Association of NPCM and HIV is rare, while diagnosis of NPCM is difficult, it should be considered a differential diagnosis in HIV patients who live in, or have visited, endemic areas and present with neurological symptoms.

Neurological and multiple organ involvement due to Paracoccidioides brasiliensis and HIV co-infection diagnosed at autopsy.

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent systemic mycosis among immunocompetent patients in Latin America; it is rare in immunocompromised patients. The estimated frequency of central nervous system (CNS) involvement in the HIV/PCM population was 2.5%. We report a case of HIV/P. brasiliensis co-infection, with neurological (NPCM) and multiple organ involvement, indicating a diagnosis of AIDS. PCM diagnosis was established during the autopsy. This is the first described case of HIV/P. brasiliensis co-infection with CNS involvement diagnosed at autopsy. In conclusion, the diagnosis of NPCM is challenging, and it must be considered in the differential diagnosis in HIV-positive patients who reside in or have visited areas in which the condition is endemic and who present with neurological symptoms.

Evaluation of Akt and RICTOR Expression Levels in Astrocytomas of All Grades.

The mammalian target of rapamycin (mTOR) binds to several protein partners and forms two complexes, termed mTOR complexes 1 and 2 (mTORC1/2), that differ in components, substrates, and regulation. mTORC2 contains the protein Rapamycin-insensitive companion of mTOR (RICTOR); phosphorylates kinases of the AGC family, such as Akt; and controls the cytoskeleton. Even though the regulation of mTORC2 activity remains poorly understood, the hyperactivation of this signaling pathway has been shown to contribute to the oncogenic properties of gliomas in experimental models. In this work, we evaluated expression and phosphorylation of Akt, and expression of RICTOR and Ki-67 in 195 human astrocytomas of different grades (38 cases of grade I, 49 grade II, 15 grade III, and 93 grade IV) and 30 normal brains. Expression and phosphorylation of Akt increased with histological grade and correlated with a worse overall survival in glioblastomas (GBMs). RICTOR was overexpressed in grade I and II astrocytomas and demonstrated a shift to nuclear localization in GBMs. Nuclear RICTOR was associated to increased proliferation in GBMs. Our results point to an increase in total and phosphorylated Akt in high-grade gliomas and to a possible role of RICTOR in proliferations of high-grade GBM cells.

Reactivation of herpes simplex virus-1 following epilepsy surgery.

PURPOSE: The present study reports a case of encephalitis due to herpes simplex virus-1 (HSV-1), following surgical manipulation of the site of a primary infection. METHODS: Herpes simplex virus-1 infection was confirmed by CSF PCR and DNA sequencing. RESULTS: The patient was an 11-year-old girl who required temporal lobe surgery for epilepsy. She had meningoencephalitis due to HSV at the age of 20 months, and she was treated with acyclovir. Three years later, the patient developed uncontrolled seizures that became more frequent and changed in character at 11 years of age. On the 12th postoperative day, she developed fever and seizures, and she was diagnosed with HSV-1 by positive CSF PCR. She was treated with acyclovir (30 mg/kg/day for 21 days). In this report, we describe the patient and review the relevant literature. CONCLUSION: The authors stress the potential risk of reactivation of HSV encephalitis after intracranial surgery. Herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever.

Ganglioglioma da medula espinhal: relato de caso / Spinal cord ganglioglioma: case report

Os gangliogliomas säo tumores raros do SNC, compreendendo apenas 2,7 a 3,8 por cento dos tumores primários do SNC e as lesöes medulares perfazem 7,6 a 14,3 por cento do total de gangliogliomas. O tratamento preconizado pela literatura é a ressecçäo total, ficando a radioterapia reservada apenas em casos de progressäo da doença após a cirurgia ou em casos de lesöes de comportamento histológico mais agressivo. Neste artigo relatamos um caso de uma paciente portadora de um ganglioglioma medular envolvendo os níveis T5 a T10 que foi submetida a tratamento cirúrgico em nosso serviço, sendo também realizada revisäo da literatura analisando diversos aspectos, incluindo as diversas modalidades de tratamento indicadas neste tipo incomum de lesäo.

Epilepsia do lobo temporal mesial, um estudo comparativo de 24 casos / The mesial temporal lobe epilepsy, a study of 24 cases

A epilepsia do lobo temporal mesial (E.L.T.M./Engle Jr, Neurology 1993) é definida pela presença de crises parciais simples ou complexas com ou sem generalizaçäo secundária, originadas na porçäo mesial do lobo temporal, ou seja no hipocampo e amígdala. Visando delinear as características clínicas, eletrencefalográficas e de imagem desta forma de epilepsia, foram estudados 2 grupos de pacientes: um com E.L.T.M. (n=12), e outro com epilepsia generalizada idiopática (n=12). A idade média ñ desvio padräo , foi de 37ñ9 e 23ñ4 anos. A idade média do início das crises foi de 8.72416 e 11ñ1 anos e a proporçäo masculini/feminino de 5/7, e 5/7; nos grupos com E.L.T.M. e epilepsia generalizada idiopática, respectivamente. O grupo com E.L.T.M. apresentou crises parciais complexas (nñ12), parciais simples (n=9), parciais com generalizaçäo (n=8). O grupo com epilepsia generalizada idiopática apresentou crises generalizadas tônico-clônicas (n=12), mioclônicas (n=8). No grupo dos pacientes com epilepsia generalizada idiopática, 5 tinham epilepsia mioclônica juvenil, 4 epilepsia juvenil com ausências, 2 epilepsia infantil com ausências e 1 epilepsia mioclônica infantil. O grupo com E.L.T.M. apresentou 6 pacientes com foco temporal direito ao EEG, 3 pacientes com foco temporal esquerdo, um paciente com foco bitemporal independente e 2 pacientes com EEG normal. Em 4 pacientes com epilepsia generalizada idiopática, ocorreram ponta-onda e complexos poli ponta onda no EEG, tendo sido normal em 8 pacientes. No grupo com E.L.T.M. 8 pacientes tinham tomografia normal, 1 com atrofia do lobo temporal direito e outro com atrofia do lobo temporal esquerdo. A ressonância magnética mostrou menor volumetria hipocampal esquerda em 3 pacientes e direita em 4, sendo que um paciente foi normal; 4 pacientes com alteraçäo na ressonância magnética tinham tomografia normal. Um paciente do grupo das epilepsias generalizadas apresentou na tomografia, displasia fibrosa periorbital esquerda. A carbamazepina foi usada em 12, o valproato de sódio em 3 e a lamotrigina em 1 paciente do grupo das E.L.T.M.; apenas 2 pacientes obtiveram controle de crises. Os 12 pacientes do grupo com epilepsia generalizada foram manejados com valproato de sódio. Dois pacientes do grupo com E.L.T.M. refratária, foram submetidos a ressecçäo cirúrgica da área epileptogênica. A E.L.T.M. apresenta aspectos específicos do ponto de vista clínico e estrutural, especialmente definidos pela ressonância magnética