The Important Role of Hemispherotomy for Rasmussen Encephalitis: Clinical and Functional Outcomes.

BACKGROUND: Rasmussen encephalitis (RE) is characterized by pharmacoresistant epilepsy and progressive neurological deficits concurrent with unilateral hemispheric atrophy. Evidence of an inflammatory autoimmune process has been extensively described in the literature; however, the precise etiology of RE is still unknown. Despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, surgical disconnection of the affected hemisphere is considered the treatment of choice for these patients. The aim of this study was to report a series of children and adolescents who underwent hemispheric surgery (HS) for the treatment of RE, analyzing their clinical, electrographic, and neuroimaging features pre-operatively, as well as their postoperative status, including seizure and functional outcomes. METHODS: All patients with RE who underwent HS in the Epilepsy Surgery Center (CIREP) of the University Hospital of Ribeirão Preto Medical School, between 1995 and 2020 were retrospectively reviewed. Preoperative and postoperative analyses included gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery; duration of epilepsy; surgical complications; duration of follow-up; histopathological findings; and postoperative seizure, cognitive, and functional outcomes. RESULTS: Forty-four patients were evaluated. Mean age at seizure onset and epilepsy duration was 6 years and 2.5 years, respectively. Mean age at surgery was 9 years, with an average follow-up ranging from 3 months to 23 years. All patients presented with severe epilepsy and distinct neurological abnormalities on MRI. Before HS, different degrees of abnormal intellectual performance as well as hemiparesis were seen in 86% and 90%, respectively. Histopathology examination confirmed this diagnosis in 95% patients. At the last follow-up, 68% of patients were seizure free, and 70% were classified as Engel Class I or II. Postoperatively, the cognitive status remained unchanged in 64% of patients. Likewise, the gross motor function remained unchanged in 54% of patients and 74% had functional hand ability after HS. CONCLUSIONS: Considering the progressive damage course of RE, hemispheric surgery should be offered to pediatric patients. It has manageable risks and results in good seizure outcome, and the preoperative functional status of these children is often preserved (even when the left hemisphere is involved), thus improving their quality of life.

MRI radiomics for the prediction of recurrence in patients with clinically non-functioning pituitary macroadenomas.

Twelve to 66% of patients with clinically non-functioning pituitary adenoma (NFPA) experience tumor recurrence 1-5 years after the first surgery. Nevertheless, there is still no recurrence prediction factor concisely established and reproduced in the literature for NFPA management. The present study evaluates the prognostic value of MRI Radiomics features combined with machine learning models to assess recurrence after the first surgery in patients with clinically non-functioning pituitary adenomas (NFPA). We carried out a retrospective study on 27 patients with NFPA, 10 patients having experienced tumor recurrence after the first surgery and 17 who did not. Preoperative 3D T1 contrast-enhanced MR images of patients were used to extract up to 255 Radiomics features from two and three-dimensional segmented regions. Additionally, gender, age at first surgery, and the presence of remnant tumor tissue were investigated to find the correlation with NFPA recurrence. Conventional statistics tests were used to evaluate whether the outcome patient groups (stable and recurrent) were different considering each feature individually. Additionally, five well-known machine-learning algorithms were used in combination with Radiomic features to classify recurrent and stable lesions. We found statistical evidence (p < 0.02) for 6 two-dimensional and 13 three-dimensional radiomic features. We achieved accuracies of up to 96.3% for 3D-feature based models and up to 92.6% accuracies for 2D-feature based models. 3D-feature based models achieved better performances using considerably fewer features when compared to 2D-feature based models. We concluded that Radiomics have the potential of NFPA recurrence prediction after the first surgery. Three-dimensional Radiomics have superior discrimination power to predict NFPA recurrence than two-dimensional radiomic features. Finally, the combination of Radiomics with machine-learning algorithms can offer computational models capable of non-invasive, unbiased, and quick assessment that might improve the prediction of NFPA recurrence.

A Synthetic Snake-Venom-Based Tripeptide Protects PC12 Cells from the Neurotoxicity of Acrolein by Improving Axonal Plasticity and Bioenergetics.

The synthetic peptide p-BTX-I is based on the native peptide (formed by glutamic acid, valine and tryptophan) isolated from Bothrops atrox venom. We have previously demonstrated its neuroprotective and neurotrophic properties in PC12 cells treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Now, we have investigated the neuroprotective effects and mechanisms of p-BTX-I against the toxicity of acrolein in PC12 cells. Studies have demonstrated that acrolein might play an important role in the etiology of Alzheimer's disease (AD), which is characterized by neuronal and synaptic loss. Our results showed that not only acrolein reduced cell differentiation and cell viability, but also altered the expression of markers of synaptic communication (synapsin I), energy metabolism (AMPK-α, Sirt I and glucose uptake), and cytoskeleton (ß-III-tubulin). Treatment with p-BTX-I increased the percentage of differentiation in cells treated with acrolein and significantly attenuated cell viability loss, besides counteracting the negative effects of acrolein on synapsin I, AMPK-α, Sirt I, glucose uptake, and ß-III-tubulin. Additionally, p-BTX-I alone increased the expression of apolipoprotein E (apoE) gene, associated with the proteolytic degradation of ß-amyloid peptide aggregates, a hallmark of AD. Taken together, these findings demonstrate that p-BTX-I protects against acrolein-induced neurotoxicity and might be a tool for the development of novel drugs for the treatment of neurodegenerative diseases.

Imbalance of Steroid Hormones in Hamsters Infected with Schistosoma mansoni.

OBJECTIVE: Schistosomiasis is a debilitating disease that affects 200 million people worldwide. Schistosoma haematobium and Schistosoma mansoni are the major causative agents of this disease. Cancer-association and infertility-association in Schistosoma haematobium infection have already been described and it is known that the parasite produces a catechol-estrogen molecule that induces a hormonal imbalance in the host. METHODS: In order to better understand the relation of hormonal imbalance in experimental Schistosoma mansoni infection, we investigated a serum panel of steroid hormones in Schistosoma mansoni infected hamsters. RESULTS: We found a decrease in the serum levels of Estradiol (E2), Testosterone and Progesterone in infected females and an increase of Testosterone and a decrease in Progesterone in infected males in comparison with controls. CONCLUSION: These results indicate that S. mansoni alters the levels of steroid hormones in infected males and females and it will increase the repertoire of data about the host-parasite molecular interplay and its relation with the endocrine system.

Intravoxel incoherent motion MRI in neurological and cerebrovascular diseases.

Intravoxel Incoherent Motion (IVIM) is a recently rediscovered noninvasive magnetic resonance imaging (MRI) method based on diffusion-weighted imaging. It enables the separation of the intravoxel signal into diffusion due to Brownian motion and perfusion-related contributions and provides important information on microperfusion in the tissue and therefore it is a promising tool for applications in neurological and neurovascular diseases. This review focuses on the basic principles and outputs of IVIM and details it major applications in the brain, such as stroke, tumor, and cerebral small vessel disease. A bi-exponential model that considers two different compartments, namely capillaries, and medium-sized vessels, has been frequently used for the description of the IVIM signal and may be important in those clinical applications cited before. Moreover, the combination of IVIM and arterial spin labeling MRI enables the estimation of water permeability across the blood-brain barrier (BBB), suggesting a potential imaging biomarker for disrupted-BBB diseases.

A synthetic snake-venom-based tripeptide (Glu-Val-Trp) protects PC12 cells from MPP+ toxicity by activating the NGF-signaling pathway.

Venom small peptides that target neurotrophin receptors might be beneficial in neurodegeneration, including Parkinsons disease (PD). Their small size, ease of synthesis, structural stability and target selectivity make them important tools to overcome the limitations of endogenous neurotrophins as therapeutic agents. Additionally, they might be optimized to improve resistance to enzymatic degradation, bioavailability, potency and, mainly, lipophilicity, important to cross the blood brain barrier (BBB). Here, we evaluated the neuroprotective effects and mechanisms of the synthetic snake-venom-based peptide p-BTX-I (Glu-Val-Trp) in PC12 cells treated with MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that induces Parkinsonism in vivo. The peptide p-BTX-I induced neuritogenesis, which was reduced by (i) k252a, antagonist of the NGF-selective receptor, trkA (tropomyosin receptor kinase A); (ii) LY294002, inhibitor of the PI3 K/AKT pathway and (iii) U0126, inhibitor of the MAPK-ERK pathway. Besides that, p-BTX-I also increased the expression of GAP-43 and synapsin, which are molecular markers of axonal growth and synaptic communication. In addition, the peptide increased the viability and differentiation of cells exposed to MPP+, known to inhibit neuritogenesis. Altogether, our findings suggest that the synthetic peptide p-BTX-I protects PC12 cells from MPP+ toxicity by a mechanism that mimics the neurotrophic action of NGF. Therefore, the molecular structure of p-BTX-I might be relevant in the development of drugs aimed at restoring the axonal connectivity in neurodegenerative processes.

Zika Virus Meningoencephalitis in an Immunocompromised Patient.

The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, meningoencephalitis, and Guillain-Barré syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase-polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections.

Using network dynamic fMRI for detection of epileptogenic foci.

BACKGROUND: Epilepsy is one of the most prevalent neurological disorders. It remains medically intractable for about one-third of patients with focal epilepsy, for whom precise localization of the epileptogenic zone responsible for seizure initiation may be critical for successful surgery. Existing fMRI literature points to widespread network disturbances in functional connectivity. Per previous scalp and intracranial EEG studies and consistent with excessive local synchronization during interictal discharges, we hypothesized that, relative to same regions in healthy controls, epileptogenic foci would exhibit less chaotic dynamics, identifiable via entropic analyses of resting state fMRI time series. METHODS: In order to first validate this hypothesis on a cohort of patients with known ground truth, here we test individuals with well-defined epileptogenic foci (left mesial temporal lobe epilepsy). We analyzed voxel-wise resting-state fMRI time-series using the autocorrelation function (ACF), an entropic measure of regulation and feedback, and performed follow-up seed-to-voxel functional connectivity analysis. Disruptions in connectivity of the region exhibiting abnormal dynamics were examined in relation to duration of epilepsy and patients' cognitive performance using a delayed verbal memory recall task. RESULTS: ACF analysis revealed constrained (less chaotic) functional dynamics in left temporal lobe epilepsy patients, primarily localized to ipsilateral temporal pole, proximal to presumed focal points. Autocorrelation decay rates differentiated, with 100 % accuracy, between patients and healthy controls on a subject-by-subject basis within a leave-one-subject out classification framework. Regions identified via ACF analysis formed a less efficient network in patients, as compared to controls. Constrained dynamics were linked with locally increased and long-range decreased connectivity that, in turn, correlated significantly with impaired memory (local left temporal connectivity) and epilepsy duration (left temporal - posterior cingulate cortex connectivity). CONCLUSIONS: Our current results suggest that data driven functional MRI methods that target network dynamics hold promise in providing clinically valuable tools for identification of epileptic regions.

Sonic Hedgehog mutations are not a common cause of congenital hypopituitarism in the absence of complex midline cerebral defects.

CONTEXT AND OBJECTIVE: Sonic Hedgehog (SHH) and GLI2, an obligatory mediator of SHH signal transduction, are holoprosencephaly (HPE)-associated genes essential in pituitary formation. GLI2 variants have been found in patients with congenital hypopituitarism without complex midline cerebral defects (MCD). However, data on the occurrence of SHH mutations in these patients are limited. We screened for SHH and GLI2 mutations or copy number variations (CNV) in patients with congenital hypopituitarism without MCD or with variable degrees of MCD. PATIENTS AND METHODS: Detailed data on clinical, laboratory and neuroimaging findings of 115 patients presenting with congenital hypopituitarism without MCD, septo-optic dysplasia or HPE were analysed. The SHH and GLI2 genes were directly sequenced, and the presence of gene CNV was analysed by multiplex ligation-dependent probe amplification (MLPA). RESULTS: Anterior pituitary deficiency was found in 74% and 53% of patients with SOD or HPE, respectively. Diabetes insipidus was common in patients with HPE (47%) but infrequent in patients with congenital hypopituitarism or SOD (7% and 8%, respectively). A single heterozygous nonsense SHH mutation (p.Tyr175Ter) was found in a patient presenting with hypopituitarism and alobar HPE. No other SHH mutations or CNV were found. Nine GLI2 variations (8 missense and 1 frameshift) including a homozygous and a compound heterozygous variation were found in patients with congenital hypopituitarism or SOD, but not in HPE patients. No GLI2 CNV were found. CONCLUSION: SHH mutations or copy number variations are not a common cause of congenital hypopituitarism in patients without complex midline cerebral defects. GLI2 variants are found in some patients with congenital hypopituitarism without complex midline cerebral defects or septo-optic dysplasia. However, functional analyses of these variants are needed to strengthen genotype-phenotype relationship.

Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia.

Increasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. The aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12months of adjuvant treatment with minocycline (200mg/d) or placebo. MRI (1.5T) and [(99m)Tc]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. The VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. In addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period.

Trigeminal neuralgia as the sole symptom of pancreatic cancer.

Trigeminal neuralgia (TN) is a condition characterized by brief electric shock-like pains in the topography of the trigeminal nerve. The most common cause of this disorder is the compression of the trigeminal nerve root by tortuous or aberrant vessels. In this report, we describe a patient who presented due to paroxysmal and excruciating facial pain that was found to be secondary to pancreatic cancer.

Supine sleep and positional sleep apnea after acute ischemic stroke and intracerebral hemorrhage

OBJECTIVE: Obstructive sleep apnea is frequent during the acute phase of stroke, and it is associated with poorer outcomes. A well-established relationship between supine sleep and obstructive sleep apnea severity exists in non-stroke patients. This study investigated the frequency of supine sleep and positional obstructive sleep apnea in patients with ischemic or hemorrhagic stroke. METHODS: Patients who suffered their first acute stroke, either ischemic or hemorrhagic, were subjected to a full polysomnography, including the continuous monitoring of sleep positions, during the first night after symptom onset. Obstructive sleep apnea severity was measured using the apnea-hypopnea index, and the NIHSS measured stroke severity. RESULTS: We prospectively studied 66 stroke patients. The mean age was 57.6±11.5 years, and the mean body mass index was 26.5±4.9. Obstructive sleep apnea (apnea-hypopnea index >5) was present in 78.8% of patients, and the mean apnea-hypopnea index was 29.7±26.6. The majority of subjects (66.7%) spent the entire sleep time in a supine position, and positional obstructive sleep apnea was clearly present in the other 23.1% of cases. A positive correlation was observed between the NIHSS and sleep time in the supine position (r s = 0.5; p<0.001). CONCLUSIONS: Prolonged supine positioning during sleep was highly frequent after stroke, and it was related to stroke severity. Positional sleep apnea was observed in one quarter of stroke patients, which was likely underestimated during the acute phase of stroke. The adequate positioning of patients during sleep during the acute phase of stroke may decrease obstructive respiratory events, regardless of the stroke subtype.

Release of NO from a nitrosyl ruthenium complex through oxidation of mitochondrial NADH and effects on mitochondria.

Nitrosyl ruthenium complexes are promising NO donor agents with numerous advantages for the biologic applications of NO. We have characterized the NO release from the nitrosyl ruthenium complex [Ru(NO(2))(bpy)(2)(4-pic)](+) (I) and the reactive oxygen/nitrogen species (ROS/RNS)-mediated NO actions on isolated rat liver mitochondria. The results indicated that oxidation of mitochondrial NADH promotes NO release from (I) in a manner mediated by NO(2) formation (at neutral pH) as in mammalian cells, followed by an oxygen atom transfer mechanism (OAT). The NO released from (I) uncoupled mitochondria at low concentrations/incubation times and inhibited the respiratory chain at high concentrations/incubation times. In the presence of ROS generated by mitochondria NO gave rise to peroxynitrite, which, in turn, inhibited the respiratory chain and oxidized membrane protein-thiols to elicit a Ca(2+)-independent mitochondrial permeability transition; this process was only partially inhibited by cyclosporine-A, almost fully inhibited by the thiol reagent N-ethylmaleimide (NEM) and fully inhibited by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). These actions correlated with the release of cytochrome c from isolated mitochondria as detected by Western blotting analysis. These events, typically involved in cell necrosis and/or apoptosis denote a potential specific action of (I) and analogs against tumor cells via mitochondria-mediated processes.

Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease / Degeneração hepatocerebral adquirida e encefalopatia hepática: correlações e variedade de apresentações clínicas na doença hepática evidente e subclínica

Acquired hepatocerebral degeneration (AHD) and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE) can be even more complicated. We describe three cases of AHD (two having HE) with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.

A degeneração hepatocerebral adquirida (AHD) e a degeneração hepatolenticular podem ter apresentações clínicas semelhantes, mas quando uma doença hepática crônica e achados motores atípicos coexistem, a distinção entre AHD e encefalopatia hepática (HE) pode ser ainda mais complicada. Descrevemos três casos de AHD (dois tendo HE) com diferentes achados em neuroimagem, doenças hepáticas distintas e apresentações motoras semelhantes, todos com hipertensão arterial e perda de peso antes das manifestações motoras. O diagnóstico e a fisiopatologia são comentados e comparados com relatos prévios. Concluímos que existem muitas correlações entre HE, degeneração hepatolenticular e AHD, mas a sobreposição de HE e AHD pode ser mais comum dependendo do conhecimento clínico e da acurácia dos critérios diagnósticos adotados para cada enfermidade. Como a AHD não é considerada prioridade na lista de transplante hepático, o prognóstico dos pacientes com AHD permanece ruim, e a interrupção do fluxo nos shunts portossistêmicos deve ser sempre considerada.

Utility of ictal single photon emission computed tomography in mesial temporal lobe epilepsy with hippocampal atrophy: a randomized trial.

BACKGROUND: The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). OBJECTIVE: To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. METHODS: MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. RESULTS: The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). CONCLUSION: Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.

A comparison between magnetic resonance angiography at 3 teslas (time-of-flight and contrast-enhanced) and flat-panel digital subtraction angiography in the assessment of embolized brain aneurysms

PURPOSE: To compare the time-of-flight and contrast-enhanced- magnetic resonance angiography techniques in a 3 Tesla magnetic resonance unit with digital subtraction angiography with the latest flat-panel technology and 3D reconstruction in the evaluation of embolized cerebral aneurysms. INTRODUCTION: Many embolized aneurysms are subject to a recurrence of intra-aneurismal filling. Traditionally, imaging surveillance of coiled aneurysms has consisted of repeated digital subtraction angiography. However, this method has a small but significant risk of neurological complications, and many authors have advocated the use of noninvasive imaging methods for the surveillance of embolized aneurysms. METHODS: Forty-three aneurysms in 30 patients were studied consecutively between November 2009 and May 2010. Two interventional neuroradiologists rated the time-of-flight-magnetic resonance angiography, the contrast-enhanced-magnetic resonance angiography, and finally the digital subtraction angiography, first independently and then in consensus. The status of aneurysm occlusion was assessed according to the Raymond scale, which indicates the level of recanalization according to degrees: Class 1: excluded aneurysm; Class 2: persistence of a residual neck; Class 3: persistence of a residual aneurysm. The agreement among the analyses was assessed by applying the Kappa statistic. RESULTS: Inter-observer agreement was excellent for both methods (K = 0.93; 95 percent CI: 0.84-1). Inter-technical agreement was almost perfect between time-of-flight-magnetic resonance angiography and digital subtraction angiography (K = 0.98; 95 percent CI: 0.93-1) and between time-of-flight-magnetic resonance angiography and contrast-enhanced-magnetic resonance angiography (K = 0.98; 95 percent CI: 0.93-1). Disagreement occurred in only one case (2.3 percent), which was classified as Class I by time-of-flight-magnetic resonance angiography and Class II by digital subtraction angiography. The agreement between contrast-enhanced-magnetic resonance angiography and digital subtraction angiography was perfect (K = 1; 95 percent CI: 1-1). In three patients, in-stent stenosis was identified by magnetic resonance angiography but not confirmed by digital subtraction angiography. CONCLUSION: Digital subtraction angiography and both 3T magnetic resonance angiography techniques have excellent reproducibility for the assessment of aneurysms embolized exclusively with coils. In those cases also treated with stent remodeling, digital subtraction angiography may still be necessary to confirm eventual parent artery stenosis, as identified by magnetic resonance angiography.

Endovascular therapy for selected (most non-surgical) intracranial aneurysms in a Brazilian University Hospital / Tratamento endovascular de aneurismas selecionados (maioria não cirúrgicos) em um hospital universitário brasileiro

OBJECTIVE: The objective of this study was to evaluate technical, clinical and angiographic results of a nonsurgical series of intracranial aneurysms treated by endovascular approach at Hospital das Clínicas of Medical School of Ribeirão Preto - University of São Paulo. METHOD: Between August 2005 and November 2008, 137 aneurysms in 106 patients were endovascularly treated. Of these, 101 were unruptured in 75 patients and 36 aneurysms in 31 patients were treated during the acute phase. The data were prospectively studied. RESULTS: Sixty three aneurysms (46 percent) were treated with coils alone, 52 (38 percent) with balloon remodeling, 15 (10.9 percent) with stent remodeling, and 7 (5.1 percent) with therapeutic occlusion of the internal carotid artery. Six clinical complications (5.7 percent) were related to the procedures, 3 (2.8 percent) transitory and 3 (2.8 percent) permanent. Angiographic follow-up was available for 97 aneurysms (70.8 percent), clinical monitoring for 77 patients (72.6 percent) and telephone contact for 97 (91.5 percent). CONCLUSION: The technical, clinical and angiographic results found in this study are similar to those reported in the literature.

OBJETIVO: Nosso objetivo foi avaliar os resultados técnicos, clínicos e angiográficos de uma série de aneurismas intracranianos não cirúrgicos tratados por via endovascular no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e comparar com os dados disponíveis na literatura atualmente. MÉTODO: Entre agosto de 2005 e novembro de 2008, 137 aneurismas foram tratados por via endovascular em 106 pacientes. Destes, 101 eram não rotos em 75 pacientes e 36 aneurismas foram tratados em 31 pacientes durante a fase aguda de ruptura. Os dados foram incluídos de maneira prospectiva. RESULTADOS: Sessenta e três aneurismas (46 por cento) foram tratados com técnica simples, 52 (38 por cento) com remodelagem por balão, 15 (10,9 por cento) com remodelagem por stent e 7 (5,1 por cento) por oclusão terapêutica da carótida interna. Seis complicações clínicas ocorreram (5,7 por cento), 3 (2,8 por cento) transitórias e 3 (2,8 por cento) permanentes. Seguimento angiográfico foi realizado para 97 aneurismas (70,8 por cento), clínico para 77 pacientes (70,8 por cento) e contato telefônico para 97 pacientes (91,5 por cento). CONCLUSÃO: Os resultados encontrados nesta série, em termos técnicos, clínicos e angiográficos, são semelhantes aos encontrados na literatura.

Impact of adenosine nucleotide translocase (ANT) proline isomerization on Ca2+-induced cysteine relative mobility/mitochondrial permeability transition pore.

Mitochondrial membrane carriers containing proline and cysteine, such as adenine nucleotide translocase (ANT), are potential targets of cyclophilin D (CyP-D) and potential Ca(2+)-induced permeability transition pore (PTP) components or regulators; CyP-D, a mitochondrial peptidyl-prolyl cis-trans isomerase, is the probable target of the PTP inhibitor cyclosporine A (CsA). In the present study, the impact of proline isomerization (from trans to cis) on the mitochondrial membrane carriers containing proline and cysteine was addressed using ANT as model. For this purpose, two different approaches were used: (i) Molecular dynamic (MD) analysis of ANT-Cys(56) relative mobility and (ii) light scattering techniques employing rat liver isolated mitochondria to assess both Ca(2+)-induced ANT conformational change and mitochondrial swelling. ANT-Pro(61) isomerization increased ANT-Cys(56) relative mobility and, moreover, desensitized ANT to the prevention of this effect by ADP. In addition, Ca(2+) induced ANT "c" conformation and opened PTP; while the first effect was fully inhibited, the second was only attenuated by CsA or ADP. Atractyloside (ATR), in turn, stabilized Ca(2+)-induced ANT "c" conformation, rendering the ANT conformational change and PTP opening less sensitive to the inhibition by CsA or ADP. These results suggest that Ca(2+) induces the ANT "c" conformation, apparently associated with PTP opening, but requires the CyP-D peptidyl-prolyl cis-trans isomerase activity for sustaining both effects.

Ca(2+) binding to c-state of adenine nucleotide translocase (ANT)-surrounding cardiolipins enhances (ANT)-Cys(56) relative mobility: a computational-based mitochondrial permeability transition study.

The oxidation of critical cysteines/related thiols of adenine nucleotide translocase (ANT) is believed to be an important event of the Ca(2+)-induced mitochondrial permeability transition (MPT), a process mediated by a cyclosporine A/ADP-sensitive permeability transition pores (PTP) opening. We addressed the ANT-Cys(56) relative mobility status resulting from the interaction of ANT/surrounding cardiolipins with Ca(2+) and/or ADP by means of computational chemistry analysis (Molecular Interaction Fields and Molecular Dynamics studies), supported by classic mitochondrial swelling assays. The following events were predicted: (i) Ca(2+) interacts preferentially with the ANT surrounding cardiolipins bound to the H4 helix of translocase, (ii) weakens the cardiolipins/ANT interactions and (iii) destabilizes the initial ANT-Cys(56) residue increasing its relative mobility. The binding of ADP that stabilizes the conformation "m" of ANT and/or cardiolipin, respectively to H5 and H4 helices, could stabilize their contacts with the short helix h56 that includes Cys(56), accounting for reducing its relative mobility. The results suggest that Ca(2+) binding to adenine nucleotide translocase (ANT)-surrounding cardiolipins in c-state of the translocase enhances (ANT)-Cys(56) relative mobility and that this may constitute a potential critical step of Ca(2+)-induced PTP opening.