WEN HUNG TZU

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 21
  • article 23 Citação(ões) na Scopus
    Texture analysis of high resolution MRI allows discrimination between febrile and afebrile initial precipitating injury in mesial temporal sclerosis
    (2012) ALEGRO, Maryana de Carvalho; SILVA, Alexandre Valotta; BANDO, Silvia Yumi; LOPES, Roseli de Deus; CASTRO, Luiz Henrique Martins de; HUNGTSU, Wen; MOREIRA-FILHO, Carlos Alberto; AMARO JR., Edson
    A computational pipeline combining texture analysis and pattern classification algorithms was developed for investigating associations between high-resolution MRI features and histological data. This methodology was tested in the study of dentate gyrus images of sclerotic hippocampi resected from refractory epilepsy patients. Images were acquired using a simple surface coil in a 3.0T MRI scanner. All specimens were subsequently submitted to histological semiquantitative evaluation. The computational pipeline was applied for classifying pixels according to: a) dentate gyrus histological parameters and b) patients' febrile or afebrile initial precipitating insult history. The pipeline results for febrile and afebrile patients achieved 70% classification accuracy, with 78% sensitivity and 80% specificity [area under the reader observer characteristics (ROC) curve: 0.89]. The analysis of the histological data alone was not sufficient to achieve significant power to separate febrile and afebrile groups. Interesting enough, the results from our approach did not show significant correlation with histological parameters (which per se were not enough to classify patient groups). These results showed the potential of adding computational texture analysis together with classification methods for detecting subtle MRI signal differences, a method sufficient to provide good clinical classification. A wide range of applications of this pipeline can also be used in other areas of medical imaging. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.
  • article 7 Citação(ões) na Scopus
    Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
    (2021) BANDO, Silvia Yumi; BERTONHA, Fernanda Bernardi; PIMENTEL-SILVA, Luciana Ramalho; OLIVEIRA, Joao Gabriel Mansano de; CARNEIRO, Marco Antonio Duarte; OKU, Mariana Hiromi Manoel; WEN, Hung-Tzu; CASTRO, Luiz Henrique Martins; MOREIRA-FILHO, Carlos Alberto
    In about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules' main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.
  • article 4 Citação(ões) na Scopus
    Contralateral ictal electrographic involvement is associated with decreased memory performance in unilateral mesial temporal sclerosis
    (2015) PASSARELLI, Valmir; CASTRO-LIMA FILHO, Humberto; ADDA, Carla C.; PRETURLON-SANTOS, Ana P.; VALERIO, Rosa M.; JORGE, Carmen L.; PUGLIA- JR., Paulo; LYRA, Katarina; OTADUY, Maria G.; WEN, Hung-Tzu; CASTRO, Luiz H.
    Purpose: To evaluate the effect of contralateral electrographic involvement on memory performance (measured by neuropsychological and Wada memory testing) in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS). Methods: We studied 51 patients with medically-refractory epilepsy associated with unilateral MTS (27 women, 30/51, left MTS) submitted to prolonged non-invasive video-EEG monitoring and bilateral Wada testing. According to ictal electrographic involvement, patients were classified as: Contralateral ictal involvement, when one or more seizures evolved with rhythmic activity in the temporal region contralateral to the MTS or exclusive ipsilateral ictal involvement if all seizures showed ictal EEG activity exclusively on the MTS side. Wada testing involved a twelve-item memory paradigm. Wada memory asymmetry score was calculated for each patient subtracting the number of recalled items after injection on the lesion side from the number of recalled items after contralateral injection. Expected asymmetry (EA) was considered if Wade memory asymmetry > 0, and Symmetrical or Reversed memory asymmetry (S-RA) when <= 0. Neuropsychological testing was applied in the 51 patients and in 40 healthy controls. Verbal Memory was evaluated with the Rey Auditory Verbal Learning Test (RAVLT), considering the number of recalled items on immediate recall after the initial five consecutive encoding trials (RAVLT 6), a post-interference delayed (30 min) recall (RAVLT 7), and recall after 7 days. Nonverbal memory was tested with Wechsler Memory Scale-III (WMS-III) Faces subtests 1 e 2. Results: Groups did not differ in demographic, clinical and video-EEG monitoring variables. S-RA was observed more frequently in the group with contralateral ictal involvement (57.2% vs. 27.0%; p: 0.03). Logistic regression analysis considering demographic, clinical, hippocampal volume and video-EEG monitoring variables showed contralateral ictal involvement as the only independent variable associated with S-RA (coefficient = 1.32, p = 0.029, odds ratio 3.77; 95% CI 1.1-12.47). Additionally, the patient group with contralateral ictal EEG involvement displayed worse verbal and nonverbal memory scores compared to healthy controls. Conclusion: In this cohort of unilateral MTS patients, contralateral ictal involvement was associated with decreased memory performance on Wada and on neuropsychological testing.
  • bookPart
    HEMISFEROTOMIAS: TÉCNICA CIRÚRGICA
    (2016) TZU, Wen Hung; CASTRO, Luiz Henrique Martins; TEIXEIRA, Manoel Jacobsen
  • bookPart
    Tratamento Cirúrgico das Epilepsias: a Cirurgia
    (2015) TZU, Wen Hung; FLORES, Juan Antônio Castro
  • article 14 Citação(ões) na Scopus
    Postmortem Dissections of the Papez Circuit and Nonmotor Targets for Functional Neurosurgery
    (2020) JR, Tancredo Alcantara Ferreira; MIDDLEBROOKS, Erik H.; TZU, Wen Hung; REGHIN NETO, Mateus; HOLANDA, Vanessa Milanesi
    BACKGROUND: The Papez circuit was first described as the anatomic basis of emotion. Subsequent studies consolidated recognition of its limbic activities but showed a more important role in memory. Anatomic dissections and advanced neuroimaging have deepened our understanding of the various interconnections and white matter tracts present in this circuit. The aim of our study is to describe the anatomy of the Papez circuit through cadaveric dissection with correlation to ultrahigh-field magnetic resonance imaging (MRI) and MRI tractography. METHODS: White fiber dissection was performed on 5 cadaveric human brain hemispheres. The Papez circuit was dissected mediolaterally to show its anatomy and relation to other nuclei and tracts. Open-source MRI tractography data from the Human Connectome Project is combined with ultrahigh resolution, 7T structural MRI, and 17.6T diffusion tractography to further show the anatomy. RESULTS: The network connecting the anterior and posterior cingulate, entorhinal cortex, hippocampus, fimbria, dentate gyrus, fornix, mammillary bodies, and anterior thalamus was described using white matter fiber dissection and compared with MRI tractography and ultrahigh-field structural and diffusion MRI. We showed for the first time (through portmortem dissection) fibers directly connecting the anterior thalamic nucleus and the subgenual cingulate via the septal area. CONCLUSIONS: The description of the anatomy of the Papez circuit through cadaveric dissection and comparisons with advanced neuroimaging studies allow a better understanding of its three-dimensional spatial layout, in addition to showing new areas of connectivity with adjacent structures and possibilities for surgical approaches or stimulation.
  • article 11 Citação(ões) na Scopus
    Frontal Lobe Decortication (Frontal Lobectomy with Ventricular Preservation) in Epilepsy-Part 1: Anatomic Landmarks and Surgical Technique
    (2017) WEN, Hung Tzu; ROZ, Leila Maria Da; RHOTON JR., Albert L.; CASTRO, Luiz Henrique Martins; TEIXEIRA, Manoel Jacobsen
    BACKGROUND: An extensive frontal resection is a frequently performed neurosurgical procedure, especially for treating brain tumor and refractory epilepsy. However, there is a paucity of reports available regarding its surgical anatomy and technique. OBJECTIVES: We sought to present the anatomic landmarks and surgical technique of the frontal lobe decortication (FLD) in epilepsy. The goals were to maximize the gray matter removal, spare primary and supplementary motor areas, and preserve the frontal horn. MATERIAL AND METHODS: The anatomic study was based on dissections performed in 15 formalin-fixed adult cadaveric heads. The clinical experience with 15 patients is summarized. RESULT: FLD consists of 5 steps: 1) coagulation and section of arterial branches of lateral surface; 2) paramedian subpial resection 3 cm ahead of the precentral sulcus to reach the genu of corpus callosum; 3) resection of gray matter of lateral surface, preserving the frontal horn; 4) removal of gray matter of basal surface preserving olfactory tract; 5) removal of gray matter of the medial surface under the rostrum of corpus callosum. The frontal horn was preserved in all 15 patients; 12 patients (80%) had no complications; 2 patients presented temporary hemiparesis; and 1 Rasmussen syndrome patient developed postoperative fever. The best seizure control was in cases with focal magnetic resonance imaging abnormalities limited to the frontal lobe. CONCLUSION: FLD is an anatomy-based surgical technique for extensive frontal lobe resection. It presents reliable anatomic landmarks, selective gray matter removal, preservation of frontal horn, and low complication rate in our series. It can be an alternative option to the classical frontal lobectomy.
  • article 68 Citação(ões) na Scopus
    Prospective randomized study comparing clinical, functional, and aesthetic results of minipterional and classic pterional craniotomies
    (2015) WELLING, Leonardo C.; FIGUEIREDO, Eberval G.; WEN, Hung T.; GOMES, Marcos Q. T.; BOR-SENG-SHU, Edson; CASAROLLI, Cesar; GUIRADO, Vinicius M. P.; TEIXEIRA, Manoel Jacobsen
    OBJECT The object of this study was to compare the clinical, functional, and aesthetic results of 2 surgical techniques, pterional (PT) and minipterional (MPT) craniotomies, for microsurgical clipping of anterior circulation aneurysms. METHODS Fifty-eight patients with ruptured and unruptured anterior circulation aneurysms were enrolled into a prospective randomized study. The first group included 28 patients who underwent the MPT technique, and the second group comprised 30 patients who underwent the classic PT craniotomy. To evaluate the aesthetic effects, patients were asked to grade on a rule from 0 to 100 the best and the worst aesthetic result. Photographs were also taken, assessed by 2 independent observers, and classified as showing excellent, good, regular, or poor aesthetic results. Furthermore, quantitative radiological assessment (percentage reduction in thickness and volumetric analysis) of the temporal muscle, subcutaneous tissue, and skin was performed. Functional outcomes were compared using the modified Rankin Scale (mRS). Frontal facial palsy, postoperative hemorrhage, cerebrospinal fistula, hydrocephalus, and mortality were also analyzed. RESULTS Demographic and preoperative characteristics were similar in both groups. Satisfaction in terms of aesthetic result was observed in 19 patients (79%) in the MPT group and 13 (52%) in the PT group (p = 0.07). The mean score on the aesthetic rule was 27 in the MPT group and 45.8 in the PT group (p = 0.03). Two independent observers analyzed the patient photos, and the kappa coefficient for the aesthetic results was 0.73. According to these observers, excellent and good results were seen in 21 patients (87%) in the MPT and 12 (48%) in the PT groups. The degree of temporal muscle, subcutaneous tissue, and skin atrophy was 14.9% in the MPT group and 24.3% in the PT group (p = 0.01). Measurements of the temporal muscle revealed 12.7% atrophy in the MPT group and 22% atrophy in the PT group (p = 0.005). The volumetric reduction was 14.6% in the MPT and 24.5% in the PT groups (p = 0.012). Mortality and mRS score were similar in both groups at the 6-month evaluation (p = 0.99). CONCLUSIONS Minipterional craniotomy provides clinical results similar to those of the PT technique. Moreover, it provides better cosmetic results. It can be used safely and effectively to surgically treat aneurysms of the anterior circulation instead of the PT approach.
  • article 1 Citação(ões) na Scopus
    Natural history and neuro-oncological approach in spinal gangliogliomas: a systematic review
    (2024) PEREIRA, Benedito Jamilson Araujo; ALMEIDA, Antonio Nogueira de; PAIVA, Wellingson Silva; TZU, Wen Hung; MARIE, Suely Kazue Nagahashi
    To describe the natural history of spinal gangliogliomas (GG) in order to determine the most appropriate neuro-oncological management. A Medline search for relevant publications up to July 2023 using the key phrase ""ganglioglioma spinal"" and ""ganglioglioma posterior fossa"" led to the retrieval of 178 studies. This corpus provided the basis for the present review. As an initial selection step, the following inclusion criteria were adopted: (i) series and case reports on spinal GG; (ii) clinical outcomes were reported specifically for GG; (iii) GG was the only pathological diagnosis for the evaluation of the tumor; (iv) papers written only in English was evaluated; and (v) papers describing each case in the series were included. The World Health Organization (WHO) 2021 grading criteria for gangliogliomas were applied. A total of 107 tumors were evaluated (63 from male patients and 44 from female patients; 1.43 male/1.0 female ratio, mean age 18.34 +/- 15.84 years). The most common site was the cervical spine, accounting for 43 cases (40.18%); GTR was performed in 35 cases (32.71%) and STR in 71 cases (66.35%), while this information was not reported in 1 case (0.94%). 8 deaths were reported (7.47%) involving 2 males (25%) and 6 females (75%) aged 4-78 years (mean 34.27 +/- 18.22) years. GGs located on the spine displayed the same gender ratio as these tumors in general. The most frequent symptom was pain and motor impairment, while the most prevalent location was the cervical spinal cord. GTR of the tumor posed a challenge for neurosurgeons, due to the difficulty of resecting the lesion without damaging the spinal eloquent area, explaining the lower rate of cure for this tumor type.
  • article 25 Citação(ões) na Scopus
    Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy
    (2011) BANDO, Silvia Y.; ALEGRO, Maryana C.; AMARO JR., Edson; SILVA, Alexandre V.; CASTRO, Luiz H. M.; WEN, Hung-Tzu; LIMA, Leandro de A.; BRENTANI, Helena; MOREIRA-FILHO, Carlos Alberto
    Background: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). In order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations. Methodology/Principal Findings: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi. Conclusions/Significance: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions.