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1.
Neurosurgery ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007600

RESUMO

BACKGROUND AND IMPORTANCE: Partially thrombosed vertebral artery aneurysms (PTVAs) are rare, most of which are not easy to treat. Furthermore, endovascular treatment of PTVAs may not have favorable outcomes. The relationship between PTVAs and well-developed vasa vasorum (VV), including the mechanism of aneurysm growth, has been reported, but there are no reports of imaging findings by digital subtraction angiography (DSA). In this case, we successfully performed superselective angiography of well-developed VV and evaluated its imaging characteristics. We present the first DSA report of a well-developed VV of PTVA. CLINICAL PRESENTATION: A 54-year-old patient presented with a PTVA that exerted a mass effect on the medulla oblongata. The aneurysm had no cavity due to thrombosis. The 3-dimensional DSA images indicated VV. Superselective angiography of the VV indicated staining of the thrombosed aneurysm and draining into the suboccipital cavernous sinus through the venous VV. Thus, VV embolization with n-butyl cyanoacrylate was performed. After 3 months, the contrast effect of the aneurysm on contrast-enhanced magnetic resonance imaging disappeared and aneurysm shrinkage was observed. CONCLUSION: We successfully identified a VV within PTVA. Superselective VV angiography showed staining of the thrombosed component and venous return draining into the suboccipital cavernous sinus. In this case, the embolization of the VV proved to be an effective endovascular treatment of PTVA, but the safety of this method is a challenge. Further case studies are required to validate this method, and we hope it will evolve into a new treatment of PTVA.

2.
Nagoya J Med Sci ; 86(2): 304-313, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38962412

RESUMO

Radiotherapy combined with temozolomide (TMZ+RT) is the primary treatment for high-grade glioma. TMZ is classified as a moderate emetic risk agent and, thus, supportive care for nausea and vomiting is important. In Nagoya University Hospital, all patients are treated with a 5-hydroxy-tryptamine 3 receptor antagonist (5-HT3RA) for the first 3 days. The daily administration of 5-HT3RA is resumed after the 4th day based on the condition of patients during TMZ+RT. Therefore, the present study investigated risk factors for nausea and vomiting in patients requiring the daily administration of 5-HT3RA. Patients with high-grade glioma who received TMZ+RT between January 2014 and December 2019 at our hospital were included. Patients were divided into two groups: a control group (patients who did not resume 5-HT3RA) and resuming 5-HT3RA group (patients who resumed 5-HT3RA after the 4th day), and both groups were compared to identify risk factors for nausea and vomiting during TMZ+RT. There were 78 patients in the control group (68%) and 36 in the resuming 5-HT3RA group (32%). A multivariate analysis of patient backgrounds in the two groups identified age <18 years, PS 2 or more, and occipital lobe tumors as risk factors for nausea and vomiting. Nausea and vomiting were attenuated in 30 patients (83%) in the resuming 5-HT3RA group following the resumption of 5-HT3RA. The results obtained highlight the importance of extracting patients with these risk factors before the initiation of therapy and the early resumption or daily administration of 5-HT3RA according to the condition of each patient.


Assuntos
Glioma , Náusea , Antagonistas do Receptor 5-HT3 de Serotonina , Temozolomida , Vômito , Humanos , Temozolomida/uso terapêutico , Temozolomida/administração & dosagem , Temozolomida/efeitos adversos , Masculino , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Antagonistas do Receptor 5-HT3 de Serotonina/administração & dosagem , Feminino , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Pessoa de Meia-Idade , Glioma/tratamento farmacológico , Glioma/radioterapia , Fatores de Risco , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/administração & dosagem , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos
3.
Childs Nerv Syst ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958731

RESUMO

PURPOSE: Filum terminale lipoma (FTL) causes spinal-cord tethering and is associated with tethered-cord syndrome, which is treated by dissection of the entrapment. The conventional treatment for FTL involves dissection of the spinal cord through a laminotomy open approach (LOA). However, in recent years, the interlaminar approach (ILA) has gained popularity as a minimally invasive surgery. This study compares the effectiveness of the minimally invasive ILA with the conventional LOA in treating FTL. METHODS: We retrospectively evaluated data on the ILA and LOA for FTL at our center. In total, 103 participants were enrolled, including 55 in the ILA group and 48 in the LOA group. RESULTS: The ILA required significantly less surgical time and resulted in less blood loss. The improvement rate of symptoms in symptomatic patients was 84%, and for urinary symptoms and abnormal urodynamic study findings, it was 77%. The postoperative maintenance rate for asymptomatic patients was 100%. Postoperative complications of ILA included delayed wound healing in two patients (3.6%). CONCLUSION: Compared with LOA, ILA offers advantages in terms of shorter operative time and less blood loss, with no significant difference in long-term symptom-improvement rates between the groups.

4.
Neurol Med Chir (Tokyo) ; 64(7): 253-260, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38839295

RESUMO

Brain tumor-related epilepsy (BTRE) is a complication that significantly impairs the quality of life and course of treatment of patients with brain tumors. Several recent studies have shed further light on the mechanisms and pathways by which genes and biological molecules in the tumor microenvironment can cause epilepsy. Moreover, epileptic seizures have been found to promote the growth of brain tumors, making the control of epilepsy a critical factor in treating brain tumors. In this study, we summarize the previous research and recent findings concerning BTRE. Expectedly, a deeper understanding of the underlying genetic and molecular mechanisms leads to safer and more effective treatments for suppressing epileptic symptoms and tumor growth.


Assuntos
Neoplasias Encefálicas , Epilepsia , Glioma , Humanos , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapia , Glioma/complicações , Glioma/terapia , Glioma/genética , Epilepsia/etiologia
5.
Front Oncol ; 14: 1368277, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919531

RESUMO

Background: Posterior clinoid process (PCP) meningioma is an exceedingly rare entity. It remains the most challenging skull base lesion for neurosurgeons due to its treacherous location that insinuates amongst critical neurovascular structures. This article will describe the technical notes using the endoscopic endonasal approach that provide the earliest devascularization and detachment of the tumor PCP meningioma. Methods: We are introducing the surgical implementation of an endoscopic endonasal approach to removing PCP meningioma. Furthermore, we perform a literature review of posterior clinoid process meningioma that undergoes surgical intervention, then summarize the benefits and limitations of each approach. Results: We present a case of right PCP meningioma that was removed using an endoscopic endonasal approach through the transposterior clinoid corridor in a 52-year-old-woman. We describe the technical notes in performing this approach to have the earliest devascularization and detachment of the tumor by performing posterior clinoidectomy. Safe tumor removal is performed with a wide and clear view of the surrounding neurovascular structure. Based on our database search, we found nine articles reported on the surgical management of PCP meningiomas, with a total number of 15 cases. All of the reported cases performed the tumor removal using the transcranial approach. Conclusion: The endoscopic endonasal transposterior clinoid approach circumvents all disadvantages faced by the traditional transcranial approach, providing the earliest approach to devascularized and detaching the tumor from its attachment at PCP. This approach demonstrates safety and efficacy, making it an acceptable alternative for PCP meningioma resections.

6.
Parkinsonism Relat Disord ; 124: 107020, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823170

RESUMO

INTRODUCTION: Parkinson's disease (PD) presents with decreased heart rate variability (HRV) from its early stages. However, most of its evidence originates from HRV measurements in parasympathetic dominant states. In this study, we aimed to examine whether HRV in sympathetic dominant states during the head-up tilt table test (HUT) serves as a marker of autonomic dysfunction in PD and isolated REM sleep behavior disorder (iRBD). METHODS: We retrospectively assessed 102 patients with PD, 10 patients with iRBD, and 43 healthy controls. We then measured the coefficient of variation of RR intervals as an HRV parameter in sympathetic dominant states (CVRR-S) and parasympathetic dominant states (CVRR-P). Furthermore, we evaluated parameters of cardiac autonomic function, including HUT and the heart-to-mediastinum (H/M) ratio of cardiac metaiodobenzylguanidine scintigraphy. RESULTS: Patients with iRBD and PD at Hoehn and Yahr stage I exhibited a significantly decreased CVRR-S compared to healthy controls (controls vs. iRBD vs. PD; 1.82 ± 0.64 % vs. 1.13 ± 0.41 % vs. 1.15 ± 0.51 %, p < 0.001), although no further deterioration was observed in PD at more severe Hoehn and Yahr stages. CVRR-S showed a significant correlation with the H/M ratio in PD (r = 0.51, p < 0.001). Additionally, receiver operating characteristic (ROC) analysis revealed a larger area under the ROC curve in CVRR-S compared to that in CVRR-P for discriminating PD or iRBD from healthy controls. CONCLUSION: HRV in sympathetic dominant states shows the potential to be a marker of autonomic dysfunction in iRBD and early-stage PD, aiding in early diagnosis and patient stratification.


Assuntos
Frequência Cardíaca , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Transtorno do Comportamento do Sono REM/fisiopatologia , Masculino , Feminino , Idoso , Frequência Cardíaca/fisiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Sistema Nervoso Simpático/fisiopatologia , Teste da Mesa Inclinada , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/diagnóstico
7.
J Neurosci Methods ; 409: 110198, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878975

RESUMO

BACKGROUND: Ependymal cilia play a major role in the circulation of cerebrospinal fluid. Although isolation of cilia is an essential technique for investigating ciliary structure, to the best of our knowledge, no report on the isolation and structural analysis of ependymal cilia from mouse brain is available. NEW METHOD: We developed a novel method for isolating ependymal cilia from mouse brain ventricles. We isolated ependymal cilia by partially opening the lateral ventricles and gently applying shear stress, followed by pipetting and ultracentrifugation. RESULTS: Using this new method, we were able to observe cilia separately. The results demonstrated that our method successfully isolated intact ependymal cilia with preserved morphology and ultrastructure. In this procedure, the ventricular ependymal cell layer was partially detached. COMPARISON WITH EXISTING METHODS: Compared to existing methods for isolating cilia from other tissues, our method is meticulously tailored for extracting ependymal cilia from the mouse brain. Designed with a keen understanding of the fragility of the ventricular ependyma, our method prioritizes minimizing tissue damage during the isolation procedure. CONCLUSIONS: We isolated ependymal cilia from mouse brain by applying shear stress selectively to the ventricles. Our method can be used to conduct more detailed studies on the structure of ependymal cilia.

8.
J Neurooncol ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839702

RESUMO

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

9.
Drug Metab Pharmacokinet ; 56: 101019, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38797092

RESUMO

The quantitative systems pharmacology (QSP) approach is widely applied to address various essential questions in drug discovery and development, such as identification of the mechanism of action of a therapeutic agent, patient stratification, and the mechanistic understanding of the progression of disease. In this review article, we show the current landscape of the application of QSP modeling using a survey of QSP publications over 10 years from 2013 to 2022. We also present a use case for the risk assessment of hyperkalemia in patients with diabetic nephropathy treated with mineralocorticoid receptor antagonists (MRAs, renin-angiotensin-aldosterone system inhibitors), as a prospective simulation of late clinical development. A QSP model for generating virtual patients with diabetic nephropathy was used to quantitatively assess that the nonsteroidal MRAs, finerenone and apararenone, have a lower risk of hyperkalemia than the steroidal MRA, eplerenone. Prospective simulation studies using a QSP model are useful to prioritize pharmaceutical candidates in clinical development and validate mechanism-based pharmacological concepts related to the risk-benefit, before conducting large-scale clinical trials.


Assuntos
Nefropatias Diabéticas , Desenvolvimento de Medicamentos , Hiperpotassemia , Antagonistas de Receptores de Mineralocorticoides , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/diagnóstico , Nefropatias Diabéticas/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Desenvolvimento de Medicamentos/métodos , Estudos Prospectivos , Farmacologia em Rede , Ensaios Clínicos como Assunto/métodos
10.
Cureus ; 16(4): e58697, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38779293

RESUMO

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome caused by germline alteration of the NF1gene. Among various NF1-related manifestations, obstructive hydrocephalus especially in adult NF1 cases is less frequently found. We report two adult NF1 cases exhibiting obstructive hydrocephalus due to an aggressive posterior fossa tumor exhibiting pathological characteristics of pilocytic astrocytoma as NF1-related manifestations. In these two cases, we performed endoscopic third ventriculostomy (ETV) and tumor biopsy as an initial treatment. The initial pathological diagnosis of the tumor is conventional pilocytic astrocytoma. After biopsy both cases revealed rapid tumor growth, therefore, we performed tumor removal, chemotherapy, and radiation therapy during an aggressive clinical course. However, both cases revealed dismal prognosis due to the progression of the tumor in spite of successful management of hydrocephalus by an initial ETV. DNA methylation analysis revealed that the tumor of one case matched high-grade astrocytoma with piloid features (HGAP). Most central nervous system tumors developed in NF1 are less aggressive such as pilocytic astrocytoma; however, recently a few studies revealed that HGAP, which has been a newly introduced malignant tumor in the World Health Organization Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS 5), rarely develops in NF1 cases. These findings suggested that HGAP might be one of the important causes of obstructive hydrocephalus in adult NF1 cases.

11.
World Neurosurg ; 187: e610-e619, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38677649

RESUMO

OBJECTIVE: Transient neurological deficits (TNDs) are known to develop after direct bypass for Moyamoya disease and may be risk factors for subsequent stroke. However, the factors involved in the development of TNDs and stroke after indirect revascularization alone, including their association with subsequent stroke, remain unclear. The purpose of this study was to investigate this issue. METHODS: The subjects of the study were 30 patients with Moyamoya disease who underwent a total of 40 indirect revascularization procedures at our institution. Clinical and radiological data were collected retrospectively. To examine factors associated with the development of postoperative TND/stroke/asymptomatic disease, the clinical characteristics of each group were statistically compared. RESULTS: The mean age at surgery was 7 years (range 1-63). TNDs developed after surgery in 9 out of 40 patients (22.5%). Stroke in the acute postoperative period occurred in 3 patients (7.5%), all of whom experienced cerebral infarctions. Demographic data and preoperative clinical information were not different between the groups. However, posterior cerebral artery involvement on preoperative imaging was significantly associated with the development of TNDs and stroke (P = 0.006). Furthermore, postoperative stroke was associated with unfavorable outcomes (P = 0.025). CONCLUSIONS: Posterior cerebral artery involvement is significantly associated with the occurrence of TNDs. In contrast, TNDs after indirect revascularization have little relationship with the subsequent development of stroke. TNDs usually resolve without new strokes, and a better understanding of this particular pathology could help establish an optimal treatment regimen.


Assuntos
Revascularização Cerebral , AVC Isquêmico , Doença de Moyamoya , Artéria Cerebral Posterior , Complicações Pós-Operatórias , Humanos , Doença de Moyamoya/cirurgia , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/complicações , Feminino , Masculino , Revascularização Cerebral/efeitos adversos , Revascularização Cerebral/métodos , Adulto , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Estudos Retrospectivos , Criança , Adulto Jovem , Artéria Cerebral Posterior/diagnóstico por imagem , Artéria Cerebral Posterior/cirurgia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , AVC Isquêmico/cirurgia , Pré-Escolar , Lactente , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/diagnóstico por imagem
12.
Acta Neuropathol Commun ; 12(1): 57, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605367

RESUMO

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.


Assuntos
Neoplasias Encefálicas , Glioma , Síndrome de Li-Fraumeni , Adulto , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Genes p53 , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Glioma/patologia , Isocitrato Desidrogenase/genética , Síndrome de Li-Fraumeni/genética , Mutação/genética
13.
Cureus ; 16(3): e55896, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38595901

RESUMO

Chiari III malformation, a rare and severe subtype of Chiari malformations, is frequently associated with hydrocephalus. The conventional treatment approaches for hydrocephalus in Chiari III malformations have mainly focused on ventriculoperitoneal (VP) shunting, but optimal methods and timing remain uncertain. We report a case of a newborn girl with Chiari III malformation who underwent surgical closure of an occipitocervical encephalocele and ventricular reservoir implantation on her third day of life. This procedure successfully managed her hydrocephalus without significant short-term complications. Three months post-surgery, she developed secondary external hydrocephalus, which was managed through subdural-peritoneal shunting, allowing her to thrive until at least five years of age. This case demonstrates the potential of ventricular reservoir implantation in treating hydrocephalus associated with Chiari III malformation and brings to light secondary external hydrocephalus, subsequently managed by VP shunting.

14.
J Neurosurg ; : 1-9, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579355

RESUMO

OBJECTIVE: Cerebral infarction is a common complication in patients undergoing revascularization surgery for moyamoya disease (MMD). Although previous statistical evaluations have identified several risk factors for postoperative brain ischemia, the ability to predict its occurrence based on these limited predictors remains inadequately explored. This study aimed to assess the feasibility of machine learning algorithms for predicting cerebral infarction after revascularization surgery in patients with MMD. METHODS: This retrospective study was conducted across two centers and harnessed data from 512 patients with MMD who had undergone revascularization surgery. The patient cohort was partitioned into internal and external datasets. Using perioperative clinical data from the internal cohort, three distinct machine learning algorithms-namely the support vector machine, random forest, and light gradient-boosting machine models-were trained and cross-validated to predict the occurrence of postoperative cerebral infarction. Predictive performance validity was subsequently assessed using an external dataset. Shapley additive explanations (SHAP) analysis was conducted to augment the prediction model's transparency and to quantify the impact of each input variable on shaping both the aggregate and individual patient predictions. RESULTS: In the cohort of 512 patients, 33 (6.4%) experienced postrevascularization cerebral infarction. The cross-validation outcomes revealed that, among the three models, the support vector machine model achieved the largest area under the receiver operating characteristic curve (ROC-AUC) at mean ± SD 0.785 ± 0.052. Notably, during external validation, the light gradient-boosting machine model exhibited the highest accuracy at 0.903 and the largest ROC-AUC at 0.710. The top-performing prediction model utilized five input variables: postoperative serum gamma-glutamyl transpeptidase value, positive posterior cerebral artery (PCA) involvement on preoperative MRA, infarction as the rationale for surgery, presence of an infarction scar on preoperative MRI, and preoperative modified Rankin Scale score. Furthermore, the SHAP analysis identified presence of PCA involvement, infarction as the rationale for surgery, and presence of an infarction scar on preoperative MRI as positive influences on postoperative cerebral infarction. CONCLUSIONS: This study indicates the usefulness of employing machine learning techniques with routine perioperative data to predict the occurrence of cerebral infarction after revascularization procedures in patients with MMD.

15.
J Cell Mol Med ; 28(7): e18214, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38509731

RESUMO

The majority of the population of glial cells in the central nervous system consists of astrocytes, and impairment of astrocytes causes various disorders. It is useful to assess the multiple astrocytic properties in order to understand their complex roles in the pathophysiology. Although we can differentiate human astrocytes from induced pluripotent stem cells (iPSCs), it remains unknown how we can analyse and reveal the multiple properties of astrocytes in complexed human disease conditions. For this purpose, we tested astrocytic differentiation protocols from feeder-free iPSCs based on the previous method with some modifications. Then, we set up extra- and intracellular assessments of iPSC-derived astrocytes by testing cytokine release, calcium influx, autophagy induction and migration. The results led us to analytic methods with conditions in which iPSC-derived astrocytes behave as in vivo. Finally, we applied these methods for modelling an astrocyte-related disease, Alexander disease. An analytic system using iPSC-derived astrocytes could be used to recapture complexities in human astrocyte diseases.


Assuntos
Astrócitos , Células-Tronco Pluripotentes Induzidas , Humanos , Células Cultivadas , Neurogênese , Citocinas , Diferenciação Celular
16.
Nagoya J Med Sci ; 86(1): 82-90, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505724

RESUMO

For patients with moyamoya disease, antiplatelet agents are often used during the perioperative periods of revascularization surgeries to prevent ischemic events. However, antiplatelet therapy is associated with the risk of hemorrhagic complications. Further, the influence of antiplatelet therapy on perioperative ischemic or hemorrhagic complications has not been investigated. This study aimed to determine the impact of antiplatelet agents on adult moyamoya disease patients with ischemic onset during the perioperative period. From January 2016 to December 2020, 183 consecutive combined (direct and indirect) revascularization surgeries for moyamoya disease patients were performed. Among these surgeries, 96 consecutive combined revascularization surgeries for adult moyamoya disease patients with ischemic onset were analyzed and perioperative ischemic and hemorrhagic complications were reviewed. Antiplatelet agents were continued during the perioperative period including on the day of surgery and the day after the surgery. Among 96 surgeries, no hemorrhagic complications occurred postoperatively. Infarction occurred in five cases (5.2%). Among the five cases, neurological deficits persisted in two cases and improved in three. The median value of bleeding volume was 112.5 mL (interquartile range, 80.0 - 200.0). Twenty-five cases (26.0%) needed blood transfusion. The modified Rankin Scale score deteriorated in two cases due to cerebral infarction. The incidence of hemorrhagic and ischemic complications after combined revascularization surgery in patients with ischemic moyamoya disease under antiplatelet therapy was low, indicating the safety of continued antiplatelet therapy.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Adulto , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Resultado do Tratamento , Doença de Moyamoya/cirurgia , Período Perioperatório/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Revascularização Cerebral/efeitos adversos
17.
Acta Neurochir (Wien) ; 166(1): 154, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538929

RESUMO

BACKGROUND: In recent years, molecular findings on spinal gliomas have become increasingly important. This study aimed to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis of spinal glioma. METHODS: This study included patients diagnosed with spinal cord glioma who underwent 18F-FDG-PET examination at the Department of Neurosurgery, Nagoya University Hospital between January 2016 and November 2023. The gliomas were divided into two groups, high-grade and low-grade, based on pathological and molecular studies. The maximum standardized uptake values (SUVmax) of the tumors were quantified and subsequently represented using receiver operating characteristic (ROC) curves. RESULTS: Eighteen participants were included in this study. Of the participants, seven had high-grade glioma with an SUVmax of 6.76 ± 0.72, and eleven had low-grade glioma with an SUVmax of 4.02 ± 1.78, and a statistically significant difference between the two groups. The ROC curve delineated an SUVmax cutoff value of 5.650, with an area under the curve (AUC) of approximately 0.909. Based on the cutoff value, the results of the diagnostic performance rendered a sensitivity and negative predictive value of 1.0, whereas the specificity and positive predictive value were 0.909 and 0.875, respectively. CONCLUSIONS: The present study shows that 18F-FDG-PET exhibits a markedly sensitive and negative predictive value in the assessment of spinal gliomas. Additionally, these findings have potential implications for the qualitative assessment of spinal gliomas using 18F-FDG-PET/CT. This imaging modality may be useful for making timely treatment decisions in situations where a detailed diagnosis by molecular analysis is not possible.


Assuntos
Fluordesoxiglucose F18 , Glioma , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Glioma/diagnóstico por imagem , Glioma/patologia , Tomografia por Emissão de Pósitrons/métodos , Estudos Retrospectivos
18.
Cancers (Basel) ; 16(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38539496

RESUMO

Awake surgery has become a standard practice for managing diffuse low-grade gliomas (LGGs), particularly in eloquent brain areas, and is established as a gold standard technique for left-dominant-hemisphere tumors. However, the intraoperative monitoring of functions in the right non-dominant hemisphere (RndH) is often neglected, highlighting the need for a better understanding of neurocognitive testing for complex functions in the right hemisphere. This article aims to comprehensively review the current literature on the benefits of awake craniotomy in gliomas of the non-dominant right hemisphere. A systematic review was conducted using the PubMed and ScienceDirect databases with keywords such as "right hemisphere", "awake surgery", "direct electrical brain stimulation and mapping", and "glioma". The search focused on anatomical and surgical aspects, including indications, tools, and techniques of awake surgery in right cerebral hemisphere gliomas. The literature search identified 74 sources, including original articles, books, monographs, and review articles. Two papers reported large series of language assessment cases in 246 patients undergoing awake surgery with detailed neurological semiology and mapping techniques, while the remaining studies were predominantly neuroradiological and neuroimaging in nature. Awake craniotomy for non-dominant-hemisphere gliomas is an essential tool. The term "non-dominant" should be revised, as this hemisphere contributes significantly to essential cognitive functions in the human brain.

19.
Brain Tumor Pathol ; 41(2): 50-60, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38332448

RESUMO

A prompt and reliable molecular diagnosis for brain tumors has become crucial in precision medicine. While Comprehensive Genomic Profiling (CGP) has become feasible, there remains room for enhancement in brain tumor diagnosis due to the partial lack of essential genes and limitations in broad copy number analysis. In addition, the long turnaround time of commercially available CGPs poses an additional obstacle to the timely implementation of results in clinics. To address these challenges, we developed a CGP encompassing 113 genes, genome-wide copy number changes, and MGMT promoter methylation. Our CGP incorporates not only diagnostic genes but also supplementary genes valuable for research. Our CGP enables us to simultaneous identification of mutations, gene fusions, focal and broad copy number alterations, and MGMT promoter methylation status, with results delivered within a minimum of 4 days. Validation of our CGP, through comparisons with whole-genome sequencing, RNA sequencing, and pyrosequencing, has certified its accuracy and reliability. We applied our CGP for 23 consecutive cases of intracranial mass lesions, which demonstrated its efficacy in aiding diagnosis and prognostication. Our CGP offers a comprehensive and rapid molecular profiling for gliomas, which could potentially apply to clinical practices and research primarily in the field of brain tumors.


Assuntos
Neoplasias Encefálicas , Variações do Número de Cópias de DNA , Metilação de DNA , Glioma , Mutação , Proteínas Supressoras de Tumor , Humanos , Glioma/genética , Glioma/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Metilação de DNA/genética , Proteínas Supressoras de Tumor/genética , Variações do Número de Cópias de DNA/genética , Genômica , Metilases de Modificação do DNA/genética , Regiões Promotoras Genéticas/genética , Enzimas Reparadoras do DNA/genética , Feminino , Masculino , Perfilação da Expressão Gênica , Adulto , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
20.
World Neurosurg ; 185: e451-e460, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38367858

RESUMO

OBJECTIVE: Intracranial dural arteriovenous fistulae (DAVFs) represent a subset of cerebral vascular malformations associated with significant morbidity and mortality. In Japan, DAVF exhibits sex-based differences in anatomical distribution, with female predominance in the cavernous sinus (CS) and male predominance in the transverse sinus (TS). Nevertheless, the pathophysiology of DAVF is not fully understood, and hormonal influences are hypothesized to play a role in its development. This study aimed to investigate changes in the concentrations of sex steroid hormones between intracranial and peripheral sampling sites in patients with CS- and TS-DAVF. METHODS: We recruited 19 patients with CS-DAVF (n = 12) and TS-DAVF (n = 7) in this study. Blood hormone measurements were obtained from peripheral and jugular bulb samples during endovascular intervention. Hormone concentrations were analyzed using enzyme-linked immunosorbent assay kits, and statistical analyses were performed. RESULTS: Our study revealed a higher prevalence of CS-DAVF in females and TS-DAVF in males, which is consistent with previous studies. Estradiol concentration was significantly lower in the jugular bulb compared with in the periphery in both patients with CS- and TS-DAVF. This decrease in estradiol was observed irrespective of the patient's sex and independent of follicle-stimulating hormone levels. CONCLUSIONS: These findings indicate a local decrease in estradiol levels within the intracranial vasculature of patients with DAVF. This suggests a potential multifactorial role of estradiol in the pathomechanism of DAVFs, warranting further investigation to understand its influence on DAVF formation and potential targeted therapies, thereby enhancing patient outcomes.


Assuntos
Seio Cavernoso , Malformações Vasculares do Sistema Nervoso Central , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estradiol/sangue , Seios Transversos , Adulto
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