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OBJECTS: Cerebral infarction, resulting from acute internal carotid artery (ICA) occlusion, typically manifests with a wide ischemic area and severe symptoms. Mechanical thrombectomy proves effective within 24 hours of disease onset and in less ischemic infarction core. However, in cases with well-developed collateral flow and mild symptoms, conservative treatment is initially selected. If symptoms worsen or ipsilateral hemisphere perfusion decreases, superficial temporal artery (STA) - middle cerebral artery (MCA) anastomosis is considered. Revascularization therapy may also be effective. Contralateral angiography allows for ipsilateral blood flow verification once complete revascularization is achieved, albeit with potential treatment-related complications. Here, we describe retrograde angiography using an intermediate catheter (IMC) and contralateral contrast injection to achieve safer revascularization. METHODS: We present ten acute ICA occlusion cases caused by thromboembolism, arteriosclerosis, carotid artery stent occlusion, or embolic stroke of undetermined source. Employing bilateral femoral artery puncture, one catheter was guided to the occluded ICA, while another was positioned for diagnostic purposes in the contralateral ICA or vertebral artery. The IMC was navigated through the occluded vessel, with contralateral imaging performed during aspiration. The catheter was gradually retracted to confirm the extent of occlusion and recognize recanalization. RESULTS: Recanalization was successfully achieved in all cases. Symptomatic ischemic complication and hyperperfuison was not seen in all cases. No cases were decreased modified Rankin scale after treatment. CONCLUSION: Advancements in IMC technology facilitate distal catheter guidance to the ICA, even in proximal occlusion. Combining this technique with contralateral imaging allows us to confirm the extent of occlusion and recanalization status without antegrade imaging, making recanalization therapy safer.
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OBJECTIVE: Sphenoid wing meningiomas (SWMs) often cause occlusion or stenosis of the superficial middle cerebral vein (SMCV) by tumor compression. This study aimed to analyze the correlation between SMCV compression and peritumoral brain edema (PTBE) in SWM patients and to clarify the importance of surgical preservation of the SMCV in SWM surgery. METHODS: This retrospective study included 31 patients who underwent surgery for SWM at our institution from April 2011 to March 2022. Patient demographics, tumor characteristics, PTBE size, and SMCV patency before and after surgery were evaluated using preoperative and postoperative MRI or digital subtraction angiography. RESULTS: Of the 31 patients, 24 (77.4â¯%) exhibited PTBE, with varying degrees of severity: mild (32.3â¯%), moderate (25.8â¯%), and severe (41.9â¯%). Preoperative MRI showed SMCV patency in 14 patients (45.2â¯%) and SMCV compression in 17 patients (54.8â¯%). There was a significant association between PTBE severity and SMCV compression (p = 0.002). Postoperatively, SMCV recanalization was observed in 4 out of 16 patients (25.0â¯%) with preoperative SMCV compression. These patients had significantly smaller tumors (p = 0.013) and larger preoperative PTBE volumes (p = 0.042) compared to those without recanalization. CONCLUSIONS: Our study demonstrates a significant correlation between SMCV compression and severe PTBE in SWM patients. A subset of patients showed postoperative SMCV recanalization, particularly those with smaller tumors and more pronounced PTBE. These findings highlight the importance of SMCV preservation during SWM surgery to potentially improve postoperative outcomes.
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Edema Encefálico , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/cirugía , Meningioma/complicaciones , Meningioma/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Edema Encefálico/cirugía , Anciano , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Venas Cerebrales/diagnóstico por imagen , Venas Cerebrales/cirugía , Hueso Esfenoides/cirugía , Hueso Esfenoides/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Background: Neurofibromatosis type 1 (NF-1) is often characterized by vascular disorders related to vessel vulnerability that can lead to unfavorable outcomes. Here, we describe a case of NF-1 complicated with a massive subcutaneous hematoma posing a risk of visual impairment for which rapid decompression and a subsequent less invasive approach result in a favorable outcome. Case Description: A 40-year-old woman with NF-1 presented with a massive left subcutaneous temporal hematoma following a mild head contusion. Four days after hospitalization, the hematoma increased in size and severely compressed the left eye, prompting immediate hematoma removal to preserve visual function. Immediately after the hematoma removal, a superficial temporal arteriovenous fistula was found on the digital subtraction angiography and embolized by the endovascular procedure. Her visual acuity was preserved, and no bleeding recurrence was observed throughout the follow-up. Conclusion: Surgical hematoma removal followed by endovascular treatment was effective in preserving visual function. Since vessel fragility is characteristic of patients with NF-1, it should be kept in mind that vascular complications may lead to serious clinical outcomes. In certain NF-1 cases, less invasive treatments for vascular abnormalities may be preferable.
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Magnetic resonance imaging (MRI) is an indispensable tool in neurosurgery, though it sometimes faces challenges such as "tumor mimicry." While intraoperative MRI (iMRI) is widely recognized for its usefulness in achieving maximal safe resection during glioma surgery, instances of tumor mimicry still occur on iMRI. Moreover, reports on tumor mimics observed through iMRI, particularly in low-grade gliomas, remain scarce. In this article, we present a case of oligodendroglioma, where a newly emerged T2 high-signal intensity region on iMRI necessitated differentiation from tumor expansion. A 23-year-old man presented with a newly diagnosed brain tumor and underwent surgical removal. An iMRI taken after tumor removal revealed a newly emerged T2 hyperintense area without diffusion restriction around the resection cavity, which was not observed in the preoperative MRI. Suspecting residual tumor, we performed additional resection. An MRI on the following day confirmed that the T2 hyperintense area identified on the iMRI had been completely resected but also revealed an enlarged T2 high-signal area over a wider region. Histopathology found no tumor cells in the additionally resected area, indicating that the iMRI finding was a tumor mimic. Six months later, the T2 high-signal area around the resection cavity had disappeared on MRI without any additional treatment. This case highlights the challenge of distinguishing between T2 hyperintense mimicry and tumor enlargement during glioma surgery seen on iMRI. Despite the significant value of iMRI, our report underscores the need for careful interpretation in neurosurgical practice, particularly with non-contrast-enhancing tumors.
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BACKGROUND: Carotid artery dissection is a common cause of ischemic stroke, predominantly affecting the internal carotid artery, with rare involvement of the common carotid artery (CCA). The limited literature makes diagnosis and management challenging, particularly in asymptomatic patients. In this report, the authors present a unique case of spontaneous, asymptomatic CCA dissection that resembled a carotid web, shedding light on its clinical spectrum and management. OBSERVATIONS: A 70-year-old man was diagnosed with an intimal flap in the left CCA. Although the findings resembled those of a carotid web, cerebral angiography confirmed the presence of an intimal flap and arterial wall irregularities indicative of vascular dissection. Endarterectomy successfully prevented the stroke, and the postoperative recovery was uneventful. Pathological examination confirmed the diagnosis of CCA dissection. LESSONS: Spontaneous CCA dissection, though rare, presents significant diagnostic and therapeutic challenges. Because of morphological similarities, differentiating the diagnosis from a carotid web can be difficult. Available treatment strategies include antiplatelet therapy and surgical intervention. In this case, endarterectomy was chosen to avoid antithrombic treatment in anticipation of further invasive treatments for other conditions. The successful outcome highlights the potential as a treatment option, emphasizing the need for an individualized approach to each patient. https://thejns.org/doi/10.3171/CASE24344.
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The choroid plexus is the secretory tissue responsible for cerebrospinal fluid production in the brain. Ischemia of the choroid plexus is rare because of its abundant blood supply from multiple arterial systems, including the anterior and posterior choroidal arterial anastomoses. It is not clear under what circumstances isolated choroid plexus infarction occurs. A 56-year-old woman presented to our hospital after experiencing several episodes of paroxysmal dizziness and weakness in her right upper extremity that lasted several hours. She had a 10-year history of hypertension, diabetes mellitus, and hyperlipidemia, which were very poorly controlled. Magnetic resonance imaging confirmed isolated right choroid plexus infarction. Magnetic resonance angiography showed severe stenosis of the cavernous portion of the right internal carotid artery, occlusion of the distal portion of the right posterior cerebral artery, and occlusion of the contralateral left internal carotid artery. Thus, we hypothesized that isolated choroid plexus infarction was caused by ischemia due to both atherosclerotic changes in large vessels spanning multiple vasculatures and microangiopathy around the choroid plexus due to diabetes, hypertension, and hyperlipidemia. In choroid plexus infarction, both occlusive changes in multiple large vessels and microangiopathy may be involved, and the underlying cause of these changes should be thoroughly investigated. Although choroid plexus infarction may not be significant neurologically, it may shed light on further pathogenesis in this complex structure.
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Techniques for triggering neural differentiation of embryonic and induced pluripotent stem cells into neural stem cells and neurons have been established. However, neural induction of mesenchymal stem cells, including dental pulp stem cells (DPSCs), has been assessed primarily based on neural-related gene regulation, and detailed studies into the characteristics and differentiation status of cells are lacking. Therefore, this study was aimed at evaluating the cellular components and differentiation pathways of neural lineage cells obtained via neural induction of human DPSCs. Human DPSCs were induced to neural cells in monolayer culture and examined for gene expression and mechanisms underlying differentiation using microarray-based ingenuity pathway analysis. In addition, the neural lineage cells were subjected to single-cell RNA sequencing (scRNA-seq) to classify cell populations based on gene expression profiles and to elucidate their differentiation pathways. Ingenuity pathway analysis revealed that genes exhibiting marked overexpression, post-neuronal induction, such as FABP7 and ZIC1, were associated with neurogenesis. Furthermore, in canonical pathway analysis, axon guidance signals demonstrated maximum activation. The scRNA-seq and cell type annotations revealed the presence of neural progenitor cells, astrocytes, neurons, and a small number of non-neural lineage cells. Moreover, trajectory and pseudotime analyses demonstrated that the neural progenitor cells initially engendered neurons, which subsequently differentiated into astrocytes. This result indicates that the aforementioned neural induction strategy generated neural stem/progenitor cells from DPSCs, which might differentiate and proliferate to constitute neural lineage cells. Therefore, neural induction of DPSCs may present an alternative approach to pluripotent stem cell-based therapeutic interventions for nervous system disorders.
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Diferenciación Celular , Pulpa Dental , Células-Madre Neurales , Neurogénesis , Neuronas , Humanos , Pulpa Dental/citología , Diferenciación Celular/genética , Neuronas/citología , Neuronas/fisiología , Células-Madre Neurales/citología , Células-Madre Neurales/fisiología , Células Cultivadas , Neurogénesis/genética , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Expresión Génica/genética , Linaje de la Célula/genética , Células Madre/citología , Células Madre/fisiología , Astrocitos/citología , Astrocitos/fisiologíaRESUMEN
Histopathologic examinations of primary central nervous system lymphoma (PCNSL) reveal concentric accumulation of lymphocytes in the perivascular area with fibrosis. However, the nature of this fibrosis in "stiff" PCNSL remains unclear. We have encountered some PCNSLs with hard masses as surgical findings. This study investigated the dense fibrous status and tumor microenvironment of PCNSLs with or without stiffness. We evaluated by silver-impregnation nine PCNSLs with stiffness and 26 PCNSLs without stiffness. Six of the nine stiff PCNSLs showed pathological features of prominent fibrosis characterized by aggregation of reticulin fibers, and collagen accumulations. Alpha-smooth muscle actin (αSMA)-positive spindle cells as a cancer-associated fibroblast, the populations of T lymphocytes, and macrophages were compared between fibrous and control PCNSLs. Fibrous PCNSLs included abundant αSMA-positive cells in both intra- and extra-tumor environments (5/6, 87% and 3/6, 50%, respectively). Conversely, only one out of the seven control PCNSL contained αSMA-positive cells in the intra-tumoral area. Furthermore, the presence of extra-tumoral αSMA-positive cells was associated with infiltration of T lymphocytes and macrophages. In conclusion, recognizing the presence of dense fibrosis in PCNSL can provide insights into the tumor microenvironment. These results may help stratify patients with PCNSL and improve immunotherapies for these patients.
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Actinas , Neoplasias del Sistema Nervioso Central , Fibrosis , Macrófagos , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Actinas/metabolismo , Masculino , Femenino , Anciano , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/inmunología , Macrófagos/patología , Macrófagos/inmunología , Linfoma/patología , Linfoma/inmunología , Adulto , Anciano de 80 o más Años , Linfocitos T/patología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG. METHODS: 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up. CONCLUSIONS: The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy.
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Ácido Aminolevulínico , Neoplasias Encefálicas , Glioma , Recurrencia Local de Neoplasia , Fotoquimioterapia , Fármacos Fotosensibilizantes , Porfirinas , Humanos , Ácido Aminolevulínico/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Fotoquimioterapia/métodos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/cirugía , Glioma/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/efectos adversos , Anciano , Porfirinas/uso terapéutico , Porfirinas/administración & dosificación , AdultoRESUMEN
Background Symptomatic cerebellar cyst formation after surgery is rare and the mechanism remains unknown. We describe a cerebellar cyst that gradually expanded, becoming symptomatic, after the removal of a foramen magnum meningioma and discuss the mechanism of cyst formation. Case Description A 76-year-old woman with a tumor at the foramen magnum was treated by posterior fossa craniotomy and C1 hemilaminectomy. The patient suddenly developed cerebellar symptoms and consciousness disturbance approximately 1 week into an otherwise good postoperative course. Imaging showed a subcutaneous pseudomeningocele in the occipital region and cerebellar cyst formation. After resolution by fenestration of the cerebellar cyst and duraplasty, the patient's symptoms gradually improved. No tumor or cerebellar cyst recurrence has been detected in over 5 years since the surgery. Conclusion Postoperative pseudomeningocele appeared crucial for cerebellar cyst formation. Postoperative development of symptomatic cerebellar cysts is rare but should be recognized as a serious, sometimes life-threatening, postoperative complication of posterior fossa surgery.
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Background: Treatment outcome data of stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) in patients ≥75 years (late elderly) are lacking. Approximately 39% of patients ≥75 years with VS were reported to experience severe facial palsy after surgical removal. This study compared the treatment outcomes post-SRS for VS between patients ≥75 and 65-74 years (early elderly). Methods: Of 453 patients who underwent gamma knife SRS for VS, 156 were ≥65 years old. The late and early elderly groups comprised 35 and 121 patients, respectively. The median tumor volume was 4.4 cc, and the median radiation dose was 12.0 Gy. Results: The median follow-up periods were 37 and 56 months in the late and early elderly groups, respectively. Tumor volume control was observed in 27 (88%) and 95 (83%) patients (P = 0.78), while additional procedures were required in 2 (6%) and 6 (6%) patients (P = 1.00) in the late and early elderly groups, respectively. At the 60th and 120th months post-SRS, the cumulative tumor control rates were 87%, 75%, 85%, and 73% (P = 0.81), while the cumulative clinical control rates were 93% and 87%, 95%, and 89% (P = 0.80), in the late and early elderly groups, respectively. In the early elderly group, two patients experienced facial pain, and one experienced facial palsy post-SRS; there were no adverse effects in the late elderly group (both P = 1.00). Conclusion: SRS is effective for VS and beneficial in patients ≥75 years old as it preserves the facial nerve.
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BACKGROUND: Neurenteric cysts are relatively rare benign congenital intracranial cystic lesions that enlarge rarely and very slowly. The authors present a case of an enlarging neurenteric cyst at the craniocervical junction with a fluid-fluid level on magnetic resonance imaging (MRI). OBSERVATIONS: A 34-year-old man with no significant medical history underwent head MRI to investigate mild headaches. An incidental cystic lesion, approximately 8 mm in diameter, was revealed at the craniocervical junction. Serial follow-up MRI showed cyst enlargement with a fluid-fluid level. Four years later, the cyst reached a size of 15 mm and was surgically removed. The cyst contained cloudy fluid with a high protein concentration, without any bleeding or tissue fragments. Pathological examination confirmed the diagnosis of a neurenteric cyst. The patient recovered well, was discharged home, and has remained recurrence free for 2 years. LESSONS: The growth dynamics of the relatively rapidly expanding neurenteric cyst at the craniocervical junction were monitored over time using MRI. This cyst exhibited the distinctive feature of a fluid-fluid level as it enlarged. Investigating the mechanisms underlying fluid-fluid level formation may offer novel insights into the pathogenesis of cyst enlargement. https://thejns.org/doi/10.3171/CASE24180.
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The pathology of idiopathic intracranial hypertension (IIH), a disease characterized by papillary edema and increased intracranial pressure (IICP), is not yet understood; this disease significantly affects quality of life due to symptoms including vision loss, headache, and pulsatile tinnitus. By contrast, superficial siderosis (SS), a disorder in which hemosiderin is deposited on the surface of the cerebral cortex and cerebellum, potentially causes cerebellar ataxia or hearing loss. So far, no cases of IIH with infratentorial and supratentorial cortical SS have been reported. Herein, we report a case of a 31-year-old woman with obesity who developed this condition. The patient suddenly developed headache and dizziness, had difficulty walking, and subsequently became aware of diplopia. Fundus examination revealed bilateral optic nerve congestive papillae and right eye abducens disturbance. Head magnetic resonance imaging (MRI) showed prominent SS on the cerebellar surface and cerebral cortex. Lumbar puncture revealed IICP of 32 cmH2O, consistent with the diagnostic criteria for IIH, and treatment with oral acetazolamide was started; subsequently, the intracranial pressure decreased to 20 cmH2O. Her abduction disorder disappeared, and the swelling of the optic papilla improved. She was now able return to her life as a teacher without any sequelae. SS is caused by persistent slight hemorrhage into the subarachnoid space. In this case, both infratentorial and supratentorial cortical superficial SS was observed. Although cases of IIH complicated by SS are rare, it should be kept in mind that a causal relationship between IIH and SS was inferred from our case. Our findings also suggest that cerebrospinal fluid dynamic analysis using MRI is effective in diagnosing IIH and in determining the efficacy of treatment.
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The recurrence of chronic subdural hematoma (CSDH) after surgical treatment is a severe problem with no effective prevention method. This retrospective study aimed to investigate factors associated with CSDH recurrence after burr hole surgery and hematoma changes on computed tomography before surgery to examine prevention methods for recurrence. A total of 166 hematomas were enrolled in this study, with 139 patients undergoing burr hole surgery for CSDH. Among these patients, 17 (12â¯%) had recurrence. Propensity score matching was performed based on postoperative drug therapy, including goreisan, carbazochrome sodium sulfonate hydrate, and tranexamic aid, resulting in 39 matched cases in 0-2 and 3 drug therapy groups. The recurrence rates were 18â¯% for the 0-2-drug therapy group and 3â¯% for the 3-drug therapy group. Univariate analysis revealed that the use of 0-2 drugs was associated with a higher risk of CSDH recurrence (odds ratio [OR], 8.31; 95â¯% confidence interval [CI], 0.97-71.17; p = 0.05) compared to the use of 3 drugs. Multivariate regression analysis further confirmed that 0-2 drug therapy after surgery was associated with an increased risk of CSDH recurrence (OR, 11.06; 95â¯% CI, 1.16-105.4; p = 0.037). Additionally, 36 hematomas were evaluated before surgery, with hematoma changes such as lower density and new trabecular formation detected in 14 CSDHs (39â¯%). Multivariate regression analysis showed that 3-drug therapy was associated with more cases of hematoma change than 0-2-drug therapy (OR, 13.9; 95â¯% CI, 1.09-177.65; p = 0.043). The 3-drug therapy was effective in reducing the recurrence of hematoma after burr hole surgery and promoted hematoma thrombosis.
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Hematoma Subdural Crónico , Humanos , Hematoma Subdural Crónico/cirugía , Hematoma Subdural Crónico/tratamiento farmacológico , Masculino , Femenino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Anciano de 80 o más Años , Resultado del Tratamiento , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/efectos adversos , Recurrencia , Prevención Secundaria , Medicamentos Herbarios Chinos , Medicina KampoRESUMEN
Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 1010 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting.
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BACKGROUND: Venous varices in the draining vein of arteriovenous malformations (AVMs) can result in compression symptoms. This condition is extremely rare, and its treatments and long-term outcomes are unresolved. METHODS: Herein, we describe the treatment of a thrombosed venous varix in a draining vein and review the relevant literature. RESULTS: The patient presented with progressive right-sided hemiparesis and aphasia. Magnetic resonance imaging revealed flow void accumulation from the corpus callosum to the left ventricle and a 30-mm mass in the left putamen. The patient underwent targeted transarterial embolization to reduce the blood flow to the venous varix and relieve the neurologic symptoms. The patient had recovered completely from the right hemiparesis and aphasia 4 years after treatment, with a modified Rankin scale score of 0. CONCLUSION: Targeted transarterial embolization for symptomatic venous varix is a palliative treatment that may improve long-term functional outcomes.
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Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.
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BACKGROUND: Appropriate exploratory efficacy data from Phase I trials are vital for subsequent phases. Owing to the uniqueness of brain tumors (BTs), use of different strategies to evaluate efficacy is warranted. We studied exploratory efficacy evaluation in Phase I trials involving BTs. METHODS: Using Clarivate's Cortellis™, 42 Phase I trials of BT interventions conducted from 2020 to 2022 were analyzed for efficacy endpoints, which were set as primary endpoints (PEs) or secondary endpoints (SEs). Additionally, these metrics were compared in two subgroups: trials including only BTs (Group-A) and those including BTs among mixed solid tumors (Group-B). RESULTS: Selected studies included a median of 1.5 PEs (range, 1-6) and 5 SEs (range, 0-19). Efficacy endpoints were included as PEs and SEs in 2 (5%) and 31 (78%) trials, respectively. Among the latter 31 trials that included 94 efficacy endpoints, 24, 22, 20, 9, and 8 reflected overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), respectively. ORR for BT was determined using various methods; however, the Response Evaluation Criteria in Solid Tumors (RECIST) was used less frequently in Group-A than in Group-B (p = 0.0039). CONCLUSIONS: Recent Phase I trials included efficacy endpoints as SEs, with ORR, PFS, or OS included in ~ 50% trials and DOR or DCR in ~ 25%. No established criteria exist for imaging evaluation of BTs. Phase I trials involving mixed solid tumor cohorts revealed challenges in designing methods to assess the exploratory efficacy of BTs.
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Neoplasias Encefálicas , Ensayos Clínicos Fase I como Asunto , Determinación de Punto Final , Humanos , Neoplasias Encefálicas/tratamiento farmacológico , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
BACKGROUND: Spontaneous intracranial hypotension (SIH) is a rare condition characterized by positional headache, for which contrast-enhanced magnetic resonance imaging (MRI) is the preferred diagnostic method. Although MRI reveals characteristic findings, head computed tomography (CT) is usually the first diagnostic step, but identifying features of SIH on CT is often difficult. This study was specifically designed to evaluate the utility of head CT in detecting upper cervical epidural venous engorgement as a sign of SIH. OBSERVATIONS: Of 24 patients with SIH diagnosed between March 2011 and May 2023, 10 did not undergo upper cervical CT. In the remaining 14 patients, engorgement of the upper cervical epidural venous plexus was observed. CT detection rates were consistent with MRI for spinal fluid accumulation or dural thickening. After treatment, in 92.9% of patients, the thickness of the epidural venous plexus decreased statistically significantly from 4.8 ± 1.3 mm to 3.6 ± 1.2 mm. LESSONS: This study suggests that upper cervical spine CT focused on epidural venous engorgement may be helpful in the initial diagnosis of SIH and may complement conventional MRI evaluation. Extending CT imaging to the upper cervical spine will improve the diagnostic accuracy of patients with positional headaches suspected to be SIH.
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Objective: Intraoperative rebleeding during endovascular treatment for ruptured intracranial aneurysms is associated with poor prognosis. Lumbar drainage is performed preoperatively to control intracranial pressure; however, it is associated with a risk of brain herniation or rebleeding because intracranial pressure may change rapidly. Therefore, this study aimed to examine the efficacy and safety of preoperative lumbar drainage. Methods: This retrospective study enrolled 375 patients who underwent endovascular treatment of ruptured intracranial aneurysms at our institution between April 2013 and March 2018. The incidence of rebleeding and clinical outcomes were compared between patients who did and did not undergo preoperative lumbar drainage. Results: Among the 375 patients with ruptured intracranial aneurysms, 324 (86.0%) and 51 (14.0%) patients did and did not undergo lumbar drainage, respectively. The incidence of rebleeding was 11/324 (3.4%) and 2/51 (3.9%) in lumbar drainage and nonlumbar drainage groups, respectively, with no statistical differences (p = 0.98). Of the rebleeding cases, 9/11 (81%) and 2/2 (100%) in lumbar drainage and nonlumbar drainage groups, respectively, were due to intraoperative bleeding, and 2/11 (19%) in the lumbar drainage group, the causes of the rebleeding were undetermined. The incidence of symptomatic vasospasm did not differ significantly between the groups (13.2% vs. 11.8%, P = 0.776), while the incidence of hydrocephalus (24.6% vs. 11.8%, P = 0.043) and meningitis (15.2% vs. 5.9%, P = 0.075) were slightly higher in the lumbar drainage group. Favorable clinical outcomes (modified Rankin Scale score <2) at discharge were less frequent in the lumbar drainage group (55.3% vs. 70.0%, P = 0.051). No significant differences were observed in the propensity score-matched analysis. Conclusion: Lumbar drainage before endovascular treatment for ruptured intracranial aneurysms is a safe procedure that does not increase the incidence of rebleeding.