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1.
Life (Basel) ; 14(8)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39202716

RESUMEN

Glioma, a diverse group of brain and spinal cord tumors arising from glial cells, is characterized by varying degrees of malignancy, with some types exhibiting highly aggressive behavior, rapid proliferation, and invasive growth patterns, posing significant therapeutic challenges. This review delves into the complex interactions between glioma cells, neurotransmitters, and neurosteroids, emphasizing their potential as therapeutic targets. Key neurotransmitters, like glutamate and gamma-aminobutyric acid (GABA), play crucial roles in glioma growth, invasion, and treatment response. This review examines the involvement of neurosteroids in glioma biology and explores innovative therapeutic strategies targeting these systems. It encompasses the biosynthesis and mechanisms of neurosteroids, interactions between gliomas and neurotransmitters, the spatial distribution of neurosteroid synthesis in gliomas, the role of ion channels, hormonal influences, enzyme modulation, and the neuroimmune system in glioma progression. Additionally, it highlights the potential of neurosteroids to modulate these pathways for therapeutic benefit.

2.
Front Neurol ; 15: 1387958, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911587

RESUMEN

Surgical decision-making for glioblastoma poses significant challenges due to its complexity and variability. This study investigates the potential of artificial intelligence (AI) tools in improving "decision-making processes" for glioblastoma surgery. A systematic review of literature identified 10 relevant studies, primarily focused on predicting resectability and surgery-related neurological outcomes. AI tools, especially rooted in radiomics and connectomics, exhibited promise in predicting resection extent through precise tumor segmentation and tumor-network relationships. However, they demonstrated limited effectiveness in predicting postoperative neurological due to dynamic and less quantifiable nature of patient-related factors. Recognizing these challenges, including limited datasets and the interpretability requirement in medical applications, underscores the need for standardization, algorithm optimization, and addressing variability in model performance and then further validation in clinical settings. While AI holds potential, it currently does not possess the capacity to emulate the nuanced decision-making process utilized by experienced neurosurgeons in the comprehensive approach to glioblastoma surgery.

3.
Front Neurol ; 15: 1387986, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38813245

RESUMEN

Ultrasound waves were initially used as a diagnostic tool that provided critical insights into several pathological conditions (e.g., gallstones, ascites, pneumothorax, etc.) at the bedside. Over the past decade, advancements in technology have led to the use of ultrasound waves in treating many neurological conditions, such as essential tremor and Parkinson's disease, with high specificity. The convergence of ultrasound waves at a specific region of interest/target while avoiding surrounding tissue has led to the coined term "focused ultrasound (FUS)." In tumor research, ultrasound technology was initially used as an intraoperative guidance tool for tumor resection. However, in recent years, there has been growing interest in utilizing FUS as a therapeutic tool in the management of brain tumors such as gliomas. This mini-review highlights the current knowledge surrounding using FUS as a treatment modality for gliomas. Furthermore, we discuss the utility of FUS in enhanced drug delivery to the central nervous system (CNS) and highlight promising clinical trials that utilize FUS as a treatment modality for gliomas.

4.
J Neurosurg ; 141(2): 555-563, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38518287

RESUMEN

OBJECTIVE: The aim of this study was to examine the distribution of olfactory filaments (OFs) in the nasal mucosa to facilitate preservation of olfactory function in endonasal approaches and preparation of a nasoseptal flap. METHODS: One formalin-fixed and 9 fresh cadaveric silicone-injected specimens with 20 total sides were studied to measure the distance of the OFs to the anatomical landmarks and compare the OF presence in the nasal septum mucosa (NSM) and ethmoidal mucosa (EM). RESULTS: The mean distance from the first to the last OF was 19.37 ± 2.16 mm in the NSM and 23.44 ± 5.42 mm in the EM. The NSM had a mean of 7.55 ± 1.31 OFs and the EM had 14.3 ± 1.78. Average OF lengths were measured at 6.44 ± 1.48 (range 3.75-12.40) mm in the NSM and 8.05 ± 1.76 (range 4.14-13.20) mm in the EM. The mean values of the EM measurements were compared with those of the NSM; the number of OFs, the distance between the first and last OF, the average OF length, and the number of OFs between anterior and posterior ethmoidal arteries in the NSM were significantly less (p < 0.05) than those in the EM. The distance between the first OF to the nasal bone on the NSM was greater than on the EM. CONCLUSIONS: Compared with the EM, the OFs are significantly fewer in number and smaller in size in the NSM. The uppermost edge of the nasoseptal flap incision in the NSM might be safer to start below 12 mm from the cribriform plate for OF protection.


Asunto(s)
Cadáver , Microcirugia , Mucosa Nasal , Tabique Nasal , Humanos , Mucosa Nasal/anatomía & histología , Tabique Nasal/cirugía , Tabique Nasal/anatomía & histología , Microcirugia/métodos , Colgajos Quirúrgicos
5.
J Pharm Sci ; 113(6): 1455-1469, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38555997

RESUMEN

The use of antibody-conjugated nanoparticles for brain tumor treatment has gained significant attention in recent years. Nanoparticles functionalized with anti-transferrin receptor antibodies have shown promising results in facilitating nanoparticle uptake by endothelial cells of brain capillaries and post-capillary venules. This approach offers a potential alternative to the direct conjugation of biologics to antibodies. Furthermore, studies have demonstrated the potential of antibody-conjugated nanoparticles in targeting brain tumors, as evidenced by the specific binding of these nanoparticles to brain cancer cells. Additionally, the development of targeted nanoparticles designed to transcytoses the blood-brain barrier (BBB) to deliver small molecule drugs and therapeutic antibodies to brain metastases holds promise for brain tumor treatment. While the use of nanoparticles as a delivery method for brain cancer treatment has faced challenges, including the successful delivery of nanoparticles to malignant brain tumors due to the presence of the BBB and infiltrating cancer cells in the normal brain, recent advancements in nanoparticle-mediated drug delivery systems have shown potential for enhancing the efficacy of brain cancer therapy. Moreover, the development of brain-penetrating nanoparticles capable of distributing over clinically relevant volumes when administered via convection-enhanced delivery presents a promising strategy for improving drug delivery to brain tumors. In conclusion, the use of antibody-conjugated nanoparticles for brain tumor treatment shows great promise in overcoming the challenges associated with drug delivery to the brain. By leveraging the specific targeting capabilities of these nanoparticles, researchers are making significant strides in developing effective and targeted therapies for brain tumors.


Asunto(s)
Barrera Hematoencefálica , Neoplasias Encefálicas , Sistemas de Liberación de Medicamentos , Nanopartículas , Humanos , Neoplasias Encefálicas/tratamiento farmacológico , Animales , Barrera Hematoencefálica/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Inmunoconjugados/administración & dosificación , Inmunoconjugados/farmacocinética , Inmunoconjugados/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Anticuerpos/administración & dosificación , Anticuerpos/química
6.
Cancers (Basel) ; 15(15)2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37568598

RESUMEN

Glioblastoma is one of the most devastating neoplasms of the central nervous system. This study focused on the development of serum extracellular vesicle (EV)-based glioblastoma tumor marker panels that can be used in a clinic to diagnose glioblastomas and to monitor tumor burden, progression, and regression in response to treatment. RNA sequencing studies were performed using RNA isolated from serum EVs from both patients (n = 85) and control donors (n = 31). RNA sequencing results for preoperative glioblastoma EVs compared to control EVs revealed 569 differentially expressed genes (DEGs, 2XFC, FDR < 0.05). By using these DEGs, we developed serum-EV-based biomarker panels for the following glioblastomas: wild-type IDH1 (96% sensitivity/80% specificity), MGMT promoter methylation (91% sensitivity/73% specificity), p53 gene mutation (100% sensitivity/89% specificity), and TERT promoter mutation (89% sensitivity/100% specificity). This is the first study showing that serum-EV-based biomarker panels can be used to diagnose glioblastomas with a high sensitivity and specificity.

7.
Turk Neurosurg ; 33(4): 635-641, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37470513

RESUMEN

AIM: To investigate the predictors of recurrence after gross total resection (GTR) that require early adjuvant radiotherapy upfront rather than at initial recurrence of atypical meningiomas (AMs). MATERIAL AND METHODS: A retrospective study of gross totally resected AMs was conducted in a tertiary care center within ten years. The clinical, radiological, and pathological parameters were analyzed statistically, and the factors associated with recurrence after GTR were determined with univariate analysis. RESULTS: Among 23 AMs with GTR, 34.8% showed recurrence in a median follow-up of 40 months after the surgery. Preoperative tumor volume, tumor location in the skull base or tentorium, and lack of progesterone expression were associated with the higher recurrence rate. AMs with a preoperative volume of 27.5 cm³ were the most significant risk factor for the recurrence (a 9.3-fold increase) than those with < 27.5 cm < sup > 3 < /sup > (66.7% vs. 14.3%, respectively). CONCLUSION: Patients diagnosed with larger AMs ( > 27.5 cm < sup > 3 < /sup > ) might have higher recurrence rates after GTR and, therefore, would benefit from early adjuvant radiotherapy without waiting for a recurrence. AMs located in the skull base or tentorium and AMs having no progesterone expression might also be potential predictors for recurrence.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/radioterapia , Meningioma/cirugía , Meningioma/patología , Radioterapia Adyuvante , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía
8.
Cerebellum ; 22(2): 305-315, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35325392

RESUMEN

This study aims to measure the effects of two different exercise programs on neck pain, proprioception, balance, coordination, posture, and quality of life in patients with Chiari malformation (CM) type 1. Sixteen patients were randomized to two different exercise programs: a tailored exercise protocol for CM (TEP-CM) and cervical spinal stabilization exercises (CSSE). Both exercise programs were implemented by a physiotherapist 3 days a week for 6 weeks. The primary outcome was Neck Disability Index. Secondary outcomes were visual analogue scale for pain, joint position sense error measurement, Berg Balance Scale, Time Up and Go Test, International Coordination Ataxia Rating Scale, PostureScreen Mobile, and Short Form-36. Assessments were done immediately before and after the intervention programs. Both groups showed significant improvement in Neck Disability Index, and some secondary outcome measures (P < 0.05). However, there were no statistical differences in post-intervention changes between the groups (P > 0.05). This is the first study to examine the effects of different exercise programs on symptoms in patients with CM type 1. Our preliminary findings indicate that exercise programs can improve pain, balance, proprioception, posture, coordination, and quality of life in CM type 1. Therefore, exercise should be considered safe, beneficial, and low-cost treatment option for CM type 1 patients without surgical indications.


Asunto(s)
Equilibrio Postural , Calidad de Vida , Humanos , Resultado del Tratamiento , Estudios de Tiempo y Movimiento , Dolor de Cuello/diagnóstico , Dolor de Cuello/terapia
9.
CA Cancer J Clin ; 72(5): 454-489, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35708940

RESUMEN

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Encefálicas/terapia , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Terapia Combinada , Humanos , Neoplasias Renales/patología , Neoplasias Renales/terapia
10.
Turk Neurosurg ; 32(3): 488-499, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35615768

RESUMEN

AIM: To investigate the spatiotemporal dynamics of early cerebral blood flow (CBF) changes, cerebrovascular reactivity (CVR), and vascular responses to cortical spreading depolarization (CSD) in an experimental mild traumatic brain injury (mTBI) model with laser speckle contrast imaging (LSCI) technique. MATERIAL AND METHODS: The weight-drop model was used to induce blunt head trauma. The mice were divided into two groups as mild TBI (n=12), and sham (n=6). The animals underwent continuous LSCI before and for 1 hour after trauma to evaluate the regional CBF changes, CVR in response to CO2, and CSD-associated vascular responses induced by pinprick. RESULTS: Our minor blunt head trauma protocol induced CSD in only 2 (16.7%) animals, which were excluded from further analyses. Of the remaining animals, 30% showed slight hyperemia following trauma, with mild ipsilateral hemisphere oligemia (15%?20% decrease in CBF) on average compared to baseline (p=0.027) and contralateral hemisphere (p=0.029). Maximal CBF decrease was measured in the peri-impact area (24.1% ± 5.1%). No significant difference was found between the sham and mTBI groups and two hemispheres of the mTBI group or pre/post-CSD periods of CO2 reactivity, as well as the characteristics of vascular CSD responses (net ischemia: 52.3% ± 2.6% vs. 56.3% ± 1.9% and prolonged oligemia duration 44.8 ± 1.8 min vs. 49.8 ± 2.3 min). CONCLUSION: The ipsilateral hemisphere, particularly in the peri-impact area, had mild hypoperfusion, within the first hour of minor blunt head trauma in mice. Nonetheless, mTBI does not alter CVR and vascular responses to an induced CSD, thus the overall CVR is largely preserved in mTBI without significant structural damage despite a mildly decreased CBF in the hyperacute phase.


Asunto(s)
Conmoción Encefálica , Depresión de Propagación Cortical , Hiperemia , Animales , Conmoción Encefálica/diagnóstico por imagen , Dióxido de Carbono , Circulación Cerebrovascular/fisiología , Depresión de Propagación Cortical/fisiología , Hiperemia/diagnóstico por imagen , Ratones
11.
Eur J Endocrinol ; 186(6): 667-675, 2022 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-35380988

RESUMEN

Objective: The pituitary gland is responsible for hormonal balance in the body, and disruption of hormonal balance in patients with pituitary adenoma (PA) indirectly affects the quality of life. This study aimed to examine the effects of yoga and combined aerobic and strength training (A+ST) on quality of life and related parameters such as sleep, fatigue, emotional state, sexual function, and cognitive status in women with PA. Design: Ten women with PA were included in this randomized crossover study. Group 1 (n = 5, mean age: 52 ± 13.5 years) received A+ST for the first 6 weeks, a 2-week washout period, and yoga for the second 6 weeks. Group 2 (n = 5, mean age: 41.8 ± 14 years) received the yoga program first, followed by the A+ST program. Methods: Participants were assessed using the following tools before and after each exercise intervention: Functional Assessment of Cancer Therapy-Brain (FACT-Br) (quality of life), Pittsburg Sleep Quality Index, Fatigue Severity Scale (FSS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS), and Montreal Cognitive Assessment Scale (MOCA). Results: FACT-Br scores were higher after the yoga program, HADS anxiety score was lower after the A+ST program, and MOCA scores increased after both exercise programs (P < 0.05). FSS score decreased after both exercise programs, but not significantly. In addition, nonsignificant decreases in HADS anxiety and depression scores and increased FSFI scores were observed after the yoga program. Conclusion: A+ST and yoga have positive effects on the quality of life in PA. We recommend yoga and A+ST as a supportive therapy for this population that may face comorbidities after surgical and medical treatment. Our results indicate these patients may benefit from physiotherapist-guided exercise programs.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Entrenamiento de Fuerza , Yoga , Adenoma/cirugía , Adulto , Anciano , Ansiedad/etiología , Estudios Cruzados , Depresión/psicología , Fatiga/etiología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Hipofisarias/cirugía , Calidad de Vida , Yoga/psicología
12.
Nanomedicine (Lond) ; 17(7): 447-460, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35142565

RESUMEN

Aim: A requirement for nanoparticle (NP) research is visualization of particles within cells and tissues. Limitations of electron microscopy and low yields of NP fluorescent tagging warrant the identification of alternative imaging techniques. Method: Confocal reflectance microscopy (CRM) in combination with fluorescence imaging was assessed for visualizing rhodamine B-conjugated silver and fluorescein isothiocyanate-conjugated lipid core-stearylamine NP uptake in vitro and in vivo. Results: CRM successfully identified cellular uptake and blood-brain barrier penetration of NPs owing to their distinguishing refractive indices. NP-dependent reflectance signals in vitro were dose and incubation time dependent. Finally, CRM facilitated the distinction between nonspecific fluorescence signals and NPs. Conclusion: These findings demonstrate the value of CRM for NP visualization in tissues, which can be performed with a standard confocal microscope.


Nanoparticles (NPs) are extremely small materials utilized in the healthcare sector mainly for the delivery of drugs into tissues that are not easily accessible with regular pharmaceuticals. One such tissue is the brain, which has a barrier between it and the bloodstream that prevents the passage of most drugs. For NP research, the successful entry of NPs into target tissues must be demonstrated, but this is complicated by the small size and weak labeling of NPs. In this article, the authors demonstrate a low-cost, complementary microscopy technique that is readily available in most biological research laboratories and that can be used to detect and analyze the entry of different NP types into brain tissue and their uptake by brain tumor cells. These data create new opportunities for research on NP-assisted drug delivery to the central nervous system.


Asunto(s)
Encéfalo , Microscopía Confocal , Nanopartículas , Encéfalo/diagnóstico por imagen , Liposomas , Microscopía Confocal/métodos
13.
Neurocrit Care ; 36(3): 802-814, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34782991

RESUMEN

BACKGROUND: Understanding the secondary damage mechanisms of traumatic brain injury (TBI) is essential for developing new therapeutic approaches. Neuroinflammation has a pivotal role in secondary brain injury after TBI. Activation of NLRP3 inflammasome complexes results in the secretion of proinflammatory mediators and, in addition, later in the response, microglial activation and migration of the peripheral immune cells into the injured brain are observed. Therefore, these components involved in the inflammatory process are becoming a new treatment target in TBI. Dexmedetomidine (Dex) is an effective drug, widely used over the past few years in neurocritical care units and during surgical operations for sedation and analgesia, and has anti-inflammatory effects, which are shown in in vivo studies. The aim of this original research is to discuss the anti-inflammatory effects of different Dex doses over time in TBI. METHODS: Brain injury was performed by using a weight-drop model. Half an hour after the trauma, intraperitoneal saline was injected into the control groups and 40 and 200 µg/kg of Dex were given to the drug groups. Neurological evaluations were performed with the modified Neurological Severity Score before being killed. Then, the mice were killed on the first or the third day after TBI and histopathologic (hematoxylin-eosin) and immunofluorescent (Iba1, NLRP3, interleukin-1ß, and CD3) findings of the brain tissues were examined. Nonparametric data were analyzed by using the Kruskal-Wallis test for multiple comparisons, and the Mann-Whitney U-test was done for comparing two groups. The results are presented as mean ± standard error of mean. RESULTS: The results showed that low doses of Dex suppress NLRP3 and interleukin-1ß in both terms. Additionally, high doses of Dex cause a remarkable decrease in the migration and motility of microglial cells and T cells in the late phase following TBI. Interestingly, the immune cells were influenced by only high-dose Dex in the late phase of TBI and it also improves neurologic outcome in the same period. CONCLUSIONS: In the mice head trauma model, different doses of Dex attenuate neuroinflammation by suppressing distinct components of the neuroinflammatory process in a different timecourse that contributes to neurologic recovery. These results suggest that Dex may be an appropriate choice for sedation and analgesia in patients with TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Dexmedetomidina , Animales , Antiinflamatorios , Lesiones Traumáticas del Encéfalo/complicaciones , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Interleucina-1beta/uso terapéutico , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedades Neuroinflamatorias
14.
J Neuroimmunol ; 359: 577672, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34364104

RESUMEN

Traumatic brain injury (TBI) is one of the significant causes of death among young people worldwide. Doxycycline (DOX), an antibiotic with anti-inflammatory effects, has not been used as a therapeutic agent to modify the inflammatory response after the traumatic brain injury. In this study, intraperitoneal administration of DOX reduced significantly the acute inflammatory markers like IL-6 and CD3, microglial migration to the damaged area marked with Iba-1, and neuronal apoptosis assessed with TUNEL assay at 72 h after the trauma. The low dose, 10 mg/kg of DOX had a dominant anti-inflammatory effect; while the high dose, 100 mg/kg of DOX, was more effective in decreasing neuronal apoptosis. In early hours after the head trauma, use of a low dose (10 mg/kg) of DOX for decreasing the acute form of inflammation followed by a high dose (100 mg/kg) for the anti-apoptotic effects particularly in severe head traumas, would be a promising approach to alleviate the brain injury.


Asunto(s)
Apoptosis/efectos de los fármacos , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/metabolismo , Doxiciclina/uso terapéutico , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Animales , Apoptosis/fisiología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Doxiciclina/farmacología , Masculino , Ratones
15.
Cureus ; 13(6): e15852, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34327080

RESUMEN

Background Radiotherapy (RT) with immune checkpoint inhibitors (ICI) has yielded good responses in many cancers. We aimed to report the results of combined fractionated stereotactic radiotherapy (FSRT) and ICI in patients with recurrent high-grade glioma. Methodology Patients were treated with FSRT and nivolumab which were continued until progression or toxicity. The Response Assessment in Neuro-oncology and Immunotherapy Response Assessment in Neuro-oncology criteria were used to assess treatment response on magnetic resonance imaging. Treatment-related toxicity was noted in all patients. Results A total of eight patients were included. Recurrence was detected after a median of 5.8 months following the first RT, all in the treatment field. FSRT (3 × 8 Gy) was applied with neoadjuvant, concurrent, and adjuvant nivolumab. After a median follow-up of 21.3 months from diagnosis and 12.6 months from recurrence, one patient was alive and seven succumbed to the disease. The median overall survival was 20.9 months after diagnosis and 12.9 months after recurrence. The median progression-free interval was 2.3 months after FSRT. The local control (LC) rate was 62.5% with a median local recurrence-free survival of nine months. Progression in other regions of the brain was observed in four patients with a median progression-free survival of 2.1 months. Acute toxicity was not observed. ICI-related grade 3 late pneumonitis was observed in two patients, and grade 1 late thyroid toxicity in two patients. One patient with pneumonitis also developed osteoporosis and radiation necrosis. Conclusions A high LC rate was achieved with concurrent FSRT and ICI with a severe late toxicity rate of 25%. This combination can be an option in recurrent high-grade gliomas.

16.
Turk Neurosurg ; 2021 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-35416262

RESUMEN

AIM: In this study, suppression of Aquaporin-4 (AQP4) synthesis via intracerebroventricular (i.c.v.) injection of antisense oligonucleotide after focal cortical contusion injury in mice was investigated. MATERIAL AND METHODS: 12-week female Swiss albino mice of 20-25 g were used to create a focal cortical contusion model by the weight drop method (35 grams blunt weight, 70 cm height) onto the parietal cortex after craniectomy. The sham group underwent craniectomy without trauma. In the control group, weight was dropped onto the parietal cortex immediately after Dulbecco\'s Modified Eagle Medium (DMEM) i.c.v. injection following craniectomy. In addition, 1 nM of aquaporin-4 (AQP4) antisense oligonucleotide (ASO) was injected via i.c.v route immediately after trauma (0 hours) and 4 hours after trauma. All animals underwent magnetic resonance (MR) imaging and were sacrificed at 24 h. Brain water content was determined using the wet/dry weight method. RESULTS: In the sham group, the average percentage of brain water content was 77.75% compared to the control group with 79.87%. The difference was statistically significant (*p=0.017). In the therapy group, the average was 78.81% and significantly reduced compared to the control group (*p=0.026) at 0 hours. In the 4-hour treatment group, the average of 79.11% was not statistically significant (p=0.39). MR imaging findings also showed a substantial reduction in brain edema in the 0-hour treatment group. However, the 4-hour treatment results, when compared with the control trauma group, did not show a significant difference. CONCLUSION: This study demonstrated that AQP4 antisense oligonucleotide therapy, when administered early after diffuse traumatic brain injury, leads to a significant reduction in brain edema.

17.
Clin Endocrinol (Oxf) ; 94(4): 598-605, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33296101

RESUMEN

BACKGROUND: Klotho is a new identified anti-ageing gene with tumour suppressor activities. Current data suggest that there is a tight relationship between Klotho protein and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. PURPOSE: This study aimed to investigate the possible association of Klotho gene polymorphisms with acromegaly and to assess whether these polymorphisms contribute to clinical characteristics, comorbidities and biochemical variables in these patients. METHODS: The study included 52 patients with acromegaly and 52 unrelated healthy subjects. The Klotho G395A and C1818T polymorphisms were assessed by Sanger sequencing. Serum levels of sKlotho were determined by ELISA method. RESULTS: Subjects carrying GA genotype of Klotho G395A polymorphism had 3.27 times higher risk of developing acromegaly [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.37-7.81; p = .023]. The A allele of G395A was significantly associated with acromegaly risk (OR, 2.27; 95% CI: 1.1-4.72; p = .022). No association was observed between the studied polymorphisms and disease characteristics including age at acromegaly diagnosis, size of adenoma, baseline GH and IGF-1 concentrations, and final outcome. G395A polymorphism was associated with the presence of malignancy (OR, 2.24, 95% CI: 1.63-3.08; p = .019) and colorectal polyps (OR, 1.99; 95% CI: 1.02-3.88; p = .047) in patients with acromegaly. Serum sKlotho levels were significantly higher and correlated with GH and IGF-1 levels among acromegaly patients. There was no association between the studied polymorphisms and sKlotho levels. CONCLUSIONS: Klotho G395A polymorphism is associated with acromegaly susceptibility and increased risk of malignancy and colorectal polyps in these patients.


Asunto(s)
Acromegalia , Glucuronidasa , Hormona de Crecimiento Humana , Acromegalia/genética , Predisposición Genética a la Enfermedad , Glucuronidasa/genética , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Proteínas Klotho , Polimorfismo Genético
18.
Brain Sci ; 10(12)2020 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-33316930

RESUMEN

BACKGROUND: Studies in rodents have re-kindled interest in the study of lymphatics in the central nervous system. Animal studies have demonstrated that there is a connection between the subarachnoid space and deep cervical lymph nodes (DCLNs) through dural lymphatic vessels located in the skull base and the parasagittal area. OBJECTIVE: To describe the connection of the DCLNs and lymphatic tributaries with the intracranial space through the jugular foramen, and to address the anatomical features and variations of the DCLNs and associated lymphatic channels in the neck. METHODS: Twelve formalin-fixed human head and neck specimens were studied. Samples from the dura of the wall of the jugular foramen were obtained from two fresh human cadavers during rapid autopsy. The samples were immunostained with podoplanin and CD45 to highlight lymphatic channels and immune cells, respectively. RESULTS: The mean number of nodes for DCLNs was 6.91 ± 0.58 on both sides. The mean node length was 10.1 ± 5.13 mm, the mean width was 7.03 ± 1.9 mm, and the mean thickness was 4 ± 1.04 mm. Immunohistochemical staining from rapid autopsy samples demonstrated that lymphatic vessels pass from the intracranial compartment into the neck through the meninges at the jugular foramen, through tributaries that can be called intrajugular lymphatic vessels. CONCLUSIONS: The anatomical features of the DCLNs and their connections with intracranial lymphatic structures through the jugular foramen represent an important possible route for the spread of cancers to and from the central nervous system; therefore, it is essential to have an in-depth understanding of the anatomy of these lymphatic structures and their variations.

19.
J Clin Neurosci ; 78: 376-386, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32376157

RESUMEN

The insular gliomas were classified based on their locations and extensions to the adjacent areas. The insular and orbitofrontal cortices with underlying fiber tracts were studied on ten (20 sides) human cadaveric brains and two heads. Twenty patients with insular gliomas with the orbitofrontal or septal region extensions were studied on preoperative magnetic resonance imaging (MRI). Insular gliomas can extend to the orbitofrontal area dorsolaterally and/or ventromedially through the subdivision of the uncinate fasciculus. The dorsolateral part of the uncinate fasciculus interconnects the temporopolar area to the lateral orbitofrontal cortex through insula, and the ventromedial part of the uncinate fasciculus interconnects the temporopolar area to the medial orbital cortex, gyrus rectus, and septal region. The gyrus rectus infiltration on MRI indicates a ventromedial involvement by passing through the ventromedial part of the uncinate fasciculus. Diffusion tensor imaging (DTI) MRI demonstration of the UF is difficult due to the interruption of the fiber tracts by tumor. Tumor infiltration extending to the gyrus rectus requires a 15° lateral tilting with vertex toward contralateral side, as well as 70° head rotation to the contralateral side of lesion, for exposure of frontal base, septal region, and lateral border of the anterior perforating substance at the same time with the exposure of whole sylvian fissure via transsylvian approach of the insular tumors. An understanding of the orbitofrontal extension of the insular tumor based on the subdivisions of UF is useful in preoperative surgical planning and can assist for gross total resection.


Asunto(s)
Glioma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Invasividad Neoplásica/diagnóstico por imagen , Corteza Prefrontal/patología , Sustancia Blanca/diagnóstico por imagen , Adulto , Corteza Cerebral/cirugía , Imagen de Difusión Tensora/métodos , Femenino , Glioma/cirugía , Humanos , Masculino , Fibras Nerviosas , Corteza Prefrontal/diagnóstico por imagen
20.
Horm Metab Res ; 52(4): 220-227, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32268423

RESUMEN

Primary hypophysitis (PH) is a rare autoimmune inflammatory disease of the pituitary gland. The aim of the study was to evaluate clinical characteristics, disease management, and outcomes of cases with PH. Medical records of PH patients admitted to Hacettepe University Hospital between 1999 and 2017 were analyzed retrospectively. Paraffin-embedded pathology blocks were obtained for both re-examination and IgG4 immunostaining. Twenty PH patients (15 females, 5 males) were evaluated. Mean age at diagnosis was 41.5±13.4 years. Some form of hormonal disorder was present in 63.2% of cases, hypogonadism (66.6%) being the most common. Panhypopituitarism was present in 36.8%. All patients had pituitary gland enlargement on magnetic resonance imaging; stalk thickening and loss of neurohypophyseal bright spot were present in 17.6 and 23.5%, respectively. Lymphocytic hypophysitis was the most common histopathological subtype (50%). Among pathology specimens available for IgG and IgG4 immunostaining (n=10), none fulfilled the criteria for IgG4-related hypophysitis. Four patients were given glucocorticoid treatment in diverse protocols; as initial therapy in 3. Sixteen cases underwent surgery, 7 of whom due to neuro-ophthalmologic involvement. Only 1 patient was observed without any intervention. Reduction of pituitary enlargement was seen in all surgical and glucocorticoid treated cases. None of the surgical patients showed hormonal improvement while one case in glucocorticoid group improved. PH should be considered in the differential diagnosis of sellar masses causing hormonal deficiencies. MRI findings are usually helpful, but not yet sufficient for definitive diagnosis of PH. Treatment usually improves symptoms and reduces sellar masses while hormonal recovery is less common.


Asunto(s)
Hipofisitis , Adulto , Estudios de Cohortes , Femenino , Humanos , Hipofisitis/diagnóstico , Hipofisitis/epidemiología , Hipofisitis/etiología , Hipofisitis/terapia , Hipopituitarismo/diagnóstico , Hipopituitarismo/epidemiología , Hipopituitarismo/etiología , Hipopituitarismo/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Turquía/epidemiología , Adulto Joven
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