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Vascular compression of neural tissue causing neurological symptoms is a wellknown phenomenon. This is commonly seen in trigeminal neuralgia and, less commonly, in hemifacial spasm by small arteries, which can be treated by microvascular decompression. Rarely, larger arteries, such as the vertebral arteries, may compress the brainstem. This can lead to symptoms of pontine or medullary distress like hemiparesis, dysphagia, or respiratory distress. This is treated by macrovascular decompression. Due to the rare and heterogenous nature of this disease, there is no standardized approach. We describe a novel technique whereby the vertebrobasilar system is mobilized anterolaterally towards the occipital condyle with a sling to decompress the brainstem.
We report two cases of vertebrobasilar dolichoectasia causing brainstem compression. A carotid patch graft sling with anterolateral mobilization to the occipital condyle is described as a surgical nuance to macrovascular decompressive surgery. Briefly, the vertebral artery was identified and dissected away from the brainstem and the bulbar cranial nerves. Bovine pericardium graft was used to create a sling around the artery by suturing the two ends together. The sling was then fixed either to the occipital condyle using cranial plating screws or suturing to the dura of the occipital condyle.
A novel surgical technique for management of vertebrobasilar dolichoectasia causing brainstem compression with progressive neurological deterioration is reported. Anatomical location and the offending vessel should guide neurosurgeons to select the best surgical option to achieve complete decompression of the involved neural structures.
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Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures. Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor. Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients. Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor.
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Chemotherapeutics play a significant role in the management of most brain tumors. First pass effect, systemic toxicity, and more importantly, the blood-brain barrier pose significant challenges to the success of chemotherapy. Over the last 80 years, different techniques of intraarterial chemotherapy delivery have been performed in many studies but failed to become standard of care. The purpose of this article is to review the history of intraarterial drug delivery and osmotic blood-brain barrier disruption, identify the challenges for clinical translation, and identify future directions for these approaches.
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Barrera Hematoencefálica , Neoplasias Encefálicas , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Sistemas de Liberación de Medicamentos , HumanosRESUMEN
Microvascular decompression (MVD) is a common surgical technique used for treatment of trigeminal neuralgia (TN) caused by direct vascular compression of the nerve at the brainstem entry zone (BEZ). Here we report a case of a patient (status postcraniotomy for microsurgical clip obliteration of a ruptured mid-basilar artery aneurysm) who developed right-sided TN 6 years after the procedure. During MVD surgery the clip head was found to be compressing the trigeminal nerve at the BEZ, causing Type 1 TN in V3 distribution. This is consistent with the commonly held theory that a pulsatile stimulus is needed to cause TN. To our knowledge there are no previous reports in the literature of an instrument causing TN.
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Aneurisma , Cirugía para Descompresión Microvascular , Neuralgia del Trigémino , Humanos , Instrumentos Quirúrgicos , Resultado del Tratamiento , Nervio Trigémino , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/etiología , Neuralgia del Trigémino/cirugíaRESUMEN
BACKGROUND: Cerebral angiography including internal and external carotid artery injections is crucial in young patients with a spontaneous subdural hematoma. CASE DESCRIPTION: We present the first reported case of an accessory meningeal artery aneurysm in a 46-year-old male with a history of hypertension that led to a spontaneous nontraumatic acute subdural hematoma. A PubMed review of the literature was performed using a keyword search to identify cases examining nontraumatic spontaneous intracranial hematomas related to meningeal artery aneurysms. The literature review summarizes all published reports of middle meningeal artery aneurysms resulting in nontraumatic acute intracranial bleeds. The patient underwent successful coiling of the accessory meningeal artery. CONCLUSION: We propose endovascular treatment for accessory meningeal artery aneurysms and emphasize the utility of angiography of internal and external carotid arteries in a patient with an unexplained intracranial hematoma.
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BACKGROUND: Progressive and/or unresectable pilocytic astrocytomas (PAs) carry a poor prognosis compared to typical PA. Early radiotherapy (RT) may have severe long-term neurocognitive side effects in this patient population. Intra-arterial (IA) chemotherapy is a viable alternative or addition to intravenous (IV) chemotherapy, which may be beneficial in avoidance of early RT. OBJECTIVE: To evaluate the safety and efficacy of IA chemotherapy in this subset of patients. METHODS: This is a retrospective review of medical records of PA patients who are treated with IA chemotherapy at Oregon Health & Science University from 1997 until 2019. Response to treatment was categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Progression free survival (PFS) and overall survival (OS) are also reported. RESULTS: Twelve patients were identified. All patients experienced progression prior to initiation of IA chemotherapy. The most common grade 3 or 4 toxicities related to chemotherapy were thrombocytopenia (66%), neutropenia (66%), leukopenia (50%), anemia (33%), and lymphopenia (16%). Responses achieved were CR in 1, PR in 3, SD in 7, and PD in 1. Median PFS and median OS were 16.5 and 83.5 mo, respectively. A total of 112 procedures (IA injections) were performed and 250 arteries were catheterized. There were 3 minor and no major complications attributable to procedures. CONCLUSION: This study demonstrates that IA chemotherapy can be safely used in patients with unresectable or progressive PA.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Progresión de la Enfermedad , Infusiones Intraarteriales/métodos , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Adolescente , Adulto , Astrocitoma/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Niño , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Gross total resection of arteriovenous malformations (AVMs) of the central nervous system confirmed by formal angiography is accepted as a cure for patients. In some cases, this may not be possible. Even though in these cases other treatment modalities such as endovascular embolization and radiotherapy can be used, long-term follow-up is lacking in the literature. CASE DESCRIPTION: Here we report a case of a 57-year-old woman with history of a right-sided parieto-occipital/periatrial AVM, initially treated with a combination of endovascular embolization and radiotherapy. CONCLUSIONS: The patient subsequently presented (12 years later) with a symptomatic, enlarging, contrast-enhancing mass at the same location that was angiographically occult but ultimately proven to be an AVM on a background of reactive changes on pathology.
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Fístula Arteriovenosa/patología , Fístula Arteriovenosa/terapia , Malformaciones Arteriovenosas Intracraneales/patología , Malformaciones Arteriovenosas Intracraneales/terapia , Embolización Terapéutica/métodos , Procedimientos Endovasculares/métodos , Femenino , Humanos , Persona de Mediana Edad , Radioterapia/métodosRESUMEN
BACKGROUND: In contemporary microneurosurgery reducing retraction-induced injury to the brain is essential. Self-retaining retractor systems are commonly used to improve visualization and decrease the repetitive microtrauma, but sometimes self-retaining retractor systems can be cumbersome and the force applied can cause focal ischemia or contusions. This may increase the morbidity and mortality. Here, we describe a technique of retraction using 10-0 sutures in the arachnoid. OBJECTIVE: To evaluate the imaging and clinical results in patients where 10-0 suture retraction was used to aid the surgical procedure. METHODS: Adjacent cortex was retracted by placing 10-0 nylon suture in the arachnoid of the bank or banks of the sulcus. The suture was secured to the adjacent dural edge by using aneurysm clips, allowing for easy adjustability of the amount of retraction. We retrospectively analyzed the neurological outcome, signal changes in postoperative imaging, and ease of performing surgery in 31 patients with various intracranial lesions including intracranial aneurysms, intra- and extra-axial tumors, and cerebral ischemia requiring arterial bypass. RESULTS: Clinically, there were no injuries, vascular events, or neurological deficits referable to the relevant cortex. Postoperative imaging did not show changes consistent with ischemia or contusion due to the retraction. This technique improved the visualization and illumination of the surgical field in all cases. CONCLUSION: Retraction of the arachnoid can be used safely in cases where trans-sulcal dissection is required. This technique may improve initial visualization and decrease the need for dynamic or static retraction.
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Neoplasias Encefálicas/cirugía , Aneurisma Intracraneal/cirugía , Microcirugia/métodos , Procedimientos Neuroquirúrgicos/métodos , Técnicas de Sutura , Suturas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Aneurysms of the distal anterior cerebral artery (dACA) are rare, consisting only 2-6% of all intracranial aneurysms. dACA aneurysms are often associated with anomalies such as azygous, bihemispheric and triplication of ACA. Among these anomalies accessory anterior cerebral artery (accACA) is an anatomical variant found in 3.3% to 15% of the population. Here we report a case of a 60-year-old female who presented with a Hunt and Hess grade II, Fisher grade III subarachnoid hemorrhage secondary to a ruptured saccular aneurysm originating from the pericallosal-callosomarginal artery bifurcation at the A3 segment of the accessory ACA and underwent an uncomplicated microsurgical clipping.
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BACKGROUND The purpose of this study was to present the clinical results of our retrospective series of carpal tunnel release (CTR) operations. For these operations we used a unique type of incision, for the first time, for treatment of carpal tunnel syndrome (CTS) consisting of a 1-cm semi-vertical (SV) incision made into the wrist crease for macroscopic open CTR. MATERIAL AND METHODS This retrospective study included 114 patients (101 females and 13 males) with CTR who were operated upon in our neurosurgery clinic between December 2010 and June 2015. Patient ages ranged from 35 to 83 years (mean 55.05±12.04 years). In total, 127 hands (73 right and 54 left) were operated upon using the SV skin incision technique. After an average follow-up of 18 months (ranging from 6 to 30 months), clinical and electrophysiological (EP) evaluations were performed. RESULTS A review of the English language literature published since 1957, when Phalen first popularised the diagnosis and treatment of this disease, determined that no previous reports of the mini-open incision technique as described in our study have been published. In our retrospective patient case review, we found that after operations using the SV incision technique, statistically significant differences were detected in electromyography (EMG) improvements (p<0.01). In addition, patients who showed improvement in EMG studies (n=90) were satisfied with the result of their surgery. CONCLUSIONS Our study demonstrated that 1-cm skin SV incision was a cosmetically satisfying, fast, and safe approach to CTR that was not only clinically effective but also electrophysiologically effective.
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Síndrome del Túnel Carpiano/fisiopatología , Síndrome del Túnel Carpiano/cirugía , Descompresión Quirúrgica/métodos , Fenómenos Electrofisiológicos , Adulto , Anciano , Anciano de 80 o más Años , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Cuidados PreoperatoriosRESUMEN
AIM: We have applied diffusion tensor imaging (DTI) to interrogate microstructural changes in white matter integrity in a widely used middle cerebral artery occlusion (MCAO) model of cerebral ischemia. MATERIAL AND METHODS: We performed ex vivo DTI 35 days after 60 minutes transient focal ischemia in male spontaneously hypertensive rats and generated fractional anisotropy (FA), mean, axial and radial diffusivity maps. Regions of interest corresponding to external capsule (EC), corpus callosum (CC) and internal capsule (IC) were compared among sham and stroked rats. We compared tractographic projections of white matter fiber patterns and examined white matter integrity by Luxol fast blue histological analysis. We also determined infarct lesion volumes at 24 hours post-ischemia by T2-weighted magnetic resonance imaging (MRI) or at 35 days by histological staining with cresyl violet. RESULTS: We found alterations in EC and IC, but not CC, as represented by decreased FA and increased mean, axial and radial diffusivities. The size of the ischemic lesion detected subacutely by T2-weighted MRI or at 35 days by histological staining correlated with the decline in FA in the affected structures. Tractography revealed disruption of fiber trajectories through the EC and reorientation of fibers within the caudate/putamen of rats subjected to MCAO. Similarly, loss of white matter integrity in the EC and increased white matter density in the caudate/putamen along the infarct border zone was evidenced by Luxol fast blue staining. CONCLUSION: Diffusion tensor imaging therefore allows for monitoring of white matter injury and reorganization in hypertensive rats.
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Encéfalo/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Animales , Anisotropía , Encéfalo/patología , Cuerpo Calloso/patología , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratas , Ratas Endogámicas SHR , Accidente Cerebrovascular/patologíaRESUMEN
Tumors of the lateral and third ventricles are cradled on all sides by vital vascular and eloquent neural structures. Microsurgical resection, which always requires attentive planning, plays a critical role in the contemporary management of these lesions. This article provides an overview of the open microsurgical approaches to the region highlighting key clinical perspectives.
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Neoplasias del Ventrículo Cerebral/cirugía , Ependimoma/cirugía , Ventrículos Laterales/cirugía , Microcirugia/métodos , Procedimientos Neuroquirúrgicos/métodos , Tercer Ventrículo/cirugía , Humanos , Complicaciones Posoperatorias , Resultado del TratamientoRESUMEN
The supracerebellar transtentorial approach via a suboccipital craniotomy provides a corridor to reach lesions of the tentorial incisura and supratentorial lesions of the posterior medial basal temporal lobe, such as lesions of the posterior parahippocampal and fusiform gyri. The supracerebellar transtentorial approach obviates the need for either retraction of eloquent cortex or a transcortical route to reach lesions in this region. We present three cases that demonstrate the utility of this approach: a left-sided tentorial meningioma with superior projection, a left-sided posterior parahippocampal cavernous malformation, and a left-sided posterior parahippocampal grade 2 oligodendroglioma. The video can be found here: https://youtu.be/OLnzUGZfUqk .
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Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Procedimientos Neuroquirúrgicos , Lóbulo Temporal/cirugía , Cerebelo/cirugía , Duramadre/cirugía , Humanos , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Microcirugia/métodos , Procedimientos Neuroquirúrgicos/métodos , Lóbulo Occipital/cirugíaRESUMEN
BACKGROUND: Although configurations of the posterior cerebral artery (PCA) and posterior communicating artery (PComA) have been extensively studied, reported rates of adult (AC), fetal (FC) and transitional configurations (TC) vary widely due to techniques used. A histological technique was applied to measure the circumference of the arteries and this was compared with caliper measurements taken from the same arteries. METHODS: Ninety-five brains were examined. The external diameters of all pre-communicating, post-communicating PCAs and PComAs were measured under operating microscope with a micrometer caliper. After measurements, all arteries were prepared for histology, sections were stained with Verhoff's elastic technique and the circumferences were measured using the light microscope. In the caliper group, AC was found in 77.2%, FC was found in 17.3% and TC was found in 5.5% of the right hemispheres, while on the left AC was found in 81.7%, FC in 18.3% and no TC was found. In the histology group, AC was found in 78.3% and FC was found in 21.7% of the right, while on the left AC was found in 81.7% and FC was found in 18.3% of cases. No TC was found in any hemisphere. There was no statistical significance between the two groups. RESULTS: Results of the present study reveal several important findings. When the PComA was absent in one hemisphere, the PComA was FC on the contralateral hemisphere. CONCLUSIONS: Transitional configuration was found in a very small number of cases in the caliper group compared to previous studies, and no TC was found in the histology group.
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Encéfalo/irrigación sanguínea , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/patología , Circulación Cerebrovascular/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Cadáver , Femenino , Humanos , Aneurisma Intracraneal/patología , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodosRESUMEN
Giant posterior circulation aneurysms pose a significant challenge to neurovascular surgeons. Among various treatment methods that have been applied individually or in combination, clipping under hypothermic circulatory arrest (HCA) is rarely used. We present a 62-year-old man who initially underwent coil occlusion of the right vertebral artery (VA) for a 2.5 cm giant vertebrobasilar junction (VBJ) aneurysm. His neurological condition had declined gradually and the aneurysm grew to 4 cm in size. The patient underwent clip reconstruction of giant VBJ aneurysm under HCA. His postoperative course was prolonged due to his preexisting neurological deficits. His preoperative Modified Rankin Score was 5, and improved postoperatively to 3 at three and six months, and to 2 at one year. The video can be found here: http://youtu.be/L53SiLV8eJY.
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Arteria Basilar/cirugía , Hipotermia Inducida/métodos , Aneurisma Intracraneal/cirugía , Microcirugia/métodos , Instrumentos Quirúrgicos , Angiografía Cerebral , Humanos , Masculino , Persona de Mediana Edad , Tomógrafos Computarizados por Rayos XRESUMEN
Thrombosed giant intracranial aneurysms usually present with symptoms and signs from their mass effect. Although multiple treatment options are available, direct clip reconstruction with thromboendarterectomy remains the gold standard. Here we present a 66-year-old man with seizure, aphasia and hemiparesis. Work-up revealed a giant partially thrombosed aneurysm of the internal carotid artery bifurcation with surrounding vasogenic edema. He underwent clip reconstruction of the aneurysm via a cranio-orbital approach. Although we prepared for bypass with the radial artery and/or the superficial temporal artery, we were able to clip-reconstruct the aneurysm without bypass. The patient improved upon his pre-morbid state after surgery and made an excellent recovery. The video can be found here: http://youtu.be/P_10hRQFuPo .
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Arteria Carótida Interna/cirugía , Aneurisma Intracraneal/cirugía , Microcirugia/métodos , Procedimientos de Cirugía Plástica/métodos , Instrumentos Quirúrgicos , Anciano , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/cirugía , Humanos , MasculinoRESUMEN
The aim of this study was to analyze the topographical anatomy of the dorsal spinal cord (SC) in relation to the posterior median septum (PMS). This included the course and variations in the PMS, and its relationship to and distance from other dorsal spinal landmarks. Microsurgical anatomy of the PMS was examined in 12 formalin-fixed adult cadaveric SCs. Surface landmarks such as the dorsal root entry zone (DREZ), the denticulate ligament, the architecture of the leptomeninges and pial vascular distribution were noted. The PMS was examined histologically in all spinal segments. The PMS extended most deeply at spinal segments C7 and S4. This was statistically significant for all spinal segments except C5. The PMS was shallowest at segments T4 and T6, where it was statistically significantly thinner than at any other segment. In 80% of the SCs, small blood vessels were identified that traveled in a rostrocaudal direction in the PMS. The longest distance between the PMS and the DREZ was at the C1-C4 vertebral levels and the shortest distance was at the S5 level. Prevention of deficits following a dorsal midline neurosurgical approach to deep-seated SC lesions requires careful identification of the midline of the cord. The PMS and septum define the midline on the dorsum of the SC and their accurate identification is essential for a safe midline surgical approach. In this anatomical study, we describe the surface anatomy of the dorsal SC and its relationship with the PMS, which can be used to determine a safe entry zone into the SC.
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Puntos Anatómicos de Referencia , Microcirugia , Médula Espinal/anatomía & histología , Adulto , Anciano , Anciano de 80 o más Años , Vasos Sanguíneos/anatomía & histología , Pesos y Medidas Corporales , Cadáver , Femenino , Humanos , Masculino , Microscopía , Persona de Mediana Edad , Médula Espinal/irrigación sanguínea , Columna VertebralRESUMEN
Background and Study Aim To enhance the visualization of the intracranial vasculature of cadavers under gross examination with a combination of imaging modalities. Material and Methods A total of 20 cadaver heads were used to test two different perfusion techniques. First, fixed cadaver heads were perfused with water; second, fresh cadavers were perfused with saline and 10% formalin. Subsequently, brains were removed and fixed. The compounds used were silicone rubber, silicone rubber mixed with powdered barium sulfate, and silicone rubber mixed with tantalum dioxide prepared by the first perfusion technique and gelatin mixed with liquid barium prepared with the second technique. Conventional X-ray imaging, computed tomography (CT), dynamic computed tomography (dCT), and postprocessing three-dimensional (3D) images were used to evaluate all the heads. Results Gelatinized barium was better visualized when compared with tantalum dioxide in conventional X-ray images. The blood vessels injected with either tantalum dioxide or gelatinized barium demonstrated a higher enhancement than the surrounding soft tissues with CT or dCT. The quality of the 3D reconstruction of the intracranial vasculature was significantly better in the CT images obtained from the gelatinized barium group. Conclusions Radiologic examinations of the heads injected with gelatinized barium facilitates the 3D understanding of cerebrovascular anatomy as an important tool for neuroanatomy training.
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AIM: The aim of this study was to better define the microsurgical anatomy of the supra/parasellar region and describe variations of the anterior clinoid process (ACP). MATERIAL AND METHODS: Fifteen formalin-fixed cadaver heads and 25 dry skulls were used to define the microsurgical anatomy of the ACP and related structures. The presence of the caroticoclinoid foramen (CaCF) as well as other relevant measurements were all noted. Radiological examination of the CaCF was also demonstrated on dry skulls. RESULTS: Interosseous bridges, which form between the anterior and middle clinoid processes or connect all three (anterior, middle and posterior) clinoid processes, were found in 30% of the specimens. The average basal width, length and thickness of the ACP were 7.3 mm, 9.7 mm and 5.4 mm, respectively. Length of the optic nerve (ON) up to the falciform ligament (FL) was 10.9 mm; length of the ON under the FL was 2.7 mm; length of ON after removal of the ACP and unroofing the optic canal was 21.1 mm. CONCLUSION: This study contributes to the relationship of important vascular, neural, bone and dural layers of this region and also demonstrates the variations of ACP by means of microsurgical dissections and radiological examinations.
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Seno Cavernoso/anatomía & histología , Microcirugia/métodos , Procedimientos Neuroquirúrgicos/métodos , Base del Cráneo/anatomía & histología , Cadáver , Seno Cavernoso/diagnóstico por imagen , Duramadre/anatomía & histología , Humanos , Nervio Óptico/anatomía & histología , Radiografía , Cráneo/anatomía & histología , Cráneo/diagnóstico por imagen , Base del Cráneo/diagnóstico por imagenRESUMEN
Hypoxia ischemia (HI)-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na(+)/H(+) exchanger isoform 1 (NHE1) protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX). 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H(+) efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na(+) and Ca(2+) overload. The latter was mediated by reversal of Na(+)/Ca(2+) exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα) during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na(+) overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H(+) homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na(+) and Ca(2+) homeostasis, which reduces Na(+)-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.