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Background: Meningiomas represent â¼30% of primary central nervous system (CNS) tumors. Although advances in surgery and radiotherapy have significantly improved survival, there remains an important subset of patients whose tumors have more aggressive behavior and are refractory to conventional therapy. Recent advances in molecular genetics and epigenetics suggest that this aggressive behavior may be due to the deletion of the DNA repair and tumor suppressor gene, CHEK2, neurofibromatosis Type 2 (NF2) mutation on chromosome 22q12, and genetic abnormalities in multiple RTKs including FGFRs. Management of higher-grade meningiomas, such as anaplastic meningiomas (AM: WHO grade III), is truly challenging and there isn't an established chemotherapy option. We investigate the effect of active multi tyrosine receptor kinase inhibitor Dovitinib at stopping AM cell growth in in vitro with either frequent codeletion or mutated CHEK2 and NF2 gene.Methods: Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot analysis, caspases assay, and DNA fragmentation assay.Results: Treatment of CH157MN and IOMM-Lee cells with Dovitinib suppressed multiple angiokinases-mainly FGFRs, leading to suppression of downstream signaling by RAS-RAF-MAPK molecules and PI3K-AKT molecules which are involved in cell proliferation, cell survival, and tumor invasion. Furthermore, Dovitinib induced apoptosis via downregulation of survival proteins (Bcl-XL), and over-expression of apoptotic factors (Bax and caspase-3) regardless of CHEK2 and NF2 mutation status.Conclusions: This study establishes the groundwork for the development of Dovitinib as a therapeutic agent for high-grade AM with either frequent codeletion or mutated CHEK2 and NF2, an avenue with high translational potential.
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Bencimidazoles/farmacología , Quinasa de Punto de Control 2/genética , Meningioma/tratamiento farmacológico , Neurofibromina 2/genética , Quinolonas/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Meningioma/genética , Meningioma/patología , Mutación/genética , Estadificación de Neoplasias , Fosfatidilinositol 3-Quinasas/genética , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/genética , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptores de Factores de Crecimiento de Fibroblastos/genética , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/genética , Proteína bcl-X/genéticaRESUMEN
OBJECTIVE: Opening the roof of the interhemispheric microsurgical corridor to access various neurooncological or neurovascular lesions can be demanding because of the multiple bridging veins that drain into the sinus with their highly variable, location-specific anatomy. The objective of this study was to propose a new classification system for these parasagittal bridging veins, which are herein described as being arranged in 3 configurations with 4 drainage routes. METHODS: Twenty adult cadaveric heads (40 hemispheres) were examined. From this examination, the authors describe 3 types of configurations of the parasagittal bridging veins relative to specific anatomical landmarks (coronal suture, postcentral sulcus) and their drainage routes into the superior sagittal sinus, convexity dura, lacunae, and falx. They also quantify the relative incidence and extension of these anatomical variations and provide several preoperative, postoperative, and microneurosurgical clinical case study examples. RESULTS: The authors describe 3 anatomical configurations for venous drainage, which improves on the 2 types that have been previously described. In type 1, a single vein joins; in type 2, 2 or more contiguous veins join; and in type 3, a venous complex joins at the same point. Anterior to the coronal suture, the most common configuration was type 1 dural drainage, occurring in 57% of hemispheres. Between the coronal suture and the postcentral sulcus, most veins (including 73% of superior anastomotic veins of Trolard) drain first into a venous lacuna, which are larger and more numerous in this region. Posterior to the postcentral sulcus, the most common drainage route was through the falx. CONCLUSIONS: The authors propose a systematic classification for the parasagittal venous network. Using anatomical landmarks, they define 3 venous configurations and 4 drainage routes. Analysis of these configurations with respect to surgical routes indicates 2 highly risky interhemispheric surgical fissure routes. The risks are attributable to the presence of large lacunae that receive multiple veins (type 2) or venous complex (type 3) configurations that negatively impact a surgeon's working space and degree of movement and thus are predisposed to inadvertent avulsions, bleeding, and venous thrombosis.
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Venas Cerebrales , Adulto , Humanos , Venas Cerebrales/cirugía , Venas Cerebrales/anatomía & histología , Seno Sagital Superior , Procedimientos Neuroquirúrgicos/métodos , Drenaje , Duramadre/cirugíaRESUMEN
BACKGROUND AND OBJECTIVES: Access to the jugular fossa pathologies (JFPs) via the transmastoid infralabyrinthine approach (TI-A) using the nonrerouting technique (removing the bone anterior and posterior to the facial nerve while leaving the nerve protected within the fallopian canal) or with the short-rerouting technique (rerouting the mastoid segment of the facial nerve anteriorly) has been described in previous studies. The objective of this study is to compare the access to Fisch class C lesions (JFPs extending or destroying the infralabyrinthine and apical compartment of the temporal bone with or without involving the carotid canal) between the nonrerouting and the short-rerouting techniques. Also, some tailored steps to the nonrerouting technique (NR-T) were outlined to enhance access to the jugular fossa (JF) as an alternative to the short-rerouting technique. METHODS: Neuronavigated TI-A was performed using the nonrerouting, tailored nonrerouting, and short-rerouting techniques on both sides of 10 human head specimens. Exposed area, horizontal distance, surgical freedom, and horizontal angle were calculated using vector coordinates for nonrerouting and short-rerouting techniques. RESULTS: The short-rerouting technique had significantly higher values than the NR-T ( P < .01) for the exposed area (169.1 ± SD 11.5 mm 2 vs 151.0 ± SD 12.4 mm 2 ), horizontal distance (15.9 ± SD 0.6 mm vs 10.6 ± SD 0.5 mm 2 ), surgical freedom (19 650.2 ± SD 722.5 mm 2 vs 17 233.8 ± SD 631.7 mm 2 ), and horizontal angle (75.2 ± SD 5.1° vs 61.7 ± SD 4.6°). However, adding some tailored steps to the NR-T permitted comparable access to the JF. CONCLUSION: Neuronavigated TI-A with the short-rerouting technique permits wider access to the JF compared with the NR-T. However, the tailored NR-T provides comparable access to the JF and may be a better option for class C1 and selected class C2 and C3 JFPs.
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OBJECTIVE: As presented in Part 1 of this series, thalamic gliomas (TGs) are deep-seated, difficult-to-access tumors surrounded by vital neurovascular structures. Given their high operative morbidity, TGs have historically been considered inoperable lesions. Although maximal safe resection (MSR) has become the treatment standard for lobar and even deep-seated mediobasal temporal and insular gliomas, the eloquent location of TGs has precluded this management strategy, with biopsy and adjuvant treatment being the mainstay. The authors hypothesized that MSR can be achieved with low morbidity and mortality for TGs, thus resulting in improved outcomes. METHODS: A retrospective single-center study was performed on all TG patients from 2006 to 2020. Clinical, imaging, and pathology reports were obtained. Univariate and multivariate analyses were performed to determine prognostic variables. Case examples illustrate various approaches and the rationale for staging resections of more complex TGs. RESULTS: A total of 42 patients (26 males, 16 females), among them 12 pediatric (29%) cases, were included. Their mean age was 36.0 ± 21.4 (median 30, range 3-73) years. The median maximal tumor diameter was 45 (range 19-70) mm. Eighteen patients (43%) had a prior stereotactic needle tumor biopsy, with the ultimate diagnosis changed for 7 patients (39%) following microsurgical resection. The most common surgical approaches were transtemporal (29%), anterior interhemispheric transcallosal (29%), and superior parietal lobule (25%). Overall, the combined subtotal and gross-total resection rate was 95% (n = 40). Low-grade gliomas (LGGs; grades I and II) comprised one-third of the group, whereas half of the patients had glioblastoma multiforme. There were no operative mortalities. Although temporary postoperative motor deficits were observed in 12 patients (28.6%), all improved during the early postoperative period except 1 (2.4%), who had mild residual hemiparesis. Two patients required CSF diversion for hydrocephalus. The 2-year overall survival rate was 90% for LGG patients and 15% for high-grade glioma (HGG) patients. Multivariate analysis revealed that histological grade, age, and extent of resection were independent prognostic factors associated with survival. CONCLUSIONS: Management of TGs is challenging, with resection avoided by many, if not most, neurosurgeons, especially for HGGs. The results reported here demonstrate improved outcomes with resection, particularly in younger LGG patients. The authors therefore advocate for MSR for a select cohort of TG patients using carefully planned surgical approaches, contemporary intraoperative adjuncts, and meticulous microsurgical techniques.
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OBJECTIVE: The selection of appropriate microsurgical approaches to treat thalamic pathologies is currently largely subjective. The objective of this study was to provide a structured cartography map for surgical navigation to treat gliomas involving different surfaces of the thalamus. METHODS: Fifteen formalin-fixed, silicone-injected cadavers (30 sides) were dissected, and 10 adult brain specimens (20 sides) were used to illustrate thalamic microsurgical anatomy using the Klingler fiber dissection technique. Exposures and trajectories for the six most common microsurgical approaches were depicted using MR data from healthy subjects converted into surface-rendered 3D virtual brain models. Additionally, thalamic surfaces exposed with all six approaches were color mapped on the virtual 3D model and compared side-by-side in 360° views with previously reported microsurgical approaches. These 3D models were then used in conjunction with topographic data to guide cadaveric dissection steps. RESULTS: There are two general surgical routes to thalamic lesions: the subarachnoid transcisternal and transcortical routes. The transcisternal route consists of the following three approaches: 1) anterior interhemispheric transcallosal approach, which exposes the anterior and superior thalamus; 2) posterior interhemispheric transcallosal approach, which exposes the posterosuperior thalamus; and 3) supracerebellar infratentorial approach, which exposes the posteromedial cisternal thalamus and can be extended laterally to approach the posterolateral thalamus by cutting the tentorium. The three transcortical approaches are the 1) superior parietal lobule approach, which exposes the posterosuperior thalamus and is particularly advantageous in the setting of hydrocephalus; 2) transtemporal gyrus approach, which exposes the inferolateral thalamus; and 3) transsylvian transinsular approach, which exposes the lateral thalamus (slightly more superiorly and posteriorly) and is advantageous for pathologies extending laterally into the peduncle, lenticular nucleus, or insula. CONCLUSIONS: Microsurgical approaches to thalamic gliomas continue to be challenging. Nonetheless, safe and effective cisternal, ventricular, and cortical corridors can be developed with thoughtful planning, anatomical understanding, and knowledge of the advantages, risks, and limitations of each approach. In some cases, it is wise to combine these approaches with staged procedures, as the authors demonstrate in Part 2. In Part 1 of this two-part series, they discuss thalamic microsurgical anatomy and illustrate the trajectory and exposures of all six approaches to guide decision-making. Part 2 discusses their thalamic glioma microsurgical case series, which utilizes these microsurgical approaches.
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BACKGROUND: Direct common carotid artery puncture (DCP) is conventionally used as a bailout technique in stroke patients. However, little is known about the relevant anatomy. OBJECTIVE: Examine the relationship of the common carotid artery (CCA) to surrounding structures based on different DCP trajectories passing through the artery's center. METHODS: Fifty randomly selected head/neck CTAs were analyzed. The trajectory of DCP and relationship to the internal jugular vein (IJV) and thyroid were analyzed at 1 cm intervals above the clavicle on 7 axial sections. Using the trans-carotid sagittal plane (TCSP) as the 0° trajectory, we plotted 3 additional trajectories at 30° intervals and the relationship with the IJV and thyroid proximity was graded as following: 0 = absent, 1 = adjacent, and 2 = crossing. The CCA tortuosity index (TI) was also analyzed for each vessel. RESULTS: Analysis of 2800 trajectories across 100 CCAs showed that the IJV and thyroid were least encountered on the axial sections 2 cm above the clavicle, at 0° on the right (9 thyroids and 6 IJV), and at 90° on the left (0 Thyroids and 14 IJVs). The TI of the CCA was significantly lower above the clavicle than its entire length (p<0.001). CONCLUSION: DCP performed 2 cm above the clavicle at 0° on the right, and 90° on the left appears to minimize encounters with the IJV and thyroid gland, reducing potential complications. However, despite these findings, ultrasound guidance remains vital for DCP safety. Further focus on endovascular device safety in DCP is needed.
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BACKGROUND: Anatomical variants of the anterior inferior cerebellar artery (AICA), such as an anomalous "AICA loop" embedded in the dura and bone of the subarcuate fossa, increase the complexity and risk of vestibular schwannoma resections. Classically, osseous penetrating AICA loops are the most challenging to mobilize, as the dura must be dissected and the surrounding petrous bone must be drilled to mobilize the AICA away from the surgical corridor and out of harm. OBSERVATIONS: The authors present a rare case of a dura-embedded, osseous-penetrating AICA loop encountered during a hearing-preserving retrosigmoid approach in which they demonstrate safe and efficient microdissection and mobilization of the AICA loop without having to drill the surrounding bone. LESSONS: Although preoperative recognition of potentially dangerous AICA loops has been challenging, thin-sliced petrous bone computed tomography scanning and high-quality magnetic resonance imaging can be useful in preoperative diagnosis. Furthermore, this report suggests that a retrosigmoid approach is superior, as it allows early intradural recognition and proximal vascular control and facilitates more versatile mobilization of AICA loops.
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BACKGROUND: Pial arterial malformations (PAMs) are rare vascular lesions consisting of dilated tortuous arteries without venous drainage. Current PAM understanding is limited by the lesion's rarity, limited anatomopathological studies, and frequent misclassifications. OBSERVATIONS: A 23-year-old male experienced two spontaneous subarachnoid hemorrhages (SAHs) over 6 months with initially unremarkable diagnostic cerebral angiograms. Magnetic resonance imaging (MRI) and angiography after the second SAH revealed a small perimesencephalic ovoid lesion within the left crural cistern, between the left superior and posterior cerebral arteries, appearing to be an exophytic cavernoma, a thrombosed aneurysm, or a hemorrhagic tumor. Microsurgical resection was achieved with a pterional craniotomy and anterior clinoidectomy. The resected lesion was characteristic of a pure PAM arising from superior cerebellar arterial branches. LESSONS: Small pure PAMs can be deceitfully dynamic lesions causing episodes of hemorrhage, complete thrombosis (angiographically occult), recanalization, and rehemorrhage. Small thrombosed vascular malformations or aneurysms should be included in differential diagnoses of angiographically occult SAH. MRI can be diagnostic, but the true angioarchitecture can only be elucidated with microneurosurgery. The only definitive cure is removal. The microneurosurgical strategy should account for worst-case scenarios, provide adequate skull base exposures, and include bypass revascularization options when thrombosed aneurysms are encountered.
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BACKGROUND: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by a classic triad of hypertelorism, bifid uvula and/or cleft palate, and generalized arterial tortuosity. There are limited data on the prevalence and rupture risk of intracranial aneurysms (IAs) in the setting of LDS, with no established guidelines. OBJECTIVE: To analyze the prevalence and rupture risk of IA in LDS. METHODS: Electronic medical records of patients with a confirmed diagnosis of LDS and available cerebrovascular imaging were reviewed. Patients were divided into 2 groups based on the presence of IA. Unmatched and propensity-matched analyses were used to identify potential risk factors for aneurysm formation. RESULTS: Records of 1111 patients were screened yielding a total of 60 patients with a diagnosis of LDS. Eighteen (30%) patients had IA, 4 (22.2%) of whom had multiple aneurysms for a total of 24 IAs. Twenty-three (95.8%) aneurysms were located in the anterior circulation; none of them were ruptured. On unmatched analysis, age ( P = .015), smoking history ( P = .034), hypertension ( P = .035), and number of extracranial aneurysms ( P < .001) were significantly higher in patients with IA. After matching for age, sex, race, stroke history, family history, and extracranial aneurysms, smoking history ( P = .009) remained significant. CONCLUSION: Patients with LDS have an increased risk of IAs, especially with a history of smoking. The prevalence rate of IAs in our series was 30%. Screening imaging should be considered at diagnosis, and patients should be encouraged to abstain from smoking. Further studies are needed to elucidate the risk of IA rupture and treatment considerations in this unique population.
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Aneurisma Intracraneal , Síndrome de Loeys-Dietz , Diagnóstico por Imagen , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/epidemiología , Síndrome de Loeys-Dietz/complicaciones , Síndrome de Loeys-Dietz/diagnóstico , Síndrome de Loeys-Dietz/epidemiologíaRESUMEN
BACKGROUND: Spinal epidural lipomatosis (SEL) is the excessive accumulation of extradural adipose tissue. Severe cases could result in myelopathy, and very rarely, in syringomyelia formation. Surgery has been associated with high morbidity and mortality, and no proven long-term benefits. The objective was to provide a technical description of an efficient and cost-effective procedure for multilevel thoracic decompression without requiring spinal instrumentation. METHODS: A technique of multilevel hemilaminotomy windows is described in a patient with severe thoracic SEL causing syringomyelia. A 3-dimensional spine model was created to illustrate the technique and working angles. We performed a literature review by searching PubMed, Ovid Embase, and Scopus electronic databases with the predetermined inclusion criteria of cases with spinal lipomatosis and a fluid cavity within the spinal cord. RESULTS: The patient's deficit and syringomyelia resolved postoperatively. A review of the literature revealed only 3 cases of syringomyelia secondary to SEL. Syringomyelia expansion occurred in all cases leading to progressive neurologic decline, and surgery with removal of the excessive adipose tissue resolved the syringomyelia and improved the neurologic functioning in all cases. CONCLUSIONS: This technique of multilevel alternating hemilaminotomy "windows" allows for safe and effective decompression and resection of the excessive adipose tissue with reduced operative time and without requiring spine instrumentation. The technique maintains the integrity of the posterior column, thus reducing the risk of postdecompression deformity. Careful bipolar electrocoagulation of internal vertebral veins and meticulous hemostasis is key for minimizing the intraoperative blood loss and avoiding postoperative hematoma formation.
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Descompresión Quirúrgica/métodos , Laminectomía/métodos , Compresión de la Médula Espinal/cirugía , Siringomielia/cirugía , Vértebras Torácicas/cirugía , Tejido Adiposo , Adulto , Espacio Epidural , Femenino , Humanos , Imagenología Tridimensional , Lipomatosis/complicaciones , Imagen por Resonancia Magnética , Compresión de la Médula Espinal/diagnóstico por imagen , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/fisiopatología , Siringomielia/diagnóstico por imagen , Siringomielia/etiología , Siringomielia/fisiopatologíaRESUMEN
Thromboembolic complications during aneurysm coiling are rare, with higher rates noted in ruptured aneurysms as patients are not usually premedicated with dual antiplatelet therapy.1,2 Management includes a series of escalating strategies, including medical therapy and intra-arterial thrombolysis.3-6 Additional strategies include mechanical thrombectomy with suction aspiration and stent retrievers.3 Intracranial stenting can be used as a last resource, especially in ruptured cases given the need for dual antiplatelets to prevent stent thrombosis.2 We present the case of a 42-yr-old man with a ruptured left internal carotid artery aneurysm with associated intracranial and intraventricular hemorrhage. The patient was initially presented to an outside facility after he was found in bed unable to speak and with right hemiparesis. The patient consented for surgery and underwent external ventricular drain (EVD) placement for the treatment of obstructive hydrocephalus, followed by diagnostic cerebral angiogram and aneurysm coiling. After the deployment of the last coil, control angiogram showed a small filling defect at the interface between the aneurysm neck and the distal vessel. The patient received intravenous heparin for therapeutic ACT and aspirin load. After progressive enlargement of the thrombus, the patient received intra-arterial glycoprotein (GP) IIB/IIIA inhibitors with a microcatheter positioned proximal to the thrombus. As the thrombus mass continued to enlarge, mechanical thrombectomy with an aspiration catheter was performed twice. Follow-up angiogram 20 min after the second aspiration demonstrated near-complete resolution of the thrombus. The patient recovered from his right hemiparesis, and he was discharged to rehabilitation on POD #21.
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Aneurisma Roto , Embolización Terapéutica , Aneurisma Intracraneal , Aneurisma Roto/complicaciones , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/cirugía , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Masculino , Estudios Retrospectivos , StentsRESUMEN
Neuroendocrine tumors (NETs) are benign tumors of the autonomic nervous system that rarely occur in the spinal canal. The gold standard treatment is gross total resection while preserving the patient's neurologic functioning as complete surgical resection is curative. The surgical management of NETs could pose a challenge given their friable consistency, hypervascular nature, and proclivity to adhere to the cauda equina nerve roots. We present a case of a 62-year-old female with an incidental primary NET arising from the filum terminale internum, review the literature, and describe the surgical technique including the benefits of using an intraoperative ultrasound and some of the pitfalls of relying "blindly" on neuromonitoring. Early identification and disconnection of the tumor's vascular pedicle, which usually runs through the cranial filum, devascularizes the tumor, prevents systemic complications from catecholamine release, and facilitates circumferential dissection off the en passage cauda equina nerve roots. Our patient remains neurologically intact and asymptomatic two years postoperatively and neuroimaging confirmed complete resection.