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Objective: We describe a patient with leukemia-related chronic subdural hematoma (CSDH) who was successfully treated using the combination of surgical evacuation and middle meningeal artery (MMA) embolization. Case Presentation: A 73-year-old man without apparent head trauma history was admitted to our hospital because of acute myeloid leukemia (AML). Head CT on admission revealed mild CSDH on both sides. Medical treatment options, including chemotherapy, were started. Since a decrease in platelet count and disseminated intravascular coagulation were observed on day 4, recombinant thrombomodulin was administered. As the patient exhibited signs of altered consciousness due to the enlargement of the right CSDH on day 10, we performed surgical drainage. Despite subsequent platelet transfusion and administration of goreisan, the right CSDH recurred within a short period. On day 17, we performed the second surgery and MMA embolization in one stage. The postoperative clinical course was favorable without recurrence of the hematoma. The patient eventually died on day 123 from a deterioration of his general condition. Conclusion: Although MMA embolization has recently been recognized as an effective treatment option for recurrent CSDH, there are no published reports addressing the efficacy of MMA embolization for refractory CSDH associated with hematological malignancies. Findings from the management of this case suggest that MMA embolization can be the effective treatment option for CSDH in patients with severe hemorrhagic diathesis due to AML.
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BACKGROUND: We explored whether the electromyogram (EMG) and the motor evoked potential (MEP) are useful for monitoring the function of the hypoglossal nerve during surgery targeting the cervical segment of the internal carotid artery. METHODS: The present study included 6 patients with internal carotid arterial stenosis (1 patient underwent bilateral surgeries) and 1 patient with a cervical carotid artery aneurysm. In 5 of the 8 procedures, the EMGs were recorded. We examined whether changes in the MEP and/or EMG were capable of predicting postoperative hypoglossal nerve deficits. RESULTS: None of the 6 patients who underwent a total of 7 carotid endarterectomy (CEA) procedures experienced postoperative hypoglossal nerve morbidity. In 2 of the 7 procedures, the MEP disappeared or decreased significantly during CEA. In all 4 cases in which the hypoglossal nerve was directly stimulated during CEA, stable and reproducible EMGs were obtained throughout the manipulation of the internal carotid artery. Hypoglossal nerve morbidity was observed in the one case that underwent aneurysm removal and end-to-end anastomosis of the internal carotid artery. In this case, while the MEP decreased significantly during the operation, the EMG showed true-positive results and false-negative results, depending on the stimulation site. CONCLUSIONS: The monitoring of hypoglossal nerve function using EMG appears to be accurate if an appropriate stimulation site is selected. Hypoglossal nerve monitoring using MEP can produce false-positive results. Combined monitoring using both MEP and EMG is recommended in cases where exposure of the hypoglossal nerve is expected to be technically difficult.
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Aneurisma , Estenose das Carótidas , Endarterectomia das Carótidas , Humanos , Artéria Carótida Interna/cirurgia , Nervo Hipoglosso/cirurgia , Nervo Hipoglosso/fisiologia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/métodos , Potencial Evocado Motor/fisiologia , Estimulação ElétricaRESUMO
OBJECTIVE: Brain tumors often become clinically evident during pregnancy; however, the mechanism has not been well elucidated. Purpose of this study is to investigate the influence of molecular genetic factors on the progression of brain tumors during pregnancy or the postpartum period. METHODS: Twelve cases of brain tumors that presented during pregnancy or postpartum period were included: five gliomas, three meningiomas, two vestibular schwannomas, and two chordomas. Tumor samples were investigated by metaphase comparative genomic hybridization and immunohistochemistry, for chromosomal copy number aberration (CNA) and receptor expression of sex hormones and growth factors. RESULTS: The results were correlated with the timing of tumor presentation in relation to the stage of pregnancy. EGFR, VEGFR-1/2, AR, and c-Myc were expressed in gliomas, PgR, ER, HER-2, VEGFR-1, EGF and VEGFR2 in meningiomas, VEGFR-1 in vestibular schwannomas, and EGFR, VEGFR-1/2, and c-Myc in chordomas. The CNAs of the tumors varied. Four of the five gliomas presented in the 2nd trimester, all three meningiomas in the 3rd trimester or postpartum period, and both of the two schwannomas in the late 2nd trimester. Expression of VEGFR-1/2 and EGFR was observed regardless of the timing of tumor presentation, whereas female hormone receptors and HER-2 were exclusively found in meningiomas. Interestingly, one anaplastic astrocytoma (IDH mut, non-codeleted) that progressed from precedent grade 2 tumor harbored amplification of the MYC locus. CONCLUSION: Progression of brain tumors during pregnancy is associated with various growth factors as well as sex hormones. The timing of presentation is likely dependent on molecular receptors specific to each tumor type.
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Neoplasias Encefálicas/patologia , Complicações Neoplásicas na Gravidez/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Período Pós-Parto , GravidezRESUMO
Objective: We describe a rare patient with a cavernous sinus dural arteriovenous fistula (CS DAVF) in whom diagnostic rotational angiography (RA) caused sinus arrest and bradycardia. Case Presentation: A 79-year-old woman with no previous history of cardiovascular diseases presented with left oculomotor nerve paresis. Conventional angiography confirmed a bilateral CS DAVF. During a three-dimensional RA (3DRA) examination of the left internal carotid artery, sinus arrest occurred. Subsequently, the use of 3DRA to image the left external carotid artery and the use of cone beam computed tomography (CBCT) to image the left internal and external carotid artery also caused transient sinus bradycardia. Two weeks later, we inserted a temporary transvenous pacemaker and completed the transvenous embolization of the left CS DAVF. The left oculomotor paresis improved without any perioperative complications. Conclusion: RA is a standard radiological modality for the diagnosis of cerebrovascular disease. Although the physical force generated by the injection of the contrast medium at the carotid bifurcation can theoretically cause hemodynamic instability, no previous reports have described sinus arrest or bradycardia in association with diagnostic carotid angiography. The present case demonstrates that 3DRA and CBCT can provoke rare, but serious, incidences of cardiac arrhythmia.
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Heparin-induced thrombocytopenia (HIT) is an antibody-mediated drug reaction to heparin use that causes platelet aggregation, followed by thrombocytopenia. Despite the thrombocytopenia, the main complications of HIT are thromboembolic in nature rather than hemorrhagic, and in particular, intracranial hemorrhage is rare. Herein, we describe a case of atraumatic acute subdural hematoma secondary to HIT, which was treated by platelet transfusion and surgery. A 77-year-old woman was admitted to our hospital for the treatment of severe aortic valve stenosis. Unfractionated heparin was administered during the preoperative period and during the aortic valve replacement surgery. Three days after the cardiac surgery, the patient presented with coma consistent with an acute subdural hematoma in the posterior fossa and obstructive hydrocephalus. Laboratory examination revealed a marked decrease of the platelet count to 40000/µL, and subsequent serological assay confirmed the diagnosis of HIT. The patient was treated by transfusion of platelets and fresh frozen plasma, and surgical removal of the hematoma. We started the administration of argatroban for substitution of heparin 4 days after the craniotomy. On day 13 after the neurosurgery, the patient developed cerebral infarction due to left middle cerebral artery occlusion and persistent right hemiparesis. We presented a rare case of the patient who developed acute subdural hematoma complicating HIT. Emergency craniotomy was successfully performed after administering platelet transfusions. Our experience with the present case suggests that platelet transfusions may be effective for performing emergency surgery for intracranial hemorrhage, even in patients with HIT.
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BACKGROUND: Peripheral aneurysms are known to be a source of intracranial hemorrhage in patients with moyamoya disease. However, the natural history of ruptured peripheral aneurysms remains unclear. Some regress spontaneously, whereas others may rebleed. Direct treatments, such as surgical or intravascular treatment of the peripheral aneurysm, can have a risk of severe neurologic complications owing to the depth of the operative field and the fragility of the parent artery. A careful treatment policy is required. CASE DESCRIPTION: In a 29-year-old man with moyamoya disease with intraventricular hemorrhage, rupture of a right anterior choroidal artery aneurysm was diagnosed by cerebral angiography. The aneurysm was approximately 4 mm in size and existed in the plexal segment of the right anterior choroidal artery. Endovascular embolization of the aneurysm was planned. However, repeat angiography 3 weeks after aneurysm diagnosis demonstrated complete resolution of the aneurysm. Such short-term disappearance of an aneurysm is remarkably rare. We believe that the aneurysm was thrombosed for a brief period considering the slow blood flow detected inside the aneurysm during the initial angiography. The patient was discharged with no neurologic deficit and has remained recurrence-free for >1 year. CONCLUSIONS: Given that spontaneous resolution of an aneurysm may occur in a short period of time, we suggest that conservative treatment be considered as an option for ruptured peripheral aneurysms associated with moyamoya disease when direct treatment is risky.
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Aneurisma Roto/etiologia , Doença de Moyamoya/complicações , Adulto , Aneurisma Roto/diagnóstico por imagem , Angiografia Cerebral , Humanos , Masculino , Doença de Moyamoya/diagnóstico por imagem , Remissão Espontânea , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Meningioma is the most common primary brain tumor. It is graded as I, II, or III based on the World Health Organization (WHO) classification of central nervous system tumors. Meningiomas, especially those classified as grade II-III, have an aggressive history and a high recurrence rate. Cancer stem cells (CSCs) represent a small subset of tumor cells and are considered to be involved in tumor initiation, growth, and/or recurrence. To date, the CSCs of meningioma have not been well established. METHODS: We assessed 51 grade II/III meningiomas using immunohistochemistry to determine if a correlation exists with the prognosis by investigating CD133, CD44, and nestin expression as possible CSC markers and age, gender, initial WHO tumor grade, Simpson grade, and the use of adjuvant radiation therapy. RESULTS: The median overall survival was 7.1 years, and the median progression-free survival (PFS) was 1.8 years. Univariate analysis using Cox proportional hazards regression revealed a negative correlation between CD133 and nestin expression and PFS (P = 0.0176 and P = 0.0138, respectively), and high expression of CD44 demonstrated a tendency toward a shorter PFS (P = 0.0563), as did the initial WHO grade and Simpson grade found at the initial operation (P = 0.0166 and P 0.0333, respectively). Multivariate analysis showed relevance between CD133 and nestin expression and PFS. CONCLUSIONS: CD133 and nestin expression, initial WHO grade and Simpson grade were associated with PFS in patients with grade II/III meningioma. These findings might suggest that these molecules are representative of CSCs in meningioma regarding the aspect of clinical course.
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BACKGROUND: Hypoglossal nerve deficit is a possible complication caused by carotid endarterectomy (CEA). The accidental injury of the hypoglossal nerve during surgery is one of the major reasons for permanent hypoglossal nerve palsy. In this study, we investigated the usefulness of intraoperative mapping of the hypoglossal nerve to identify this nerve during CEA. METHODS: Five consecutive patients who underwent CEA for the treatment of symptomatic or asymptomatic carotid artery stenosis were studied. A hand-held probe was used to detect the hypoglossal nerve in the operative field, and the tongue motor evoked potentials (MEPs) were recorded. RESULTS: The tongue MEPs were obtained in all the patients. The invisible hypoglossal nerve was successfully identified without any difficulty when the internal carotid artery was exposed. Intraoperative mapping was particularly useful for identifying the hypoglossal nerve when the hypoglossal nerve passed beneath the posterior belly of the digastric muscle. In 1 of 2 cases, MEP was also elicited when the ansa cervicalis was stimulated, although the resulting amplitude was much smaller than that obtained by direct stimulation of the hypoglossal nerve. Postoperatively, none of the patients presented with hypoglossal nerve palsy. CONCLUSIONS: Intraoperative hypoglossal nerve mapping enabled us to locate the invisible hypoglossal nerve during the exposure of the internal carotid artery accurately without retracting the posterior belly of the digastric muscle and other tissues in the vicinity of the internal carotid artery.
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Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/métodos , Nervo Hipoglosso/fisiologia , Nervo Hipoglosso/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/fisiopatologia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Língua/inervação , Língua/fisiologiaRESUMO
The authors report a rare case of a carotid-cavernous fistula (CCF) secondary to Ehlers-Danlos syndrome (EDS) type IV which showed an aggressive angiographical change.A 59-year-old woman presented with headache, right pulsatile tinnitus, and diplopia on the right side. The diagnostic angiography demonstrated a right CCF. Accordingly transarterial embolization of the fistula was attempted 5 days later. The initial right internal carotid angiography showed an aneurysm on the petrous portion of the internal carotid artery (ICA) which was not recognized in the diagnostic angiography. Spontaneous reduction of the shunt flow and long dissection of the ICA were also revealed. The aneurysm was successfully occluded with coils, and only minor shunt flow was shown on the final angiogram. EDS type IV was diagnosed with a skin biopsy for a collagen abnormality. After the operation, the stenosis of the right ICA gradually progressed, although there was no recurrence of the CCF.Interventional treatment for patients with EDS can cause devastating vascular complication. We should be aware of the possibility of EDS type IV when a spontaneous CCF shows unusual angiographical change because early diagnosis of EDS type IV is crucial for determination of the optimum treatment option.
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Fístula Carótido-Cavernosa/diagnóstico por imagem , Fístula Carótido-Cavernosa/terapia , Síndrome de Ehlers-Danlos/diagnóstico por imagem , Síndrome de Ehlers-Danlos/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Angiografia Digital , Biópsia , Angiografia Cerebral , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Angiografia por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The metabolic preference of malignant glioma for glycolysis as an energy source is a potential therapeutic target. As a result of the cellular heterogeneity of these tumors, however, the relation between glycolytic preference, tumor formation, and tumor cell clonogenicity has remained unknown. To address this issue, we analyzed the metabolic profiles of isogenic glioma-initiating cells (GICs) in a mouse model. METHODS: GICs were established by overexpression of H-Ras(V12) in Ink4a/Arf-null neural stem cells. Subpopulations of these cells were obtained by single-cell cloning, and clones differing in extracellular acidification potential were assessed for metabolic characteristics. Tumors formed after intracranial implantation of these clones in mice were examined for pathological features of glioma and expression of glycolytic enzymes. RESULTS: Malignant transformation of neural stem cells resulted in a shift in metabolism characterized by an increase in lactic acid production. However, isogenic clonal populations of GICs manifested pronounced differences in glucose and oxygen consumption, lactate production, and nucleoside levels. These differences were paralleled by differential expression of glycolytic enzymes such as hexokinase 2 and pyruvate kinase M2, with this differential expression also being evident in tumors formed by these clones in vivo. CONCLUSIONS: The metabolic characteristics of glioma cells appear early during malignant transformation and persist until the late stages of tumor formation. Even isogenic clones may be heterogeneous in terms of metabolic features, however, suggesting that a more detailed understanding of the metabolic profile of glioma is imperative for effective therapeutic targeting.
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Neoplasias Encefálicas/patologia , Diferenciação Celular/fisiologia , Transformação Celular Neoplásica/patologia , Glioblastoma/patologia , Células-Tronco Neoplásicas/citologia , Animais , Neoplasias Encefálicas/metabolismo , Modelos Animais de Doenças , Glioblastoma/metabolismo , Humanos , Camundongos , Células Tumorais CultivadasRESUMO
Cancer stem cells (CSCs) play an important role in disease recurrence after radiation treatment as a result of intrinsic properties such as high DNA repair capability and antioxidative capacity. It is unclear, however, how CSCs further adapt to escape the toxicity of the repeated irradiation regimens used in clinical practice. Here, we have exposed a population of murine glioma stem cells (GSCs) to fractionated radiation in order to investigate the associated adaptive changes, with the ultimate goal of identifying a targetable factor that regulates acquired radioresistance. We have shown that fractionated radiation induces an increase in IGF1 secretion and a gradual upregulation of the IGF type 1 receptor (IGF1R) in GSCs. Interestingly, IGF1R upregulation exerts a dual radioprotective effect. In the resting state, continuous IGF1 stimulation ultimately induces downregulation of Akt/extracellular-signal-regulated kinases (ERK) and FoxO3a activation, which results in slower proliferation and enhanced self-renewal. In contrast, after acute radiation, the abundance of IGF1R and increased secretion of IGF1 promote a rapid shift from a latent state toward activation of Akt survival signaling, protecting GSCs from radiation toxicity. Treatment of tumors formed by the radioresistant GSCs with an IGF1R inhibitor resulted in a marked increase in radiosensitivity, suggesting that blockade of IGF1R signaling is an effective strategy to reverse radioresistance. Together, our results show that GSCs evade the damage of repeated radiation not only through innate properties but also through gradual inducement of resistance pathways and identify the dynamic regulation of GSCs by IGF1R signaling as a novel mechanism of adaptive radioprotection.
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Glioma/patologia , Glioma/radioterapia , Células-Tronco Neoplásicas/metabolismo , Receptor IGF Tipo 1/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/metabolismo , Glioma/metabolismo , Humanos , Immunoblotting , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Células Tumorais CultivadasRESUMO
The drainage of the superficial middle cerebral vein (SMCV) is classified into four subtypes. The sphenobasal vein (SBV) drains from the SMCV to the pterygoid venous plexus at the temporal skull base. Epidural procedures in the standard anterior transpetrosal approach (ATPA) may damage the route of the SBV. We report a case in which modified surgical procedures via the ATPA were used to preserve the SBV. A 45-year-old man complained of right facial pain. Magnetic resonance images revealed a right cerebellopontine tumor suggestive of an epidermoid cyst. Right carotid angiography revealed that the SMCV drained into the pterygoid venous plexus via the SBV. The convexity dura mater of the temporal lobe was cut and the anterior part of the temporal lobe was retracted subdurally. The SBV was visualized from the subdural side. The basal dura mater of the temporal lobe posterior to the SBV was cut and the posterior part of the temporal lobe was retracted epidurally. After dissecting the dura mater medial to the greater petrosal nerve and to the edge of the petrous apex, the petrous apex was exposed and drilled out without injuring the SBV. The superior petrous sinus and the tentorium were cut. The tumor compressed the root exit zone of the trigeminal nerve. The tumor was grossly totally removed. The modified ATPA (epidural anterior petrosectomy with subdural visualization of the SBV) is effective in preserving the SBV.
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Veias Cerebrais/cirurgia , Cavidades Cranianas/cirurgia , Espaço Epidural/cirurgia , Osso Petroso/cirurgia , Espaço Subdural/cirurgia , Artérias Carótidas/patologia , Ângulo Cerebelopontino/patologia , Ângulo Cerebelopontino/cirurgia , Angiografia Cerebral , Drenagem , Cisto Epidérmico/cirurgia , Dor Facial/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Período Pós-OperatórioRESUMO
Invasiveness, cellular atypia, and proliferation are hallmarks of malignant gliomas. To effectively target each of these characteristics, it is important to understand their sequence during tumorigenesis. However, because most gliomas are diagnosed at an advanced stage, the chronology of gliomagenesis milestones is not well understood. The aim of the present study was to determine the onset of these characteristics during tumor development. Brain tumor-initiating cells (BTICs) were established by overexpressing H-Ras(V12) in normal neural stem/progenitor cells isolated from the subventricular zone of adult mice harboring a homozygous deletion of the Ink4a/Arf locus. High-grade malignant brain tumors were then created by orthotopic implantation of 10(5) BTICs into the forebrain of 6-week-old wild-type mice. Micewere killed every week for 5 weeks, and tumors were assessed for cellular atypia, proliferation, hemorrhage, necrosis, and invasion. All mice developed highly invasive, hypervascular glioblastoma-like tumors. A 100% penetrance rate and a 4-week median survival were achieved. Tumor cell migration along fiber tracts started within days after implantation and was followed by perivascular infiltration of tumor cells with marked recruitment of reactive host cells. Next, cellular atypia became prominent. Finally, mass proliferation and necrosis were observed in the last stage of the disease. Video monitoring of BTICs in live brain slices confirmed the early onset of migration, as well as the main cell migration patterns. Our results showed that perivascular and intraparenchymal tumor cell migration precede tumor mass formation in the adult brain, suggesting the need for an early and sustained anti-invasion therapy.