RESUMO
Subarachnoid hemorrhage often leads to poor outcomes owing to vasospasm, even after successful aneurysm treatment. Clazosentan, an endothelin receptor inhibitor, has been proven to be an effective treatment for vasospasms in a Japanese randomized controlled trial. However, its efficacy in older patients (≥ 75 years old) and those with World Federation of Neurosurgical Societies (WFNS) grade V has not been demonstrated. We retrospectively evaluated the efficacy of clazosentan in older patients and those with WFNS grade V, using real-world data. Patients with subarachnoid hemorrhage treated before and after the introduction of clazosentan were retrospectively evaluated. The patients were categorized into two groups (clazosentan era versus pre-clazosentan era), in which vasospasm management and outcomes were compared. Vasospasms were managed with fasudil hydrochloride-based (pre-clazosentan era) or clazosentan-based treatment (clazosentan era). Seventy-eight patients were included in this study: the clazosentan era (n = 32) and pre-clazosentan era (n = 46). Overall, clazosentan significantly reduced clinical vasospasms (clazosentan era: 31.3% versus pre-clazosentan era: 60.9%, p = 0.01), delayed cerebral ischemia (DCI) (9.4% versus 39.1%, p = 0.004), and vasospasm-related morbidity and mortality (M/M) (3.1% versus 19.6%, p = 0.03). In subgroup analysis of older patients or those with WFNS grade V, no significant difference was observed in clinical outcomes, although both DCI and vasospasm-related M/M were lower in the clazosentan era. Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment.
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1-(5-Isoquinolinasulfonil)-2-Metilpiperazina , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Idoso , Humanos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Infarto Cerebral , Dioxanos , Japão , Piridinas , Pirimidinas , Estudos Retrospectivos , Hemorragia Subaracnóidea/cirurgia , Sulfonamidas , Tetrazóis , Resultado do Tratamento , Vasoespasmo Intracraniano/tratamento farmacológicoRESUMO
Variations in drug transporter activities, caused by genetic polymorphism and drug-drug interactions (DDIs), alter the systemic exposure of substrate drugs, leading to differences in drug responses. Recently, some endogenous substrates of drug transporters, particularly the solute carrier family transporters such as OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, and MATE2-K, have been identified to investigate variations in drug transporters in humans. Clinical data obtained support their performance as surrogate probes in terms of specificity and reproducibility. Pharmacokinetic parameters of the endogenous biomarkers depend on the genotypes of drug transporters and the systemic exposure to perpetrator drugs. Furthermore, the development of physiologically based pharmacokinetic models for the endogenous biomarkers has enabled a top-down approach to obtain insights into the effect of perpetrators on drug transporters and to more precisely simulate the DDI with victim drugs, including probe drugs. The endogenous biomarkers can address the uncertainty in the DDI prediction in the preclinical and early phases of clinical development and have the potential to fulfill regulatory requirements. Therefore, the endogenous biomarkers should be able to predict disease effects on the variations in drug transporter activities observed in patients. This mini-review focuses on recent progress in the identification and use of the endogenous drug transporter substrate biomarkers and their application in drug development. SIGNIFICANCE STATEMENT: Advances in analytical methods have enabled the identification of endogenous substrates of drug transporters. Changes in the pharmacokinetic parameters (Cmax, AUC, or CLR) of these endogenous biomarkers relative to baseline values can serve as a quantitative index to assess variations in drug transporter activities during clinical studies and thereby provide more precise DDI predictions.
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Proteínas de Transporte de Cátions Orgânicos , Humanos , Reprodutibilidade dos Testes , Interações Medicamentosas , BiomarcadoresRESUMO
Dural supply from the external carotid system in cerebral arteriovenous malformations (AVMs) is well known, but actual angiographic evidence of dural supply to spinal cord AVMs (SCAVMs) has not been reported. Here, we report a case of dural supply to the conus SCAVM in the spinal arteriovenous metameric syndrome segment 25-30. Thirteen years after spinal surgery (T12-L2 laminoplasty), spinal angiography showed multiple dural supplies from the dorsal somatic branches, prelaminar arteries, and radiculomeningeal arteries to the SCAVM at the level of the previous spinal surgery. To the best of our knowledge, this is the first reported case with dural supply to the spinal cord. This case demonstrates that the extradural and extraspinal branches can supply the spinal cord in rare instances of spinal dural adhesions following repeated hemorrhages and surgical intervention under a metameric link background.
Assuntos
Malformações Vasculares do Sistema Nervoso Central , Malformações Arteriovenosas Intracranianas , Humanos , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia , Artérias , Angiografia , Procedimentos Neurocirúrgicos , Síndrome , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgiaRESUMO
INTRODUCTION: With the advent of MR-guided focused ultrasound, the importance of the efficacy and safety of bilateral ventral intermediate (Vim) thalamotomy for essential tremor (ET) has increased. However, reports on bilateral Vim thalamotomy for ET remain scarce. METHODS: To review the results and complications of bilateral Vim thalamotomy for the treatment of ET in the upper extremities, we retrospectively analyzed the patients with ET who underwent bilateral Vim thalamotomy with radiofrequency (RF) thermal coagulation. As bilateral simultaneous thalamotomy can cause surgical complications, thalamotomy was performed in stages. The interval between the first and second thalamotomies was 21.3 ± 14.7 months. We evaluated the efficacy using the Clinical Rating Scale for Tremor (CRST) before and after the first and second treatments, respectively. We also evaluated the complications before and after the first and second treatments, respectively. Moreover, we assessed the adverse events. RESULTS: Seventeen patients were included in the study. The mean follow-up period following the second thalamotomy was 29.3 ± 15.0 months. The CRST part A + B scores were 34.9 ± 9.7, 20.8 ± 7.0, and 7.4 ± 6.8 before, following the first (40.4% improvement, p < 0.0001) and second thalamotomies (78.6% improvement, p < 0.0001), respectively. Nine patients presented with prolonged adverse events, including dysarthria, dysgeusia, dysphagia, tongue numbness, unsteady gait, and postural instability at the last available evaluation. All adverse events were mild and did not interfere with the patient's daily activities. DISCUSSION/CONCLUSIONS: Bilateral Vim thalamotomy with RF thermal coagulation was an effective treatment for ET in both upper extremities. Despite most possible complications being mild, additional studies with a larger sample size are required to ensure patient safety.
Assuntos
Tremor Essencial , Humanos , Tremor Essencial/cirurgia , Estudos Retrospectivos , Tálamo/cirurgia , Resultado do Tratamento , Tremor , Imageamento por Ressonância Magnética/métodosRESUMO
We present and exemplify the flow-diverted glue embolization to target lesions (FLOW-GET) technique for spinal vascular diseases. In this technique, the occlusion of the posterior intercostal artery or dorsal muscular branch by coils diverts the injected glue from the segmental artery to the target lesions. This technique was applied to a ruptured retrocorporeal artery aneurysm and spinal dural arteriovenous fistulas. The FLOW-GET accomplished the complete obliteration of all lesions. This simple and useful technique can be applied to spinal vascular lesions even if a microcatheter is not placed in proper feeders or advanced close to the shunt points or aneurysms.
Assuntos
Aneurisma , Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Humanos , Embolização Terapêutica/métodos , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/terapia , Resultado do TratamentoRESUMO
Understanding the mechanisms of drug transport across the blood-brain barrier (BBB) is an important issue for regulating the pharmacokinetics of drugs in the central nervous system. In this study, we focused on solute carrier family 35, member F2 (SLC35F2), whose mRNA is highly expressed in the BBB. SLC35F2 protein was enriched in isolated mouse and monkey brain capillaries relative to brain homogenates and was localized exclusively on the apical membrane of MDCKII cells and brain microvascular endothelial cells (BMECs) differentiated from human induced pluripotent stem cells (hiPS-BMECs). SLC35F2 activity was assessed using its substrate, YM155, and pharmacological experiments revealed SLC35F2 inhibitors, such as famotidine (half-maximal inhibitory concentration, 160 µM). Uptake of YM155 was decreased by famotidine or SLC35F2 knockdown in immortalized human BMECs (human cerebral microvascular endothelial cell/D3 cells). Furthermore, famotidine significantly inhibited the apical (A)-to-basal (B) transport of YM155 in primary cultured monkey BMECs and hiPS-BMECs. Crucially, SLC35F2 knockout diminished the A-to-B transport and intracellular accumulation of YM155 in hiPS-BMECs. By contrast, in studies using an in situ brain perfusion technique, neither deletion of Slc35f2 nor famotidine reduced brain uptake of YM155, even though YM155 is a substrate of mouse SLC35F2. YM155 uptake was decreased significantly by losartan and naringin, inhibitors for the organic anion transporting polypeptide (OATP) 1A4. These findings suggest SLC35F2 is a functional transporter in various cellular models of the primate BBB that delivers its substrates to the brain and that its relative importance in the BBB is modified by differences in the expression of OATPs between primates and rodents. SIGNIFICANCE STATEMENT: This study demonstrated that SLC35F2 is a functional drug influx transporter in three different cellular models of the primate blood-brain barrier (i.e., human cerebral microvascular endothelial cell/D3 cells, primary cultured monkey BMECs, and human induced pluripotent stem-BMECs) but has limited roles in mouse brain. SLC35F2 facilitates apical-to-basal transport across the tight cell monolayer. These findings will contribute to the development of improved strategies for targeting drugs to the central nervous system.
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Transporte Biológico/efeitos dos fármacos , Barreira Hematoencefálica , Famotidina/farmacocinética , Imidazóis/farmacocinética , Proteínas de Membrana Transportadoras/metabolismo , Naftoquinonas/farmacocinética , Transportadores de Ânions Orgânicos/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Células Cultivadas , Fármacos do Sistema Nervoso Central/farmacocinética , Desenvolvimento de Medicamentos/métodos , Células Endoteliais/metabolismo , Haplorrinos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Modelos BiológicosRESUMO
Here, we have reported a case pertaining to a 59-year-old man with bilateral traumatic carotid artery injury caused by vinyl umbrella penetration who was successfully treated. The patient fell from the stairs while holding an umbrella, which penetrated his neck. On admission, the patient was in a comatose state and the umbrella had been removed. Active bleeding was observed on the left side of the neck. Hence, tracheal intubation was performed to support respiration. Neck and head contrast-enhanced CT revealed bilateral extravasations from the carotid arteries and right middle cerebral artery(MCA)occlusion. Left carotid angiography showed extravasation from the external carotid artery(ECA), which was treated with coil embolization. Right carotid angiography revealed bleeding from the ECA and internal carotid artery(ICA)and occlusion of the MCA. The ECA and ICA were occluded by coil and n-butyl-2-cyanoacrylate embolization. After the procedures, the patient developed a large right cerebral infarction with massive brain swelling; therefore, external decompression was performed. Subsequently, the patient became alert and was able to walk with support within a month. Bilateral carotid injury is severe and difficult to treat. Endovascular therapy may be effective for the management of bilateral carotid injuries.
Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Artérias Carótidas , Artéria Carótida Externa , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Endogenous substrates are emerging biomarkers for drug transporters, which serve as surrogate probes in drug-drug interaction (DDI) studies. In this study, the results of metabolome analysis using wild-type and Oct1/2 double knockout mice suggested that N 1-methyladenosine (m1A) was a novel organic cation transporter (OCT) 2 substrate. An in vitro transport study revealed that m1A is a substrate of mouse Oct1, Oct2, Mate1, human OCT1, OCT2, and multidrug and toxin exclusion protein (MATE) 2-K, but not human MATE1. Urinary excretion accounted for 77% of the systemic elimination of m1A in mice. The renal clearance (46.9 ± 4.9 ml/min per kilogram) of exogenously given m1A was decreased to near the glomerular filtration rates by Oct1/2 double knockout or Mate1 inhibition by pyrimethamine (16.6 ± 2.6 and 24.3 ± 0.6 ml/min per kilogram, respectively), accompanied by significantly higher plasma concentrations. In vivo inhibition of OCT2/MATE2-K by a single dose of 7-[(3R)-3-(1-aminocyclopropyl)pyrrolidin-1-yl]-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxoquinoline-3-carboxylic acid in cynomolgus monkeys resulted in the elevation of the area under the curve of m1A (1.72-fold) as well as metformin (2.18-fold). The plasma m1A concentration profile showed low diurnal and interindividual variation in healthy volunteers. The renal clearance of m1A in younger (21-45 year old) and older (65-79 year old) volunteers (244 ± 58 and 169 ± 22 ml/min per kilogram, respectively) was about 2-fold higher than the creatinine clearance. The renal clearances of m1A and creatinine were 31% and 17% smaller in older than in younger volunteers. Thus, m1A could be a surrogate probe for the evaluation of DDIs involving OCT2/MATE2-K. SIGNIFICANCE STATEMENT: Endogenous substrates can serve as surrogate probes for clinical drug-drug interaction studies involving drug transporters or enzymes. In this study, m1A was found to be a novel substrate of renal cationic drug transporters OCT2 and MATE2-K. N 1-methyladenosine was revealed to have some advantages compared to other OCT2/MATE substrates (creatinine and N 1-methylnicotinamide). The genetic or chemical impairment of OCT2 or MATE2-K caused a significant increase in the plasma m1A concentration in mice and cynomolgus monkeys due to the high contribution of tubular secretion to the net elimination of m1A. The plasma m1A concentration profile showed low diurnal and interindividual variation in healthy volunteers. Thus, m1A could be a better biomarker of variations in OCT2/MATE2-K activity caused by inhibitory drugs.
Assuntos
Adenosina/análogos & derivados , Interações Medicamentosas , Rim/metabolismo , Proteínas de Transporte de Cátions Orgânicos/fisiologia , Adenosina/metabolismo , Adulto , Idoso , Animais , Biomarcadores , Creatinina/metabolismo , Células HEK293 , Humanos , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-IdadeRESUMO
A 28-year-old pregnant woman underwent an emergency caesarian section after 39 weeks of gestation because of decreased fetal movement and baseline fetal heart rate variability. The neonate was diagnosed with neonatal asphyxia and presented with right cardiac failure due to pulmonary hypertension. The neonate presented convulsion, and plane computed tomography (CT) showed dilation of the vein of Galen and sinuses on day 3. Magnetic resonance imaging and CT with contrast were performed after cardiac failure subsided, and there was no evidence of arteriovenous shunt and normalization of the vein of Galen. The patient was diagnosed with vein of Galen varix (VGV). In the previous literature, only 3 cases of VGV have been reported. VGV is considered to be caused by right cardiac failure without the presence of an arteriovenous shunt and requires treatment only for cardiac failure and its cause. Therefore, it is important to differentiate VGV from vein of Galen aneurysmal malformation.
Assuntos
Veias Cerebrais/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico , Varizes/diagnóstico por imagem , Adulto , Asfixia , Veias Cerebrais/anormalidades , Cesárea , Feminino , Humanos , Hipertensão Pulmonar , Recém-Nascido , Imageamento por Ressonância Magnética , Gravidez , Tomografia Computadorizada por Raios XRESUMO
The present study aimed to establish a humanized mouse model with which to explore OATP1A2-mediated transcellular transport of drug substrates across the blood-brain barrier (BBB) and to evaluate the usefulness of the humanized mice in preclinical studies. Sulpiride, amisulpride, sultopride, and triptans were used as probes to discriminate OATP1A2 and Oatp1a4. We generated a mouse line humanized for OATP1A2 by introducing the coding region downstream of the Oatp1a4 promoter using the CRISPR/Cas9 technique. In the mice generated, OATP1A2 mRNA in the brain was increased corresponding to disappearance of Oatp1a4. OATP1A2 was localized on both the luminal and abluminal sides of the BBB. Unfortunately, study in vivo employing sulpiride, sumatriptan, and zolmitriptan as probes did not indicate any difference in their brain-to-plasma ratio between the control and humanized mice. Quantitative targeted absolute proteomic analysis of the BBB fraction from the humanized mice revealed that almost all analyzed transporters and membrane proteins were expressed at similar levels to those in control mice. The quantitative levels of OATP1A2 differed depending on the peptide quantified, which suggests that incomplete translation or posttranslational modification may occur. The blood-to-brain transport of zolmitriptan, determined by brain perfusion in situ, was 1.6-fold higher in the humanized mice than in the controls, whereas that of sulpiride was not significantly changed. To our knowledge, we established a mouse line humanized for a BBB uptake transporter for the first time. Unfortunately, because of limited impact, there is still room for improvement of the model system.
Assuntos
Transporte Biológico/fisiologia , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Preparações Farmacêuticas/metabolismo , Animais , Linhagem Celular , Células HEK293 , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oxazolidinonas/metabolismo , Proteômica/métodos , Triptaminas/metabolismoRESUMO
Brain microvascular endothelial cells derived from human induced pluripotent stem cells (hiPS-BMECs) have been proposed as a new blood-brain barrier model, but their transport function has not been fully clarified. Therefore, in this study, we investigated the gene expression and function of transporters in hiPS-BMECs by means of quantitative reverse transcription-PCR, in vitro transcellular transport studies, and uptake experiments. mRNAs encoding ABC and SLC transporters, such as BCRP, MCT1, CAT1, and GLAST, were highly expressed in hiPS-BMECs. Transcellular transport studies showed that prazosin, [14C]l-lactate, [3H]l-arginine, and [3H]l-glutamate (substrates of BCRP, MCT1, CAT1, and GLAST, respectively) were transported asymmetrically across the hiPS-BMEC monolayer. Substrates of LAT1, OCTN2, CAT1, GLAST, MCT1, and proton-coupled organic cation (H+/OC) antiporter were taken up by hiPS-BMECs in a time-, temperature-, and concentration-dependent manner, and the uptakes were markedly decreased by inhibitors of the corresponding transporter. These results indicate that hiPS-BMECs express multiple nutrient and drug transporters.
Assuntos
Barreira Hematoencefálica/metabolismo , Células Endoteliais/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Arginina/farmacocinética , Diferenciação Celular , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Ácido Glutâmico/farmacocinética , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Ácido Láctico/farmacocinética , Proteínas de Membrana Transportadoras/genética , Microvasos/citologia , Prazosina/farmacocinética , RNA Mensageiro/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND AND PURPOSE: The prognosis of untreated spinal arteriovenous malformations (SAVMs) is poor. Embolization plays an important role in the management of intramedullary SAVMs. Delayed aggravation due to spinal venous thrombosis following successful embolization has been reported; however, perioperative management strategies to prevent thrombosis have not been explored. We present our single-center experience of SAVM embolization and perioperative management, including anticoagulation. MATERIAL AND METHODS: We retrospectively evaluated 18 patients with SAVMs who underwent transarterial embolization. Perioperative anticoagulation therapy was administered to selected patients. We compared the characteristics of the patients, including perioperative management procedures, between those with and without postoperative worsening following embolization. RESULTS: Acute postoperative worsening within 1 week occurred in 4 (22.2%) patients. Of these, immediate worsening was observed in one patient as a procedure-related complication. Delayed worsening after 24â¯h was observed in 3 patients, caused by delayed venous thrombosis with severe back pain. Rescue anticoagulation for delayed worsening improved symptoms in two patients. A comparison between patients with and without acute postoperative worsening revealed significant differences in age (median 46.5 vs. 26.5 years, pâ¯= 0.009) and the presence of postoperative back pain (75.0% vs. 0%, pâ¯= 0.005); however, there was no significant difference in use of selective anticoagulation (pâ¯= 0.274). CONCLUSION: The results of this study suggest that SAVM embolization can cause acute worsening due to postoperative venous thrombosis with severe back pain, which may be reversed by anticoagulation therapy. Back pain is an important finding that suggests venous thrombosis, and anticoagulation should be urgently administered.
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Anticoagulantes , Embolização Terapêutica , Trombose Venosa , Humanos , Embolização Terapêutica/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Anticoagulantes/uso terapêutico , Resultado do Tratamento , Dor nas Costas/etiologia , Assistência Perioperatória/métodos , Adulto Jovem , Medula Espinal/irrigação sanguínea , Medula Espinal/diagnóstico por imagem , Adolescente , Malformações Arteriovenosas/terapia , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/complicações , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND AND PURPOSE: Fraction metabolized (fm ) and fraction transported (ft ) are important for understanding drug-drug interactions (DDIs) in drug discovery and development. However, current in vitro systems cannot accurately estimate in vivo fm due to inability to reflect the ft by efflux transporters (ft,efflux ). This study demonstrates how CYP3A-mediated DDI for CYP3A/P-gp substrates can be predicted using Hu-PXB mice as human liver chimeric mice. EXPERIMENTAL APPROACH: For estimating human in vitro fm by CYP3A enzyme (fm,CYP3A,in vitro ), six drugs, including CYP3A/P-gp substrates (alprazolam, cyclosporine, docetaxel, midazolam, prednisolone, and theophylline) and human hepatocytes were incubated with or without ketoconazole as a CYP3A inhibitor. We calculated fm,CYP3A,in vitro based on hepatic intrinsic clearance. To estimate human in vivo fm,CYP3A (fm,CYP3A,in vivo ), we collected information on clinical DDI caused by ketoconazole for these six drugs. We calculated fm,CYP3A,in vivo using the change of total clearance (CLtotal ). For evaluating the human DDI predictability, the six drugs were administered intravenously to Hu-PXB and SCID mice with or without ketoconazole. We calculated the change of CLtotal caused by ketoconazole. We compared the CLtotal change in humans with that in Hu-PXB and SCID mice. KEY RESULTS: The fm,CYP3A,in vitro was overestimated compared to the fm,CYP3A,in vivo . Hu-PXB mice showed much better correlation in the change of CLtotal with humans (R2 = 0.95) compared to SCID mice (R2 = 0.0058). CONCLUSIONS AND IMPLICATIONS: CYP3A-mediated DDI can be predicted by correctly estimating human fm,CYP3A,in vivo using Hu-PXB mice. These mice could be useful predicting hepatic fm and ft,efflux .
Assuntos
Citocromo P-450 CYP3A , Cetoconazol , Humanos , Camundongos , Animais , Citocromo P-450 CYP3A/metabolismo , Cetoconazol/metabolismo , Camundongos SCID , Fígado/metabolismo , Interações MedicamentosasRESUMO
Background: Ventricular arteriovenous malformations (AVMs) are localized in the ventricles and are mainly fed by the anterior choroidal artery (AChoA) and posterior choroidal artery (PChoA). Surgical resection of ventricular AVMs is difficult as the lesions are localized deep in the brain. Therefore, endovascular treatment is expected to treat ventricular AVMs. However, embolization from the AChoA and PChoA carries the risk of ischemic complications. Even though there are some major reports on embolization strategies from the choroidal arteries, embolization of these arteries remains technically challenging. In this article, we report two successful cases of ventricular AVM embolization using AChoA and PChoA. Case Description: Case 1: A 34-year-old male presented with intraventricular hemorrhage (IVH). Subsequently, ventricular AVM embolization in the anterior horn was performed using n-butyl-2-cyanoacrylate (NBCA) through the AChoA and medial PChoA, and complete obliteration was observed without neurological deterioration. Case 2: A 71-year-old female presented with IVH. Subsequently, ventricular AVM embolization in the lateral ventricle was performed through the AChoA and lateral PChoA with Onyx and NBCA, and partial obliteration was observed without complications. Furthermore, Gamma Knife surgery for residual lesions resulted in complete obliteration. Conclusion: Embolization through the choroidal arteries for ventricular AVMs is an effective curative or adjunctive treatment.
RESUMO
De novo spinal dural arteriovenous fistulas (AVFs) have been reported as metachronous AVFs However, metachronous spinal AVFs are extremely rare, and their pathogenesis remains uncertain. We report a case of de novo radicular AVF (RAVF) following treatment for spinal AVF at the craniocervical junction (CCJ). We also reviewed the literature and discussed the pathogenesis of metachronous spinal AVF. A 64-year-old male patient diagnosed with spinal AVF at the CCJ supplied from the right C1 segmental artery was treated with Onyx-18 (eV3 Inc, CA, USA) trans-arterial embolization, resulting in partial occlusion. Angiography showed a slight residual shunt two weeks after the embolization without another shunt lesion. A five-year follow-up spinal angiography showed de novo RAVF at the C4 level and complete occlusion of the first AVF. The second AVF was not treated because it was asymptomatic, and the patient remained asymptomatic. De novo RAVF was found to develop five years after the embolization of a CCJ-spinal AVF in a patient. This is the first case of de novo RAVF post-treatment of a spinal AVF. This case demonstrated that RAVF could develop as an acquired disease.
RESUMO
Cerebral venous thrombosis (CVT) is a rare disease, occurring in 0.5%-1% of all patients with strokes. Systemic and hereditary diseases and traumas are potential causes of CVT. We report a case of CVT and systemic thromboembolism complicated with hyperhomocysteinemia and iron-deficiency anemia caused by autoimmune gastritis. A 47-year-old female patient was admitted to the emergency department due to difficulty in movement, impaired consciousness, and urinary incontinence. Brain computed tomography (CT) and magnetic resonance imaging (MRI) showed bilateral thalamic edema associated with venous sinus thrombosis and embolic cerebral infarction in the deep white matter of the bilateral cerebral hemispheres. In addition, contrast enhanced whole-trunk CT scan showed deep femoral thrombosis and pulmonary artery embolism. She had no medical history of diseases or drug use that may cause thrombosis. Blood test results revealed iron-deficiency anemia and hyperhomocysteinemia, which were determined to be the cause of systemic thromboembolism. The patient tested positive for intrinsic factor antibodies. Moreover, the patient was diagnosed with autoimmune gastritis by gastrointestinal endoscopy. Therapies including anticoagulant and replacement with iron and vitamin B12 were administered. The patient was discharged from the hospital without neurological deficits. A favorable clinical course was achieved with anticoagulant administration and replacement therapy with iron and vitamin B12 for cerebral arteriovenous embolism that developed due to autoimmune gastritis.
Assuntos
Anemia Ferropriva , Embolia , Gastrite , Hiper-Homocisteinemia , Trombose Intracraniana , Tromboembolia , Trombose Venosa , Feminino , Humanos , Pessoa de Meia-Idade , Anemia Ferropriva/complicações , Anemia Ferropriva/tratamento farmacológico , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Vitamina B 12 , Gastrite/complicações , Gastrite/tratamento farmacológico , Anticoagulantes/uso terapêutico , Trombose Venosa/complicações , Ferro , Embolia/complicações , Embolia/tratamento farmacológicoRESUMO
BACKGROUND: The functional outcomes in spinal cord arteriovenous shunts (SCAVSs) are usually unpredictable from current assessments of treatment results. We aimed to investigate and propose a new index marker, the vertebral blush (VB) sign, for assessing the treatment efficacy of SCAVSs. METHODS: This retrospective cohort study enrolled patients diagnosed with SCAVSs between June 2012 and May 2021. The VB sign was defined as the angiographic finding of reappearance or enhanced contrast staining of the vertebral bodies fed by shunt-related arteries observed after shunt occlusion. The primary outcome was the improvement in motor/sensory disturbances or sphincter impairments within 1 year after treatment. The secondary outcome was shunt recanalization. VB sign characteristics and associations with outcomes were analyzed. RESULTS: Of 65 patients with SCAVSs, 57 were eligible for VB sign assessment; among these, there were 26 with the VB sign and 31 without the VB sign. Among vascular shunts perimedullary arteriovenous fistula showed the greatest difference in prevalence rate between those with and without the VB sign (33.3%, nâ¯= 9/27 versus 10.0%, nâ¯= 3/30; Pâ¯= 0.031). On multivariable logistic regression analysis, SCAVSs with the VB sign had significantly more favorable outcomes than those without the VB sign (adjusted odds ratio, 5.61; 95% confidence interval, 1.48-21.23; Pâ¯= 0.01). There was no relationship between the VB sign and secondary outcomes (Pâ¯= 0.35). CONCLUSION: The VB sign is independently associated with functional recovery after shunt occlusion and could be an assessment tool for the treatment efficacy of SCAVSs.
Assuntos
Angiografia , Fístula Arteriovenosa , Humanos , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagem , Medula Espinal/irrigação sanguínea , Resultado do TratamentoRESUMO
Spinal osseous arteriovenous fistula (AVF) is a rare disease with a characteristic angioarchitecture involving an intraosseous venous pouch (VP) of the vertebral body where the feeders are converging. Using spinal angiography alone, it is difficult to distinguish spinal osseous AVF from classical spinal epidural AVF (EDAVF) with fistulas in the epidural VP and bone erosion because both subtypes have an angiographically similar dilated VP appearance. Thus, spinal osseous AVF may be often misdiagnosed as spinal EDAVF. With advancing imaging techniques, it would be possible to determine the exact location of the fistula. Here, we present the case of a 37-year-old woman with a pure spinal thoracic osseous AVF and radiculopathy. She was diagnosed with spinal intraosseous AVF using high-resolution three-dimensional rotational angiography (3D-RA). The fistula was located in the Th1 lateral mass with a VP where multiple osseous feeders were converging. There was paravertebral venous drainage without intradural venous drainage. Transvenous embolization with Onyx and coils was performed through the azygos vein to the lateral epidural venous plexus, resulting in complete obliteration. This case suggests that 3D-RA reconstructed images are essential for accurate diagnosis and successful treatment of this condition. It is important to occlude only intraosseous VPs by accurate subtype diagnosis. Transvenous embolization is a treatment option for spinal intraosseous AVF with paravertebral epidural venous drainage.
Assuntos
Fístula Arteriovenosa , Embolização Terapêutica , Feminino , Humanos , Adulto , Imageamento por Ressonância Magnética/efeitos adversos , Embolização Terapêutica/métodos , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/cirurgiaRESUMO
Background: Neurosurgical treatment for pistol shooting dystonia has not been studied. Case report: The patient was a 41-year-old woman who participated in the Olympic Games four times as a shooting player. Five months after the final Tokyo Olympic trials, she developed dystonia of the right index finger when shooting. Stereotactic thalamotomy was performed, and a complete resolution of dystonia was achieved. She garnered her personal best score and placed fifth in the Tokyo Olympics. Discussion: Thalamotomy along with deep brain stimulation can be a surgical modality for patients with task-specific dystonia who fail oral medications or botulinum toxin therapy.
Assuntos
Distonia , Distúrbios Distônicos , Feminino , Humanos , Adulto , Distúrbios Distônicos/cirurgia , Procedimentos NeurocirúrgicosRESUMO
BACKGROUND: Guiding catheter (GC) advancement into the target carotid artery is a crucial step in neuroendovascular therapy. In difficult anatomies, alternative methods have been reported to overcome difficult carotid access for swift GC advancement. However, studies focusing on the positional relationship between the GC and inner catheter (IC) at the aortic arch are lacking. METHODS: We evaluated the impact of the positional relationship between the GC and IC on whether the GC position affects catheter support or system straightening. We retrospectively reviewed 89 patients who underwent neuroendovascular therapy. We assessed the time to carotid access across difficult arch anatomies. The GC position was divided into Position 1, descending aorta level; Position 2, aortic arch level; and Position 3, origin of the left common carotid artery or innominate artery. We also evaluated the GC support and straightening effects in an in vitro vascular model study. RESULTS: The coaxial catheter flexion angle at the aortic arch was significantly larger when the GC was set to Position 3 (p < 0.0001). A significantly shorter time to carotid access was observed with Positions 2 and 3 than with Position 1 in the difficult arch anatomy group. In the in vitro vascular model evaluation, the catheter support effect significantly increased as the GC position became closer to the IC tip (p < 0.0001) and straightening effect significantly increased as the GC moved to Position 2 from Position 1 (p < 0.0001). CONCLUSION: During GC advancement, the GC positional relationship changed the support of the coaxial system with system straightening. The optimal GC position, Position 3, facilitated swift GC advancement.