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1.
Stroke ; 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39474689

RESUMEN

The quotation, attributed to Confucius many centuries ago, in our opinion, applies to the evolving story of defining a primary surgical treatment for spontaneous intracerebral hemorrhage. The precise quote is: "Keep it simple and focus on what matters. Don't let yourself be overwhelmed."1 The evidence from multiple trials on intracerebral hemorrhage regarding mortality benefit and potential functional benefit directs us toward the simple task of evacuating the clot, similar to our prime focus on opening the artery in ischemic stroke. We need not be overwhelmed by questions about adjustments to patient selection, comparative techniques, and precision timing, for which we do not have conclusive data. We review the consensus results from the recent MISTIE trial (Minimally Invasive Surgery Plus Alteplase in ICH Evacuation) and ENRICH trial (Early Minimally Invasive Removal of Intracerebral Hemorrhage) and articulate remaining questions where further evidence is needed to challenge equipoise and define future practice.

2.
Circ Res ; 130(8): 1204-1229, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35420918

RESUMEN

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. This review article focuses on the epidemiology, cause, mechanisms of injury, current treatment strategies, and future research directions of ICH. Incidence of hemorrhagic stroke has increased worldwide over the past 40 years, with shifts in the cause over time as hypertension management has improved and anticoagulant use has increased. Preclinical and clinical trials have elucidated the underlying ICH cause and mechanisms of injury from ICH including the complex interaction between edema, inflammation, iron-induced injury, and oxidative stress. Several trials have investigated optimal medical and surgical management of ICH without clear improvement in survival and functional outcomes. Ongoing research into novel approaches for ICH management provide hope for reducing the devastating effect of this disease in the future. Areas of promise in ICH therapy include prognostic biomarkers and primary prevention based on disease pathobiology, ultra-early hemostatic therapy, minimally invasive surgery, and perihematomal protection against inflammatory brain injury.


Asunto(s)
Hipertensión , Accidente Cerebrovascular , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/terapia , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Factores de Riesgo
3.
Neurosurg Focus ; 56(5): E5, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38691856

RESUMEN

OBJECTIVE: The authors of this study aimed to investigate independent prognostic factors of survival with a particular focus on comparing the safety and efficacy of endoscopic endonasal versus open approaches in the surgical management of skull base chordoma. METHODS: A retrospective National Cancer Database review of skull base chordoma patients was performed to capture resection cases from 2010 to 2020, evaluating overall survival (OS), early postoperative mortality, readmission rates, and hospital length of stay (LOS) between surgical approaches and the independent prognostication of death utilizing Cox multivariate regression analysis. RESULTS: Among the 736 patients included in the cohort, 456 patients (62.0%) and 280 patients (38.0%) underwent endoscopic endonasal and open resection, respectively. These values represent a rate of change over the study period of +4.1 versus -0.14 cases per year, respectively. Gross-total resection was achieved in 32.5% of cases. A positive margin status was found in 51.8% of cases. There was no association between extent of resection and surgical approach (p = 0.257). There was no difference in OS (p = 0.562), 30- and 90-day mortality (p = 0.209 and 0.126, respectively), and 30-day readmission (p = 0.438) between the two surgical groups. The mean LOS was reduced by 2.1 days in the endoscopic cohort (p = 0.013) compared with the open approach cohort. Finally, multivariate analysis revealed a tumor size ≥ 4 cm (HR 4.03, p = 0.005) and public insurance (HR 2.76, p = 0.004) as negative predictors of survival and treatment at an academic center (HR 0.36, p = 0.043) as a positive prognosticator of survival. CONCLUSIONS: The endoscopic endonasal approach has been increasingly utilized over time and touts noninferiority with respect to safety and efficacy with a marked improvement in LOS, which carries substantial implications for both healthcare costs and enhanced patient recovery. Future prospective studies are necessary to further delineate trends and surgical outcomes for skull base chordoma.


Asunto(s)
Cordoma , Bases de Datos Factuales , Neoplasias de la Base del Cráneo , Humanos , Cordoma/cirugía , Neoplasias de la Base del Cráneo/cirugía , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Tiempo de Internación/estadística & datos numéricos , Neuroendoscopía/métodos , Resultado del Tratamiento , Procedimientos Neuroquirúrgicos/métodos , Readmisión del Paciente/estadística & datos numéricos
4.
J Stroke Cerebrovasc Dis ; 33(7): 107699, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38552890

RESUMEN

BACKGROUND: Radiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations. METHODS: We retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies. RESULTS: One lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes. CONCLUSIONS: Despite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.


Asunto(s)
Mutación , Traumatismos por Radiación , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Biopsia , Hemorragia Cerebral/genética , Hemorragia Cerebral/etiología , Hemorragia Cerebral/patología , Fosfatidilinositol 3-Quinasa Clase I/genética , Irradiación Craneana/efectos adversos , Bases de Datos Factuales , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Malformaciones Arteriovenosas Intracraneales/genética , Malformaciones Arteriovenosas Intracraneales/radioterapia , Malformaciones Arteriovenosas Intracraneales/patología , Hemorragias Intracraneales/genética , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/patología , Fenotipo , Fosfohidrolasa PTEN/genética , Traumatismos por Radiación/genética , Traumatismos por Radiación/patología , Traumatismos por Radiación/etiología , Estudios Retrospectivos , Factores de Riesgo
5.
Blood ; 133(3): 193-204, 2019 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-30442679

RESUMEN

Cerebral cavernous malformations (CCMs) are common brain vascular dysplasias that are prone to acute and chronic hemorrhage with significant clinical sequelae. The pathogenesis of recurrent bleeding in CCM is incompletely understood. Here, we show that central nervous system hemorrhage in CCMs is associated with locally elevated expression of the anticoagulant endothelial receptors thrombomodulin (TM) and endothelial protein C receptor (EPCR). TM levels are increased in human CCM lesions, as well as in the plasma of patients with CCMs. In mice, endothelial-specific genetic inactivation of Krit1 (Krit1 ECKO ) or Pdcd10 (Pdcd10 ECKO ), which cause CCM formation, results in increased levels of vascular TM and EPCR, as well as in enhanced generation of activated protein C (APC) on endothelial cells. Increased TM expression is due to upregulation of transcription factors KLF2 and KLF4 consequent to the loss of KRIT1 or PDCD10. Increased TM expression contributes to CCM hemorrhage, because genetic inactivation of 1 or 2 copies of the Thbd gene decreases brain hemorrhage in Pdcd10 ECKO mice. Moreover, administration of blocking antibodies against TM and EPCR significantly reduced CCM hemorrhage in Pdcd10 ECKO mice. Thus, a local increase in the endothelial cofactors that generate anticoagulant APC can contribute to bleeding in CCMs, and plasma soluble TM may represent a biomarker for hemorrhagic risk in CCMs.


Asunto(s)
Anticoagulantes/metabolismo , Proteínas Reguladoras de la Apoptosis/fisiología , Hemorragia Cerebral/diagnóstico , Endotelio Vascular/patología , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Proteína KRIT1/fisiología , Proteínas de la Membrana/fisiología , Proteína C/metabolismo , Proteínas Proto-Oncogénicas/fisiología , Trombomodulina/sangre , Adulto , Animales , Coagulación Sanguínea , Estudios de Casos y Controles , Hemorragia Cerebral/sangre , Hemorragia Cerebral/etiología , Receptor de Proteína C Endotelial/metabolismo , Endotelio Vascular/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/fisiopatología , Humanos , Factor 4 Similar a Kruppel , Ratones , Ratones Noqueados , Transducción de Señal , Adulto Joven
6.
Neurocrit Care ; 34(3): 918-926, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33025542

RESUMEN

BACKGROUND: This study investigates the presence of cerebrovascular injuries in a large sample of civilian penetrating brain injury (PBI) patients, determining the prevalence, radiographic characteristics, and impact on short-term outcome. METHODS: We retrospectively reviewed patients with PBI admitted to our institution over a 2-year period. Computed tomography head scans, computer tomography angiograms and venograms of the intracranial vessels were evaluated to determine the wound trajectory, intracranial injury characteristics, and presence of arterial (AI) and venous sinus (VSI) injuries. Demographics, clinical presentation, and treatment were also reviewed. Discharge disposition was used as surrogate of short-term outcome. RESULTS: Seventy-two patients were included in the study. The mechanism of injury was gunshot wounds in 71 patients and stab wound in one. Forty-one of the 72 patients (60%) had at least one vascular injury. Twenty-six out of 72 patients suffered an AI (36%), mostly pseudoaneurysms and occlusions, involving the anterior and middle cerebral arteries. Of the 72 patients included, 45 had dedicated computed tomography venograms, and of those 22 had VSI (49%), mainly manifesting as superior sagittal sinus occlusion. In a multivariable regression model, intraventricular hemorrhage at presentation was associated with AI (OR 9.9, p = 0.004). The same was not true for VSI. CONCLUSION: Acute traumatic cerebrovascular injury is a prevalent complication in civilian PBI, frequently involving both the arterial and venous sinus systems. Although some radiographic features might be associated with presence of vascular injury, assessment of the intracranial vasculature in the acute phase of all PBI is essential for early diagnosis. Treatment of vascular injury remains variable depending on local practice.


Asunto(s)
Traumatismos Penetrantes de la Cabeza , Heridas por Arma de Fuego , Traumatismos Penetrantes de la Cabeza/diagnóstico por imagen , Traumatismos Penetrantes de la Cabeza/epidemiología , Humanos , Estudios Retrospectivos , Sobrevivientes , Tomografía Computarizada por Rayos X , Heridas por Arma de Fuego/complicaciones , Heridas por Arma de Fuego/diagnóstico por imagen , Heridas por Arma de Fuego/epidemiología
7.
J Stroke Cerebrovasc Dis ; 30(9): 105996, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34303090

RESUMEN

OBJECTIVE: We hypothesize that procedure deployment rates and technical performance with minimally invasive surgery and thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE) can be enhanced in post-trial clinical practice, per Phase III trial results and lessons learned. MATERIALS AND METHODS: We identified ICH patients and those who underwent MISTIE procedure between 2017-2021 at a single site, after completed enrollments in the Phase III trial. Deployment rates, complications and technical outcomes were compared to those observed in the trial. Initial and final hematoma volume were compared between site measurements using ABC/2, MISTIE trial reading center utilizing manual segmentation, and a novel Artificial Intelligence (AI) based volume assessment. RESULTS: Nineteen of 286 patients were eligible for MISTIE. All 19 received the procedure (6.6% enrollment to screening rate 6.6% compared to 1.6% at our center in the trial; p=0.0018). Sixteen patients (84%) achieved evaculation target < 15 mL residual ICH or > 70% removal, compared to 59.7% in the trial surgical cohort (p=0.034). No poor catheter placement occurred and no surgical protocol deviations. Limitations of ICH volume assessments using the ABC/2 method were shown, while AI based methodology of ICH volume assessments had excellent correlation with manual segmentation by experienced reading centers. CONCLUSIONS: Greater procedure deployment and higher technical success rates can be achieved in post-trial clinical practice than in the MISTIE III trial. AI based measurements can be deployed to enhance clinician estimated ICH volume. Clinical outcome implications of this enhanced technical performance cannot be surmised, and will need assessment in future trials.


Asunto(s)
Hemorragia Cerebral/terapia , Procedimientos Neuroquirúrgicos , Terapia Trombolítica , Adulto , Anciano , Anciano de 80 o más Años , Inteligencia Artificial , Hemorragia Cerebral/diagnóstico por imagen , Ensayos Clínicos Fase III como Asunto , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/efectos adversos , Valor Predictivo de las Pruebas , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
8.
J Magn Reson Imaging ; 51(4): 1192-1199, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31515878

RESUMEN

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative permeability (DCEQP) on magnetic resonance (MR) have been shown to correlate with neurovascular disease progression as markers of vascular leakage and hemosiderin deposition. Applying these techniques as monitoring biomarkers in clinical trials will be necessary; however, their validation across multiple MR platforms and institutions has not been rigorously verified. PURPOSE: To validate quantitative measurement of MR biomarkers on multiple instruments at different institutions. STUDY TYPE: Phantom validation between platforms and institutions. PHANTOM MODEL: T1 /susceptibility phantom, two-compartment dynamic flow phantom. FIELD STRENGTH/SEQUENCE: 3T/QSM, T1 mapping, dynamic 2D SPGR. ASSESSMENT: Philips Ingenia, Siemens Prisma, and Siemens Skyra at three different institutions were assessed. A QSM phantom with concentrations of gadolinium, corresponding to magnetic susceptibilities of 0, 0.1, 0.2, 0.4, and 0.8 ppm was assayed. DCEQP was assessed by measuring a MultiHance bolus as the consistency of the width ratio of the curves at the input and outputs over a range of flow ratios between outputs. STATISTICAL TESTS: Each biomarker was assessed by measures of accuracy (Pearson correlation), precision (paired t-test between repeated measurements), and reproducibility (analysis of covariance [ANCOVA] between instruments). RESULTS: QSM accuracy of r2 > 0.997 on all three platforms was measured. Precision (P = 0.66 Achieva, P = 0.76 Prisma, P = 0.69 Skyra) and reproducibility (P = 0.89) were good. T1 mapping of accuracy was r2 > 0.98. No significant difference between width ratio regression slopes at site 2 (P = 0.669) or site 3 (P = 0.305), and no significant difference between width ratio regression slopes between sites was detected by ANCOVA (P = 0.48). DATA CONCLUSION: The phantom performed as expected and determined that MR measures of QSM and DCEQP are accurate and consistent across repeated measurements and between platforms. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1192-1199.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Permeabilidad , Fantasmas de Imagen , Reproducibilidad de los Resultados
9.
FASEB J ; 33(2): 2132-2143, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30252535

RESUMEN

Epithelial barrier maintenance and regulation requires an intact perijunctional actomyosin ring underneath the cell-cell junctions. By searching for known factors affecting the actin cytoskeleton, we identified Krev interaction trapped protein 1 (KRIT1) as a major regulator for epithelial barrier function through multiple mechanisms. KRIT1 is expressed in both small intestinal and colonic epithelium, and KRIT1 knockdown in differentiated Caco-2 intestinal epithelium decreases epithelial barrier function and increases cation selectivity. KRIT1 knockdown abolished Rho-associated protein kinase-induced and myosin II motor inhibitor-induced barrier loss by limiting both small and large molecule permeability but did not affect myosin light chain kinase-induced increases in epithelial barrier function. These data suggest that KRIT1 participates in Rho-associated protein kinase- and myosin II motor-dependent (but not myosin light chain kinase-dependent) epithelial barrier regulation. KRIT1 knockdown exacerbated low-dose TNF-induced barrier loss, along with increased cleaved caspase-3 production. Both events are blocked by pan-caspase inhibition, indicating that KRIT1 regulates TNF-induced barrier loss through limiting epithelial apoptosis. These data indicate that KRIT1 controls epithelial barrier maintenance and regulation through multiple pathways, suggesting that KRIT1 mutation in cerebral cavernous malformation disease may alter epithelial function and affect human health.-Wang, Y., Li, Y., Zou, J., Polster, S. P., Lightle, R., Moore, T., Dimaano, M., He, T.-C., Weber, C. R., Awad, I. A., Shen, L. The cerebral cavernous malformation disease causing gene KRIT1 participates in intestinal epithelial barrier maintenance and regulation.


Asunto(s)
Apoptosis , Permeabilidad de la Membrana Celular , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Mucosa Intestinal/patología , Proteína KRIT1/metabolismo , Miosina Tipo II/metabolismo , Quinasas Asociadas a rho/metabolismo , Citoesqueleto de Actina/metabolismo , Células CACO-2 , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Proteína KRIT1/genética , Miosina Tipo II/genética , Fosforilación , Transducción de Señal , Quinasas Asociadas a rho/genética
10.
Circ Res ; 122(12): 1716-1721, 2018 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-29720384

RESUMEN

RATIONALE: The clinical course of cerebral cavernous malformations is highly unpredictable, with few cross-sectional studies correlating proinflammatory genotypes and plasma biomarkers with prior disease severity. OBJECTIVE: We hypothesize that a panel of 24 candidate plasma biomarkers, with a reported role in the physiopathology of cerebral cavernous malformations, may predict subsequent clinically relevant disease activity. METHODS AND RESULTS: Plasma biomarkers were assessed in nonfasting peripheral venous blood collected from consecutive cerebral cavernous malformation subjects followed for 1 year after initial sample collection. A first cohort (N=49) was used to define the best model of biomarker level combinations to predict a subsequent symptomatic lesional hemorrhagic expansion within a year after the blood sample. We generated the receiver operating characteristic curves and area under the curve for each biomarker individually and each weighted linear combination of relevant biomarkers. The best model to predict lesional activity was selected as that minimizing the Akaike information criterion. In this cohort, 11 subjects experienced symptomatic lesional hemorrhagic expansion (5 bleeds and 10 lesional growths) within a year after the blood draw. Subjects had lower soluble CD14 (cluster of differentiation 14; P=0.05), IL (interleukin)-6 (P=0.04), and VEGF (vascular endothelial growth factor; P=0.0003) levels along with higher plasma levels of IL-1ß (P=0.008) and soluble ROBO4 (roundabout guidance receptor 4; P=0.03). Among the 31 weighted linear combinations of these 5 biomarkers, the best model (with the lowest Akaike information criterion value, 25.3) was the weighted linear combination including soluble CD14, IL-1ß, VEGF, and soluble ROBO4, predicting a symptomatic hemorrhagic expansion with a sensitivity of 86% and specificity of 88% (area under the curve, 0.90; P<0.0001). We then validated our best model in the second sequential independent cohort (N=28). CONCLUSIONS: This is the first study reporting a predictive association between plasma biomarkers and subsequent cerebral cavernous malformation disease clinical activity. This may be applied in clinical prognostication and stratification of cases in clinical trials.


Asunto(s)
Biomarcadores/sangre , Hemangioma Cavernoso del Sistema Nervioso Central/sangre , Adolescente , Adulto , Anciano , Área Bajo la Curva , Hemorragia Cerebral/etiología , Niño , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Humanos , Interleucina-1beta/sangre , Interleucina-6/sangre , Receptores de Lipopolisacáridos/sangre , Masculino , Persona de Mediana Edad , Curva ROC , Receptores de Superficie Celular/sangre , Sensibilidad y Especificidad , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto Joven
11.
Int J Mol Sci ; 21(2)2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31968585

RESUMEN

Cerebral cavernous malformation (CCM) is a disease characterized by mulberry shaped clusters of dilated microvessels, primarily in the central nervous system. Such lesions can cause seizures, headaches, and stroke from brain bleeding. Loss-of-function germline and somatic mutations of a group of genes, called CCM genes, have been attributed to disease pathogenesis. In this review, we discuss the impact of CCM gene encoded proteins on cellular signaling, barrier function of endothelium and epithelium, and their contribution to CCM and potentially other diseases.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central/genética , Transducción de Señal , Endotelio/fisiología , Epitelio/fisiología , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Homeostasis , Humanos , Intestinos/fisiología , MAP Quinasa Quinasa Quinasa 3/genética , MAP Quinasa Quinasa Quinasa 3/metabolismo , Uniones Estrechas/fisiología , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismo
12.
Stroke ; 50(3): 738-744, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30744543

RESUMEN

Background and Purpose- Previously, murine models Krit1 +/- Msh2 -/- and Ccm2 +/- Trp53 -/- showed a reduction or no effect on cerebral cavernous malformation (CCM) burden and favorable effects on lesional hemorrhage by the robust Rock (Rho-associated protein kinase) inhibitor fasudil and by simvastatin (a weak pleiotropic inhibitor of Rock). Herein, we concurrently investigated treatment of the more aggressive Pdcd10/Ccm3 model with fasudil, simvastatin, and higher dose atorvastatin to determined effectiveness of Rock inhibition. Methods- The murine models, Pdcd10 +/- Trp53 -/- and Pdcd10 +/- Msh2 -/-, were contemporaneously treated from weaning to 5 months of age with fasudil (100 mg/kg per day in drinking water, n=9), simvastatin (40 mg/kg per day in chow, n=11), atorvastatin (80 mg/kg per day in chow, n=10), or with placebo (n=16). We assessed CCM volume in mouse brains by microcomputed tomography. Lesion burden was calculated as lesion volume normalized to total brain volume. We analyzed chronic hemorrhage in CCM lesions by quantitative intensity of Perls staining in brain sections. Results- The Pdcd10 +/- Trp53 -/- /Msh2 -/- models showed a mean CCM lesion burden per mouse reduction from 0.0091 in placebos to 0.0042 ( P=0.027) by fasudil, and to 0.0047 ( P=0.025) by atorvastatin treatment, but was not changed significantly by simvastatin. Hemorrhage intensity per brain was commensurately decreased by Rock inhibition. Conclusions- These results support the exploration of proof of concept effect of high-dose atorvastatin on human CCM disease for potential therapeutic testing.


Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Hemangioma Cavernoso del Sistema Nervioso Central/tratamiento farmacológico , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Hemorragias Intracraneales/tratamiento farmacológico , Hemorragias Intracraneales/genética , Quinasas Asociadas a rho/antagonistas & inhibidores , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/uso terapéutico , Animales , Proteínas Reguladoras de la Apoptosis , Atorvastatina/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hemorragias Intracraneales/diagnóstico por imagen , Proteína KRIT1/genética , Ratones , Ratones Noqueados , Simvastatina/uso terapéutico , Microtomografía por Rayos X
13.
Lab Invest ; 99(3): 319-330, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-29946133

RESUMEN

Cerebral cavernous malformations (CCMs) are clusters of dilated capillaries that affect around 0.5% of the population. CCMs exist in two forms, sporadic and familial. Mutations in three documented genes, KRIT1(CCM1), CCM2, and PDCD10(CCM3), cause the autosomal dominant form of the disease, and somatic mutations in these same genes underlie lesion development in the brain. Murine models with constitutive or induced loss of respective genes have been applied to study disease pathobiology and therapeutic manipulations. We aimed to analyze the phenotypic characteristic of two main groups of models, the chronic heterozygous models with sensitizers promoting genetic instability, and the acute neonatal induced homozygous knockout model. Acute model mice harbored a higher lesion burden than chronic models, more localized in the hindbrain, and largely lacking iron deposition and inflammatory cell infiltrate. The chronic model mice showed a lower lesion burden localized throughout the brain, with significantly greater perilesional iron deposition, immune B- and T-cell infiltration, and less frequent junctional protein immunopositive endothelial cells. Lesional endothelial cells in both models expressed similar phosphorylated myosin light chain immunopositivity indicating Rho-associated protein kinase activity. These data suggest that acute models are better suited to study the initial formation of the lesion, while the chronic models better reflect lesion maturation, hemorrhage, and inflammatory response, relevant pathobiologic features of the human disease.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Enfermedad Aguda , Animales , Proteínas Reguladoras de la Apoptosis , Linfocitos B/metabolismo , Linfocitos B/patología , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Encéfalo/patología , Cerebelo/irrigación sanguínea , Cerebelo/metabolismo , Cerebelo/patología , Enfermedad Crónica , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Hierro/metabolismo , Proteína KRIT1/genética , Ratones , Ratones Noqueados , Ratones Transgénicos , Proteínas de Microfilamentos/genética , Mutación , Ocludina/metabolismo , Fenotipo , Linfocitos T/metabolismo , Linfocitos T/patología , Quinasas Asociadas a rho/metabolismo
14.
J Neurol Surg B Skull Base ; 85(Suppl 2): e161-e168, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39444777

RESUMEN

Background There has been increased interest in how residents train in the subspecialty of skull base surgery. Examining which training methods are popular and effective to optimize residency learning is necessary, especially with new training adjuncts available to the modern trainee. In this study, we survey North American Skull Base Society (NASBS) members to analyze endoscopic skull base surgery education methods. Methods The NASBS membership was surveyed regarding endoscopic skull base surgery teaching and feedback methods using a Likert scale via an anonymized REDCap form over 4 months. Results With a response rate of 10.1%, we found that informal teaching methods and verbal qualitative feedback were rated significantly more effective than other teaching and feedback methods ( p < 0.01). When comparing the opinions of otolaryngologists and neurosurgeons, otolaryngologists were less likely to believe feedback is most effective with a shared grading scale ( p < 0.01). Physicians with more than 10 years of experience posttraining felt model- and rubric-based teaching were used more frequently ( p < 0.01). Respondents indicated that standardization and use of simulation, artificial intelligence, and virtual reality should be at the forefront of educational practices used in the field in the coming 5 to 10 years. Conclusion Despite the current emphasis on informal training, respondents pointed to standardization and simulation as methods of endoscopic skull base surgery education that should be used more in the future. These results indicate an unmet need in skull base education. Future multi-institutional initiatives with NASBS membership participation are warranted.

15.
J Clin Med ; 13(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38610689

RESUMEN

Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams.

16.
Am J Rhinol Allergy ; 38(4): 203-210, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38544422

RESUMEN

BACKGROUND: The concept of "time toxicity" has emerged to address the impact of time spent in the healthcare system; however, little work has examined the phenomenon in the field of otolaryngology. OBJECTIVE: To validate the use of Evaluation and Management (E/M) current procedural terminology codes as a method to assess time burden and to pilot this tool to characterize the time toxicity of office visits associated with a diagnosis of pituitary adenoma between 2016 and 2019. METHODS: A retrospective cohort study of outpatient office visits quantified differences between timestamps documenting visit length and their associated E/M code visit length. The IBM MarketScan database was queried to identify patients with a diagnosis of pituitary adenoma in 2016 and to analyze their new and return claims between 2016 and 2019. One-way ANOVA and two-sample t-tests were used to examine claim quantity, time in office, and yearly visit time. RESULTS: In the validation study, estimated visit time via E/M codes and actual visit time were statistically different (P < 0.01), with E/M codes underestimating actual time spent in 79.0% of visits. In the MarketScan analysis, in 2016, 2099 patients received a primary diagnosis of pituitary adenoma. There were 8490 additional-related claims for this cohort from 2016 to 2019. The plurality of new office visits were with endocrinologists (n = 857; 29.3%). Total time spent in office decreased yearly, from a mean of 113 min (2016) to 69 min (2019) (P < 0.001). CONCLUSIONS: E/M codes underestimate the length of outpatient visits; therefore, time toxicity experienced by pituitary patients may be greater than reported. Further studies are needed to develop additional assessment tools for time toxicity and promote increased efficiency of care for patients with pituitary adenomas.


Asunto(s)
Adenoma , Visita a Consultorio Médico , Neoplasias Hipofisarias , Humanos , Visita a Consultorio Médico/estadística & datos numéricos , Estudios Retrospectivos , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/terapia , Femenino , Masculino , Adenoma/epidemiología , Adenoma/terapia , Adenoma/diagnóstico , Persona de Mediana Edad , Adulto , Factores de Tiempo , Current Procedural Terminology , Anciano
17.
J Neurointerv Surg ; 16(3): 266-271, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-37236781

RESUMEN

BACKGROUND: The transradial approach (TRA) for neurointerventional procedures is increasingly being used given its technical feasibility and safety. However, catheter trackability and device deliverability are reported barriers to TRA adoption. METHODS: This is the first report describing the technical feasibility and performance of using the Zoom RDL Radial Access System (Imperative Care, Inc., Campbell, CA) in 29 patients who underwent neurointerventional procedures from October 2022 to January 2023 in a single-center institution. RESULTS: Mean age of the study population was 61.9±17.2 years, 79.3% were male (23/29), and 62.1% were black (18/29). The most common procedures were stroke thrombectomy (31.0%, 9/29) and aneurysm embolization (27.6%, 8/29). All the stroke thrombectomy procedures were successfully performed; first-pass effect rate (mTICI≥2 c in one pass) was achieved in 66.7% (6/9) of cases. We used TRA in 86.2% of cases (25/29), including distal radial/snuffbox access in 31.0% (9/29) of cases. The radial diameter was >2 mm for all cases. An intermediate/aspiration catheter was used in 89.7% (26/29) of cases. Access success was achieved in 89.7% of cases (26/29); two cases required conversion from TRA to transfemoral approach (6.9%) and one case required conversion to a different guide catheter (3.4%). There were no access site complications or other Zoom RDL-related complications. One intracerebral hemorrhage, and one procedure-related thrombus were observed. CONCLUSIONS: The use of Zoom RDL Radial Access System is technically feasible and effective for complex neurointerventional procedures with low complication rates.


Asunto(s)
Embolización Terapéutica , Accidente Cerebrovascular , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Femenino , Arteria Radial/diagnóstico por imagen , Arteria Radial/cirugía , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Catéteres , Estudios Retrospectivos , Resultado del Tratamiento
18.
AJNR Am J Neuroradiol ; 45(9): 1206-1213, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39054289

RESUMEN

BACKGROUND AND PURPOSE: Analysis of vessel wall contrast kinetics (ie, wash-in/washout) is a promising method for the diagnosis and risk-stratification of intracranial atherosclerotic disease plaque (ICAD-P) and the intracranial aneurysm walls (IA-W). We used black-blood MR imaging or MR vessel wall imaging to evaluate the temporal relationship of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws compared with normal anatomic reference structures. MATERIALS AND METHODS: Patients with ICAD-Ps or IAs who underwent MR vessel wall imaging with precontrast, early postcontrast (5-15 minutes), and delayed postcontrast (20-30 minutes) 3D T1-weighted TSE sequences were retrospectively studied. ROIs of a standardized diameter (2 mm) were used to measure the signal intensities of the cavernous sinus, pituitary infundibulum, temporalis muscle, and choroid plexus. Point ROIs were used for ICAD-Ps and IA-Ws. All ROI signal intensities were normalized to white matter signal intensity obtained using ROIs of 10-mm diameter. Measurements were acquired on precontrast, early postcontrast, and delayed postcontrast 3D T1 TSE sequences for each patient.ajnr;45/9/1206/T1T1T1Table 1:MR-VWI parameters for ICAD-Ps and IAsParameterValueSequence3D TSEScan planeAxialFOV (mm)160TR/TE (ms)800/28-32BW (Hx/pixel)370θ120Acceleration2ETL42Matrix acquisition0.5 mm ×0.5 mmMatrix recon0.5 mm ×0.5 mmNo. of slices/thick120/0.5Note:-FOV indicates field of view; TR, the repetition time; TE, the echo time; BW, bandwidth; ETL, echo train length; Matrix recon, matrix reconstruction. RESULTS: Ten patients with 17 symptomatic ICAD-Ps and 30 patients with 34 IA-Ws were included and demonstrated persisting contrast uptake (P < .001) of 7.21% and 10.54% beyond the early phase (5-15 minutes postcontrast) and in the delayed phase (20-30 minutes postcontrast) on postcontrast MR vessel wall imaging. However, normal anatomic reference structures including the pituitary infundibulum and cavernous sinus demonstrated a paradoxical contrast washout in the delayed phase. In both ICAD-Ps and IA-Ws, the greatest percentage of quantitative enhancement (>70%-90%) occurred in the early phase of postcontrast imaging, consistent with the rapid contrast uptake kinetics of neurovascular pathology. CONCLUSIONS: Using standard MR vessel wall imaging techniques, our results demonstrate the effects of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws with extended accumulating enhancement into the delayed phase (> 15 minutes) as opposed to normal anatomic reference structures that conversely exhibit decreasing enhancement. Because these relative differences are used to assess qualitative patterns of ICAD-P and IA-W enhancement, our findings highlight the importance of standardizing acquisition time points and MR vessel wall imaging protocols to interpret pathologic enhancement for the risk stratification of cerebrovascular pathologies.


Asunto(s)
Medios de Contraste , Aneurisma Intracraneal , Arteriosclerosis Intracraneal , Angiografía por Resonancia Magnética , Placa Aterosclerótica , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Medios de Contraste/farmacocinética , Arteriosclerosis Intracraneal/diagnóstico por imagen , Anciano , Angiografía por Resonancia Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Gadolinio DTPA/farmacocinética
19.
Artículo en Inglés | MEDLINE | ID: mdl-39443148

RESUMEN

Traditional guidance for intracranial aneurysm (IA) management is dichotomized by rupture status. Fundamental to ruptured aneurysm management is the detection and treatment of subarachnoid hemorrhage, along with securing the aneurysm by the safest technique. On the other hand, unruptured aneurysms first require a careful assessment of natural history versus treatment risk, including an imaging assessment of aneurysm size, location, and morphology, along with additional evidence-based risk factors such as smoking, hypertension, and family history. Unfortunately, a large proportion of ruptured aneurysms are in the lower risk size category (<7mm), putting a premium on discovering a more refined non-invasive biomarker to detect and stratify aneurysm instability prior to rupture. In this review of aneurysm work-up, we cover the gamut of established imaging modalities (e.g., CT, CTA, DSA, FLAIR, 3D-TOF-MRA, CE-MRA) as well as more novel MR techniques (MR-VWI, DCE-MRI, CFD). Additionally, we evaluate the current landscape of AI software and their integration into diagnostic and risk stratification pipelines for IAs. These advanced MR techniques, increasingly complemented with AI models, offer a paradigm shift by evaluating factors beyond size and morphology, including vessel wall inflammation, permeability, and hemodynamics. Additionally, we provide our institution's scan parameters for many of these modalities as reference. Ultimately, this review provides an organized, up-to-date summary on the array of available modalities/sequences for IA imaging to help build protocols focused on IA characterization.ABBREVIATIONS: IA = intracranial aneurysm; LP = lumbar puncture; UIA = unruptured intracranial aneurysm; VWI = vessel wall imaging; 3DRA = 3D Rotational Angiography.

20.
Interv Neuroradiol ; : 15910199241250078, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711176

RESUMEN

BACKGROUND: Middle meningeal artery (MMA) embolization for subdural hematomas (SDH) and dural arteriovenous fistulas (dAVFs) has gained momentum in the neuroendovascular space. However, there is variability in the technique for safe and effective embolization. The aim of this report is to describe the technical feasibility and clinical performance of using Zoom™ 45 catheter for MMA access to facilitate embolization. METHODS: We analyzed all cases of MMA embolization in which the Zoom™ 45 catheter was used and performed in our institution from February 2021 to March 2023 for SDH and dAVFs. RESULTS: A total of 32 patients were included. Mean age was 64.0 ± 18.0 years, 75.0% (4/32) were male, and 56.7% (17/30), were black. The technical success was achieved in 93.8% (30/32) of cases, with selective embolization utilizing microcatheter directly into frontal and parietal branches for most patients (96.9%, 31/32). Identification of dangerous collaterals, such as lacrimal and petrous branches, prior to embolization, was achieved in most patients (96.9%, 31/32). Bilateral MMA embolization was done in 50.0% (16/32) of patients. The transradial approach and transfemoral approach were used in 53.1% (17/32) and 46.9% (15/32) of patients, respectively. The most common embolization material was n-butyl cyanoacrylate (84.4%, 27/32). There were no access site complications or complications related to the MMA embolization procedures and used devices. CONCLUSIONS: The use of Zoom™ 45 Catheter seems to be technically feasible, safe, and effective for facilitating MMA access for embolization in the context of SDH and dAVFs.

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