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In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.
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BACKGROUND: Blister aneurysms are a rare subclass of aneurysms, which remain challenging to treat both with open cerebrovascular and endovascular techniques, and clinicians continue to see poor outcomes in some cases despite improvements in technology. Based on our clinical observations, we hypothesized that patients with a Fisher grade 3 subarachnoid hemorrhage (SAH) from a ruptured anterior circulation blister aneurysm are significantly more likely to develop poor outcome due to delayed cerebral ischemia than patients with a Fisher grade 3 SAH from a ruptured anterior circulation saccular aneurysm. METHODS: In this consecutive case series, we reviewed management, outcomes, and rates of delayed cerebral ischemia for all ruptured anterior circulation blister aneurysms from 2012 to 2018 at our institution and compared them to a concurrent cohort of ruptured saccular anterior circulation aneurysms. A blister aneurysm was defined as an aneurysm that arises from a nonbranching point and demonstrates hemispherical anatomy on diagnostic angiography. RESULTS: We identified 14 consecutive ruptured anterior circulation blister aneurysms. Thirteen aneurysms were treated operatively- 5 with clip remodeling and 8 with flow diversion embolization. While clip remodeling had a high intraoperative rupture rate (80%), there was only one (12.5%) intraoperative rupture with flow diversion embolization. Outcomes were worsened by delayed cerebral ischemia from vasospasm in patients with Fisher 3 hemorrhages from blister aneurysms (86%). The rate of delayed cerebral ischemia from vasospasm was significantly higher for ruptured blister aneurysms than for a concurrent cohort of ruptured saccular aneurysms (8.6%, P = 0.0001). CONCLUSION: Ruptured Fisher grade 3 anterior circulation blister aneurysms have a significantly higher incidence of delayed cerebral ischemia from vasospasm compared to saccular aneurysms, regardless of the treatment modality.
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Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks.
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Hemorragia Cerebral Intraventricular/complicaciones , Hemorragia Cerebral Intraventricular/patología , Trastornos de la Memoria/etiología , Trastornos de la Memoria/patología , Animales , Sangre , Masculino , Neurogénesis , Ratas , Ratas Sprague-DawleyAsunto(s)
Traumatismos del Sistema Nervioso/terapia , Adolescente , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Cuidados Críticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Traumatismos del Sistema Nervioso/diagnóstico , Adulto JovenRESUMEN
The accuracy of 3D time of Flight Magnetic Resonance Angiography (TOF MRA) has been studied extensively for following coiled intracranial aneurysms. It is used by many clinicians for non-invasive follow-up because of its adequate sensitivity in predicting aneurysmal recanalization compared to diagnostic cerebral angiography. The data on the accuracy of 3D TOF MRA for the Pipeline™ Embolization Device (PED) are sparse. In a retrospective chart review, we compared the accuracy of 3D TOF MRA of PED to coil embolization at our institution. 3D TOF MRA had a lower sensitivity and positive predictive value in detecting aneurysmal filling in PED-treated versus coiled aneurysms (57% versus 87% and 80% versus 100%, respectively). Analysis of discrepancies between conventional diagnostic angiography and 3D TOF MRA revealed that 3D TOF MRA was inaccurate in the setting of small residual necks and slow residual filling of the dome with fluid-fluid layers. Therefore, contrasted studies such as contrast-enhanced MRA may be preferred for non-invasively following PED-treated aneurysms to increase accuracy.
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Angiografía de Substracción Digital/métodos , Angiografía Cerebral/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Angiografía por Resonancia Magnética/métodos , Adulto , Anciano , Angiografía de Substracción Digital/normas , Angiografía Cerebral/normas , Medios de Contraste , Femenino , Humanos , Imagenología Tridimensional/métodos , Imagenología Tridimensional/normas , Angiografía por Resonancia Magnética/normas , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: The US Food and Drug Administration allows a previously unapproved device to be used clinically to collect safety and effectiveness data under their Investigational Device Exemption (IDE) category. The process usually falls under 3 different trial categories: noninferiority, equivalency, and superiority. To confidently inform our patients, understanding the basic concepts of these trials is paramount. The purpose of this manuscript was to provide a comprehensive review of these topics using recently published IDE trials and economic analyses of cervical total disc replacement as illustrative examples. CASE STUDY MOBI-C ARTIFICIAL CERVICAL DISC: In 2006, an IDE was initiated to study the safety and effectiveness of total disc replacement controlled against the standard of care, anterior cervical discectomy, and fusion. Under the IDE, randomized controlled trials comparing both 1 and 2 level cervical disease were completed. The sponsor designed the initial trial as noninferiority; however, using adaptive methodology, superiority could be claimed in the 2-level investigation. REVIEWING HEALTHCARE ECONOMICS: Healthcare economics are critical in medical decision making and reimbursement practices. Once both cost- and quality-adjusted life-year (QALY) are known for each patient, the incremental cost-effectiveness ratio is calculated. Willingness-to-pay is controversial, but a commonly cited guideline considers interventions costing below 20 000 $/QALY strongly cost effective and more than 100 000 $/QALY as not cost effective. CONCLUSION: While large Food and Drug Administration IDE studies are often besieged by complex statistical considerations and calculations, it is fundamentally important that clinicians understand at least the terminology and basic concepts on a practical level.
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Análisis Costo-Beneficio , Aprobación de Recursos/legislación & jurisprudencia , Aprobación de Recursos/normas , Humanos , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Reeemplazo Total de Disco/instrumentación , Estados Unidos , United States Food and Drug AdministrationRESUMEN
BACKGROUND: Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke with a variable presentation, ranging from headaches, to coma and death. Although the American Stroke Association has developed guidelines for the treatment of CVST, data are sparse on the outcome after treatment with anticoagulation, thrombolysis, and thrombectomy. METHODS: In this retrospective review, we describe the 5-year UC Davis experience with spontaneous CVST. RESULTS: Forty-one patients (mean age 37.5±23.1, range 0-96â years; 29 female) were identified with CVST. The majority of cases involved the transverse sinus (75.6%), sigmoid sinus (58.5%), and superior sagittal sinus (29.3%). The most common form of treatment was anticoagulation or antiplatelet therapy (n=35), while six patients were managed by observation alone. The overall 1-year modified Rankin score (mRS) was 1.4±1.5. Male patients and patients with a poor admission mRS had a worse outcome. Outcome was unaffected by hypercoagulable state, number of dural sinuses involved, the presence of intracranial hemorrhage, or seizures. Two patients who underwent anticoagulation therapy also required endovascular thrombectomy; both patients had a 1-year mRS of ≤2. Two patients underwent direct open surgical canalization of the superior sagittal sinus with varying outcomes (mRS 2 vs mRS 6). CONCLUSIONS: In our series, the majority (92.9%) of patients with spontaneous dural sinus thrombosis had a favorable clinical outcome as defined by a mRS ≤2. Further prospective studies are needed to study the impact of anticoagulation on the clinical course of the disease.
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Manejo de la Enfermedad , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Trombosis de los Senos Intracraneales/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada/métodos , Senos Craneales/diagnóstico por imagen , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Lactante , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Trombectomía/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Posterior communicating artery (PCOM) aneurysms may cause third nerve palsies. The optimal treatment with clipping versus coiling remains controversial. Here we report on two cases of resolution of third nerve palsy after flow diversion embolization of large and giant PCOM aneurysms without adjuvant coil placement. The resolution of third nerve palsy was not preceded by significant shrinkage of the aneurysmal sac on MRI. However, one patient showed resolution of T2-weighted signal abnormalities in the midbrain and mesial temporal lobe despite a similar size of the aneurysm. Therefore, flow diversion embolization of a PCOM aneurysm may resolve oculomotor nerve palsies through decreasing arterial pulsations against the nerve or midbrain.