Cerebral protection during retrograde brachiocephalic artery stenting using a single filter and increased subclavian steal phenomenon: illustrative case.

BACKGROUND: Cerebral protection during brachiocephalic artery (BCA) stenting is important. However, the maneuver is sometimes challenging because both the internal carotid artery (ICA) and vertebral artery (VA) should be protected. Herein, the authors present an alternative cerebral protection technique involving filter protection for the ICA and hemodynamic protection for the VA during retrograde BCA stenting. OBSERVATIONS: A 64-year-old man with a thoracic aortic aneurysm presented with cold sensation and numbness in his right arm due to BCA stenosis. Endovascular stenting under cerebral protection was planned. Cerebral protection was attempted through the brachial access. Despite the successful placement of the filter in the ICA, selective catheterization of the VA failed. Furthermore, repeated transfemoral catheterization of the BCA was unsuccessful. Concerning a thoracic aortic aneurysm injury, the authors performed retrograde BCA stenting using a transbrachial approach. Hemodynamic protection of the VA was provided by increasing the subclavian steal phenomenon that resulted in successful recanalization of the BCA. LESSONS: Retrograde BCA stenting performed while protecting the ICA with a filter and the right VA by increasing the subclavian steal phenomenon was successful. This simple technique is feasible, especially in patients with steno-occlusive lesions of the BCA concurrent with the dominant vertebra/vertebral collateral pathway.

First reported single-surgeon transpalpebral hybrid approach for indirect cavernous carotid fistula: illustrative case.

BACKGROUND: Failure to reach the cavernous sinus after multiple transvenous attempts, although rare, can be challenging for neurointerventionists. The authors sought to demonstrate technical considerations and nuances of the independent performance of a novel hybrid surgical and endovascular transpalpebral approach through the superior ophthalmic vein (SOV) for direct coil embolization of an indirect carotid cavernous fistula (CCF), and they review salient literature regarding the transpalpebral approach. OBSERVATIONS: An illustrative case, including patient history and presentation, was reviewed. PubMed, MEDLINE, and Embase databases were searched for articles published between January 1, 2000, and September 30, 2021, that reported ≥1 patient with a CCF treated endovascularly via the SOV approach. Data extracted included sample size, treatment modality, surgical technique, performing surgeon specialty, and procedure outcome. The authors' case illustration demonstrates the technique for the hybrid transpalpebral approach. For the review, 273 unique articles were identified; 14 containing 74 treated patients fulfilled the inclusion criteria. Oculoplastic surgery was the most commonly involved specialty (5 of 14 studies), followed by ophthalmology (3 of 14). Coiling alone was the treatment of choice in 12 studies, with adjunctive use of Onyx (Medtronic) in 2. LESSONS: The authors' technical case description, video, illustrations, and review provide endovascular neurosurgeons with a systematic guide to conduct the procedure independently.

Side-to-side reverse superficial temporal artery to M4 middle cerebral artery bypass for common carotid artery occlusion with bonnet collaterals: illustrative case.

BACKGROUND: The bonnet bypass was initially described for common carotid artery occlusion. Considered a second-generation bypass, it augments intracranial perfusion with contralateral external carotid artery flow through an interposition graft running over the scalp vertex. However, the traditional first-generation low-flow superficial temporal artery (STA)-M4 middle cerebral artery (MCA) bypass may be enhanced by performing a side-to-side (S-S) bypass with an intraluminal suture technique (fourth-generation bypass) to increase perfusion through antegrade and retrograde flow. OBSERVATIONS: The authors present a reimagined S-S STA-M4 bypass in the case of a patient with symptomatic common carotid occlusion, in which the ipsilateral STA filled in a reverse fashion from the contralateral external carotid branches over the scalp vertex (bonnet collaterals). By performing an S-S anastomosis, the authors were able to improve cerebral perfusion and avoid the multiple anastomosis sites of the bonnet bypass. LESSONS: The patient had a good recovery with resolution of his preoperative symptoms. Follow-up angiography showed a patent bypass supplying the MCA territory through retrograde flow in the frontal and parietal limbs of the STA, converging at the anastomosis site. In this report, the authors present a new fourth-generation bypass dubbed the "S-S reverse STA-M4 MCA bypass."

Mechanical thrombectomy and carotid artery stenting for stenosis of the internal carotid artery with free-floating thrombosis: illustrative case.

BACKGROUND: The authors report a case in which mechanical thrombectomy and carotid artery stenting (CAS) were performed for acute cerebral infarction with free-floating thrombosis (FFT) in left internal carotid artery (ICA) stenosis. Good results were obtained. OBSERVATIONS: A 63-year-old man developed sudden disturbance of consciousness and right hemiplegia. He was transported to the authors' hospital by an emergency vehicle. Head magnetic resonance imaging showed acute cerebral infarction in the left middle cerebral artery region, and magnetic resonance angiography showed poor vascular flow beyond the left ICA. Emergency angiography revealed severe stenosis at the origin of the left ICA and a free-floating thrombus attached to the stenosis and extending to the peripheral side. Percutaneous transluminal angioplasty (PTA) was performed on the stenosis with proximal protection, the thrombus was aspirated under reversal flow, and CAS was performed without exacerbation of clinical symptoms. LESSONS: PTA, thrombus aspiration, and CAS under reversal flow may be effective treatments for FFT caused by ICA stenosis.

Endovascular selective hypothermia facilitates giant aneurysm clipping: illustrative case.

BACKGROUND: The authors present a case of selective hypothermia used for neuroprotection during clipping of a giant partially thrombosed middle cerebral artery (MCA) aneurysm. Although these cases have traditionally required deep hypothermic cardiac arrest, this case illustrates a novel and entirely endovascular solution that avoids cardiac standstill and whole-body cooling. OBSERVATIONS: This is, to the authors' knowledge, the first case in human surgery of a catheter-based selective hypothermic circuit used to facilitate MCA trapping for almost 30 minutes. Core temperatures never dropped below 34°C, and the patient recovered uneventfully and has been well for over 5 years. LESSONS: The technical nuances and physiological changes unique to selective hypothermia are discussed.

A comparison of digital subtraction angiography and computed tomography angiography for the diagnosis of penetrating cerebrovascular injury.

OBJECTIVE: Penetrating cerebrovascular injury (PCVI) is a subset of traumatic brain injury (TBI) comprising a broad spectrum of cerebrovascular pathology, including traumatic pseudoaneurysms, direct arterial injury, venous sinus stenosis or occlusion, and traumatic dural arteriovenous fistulas. These can result in immediate or delayed vascular injury and consequent neurological morbidity. Current TBI guidelines recommend cerebrovascular imaging for detection, but there is no consensus on the optimum modality. The aim of this retrospective cohort study was to compare CT angiography (CTA) and digital subtraction angiography (DSA) for the diagnosis of PCVI. METHODS: The records of all patients presenting to two level I trauma centers in the United States between January 2010 and July 2016 with penetrating head or neck trauma were reviewed. Only those who had undergone both CTA and DSA were included. Clinical and neuroimaging data were collected, and PCVIs were stratified using a modified Biffl grading scheme. DSA and CTA results were then compared. RESULTS: Of 312 patients with penetrating trauma over the study period, 56 patients (91% male, mean age 32 years) with PCVI met inclusion criteria and constituted the study cohort. The mechanism of injury was a gunshot wound in 86% (48/56) of patients. Twenty-four (43%) patients had sustained an angiographically confirmed arterial or venous injury. Compared with DSA as the gold standard, CTA had a sensitivity and specificity of 72% and 63%, respectively, for identifying PCVI. CTA had a positive predictive value of 61% and negative predictive value of 70%. Seven patients (13%) required immediate endovascular treatment of PCVI; in 3 (43%) of these patients, the injury was not identified on CTA. Twenty-two patients (39%) underwent delayed DSA an average of 25 days after injury; 2 (9%) of these patients were found to harbor new pathological conditions requiring treatment. CONCLUSIONS: In this retrospective analysis of PCVI at two large trauma centers, CTA demonstrated low sensitivity, specificity, and positive and negative predictive values for the diagnosis of PCVI. These findings suggest that DSA provides better accuracy than CTA in the diagnosis of both immediate and delayed PCVI and should be considered for patients experiencing penetrating head or neck trauma.

A novel model of cerebral hyperperfusion with blood-brain barrier breakdown, white matter injury, and cognitive dysfunction.

OBJECTIVE: Cerebral hyperperfusion (CHP) is associated with considerable morbidity. Its pathophysiology involves disruption of the blood-brain barrier (BBB) with subsequent events such as vasogenic brain edema and ischemic and/or hemorrhagic complications. Researchers are trying to mimic the condition of CHP; however, a proper animal model is still lacking. In this paper the authors report a novel surgically induced CHP model that mimics the reported pathophysiology of clinical CHP including BBB breakdown, white matter (WM) injury, inflammation, and cognitive impairment. METHODS: Male Sprague-Dawley rats were subjected to unilateral common carotid artery (CCA) occlusion and contralateral CCA stenosis. Three days after the initial surgery, the stenosis of CCA was released to induce CHP. Cortical regional cerebral blood flow was measured using laser speckle flowmetry. BBB breakdown was assessed by Evans blue dye extravasation and matrix metalloproteinase-9 levels. WM injury was investigated with Luxol fast blue staining. Cognitive function was assessed using the Barnes circular maze. Other changes pertaining to inflammation were also assessed. Sham-operated animals were prepared and used as controls. RESULTS: Cerebral blood flow was significantly raised in the cerebral cortex after CHP induction. CHP induced BBB breakdown evident by Evans blue dye extravasation, and matrix metalloproteinase-9 was identified as a possible culprit. WM degeneration was evident in the corpus callosum and corpus striatum. Immunohistochemistry revealed macrophage activation and glial cell upregulation as an inflammatory response to CHP in the striatum and cerebral cortex. CHP also caused significant impairments in spatial learning and memory compared with the sham-operated animals. CONCLUSIONS: The authors report a novel CHP model in rats that represents the pathophysiology of CHP observed in various clinical scenarios. This model was produced without the use of pharmacological agents; therefore, it is ideal to study the pathology of CHP as well as to perform preclinical drug trials.

Vasa vasorum formation is associated with rupture of intracranial aneurysms.

OBJECTIVE: Subarachnoid hemorrhage (SAH) has a poor outcome despite modern advancements in medical care. The development of a novel therapeutic strategy to prevent rupture of intracranial aneurysms (IAs) or a novel diagnostic marker to predict rupture-prone lesions is thus mandatory. Therefore, in the present study, the authors established a rat model in which IAs spontaneously rupture and examined this model to clarify histopathological features associated with rupture of lesions. METHODS: Female Sprague Dawley rats were subjected to bilateral ovariectomy; the ligation of the left common carotid, the right external carotid, and the right pterygopalatine arteries; induced systemic hypertension; and the administration of a lysyl oxidase inhibitor. RESULTS: Aneurysmal SAH occurred in one-third of manipulated animals and the locations of ruptured IAs were exclusively at a posterior or anterior communicating artery (PCoA/ACoA). Histopathological examination using ruptured IAs, rupture-prone IAs induced at a PCoA or ACoA, and IAs induced at an anterior cerebral artery-olfactory artery bifurcation that never ruptured revealed the formation of vasa vasorum as an event associated with rupture of IAs. CONCLUSIONS: The authors propose the contribution of a structural change in an adventitia, i.e., vasa vasorum formation, to the rupture of IAs. Findings from this study provide important insights about the pathogenesis of IAs.

In vivo cerebral aneurysm models.

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.

Role of pregnancy and female sex steroids on aneurysm formation, growth, and rupture: a systematic review of the literature.

OBJECTIVE: Women have been shown to have a higher risk of cerebral aneurysm formation, growth, and rupture than men. The authors present a review of the recently published neurosurgical literature that studies the role of pregnancy and female sex steroids, to provide a conceptual framework with which to understand the various risk factors associated with cerebral aneurysms in women at different stages in their lives. METHODS: The PubMed database was searched for "("intracranial" OR "cerebral") AND "aneurysm" AND ("pregnancy" OR "estrogen" OR "progesterone")" between January 1980 and February 2019. A total of 392 articles were initially identified, and after applying inclusion and exclusion criteria, 20 papers were selected for review and analysis. These papers were then divided into two categories: 1) epidemiological studies about the formation, growth, rupture, and management of cerebral aneurysms in pregnancy; and 2) investigations on female sex steroids and cerebral aneurysms (animal studies and epidemiological studies). RESULTS: The 20 articles presented in this study include 7 epidemiological articles on pregnancy and cerebral aneurysms, 3 articles reporting case series of cerebral aneurysms treated by endovascular therapies in pregnancy, 3 epidemiological articles reporting the relationship between female sex steroids and cerebral aneurysms through retrospective case-control studies, and 7 experimental studies using animal and/or cell models to understand the relationship between female sex steroids and cerebral aneurysms. The studies in this review report similar risk of aneurysm rupture in pregnant women compared to the general population. Most ruptured aneurysms in pregnancy occur during the 3rd trimester, and most pregnant women who present with cerebral aneurysm have caesarean section deliveries. Endovascular treatment of cerebral aneurysms in pregnancy is shown to provide a new and safe form of therapy for these cases. Epidemiological studies of postmenopausal women show that estrogen hormone therapy and later age at menopause are associated with a lower risk of cerebral aneurysm than in matched controls. Experimental studies in animal models corroborate this epidemiological finding; estrogen deficiency causes endothelial dysfunction and inflammation, which may predispose to the formation and rupture of cerebral aneurysms, while exogenous estrogen treatment in this population may lower this risk. CONCLUSIONS: The aim of this work is to equip the neurosurgical and obstetrical/gynecological readership with the tools to better understand, critique, and apply findings from research on sex differences in cerebral aneurysms.

Spontaneous bilateral internal carotid and vertebral artery dissections with dominant-hemisphere circulation maintained by external carotid artery-ophthalmic artery anastomoses.

Spontaneous cervical artery dissection (sCAD) is a major cause of stroke in young adults. Multiple sCAD is a rarer, more poorly understood presentation of sCAD that has been increasingly attributed to cervical trauma such as spinal manipulation or genetic polymorphisms in extracellular matrix components. The authors present the case of a 49-year-old, otherwise healthy woman, who over the course of 2 weeks developed progressive, hemodynamically significant, bilateral internal carotid artery and vertebral artery dissections. Collateral response involved extensive external carotid artery-internal carotid artery anastomoses via the ophthalmic artery, which were instrumental in maintaining perfusion because circle of Willis and leptomeningeal anastomotic responses were hampered by the dissection burden in the corresponding collateral vessels. Endovascular intervention by placement of Pipeline embolization devices and Atlas stents in bilateral internal carotid arteries was successfully performed. No syndromic or systemic etiology was discovered during a thorough workup.

Extracranial-intracranial bypass approach to cerebral revascularization: a historical perspective.

While the majority of cerebral revascularization advancements were made in the last century, it is worth noting the humble beginnings of vascular surgery throughout history to appreciate its progression and application to neurovascular pathology in the modern era. Nearly 5000 years of basic human inquiry into the vasculature and its role in neurological disease has resulted in the complex neurosurgical procedures used today to save and improve lives. This paper explores the story of the extracranial-intracranial approach to cerebral revascularization.

Carotid-vertebral artery bypass with saphenous vein graft for symptomatic vertebrobasilar insufficiency.

OBJECTIVESymptomatic steno-occlusion of the proximal vertebral artery (VA) or subclavian artery (ScA) heralds a poor prognosis and high risk of stroke recurrence despite medical therapy, including antiplatelet or anticoagulant drugs. In some cases, the V2 segment of the cervical VA is patent and perfused via collateral vessels. The authors describe 7 patients who were successfully treated by external carotid artery (ECA)-saphenous vein (SV)-VA bypass.METHODSSeven cases involving symptomatic patients were retrospectively studied: 3 cases of V1 segment occlusion, 2 cases of severe in-stent restenosis in the V1 segment, and 2 cases of occlusion of the proximal ScA. All patients underwent ECA-SV-VA bypass. The ECA was isolated and retracted, and the anterior wall of the transverse foramen was unroofed. The VA was exposed, and then the 2 ends of the SV were anastomosed to the VA and ECA in an end-to-side fashion.RESULTSSurgical procedures were all performed as planned, with no intraoperative complications. There were 2 postoperative complications (severe laryngeal edema in one case and shoulder weakness in another), but both patients recovered fully and measures were taken to minimize laryngeal edema and its effects in subsequent cases. All patients experienced improvement of their symptoms. No new neurological deficits were reported. Postoperative angiography demonstrated that the anastomoses were all patent, and analysis of follow-up data (range of follow-up 12-78 months) revealed no further ischemic events in the vertebrobasilar territory.CONCLUSIONSThe ECA-SV-VA bypass is a useful treatment for patients who suffer medically refractory ischemic events in the vertebrobasilar territory when the proximal part of the VA or ScA is severely stenosed or occluded but the V2 segment of the cervical VA is patent.

Testing the Medina embolization device in experimental aneurysms.

OBJECTIVE: The Medina embolization device (MED) is a novel, braided self-expanding endovascular device designed to occlude aneurysms by constructing an in situ intrasaccular flow diverter. Although a single device can be positioned at the neck of simple spherical in vitro aneurysms, the best way to occlude more complex in vivo aneurysms (using multiple MEDs or a combination of MEDs and platinum coils) is currently unknown. METHODS: Fifty-two aneurysms of 3 different types were created in 31 canines, yielding 48 patent aneurysms. Treatments were randomly allocated by drawing lots: group 1, MEDs alone (n = 16); group 2, MEDs plus standard platinum coils (n = 16); and group 3, control aneurysms treated with coils alone (n = 16). Angiographic results were scored and compared immediately following treatment completion and at 3 months. Specimens were photographed and the extent of neointimal closure of the aneurysmal neck scored, followed by histopathological analyses. RESULTS: Angiographic scores of 0 or 1 (occlusion or near occlusion) were initially obtained in 2 of 16 (12.5%, 95% CI 1.6%-38.3%) group 1 (MEDs alone), 3 of 16 (18.7%, 95% CI 4%-45.6%) group 2 (MEDs plus coils), and 10 of 16 (62.5%, 95% CI 35.4%-84.8%) group 3 (coils alone) aneurysms (p = 0.005). At 3 months, scores of 0 or 1 were found in 11 of 16 (68.7%, 95% CI 41.3%-89.0%) group 1, 9 of 16 (56.2%, 95% CI 29.9%-80.2%) group 2, and 8 of 16 (50%, 95% CI 24.7%-75.3%) group 3 aneurysms (p = 0.82). Neointimal scores were similar for the 3 treated groups (p = 0.66). CONCLUSION: Endovascular treatment of experimental aneurysms with MEDs or MEDs and coils showed angiographic occlusion and neointimal scores at 3 months that were similar to those achieved with standard platinum coiling.

A refined model of chronic cerebral hypoperfusion resulting in cognitive impairment and a low mortality rate in rats.

OBJECTIVE: The cognitive deficits of vascular dementia and the vasoocclusive state of moyamoya disease have often been mimicked with bilateral stenosis/occlusion of the common carotid artery (CCA) or internal carotid artery. However, the cerebral blood flow (CBF) declines abruptly in these models after ligation of the CCA, which differs from "chronic" cerebral hypoperfusion. While some modified but time-consuming techniques have used staged occlusion of both CCAs, others used microcoils for CCA stenosis, producing an adverse effect on the arterial endothelium. Thus, the authors developed a new chronic cerebral hypoperfusion (CCH) model with cognitive impairment and a low mortality rate in rats. METHODS: Male Sprague-Dawley rats were subjected to unilateral CCA occlusion and contralateral induction of CCA stenosis (modified CCA occlusion [mCCAO]) or a sham operation. Cortical regional CBF (rCBF) was measured using laser speckle flowmetry. Cognitive function was assessed using a Barnes circular maze (BCM). MRI studies were performed 4 weeks after the operation to evaluate cervical and intracranial arteries and parenchymal injury. Behavioral and histological studies were performed at 4 and 8 weeks after surgery. RESULTS: The mCCAO group revealed a gradual CBF reduction with a low mortality rate (2.3%). White matter degeneration was evident in the corpus callosum and corpus striatum. Although the cellular density declined in the hippocampus, MRI revealed no cerebral infarctions after mCCAO. Immunohistochemistry revealed upregulated inflammatory cells and angiogenesis in the hippocampus and cerebral cortex. Results of the BCM assessment indicated significant impairment in spatial learning and memory in the mCCAO group. Although some resolution of white matter injury was observed at 8 weeks, the animals still had cognitive impairment. CONCLUSIONS: The mCCAO is a straightforward method of producing a CCH model in rats. It is associated with a low mortality rate and could potentially be used to investigate vascular disease, moyamoya disease, and CCH. This model was verified for an extended time point of 8 weeks after surgery.

A refined experimental model of fusiform aneurysms in a rabbit carotid artery.

OBJECTIVE: Reliable animal models are an important aspect of translational research, especially for relatively uncommon clinical entities such as fusiform aneurysms. While several animal models exist, very few are tailored to cerebral fusiform aneurysms, which have unique attributes compared to abdominal fusiform aneurysms. The authors aimed to build from previous models to create a cerebral fusiform aneurysm model that is simple to use and reliable. METHODS: Twelve female New Zealand White rabbits were assigned to 3 groups: group E, elastase only; group C, CaCl2 only; group EC, elastase + CaCl2. All rabbits underwent surgical exposure of the right common carotid artery (CCA) and 20 minutes of peri-carotid incubation with their respective chemicals. Angiography was performed 6 weeks later for arterial dilation measurements, with 50% increase in diameter being defined as fusiform aneurysm formation. The arterial segments, along with the contralateral CCAs, were harvested and assessed histologically for wall component measurements and elastin semiquantification. A separate rabbit underwent aneurysm creation per the group EC protocol and was treated with an endovascular flow-diversion device. RESULTS: All of the group EC rabbits developed fusiform aneurysms (mean dilation of 88%), while none of the group E or group C rabbits developed aneurysms (p = 0.001). Histological analysis revealed increased internal elastic lamina fragmentation in the group EC aneurysms, which also had less tunica intima hyperplasia. All aneurysms exhibited thinning of the tunica media and reduction in elastin content. The use of an endovascular flow-diverting stent was successful, with complete parent vessel remodeling, as expected, 4 weeks after deployment. CONCLUSIONS: The peri-arterial application of combined elastase and CaCl2 to the CCA appears sufficient to reliably produce fusiform aneurysms after 6 weeks. Exposure to elastase or CaCl2 individually appears insufficient, despite the observed histological changes to the arterial wall. The proposed fusiform aneurysm model is able to accommodate endovascular devices, simulating the tortuous pathway experienced in using such devices in human cerebral aneurysms and thus is a satisfactory model to use in translational research.

Hybrid vascular intervention for a giant cervical carotid artery aneurysm in a clopidogrel-hyporesponsive child.

Aneurysms of the extracranial internal carotid artery (ICA) in pediatric patients are rare and mostly treated surgically. The authors present the case of a child with a giant extracranial ICA aneurysm presenting with gradual airway compression. A plan was made to explore the aneurysm surgically and straighten the associated carotid artery kinks during the operation to enable further endovascular treatment if primary reconstruction of the carotid artery proved not to be possible. Finally, the aneurysm was successfully treated with staged hybrid intervention, which consisted of surgical correction of parent artery kinks followed by endovascular implantation of stent grafts. The child tolerated the procedure well without adverse events. A craniocervical CT angiogram at 5 months showed patency of the stent construct and relief of airway compression. However, a follow-up CT angiogram at 14 months showed total occlusion of the ipsilateral carotid artery without clinical sequelae and complete cessation of airway compression. The management of this was unique since the patient is the first reported case of clopidogrel hyporesponsiveness in a child undergoing neurovascular intervention with prasugrel monotherapy. Point-of-care testing-based adjustment of prasugrel necessitated education of the patient's family regarding the loss of effect of the prasugrel tablets upon crushing and contact with air.

Upregulation of miR-216a exerts neuroprotective effects against ischemic injury through negatively regulating JAK2/STAT3-involved apoptosis and inflammatory pathways.

OBJECTIVE: Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke-related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke. METHODS: The JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)-treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)-induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3' untranslated region (3'UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase-9 [MMP-9], tumor necrosis factor-α [TNF-α], and interleukin-1ß [IL-1ß]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V-FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits. RESULTS: JAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3'UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1ß). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit. CONCLUSIONS: These findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.

Combined interventional and surgical treatment of tandem middle cerebral artery embolus and internal carotid artery occlusion: case report.

Tandem internal carotid artery (ICA) origin occlusion and middle cerebral artery (MCA) thromboembolism is a life-threatening condition with poor neurological outcome. The authors report on a patient presenting with acute ischemic stroke from a tandem ICA and MCA occlusion with penumbra. Emergency MCA mechanical thrombectomy was performed through percutaneous cervical ICA access due to the inability to cross the cervical carotid occlusion. Emergency carotid endarterectomy to reperfuse the poorly collateralized hemisphere and repair the ICA access site was performed 2 hours after completion of tissue plasminogen activator (tPA) infusion. This case illustrates the shortest reported interval between tPA infusion and open surgical intervention for carotid revascularization, as well as the role of direct carotid artery access for mechanical thrombectomy. The authors also describe the use of a temporizing femoral artery-to-ICA shunt to maintain cerebral perfusion in the setting of ICA occlusion.

Transcirculation Pipeline embolization device deployment: a rescue technique.

The Pipeline embolization device (PED) has become a very important tool in the treatment of nonruptured cerebral aneurysms. However, a patient's difficult anatomy or vascular stenosis may affect the device delivery. The purpose of this article was to describe an alternate technique for PED deployment when ipsilateral anatomy is not amenable for catheter navigation. A 44-year-old woman with a symptomatic 6-mm right superior hypophyseal artery aneurysm and a known history of right internal carotid artery dissection presented for PED treatment of her aneurysm. An angiogram showed persistence of the arterial dissection with luminal stenosis after 6 months of dual antiplatelet treatment. The contralateral internal carotid artery was catheterized and the PED was deployed via a transcirculation approach, using the anterior communicating artery. Transcirculation deployment of a PED is a viable option when ipsilateral anatomy is difficult or contraindicated for this treatment.