Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).

Focal Cerebral Arteriopathy in a Young Adult Following SARS-CoV2 Reinfection.

Ten days after SARS-Cov2 reinfection with mild gastrointestinal symptoms and headache that occurred 2 months after an initial infection, a previously healthy 37-year-old woman developed fluctuating facial and upper limb paresthesia and weakness. Diffusion-weighted magnetic resonance imaging revealed ischemic lesions in the right parietal region of different stages within the same vascular territory. A cerebral angiography demonstrated an isolated focal arteriopathy with no other arterial involvement. Focal cerebral arteriopathy is exceedingly rare among adults and most commonly triggered by varicella-zoster virus reactivation. We present a case of focal cerebral arteriopathy in a patient with a recent reinfection with SARS-CoV-2.

Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study.

OBJECTIVE: To assess rates of cardiovascular and haemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations. DESIGN: Population based cohort study. SETTING: Nationwide healthcare registers in Denmark and Norway. PARTICIPANTS: All people aged 18-65 years who received a first vaccination with ChAdOx1-S from 9 February 2021 to 11 March 2021. The general populations of Denmark (2016-18) and Norway (2018-19) served as comparator cohorts. MAIN OUTCOME MEASURES: Observed 28 day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people compared with expected rates, based on national age and sex specific background rates from the general populations of the two countries. RESULTS: The vaccinated cohorts comprised 148 792 people in Denmark (median age 45 years, 80% women) and 132 472 in Norway (median age 44 years, 78% women), who received their first dose of ChAdOx1-S. Among 281 264 people who received ChAdOx1-S, the standardised morbidity ratio for arterial events was 0.97 (95% confidence interval 0.77 to 1.20). 59 venous thromboembolic events were observed in the vaccinated cohort compared with 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 (1.50 to 2.54) and 11 (5.6 to 17.0) excess events per 100 000 vaccinations. A higher than expected rate of cerebral venous thrombosis was observed: standardised morbidity ratio 20.25 (8.14 to 41.73); an excess of 2.5 (0.9 to 5.2) events per 100 000 vaccinations. The standardised morbidity ratio for any thrombocytopenia/coagulation disorders was 1.52 (0.97 to 2.25) and for any bleeding was 1.23 (0.97 to 1.55). 15 deaths were observed in the vaccine cohort compared with 44 expected. CONCLUSIONS: Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalisability of the study findings.

Multiple Cerebrovascular Insults in Pseudoxanthoma Elasticum.

Pseudoxanthoma elasticum (PXE) is a rare systemic genetic disorder and an uncommon cause of ischaemic and haemorrhagic strokes. Its rarity and variable presentation may delay recognition and diagnosis of the primary disorder or associated conditions. Here, we describe a patient of European ancestry diagnosed with PXE in her 20s who presented in her 50s with a haemorrhagic stroke. Subsequent workup additionally revealed clinically silent ischaemic cerebral infarcts, critical stenosis of the right internal carotid artery and intracranial vasculopathy. Though she had some typical vascular risk factors, they were well-controlled. Antiplatelet therapy has traditionally been avoided in PXE due to increased risk of GI (and potentially retinal and cerebral) haemorrhage, but the medical team opted to start aspirin for secondary stroke prevention because she had no history of GI or retinal bleed, and her risk of ischaemic stroke was considered unacceptably high compared with that of clinically significant haemorrhage. Judicious use of antiplatelet therapy may be relatively safe in carefully selected patients. Anticipatory surveillance and management of the numerous manifestations of this potentially debilitating disorder are also important to preserve function and quality of life.

Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease.

Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood-brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.

Dilated Cerebral Arteriopathy in Classical Pompe Disease: A Novel Finding.

BACKGROUND: In Pompe disease, glycogen deposition results in an augmentation of blood flow and abnormal remodeling, with resultant weakening of the arterial walls, which may result in pathologic dilatation of the cerebral arteries. This complication is rare in patients with late-onset Pompe disease, but it has not been well-described in infantile-onset Pompe disease. The effect of enzyme replacement therapy on this process is not known. METHODS: We examined clinical and imaging data on two patients who exhibit cerebrovascular arteriopathy: a 14-year-old boy with infantile-onset Pompe disease on enzyme replacement therapy and a 23-year-old woman with late-onset Pompe disease who was also receiving enzyme replacement therapy. RESULTS: Our 14-year-old patient exhibits cerebrovascular arteriopathy, primarily proximal and vertebrobasilar, while the 23-year-old patient has a more diffuse pattern. The 14-year-old patient is unique because cerebral dolichoectasias have not been described in infantile-onset Pompe disease. The 23-year-old patient is notable given the age and history of enzyme replacement therapy since age 15 years. CONCLUSIONS: Dilative cerebral arteriopathy in infantile-onset Pompe disease is novel and similarly atypical is the diffuse vascular dilation seen in our young patient with late-onset Pompe disease, both receiving enzyme replacement therapy. We should be cognizant of the risk of cerebrovascular disease in Pompe disease regardless of the disease variant and enzyme replacement therapy status.

Risk of acute arterial events associated with treatment of inflammatory bowel diseases: nationwide French cohort study.

OBJECTIVE: Patients with IBD are at increased risk of acute arterial events. Antitumour necrosis factor (TNF) agents and thiopurines may, via their anti-inflammatory properties, lower the risk of acute arterial events. The aim of this study was to assess the impact of thiopurines and anti-TNFs on the risk of acute arterial events in patients with IBD. DESIGN: Patients aged 18 years or older and affiliated to the French national health insurance with a diagnosis of IBD were followed up from 1 April 2010 until 31 December 2014. The risks of acute arterial events (including ischaemic heart disease, cerebrovascular disease and peripheral artery disease) were compared between thiopurines and anti-TNFs exposed and unexposed patients with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, traditional cardiovascular risk factors, comorbidities and IBD disease activity. RESULTS: Among 177 827 patients with IBD (96 111 (54%) women, mean age at cohort entry 46.2 years (SD 16.3), 90 205 (50.7%) with Crohn's disease (CD)), 4145 incident acute arterial events occurred (incidence rates: 5.4 per 1000 person-years). Compared with unexposed patients, exposure to anti-TNFs (HR 0.79, 95% CI 0.66 to 0.95), but not to thiopurines (HR 0.93, 95% CI 0.82 to 1.05), was associated with a decreased risk of acute arterial events. The magnitude in risk reduction was highest in men with CD exposed to anti-TNFs (HR 0.54, 95% CI 0.40 to 0.72). CONCLUSION: Exposure to anti-TNFs is associated with a decreased risk of acute arterial events in patients with IBD, particularly in men with CD.

Pediatric Moyamoya Presenting as a Subarachnoid Hemorrhage from a Ruptured Anterior Cerebral Artery Aneurysm.

BACKGROUND: The incidence of Moyamoya disease (MMD)-associated intracranial aneurysms ranges from 3% to 14% in adult patients, whereas this complication has rarely been reported in children. CASE DESCRIPTION: We herein report the first case, to our knowledge, of an extremely rare subarachnoid hemorrhage presentation of a child with a ruptured anterior cerebral artery dissecting aneurysm secondary to a newly discovered, unilateral Moyamoya-like pathology. CONCLUSIONS: MMD-associated aneurysms are extremely rare in children, and hemorrhage may be the initial presentation of the disease. Prompt intervention is essential to exclude the ruptured aneurysm that is at risk of rebleeding because of persistent hemodynamic stress.

Intracranial Artery Stenosis and Its Association With Conventional Risk Factors in a General Population of Japanese Men.

Background and Purpose- Few community-based studies have reported the prevalence of intracranial artery stenosis (ICAS) assessed with magnetic resonance angiography. The aim was to determine the prevalence of ICAS using magnetic resonance angiography in a general population of Japanese men and to investigate the associations between ICAS and conventional cardiovascular risk factors. Methods- The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited and examined participants from Kusatsu City, Shiga, Japan, in 2006 to 2008 (baseline); 740 men returned for follow-up and underwent 1.5 T brain magnetic resonance angiography in 2012 to 2015. Participants were categorized as having no-ICAS, mild-ICAS (1 to <50%), or severe-ICAS (≥50%) in any of the arteries examined. After excluding the men with a history of stroke, 709 men were analyzed using multivariable logistic regression to assess independent associations of conventional cardiovascular risk factors with reference to the no-ICAS group. Results- The participants' mean age was 68.0 years. The age-standardized prevalences of mild and severe-ICAS were 20.7% and 4.5%, respectively (with the population of the 2010 Japanese vital statistics as the reference). Age, hypertension, diabetes mellitus, and dyslipidemia were associated with a higher prevalence of severe-ICAS after simultaneous adjustment for conventional cardiovascular risk factors. Conclusions- In a community-based sample of Japanese men, ICAS was estimated to be present in 25.2%, and related to metabolic risk factors, in addition to hypertension and age. These results support the importance of comprehensive management of conventional cardiovascular risk factors for stroke prevention.

Cerebral arterial air embolism after computed tomography-guided hook-wire localization of a pulmonary nodule: A case report.

RATIONALE: Cranial arterial air embolism is a rare but potentially fatal complication after computed tomography (CT)-guided pulmonary interventions. PATIENT CONCERNS: A 64-year-old man was diagnosed with a pulmonary nodule (diameter: approximately 1 cm) in the right lower lobe. The patient developed convulsions after CT-guided hook-wire localization. DIAGNOSIS: Cranial CT revealed arborizing/linearly distributed gas in the territory of the right middle cerebral artery. INTERVENTIONS: The patient was administered hyperbaric oxygen, antiplatelet aggregation therapy, and dehydration treatment. OUTCOMES: Clinical death occurred 55 hours after air embolism. LESSONS: Systemic air embolism is a serious complication of lung puncture. Clinicians should improve their understanding of this complication and remain vigilant against air embolism.

Intravascular coil migration to bronchus: review of the literature with two case reports.

Pulmonary vascular abnormalities are important causes of hemoptysis. Arteriovenous malformation (AVM), pulmonary arterial aneurysms or invasion of the pulmonary arterial structures by the tumor may cause hemoptysis. Pulmonary artery aneurysms (PAA) are an infrequent disease of the pulmonary vasculature. Endovascular coil application is a convenient treatment option for the treatment of hemoptysis due to vascular anomalies. The migration of intravascular coil to another tissue is a rare complication. To review this extremely rare complication, herein we report two unusual cases who had pulmonary artery aneurysm and who had hemoptysis due to tumor invasion to pulmonary artery, initially treated with endovascular coil successfully. In both cases endovascular coil was migrated to the bronchus subsequently. Lobectomy may be performed in such cases with coil migration into the bronchus or conservative therapy with follow-up chest imaging may be a suitable treatment option for selected patients. The choice of treatment should be made individually for each patient considering the characteristics of the patients. In patients with coils, the biopsy can lead to massive hemorrhages that are fatal.

[A Case of Sjögren's Syndrome with Multiple Stenoses of the Cerebral Arteries and Transient Neurological Symptoms and Signs].

A 31-year-old woman was admitted to the hospital after several episodes of transient numbness in her fingers and dysarthria. No neurological symptoms and signs were observed in this patient on admission; however, blood tests revealed elevated amylase and immunoglobulin G levels, an increased erythrocyte sedimentation rate, and positive anti-Sjögren's-syndrome (SjS)-related antigen A antibodies. The cerebrospinal fluid examination revealed a slight increase in the cell count and protein content. Diffusion-weighted and fluid-attenuated inversion recovery images on magnetic resonance imaging showed high-signal-intensity lesions in the cerebral white matter and basal ganglia supplied by the left middle cerebral artery. A part of the lesions was enhanced by the administration of gadolinium contrast medium. Magnetic resonance angiography suggested stenosis in the left anterior, middle, and posterior cerebral arteries. The patient was thus diagnosed with acute cerebral infarction and was then treated with argatroban, edaravone, and clopidogrel. Furthermore, Schirmer's test, sialography, and salivary gland biopsy results led to the diagnosis of SjS. A nerve conduction study suggested concomitant mild polyneuritis or mononeuritis multiplex. Collectively, we speculate that cerebral arterial stenosis associated with SjS leads to transient ischemic attack-like episodes, transient neurological symptoms and signs, and cerebral infarction. (Received June 13, 2018; Accepted September 11, 2018; Published December 1, 2018).

Chronic Dilatation of Superficial Temporal Artery and Middle Meningeal Artery Associated with Development of Collateral Circulation After Bypass Surgery for Moyamoya Angiopathy.

OBJECTIVES: Dilatation of the superficial temporal artery (STA) and middle meningeal artery (MMA) were occasionally observed after bypass surgery for moyamoya angiopathy. The purpose of this study was to examine the correlation between angiographic outcomes and magnetic resonance imaging (MRI), specifically focusing on the postoperative dilatation ratio of the STA (rSTA) and MMA (rMMA). METHODS: Fifty-six hemispheres in 36 consecutive patients who underwent revascularization for moyamoya angiopathy were evaluated. All patients underwent angiography and MRI before surgery and during the chronic phase. Angiographic outcomes were classified as good or poor according to the extent of the blood supply through direct or indirect bypass. The rSTA and rMMA was calculated in time-of-flight magnetic resonance angiography (MRA). The signal changes of ivy signs and flow voids in basal ganglia were also evaluated. RESULTS: Postoperative collaterals through direct and indirect bypass was good in 30 (53.6%) and 33 (58.9%) patients, respectively. The mean rSTA and rMMA were 36.04 ± 28.79% and 29.15 ± 22.01%, respectively. Ivy signs and flow voids were decreased in 9 (16.1%) and 26 (46.4%) patients, respectively. Univariate analyses demonstrated no significant correlation between the angiographic outcomes and postoperative signal changes on MRI. However, rSTA was significantly correlated with good collaterals through direct bypass (P = 0.04), whereas rMMA was significantly correlated with good collaterals through indirect bypass (P < 0.001). CONCLUSIONS: MRA may be an alternative to angiography. Both rSTA and rMMA estimated the development of collaterals after bypass surgery for moyamoya angiopathy.

Cerebral Fat Embolism as Complication of Facial Fat Graft: Retrospective Analysis of Clinical Characteristics, Treatment, and Prognosis.

BACKGROUND: Cerebral fat embolism (CFE) is a rare complication that usually occurs after trauma injury. The incidence of CFE due to aesthetic surgery is extremely rare and can lead to fatal outcome. Due to the rarity of this complication, there is still lack of knowledge and standardization of the treatment. CASE DESCRIPTION: Herein, we reported 6 cases of CFE that occurred in patients who underwent cosmetic surgery. Among 5 patients who had large artery occlusion, 3 patients survived and 2 patients died due to progression of the disease. One patient had the ophthalmic artery occlusion. In addition, embolectomy was performed in 5 patients and 3 patients had decompressive craniectomy following endovascular treatment due to severe brain edema. CONCLUSIONS: CFE is associated with high morbidity and mortality, and early surgical intervention can improve the prognosis.

Hammock Middle Cerebral Artery and Delayed Infarction in Lenticulostriate Artery After Staged Resection of Giant Insular Glioma.

BACKGROUND: Delayed infarction in the lenticulostriate artery (LSA) area after insular glioma resection is not common, and its pathophysiology remains unknown. CASE DESCRIPTION: A 32-year-old right-handed man with a giant insular low-grade glioma with frontal and temporal extension underwent awake craniotomy with an intentional staged surgery strategy. Preoperative radiologic images demonstrated a diagonally elevated middle cerebral artery (MCA) by the temporal tumor and a significantly compressed striatum. With intraoperative subcortical direct electrical stimulation, the resection was finalized in the temporal part of the tumor due to the semantic paraphasia induced in the temporal stem, fatigue, and loss of concentration. The immediate postoperative clinical course was uneventful. However, on postoperative day 20, he suddenly experienced right hemiparesis. Repeated images revealed infarction in the LSA area. The previously compressed striatum was then relieved and relocated to its original position in just 20 days, and the M1 segment of the MCA was remarkably downward, in which the MCA resembled a hammock. Angiography confirmed the hammock-shaped MCA and significantly stretched LSA, suggesting the combination of freed striatum from the compression and loss of temporal structure by the tumor resection as the key mechanism of severe dislocation of the MCA and delayed ischemia. CONCLUSIONS: In a staged resection of giant insular glioma, attention should be paid to a possible severe dislocation of the MCA in a delayed postoperative period, which may lead to LSA stretching and delayed infarction.

Large Vessel Arteriopathy After Cranial Radiation Therapy in Pediatric Brain Tumor Survivors.

Among childhood cancer survivors, increased stroke risk after cranial radiation therapy may be caused by radiation-induced arteriopathy, but limited data exist to support this hypothesis. Herein, we assess the timing and presence of cerebral arteriopathy identified by magnetic resonance angiography (MRA) after cranial radiation therapy in childhood brain tumor survivors. In a cohort of 115 pediatric brain tumor survivors, we performed chart abstraction and prospective annual follow-up to assess the presence of large vessel cerebral arteriopathy by MRA. We identified 10 patients with cerebral arteriopathy. The cumulative incidence of arteriopathy 5 years post-cranial radiation therapy was 5.4% (CI 0.6%-10%) and 10 years was 16% (CI 4.6%-26%). One patient had an arterial ischemic stroke 2.4 years post-cranial radiation therapy in the distribution of a radiation-induced stenotic artery. We conclude that large vessel arteriopathies can occur within a few years of cranial radiation therapy and can become apparent on MRA in under a year.

Treatment strategies for traumatic cervico-cranial pseudoaneurysms: A single institution experience.

AIM: Limited clinical and angiographic data exists for patients with traumatic cervico-cerebral pseudoaneurysms. In this paper, we present our limited experience with various management strategies for traumatic cervico-cranial pseudoaneurysms. MATERIALS AND METHODS: We retrospectively analyzed 37 consecutive cases of traumatic pseudoaneurysms involving the cervico-cranial or the cerebral arteries diagnosed at our center from September 2009 to December 2014. The demographic data, etiology, clinical presentation, lesion location, treatment modality, and follow-up outcomes of these patients were reviewed. Among these 37 patients, 5 patients were treated by surgery, while 29 patients were treated by the endovascular approach and 3 received conservative treatment. RESULTS: During the study period, 42 pseudoaneurysms were identified in 37 patients with a history of head or neck injury. Five patients underwent surgical exploration of the lesion with an uneventful postoperative course. Twenty-nine patients were treated by endovascular interventions with various embolization materials including coils, stents, detachable balloons, liquid embolic agents, and a combination of these agents. The angiographic follow-up imaging demonstrated complete exclusion of the aneurysm from the circulation with the patient being free from any additional neurological deficits. CONCLUSION: Proper selection of an appropriate approach is essential to address the management of traumatic cervico-cerebral pseudoaneurysms. The treatment of traumatic cervico-cerebral pseudoaneurysms should be selected according to the location and the clinical features of the pseudoaneurysms. The endovascular treatment is a safe and effective modality and should be the first-line choice for treatment of traumatic pseudoaneurysms.