Treatment of moyamoya syndrome in children

Moyamoya syndrome, a known cause of pediatric stroke, is a chronic cerebrovascular occlusive disorder of unknown etiology that can lead to severe, permanent neurologic disability. It is characterized by progressive stenosis of the distal intracranial carotid arteries and branches of the circle of Willis and the nearly simultaneous appearance of basal arterial collateral vessels, which vascularize hypoperfused brain distal to the occluded vessels. Most children with moyamoya syndrome present either with transient ischemic attacks or strokes. This review summarizes the current medical and surgical practices used in the treatment of moyamoya syndrome in children.     

Childhood cerebrovascular diseases not associated with vascular malformations

Of 76 patients in the pediatric age group suffering from cerebrovascular diseases treated in the years 1970–1983, 26 patients (34%) did not harbor intracranial vascular malformations (aneurysms or arterovenous malformations). Two groups of patients were identified: (a) those suffering from a spontaneous intracranial hemorrhage (16 cases); (b) those suffering from an ischemic stroke (10 cases). Of those with spontaneous intracranial hemorrhage, 10 patients underwent surgery and evacuation of the hematoma. In 2 cases the hematoma was located in the posterior fossa, in 1 case in the upper brain stem, and in 3 cases in the basal ganglia; in the remainder the hematoma was supratentorial. Two patients died soon after the hemorrhage. Eight of the surviving patients completely recovered. In those with ischemic stroke, none suffered from congenital heart disease, a well-known predisposing factor. In this second group 1 patient died and 9 survived. Only one patient showed complete recovery. The data indicate that a hemorrhagic stroke is more common than an ischemic stroke in a child presenting with acute onset of hemiparesis and/or loss of conciousness: thus the value of CT scan as the first diagnostic procedure is clear, owing to the possibility of emergency surgical treatment. In children with ischemic strokes, a complete laboratory/clinical evaluation should be undertaken in order to exclude preexisting heart disease, coagulation disorders or lipoprotein abnormalities, and less common systemic diseases.     

Joubert syndrome presenting with young-age onset ischemic stroke: a possible etiologic association

Joubert syndrome is a rare genetic disorder of childhood that is characterized by hypoplasia or agenesis of the cerebellar vermis in addition to brainstem malformations. Ataxia, hypotonia, developmental delay, and apnea-hyperpnea are the most prominent clinical symptoms of Joubert syndrome, but this condition can also affect multiple organs, making the clinical phenomenology of Joubert syndrome quite diverse. Seizures are the most common neurological complications of Joubert syndrome, but its neurological sequelae are poorly described because Joubert syndrome is very rare. Here we report an acute ischemic stroke in a 21-year-old woman with Joubert syndrome who had no conventional risk factors for early onset cerebrovascular disease. To date, this is the first report of an ischemic stroke in a patient with Joubert syndrome, and we believe this case may suggest an association between Joubert syndrome and extremely early onset cerebrovascular disease.     

Moyamoya Syndrome in a Child with Noonan Syndrome

Previous studies have rarely described the association between Noonan syndrome and moyamoya syndrome. Although most affected children with moyamoya exhibit ischemic symptoms, headache is also a frequent symptom. We report the case of a 9-year-old girl with Noonan syndrome and moyamoya syndrome that manifested as recurrent headaches without history of transient ischemic attack. Brain magnetic resonance imaging and magnetic resonance angiography revealed bilateral moyamoya syndrome and mild ventriculomegaly with focal encephalomalacia at right peritrigonal region. Disruption of vascular development during the prenatal stage has been proposed as the cause of cerebrovascular disease in Noonan syndrome. However, genetic factors may also contribute.     

Association of Metabolic Syndrome and C-reactive Protein Levels with Intracranial Atherosclerotic Stroke

Background

The risk factors for intracranial atherosclerosis are unclear but may differ from those for other stroke subtypes. Here, we investigated whether metabolic syndrome, an emerging risk factor for cardiovascular disease, is associated with intracranial atherosclerotic stroke.

Methods

Using the Adults Treatment Panel III criteria, we evaluated the components of metabolic syndrome in 439 patients with ischemic stroke or transient ischemic attacks. The prevalence of metabolic syndrome within each stroke subtype was determined, and the association between intracranial atherosclerosis and metabolic syndrome was evaluated.

Results

Metabolic syndrome was observed more frequently in patients with intracranial atherosclerosis than in those with other types of stroke (P=0.003). In a multiple regression analysis, metabolic syndrome, but not conventional risk factors, was independently associated with intracranial atherosclerosis (P=0.016). By contrast, the serum level of C-reactive protein was correlated negatively with the presence of intracranial atherosclerosis. Intracranial atherosclerosis was most prevalent in patients with metabolic syndrome and low levels of C-reactive protein (P=0.024).

Conclusions

Our results indicate that metabolic syndrome is a strong independent risk factor for intracranial atherosclerotic stroke. Therefore, treatment of metabolic abnormalities may be an important prevention strategy for intracranial atherosclerotic stroke.     

Chinese-white differences in the distribution of occlusive cerebrovascular disease

The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (greater than or equal to 50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic territories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterolemia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.     

SPECT Imaging of Stroke

-photon emission computed tomography (SPECT) is a helpful tool for the management of stroke patients. Brain perfusion SPECT can help differentiate an ischemic event from peri-ictal phenomena such as Todd's paresis. Initial data suggest that SPECT may be useful in prognosticating the likelihood of an early stroke after a transient ischemic attack and in distinguishing lacunar from cortical stroke. After an acute stroke, early SPECT depicts the area of ischemia with greater accuracy than either computed tomography or magnetic resonance imaging. When the perfusion defect is large, the likelihood of hemorrhagic complications or herniation increases. Reperfusion of an arterial territory after thrombolysis can be documented more conveniently with SPECT than with angiography. SPECT before and after the inJection of acetazolamide has been used to assess the vascular reserve in patients with severe stenosis of the proximal vessels of the cerebrovascular tree. Combined with transcranial Doppler studies, SPECT is used to document ischemia after subarachnoid hemorrhage. It has also been used to assess the effect of arterial ligation intended to treat arteriovenous malformations or aneurysms on brain perfusion and to evaluate ischemia secondary to pressure from an intracranial hemorrhage.     

Cerebrovascular complications of coccidioidomycosis meningitis: Case report and systematic review

Coccidioidomycosis exposure is common in the southwest United States and northern Mexico. Dissemination to the meninges is the most severe form of progression. Although ischemic strokes are well-reported in these patients, other cerebrovascular complications of coccidioidomycosis meningitis (CM), as well as their treatment options and outcomes, have not been systematically studied. We present a uniquely severe case of CM with several cerebrovascular complications. We also systematically queried PubMed and EMBASE databases, including articles published before April 2020 reporting human patients with CM-induced cerebrovascular pathology other than ischemic infarcts. Sixteen articles met inclusion criteria, which describe 6 patients with aneurysmal hemorrhage, 10 with non-aneurysmal hemorrhage, one with vasospasm, and one with transient ischemic attacks. CM-associated aneurysms invariably presented with hemorrhage. These were universally fatal until the past decade, when advances in surgical clipping and/or combined surgical and endovascular treatment have improved outcomes. We found that non-aneurysmal intracranial hemorrhages were limited to male patients, involved a diverse set of intracranial vasculature, and had a mortality rate surpassing 80%. Vasospasm was reported once, and was treated with percutaneous transluminal angioplasty. Transient ischemic attacks were reported once, and were successfully treated with fluconazole and dexamethasone. This review suggests that CM can present with a wide array of cerebrovascular complications, including ischemic infarcts, aneurysmogenesis, non-aneurysmal intracranial hemorrhage, vasospasm, and transient ischemic attacks. Mortality has improved over time due to advances in surgical and endovascular treatment modalities. The exception is non-aneurysmal intracranial hemorrhage, which remains associated with high mortality rates and few targeted therapeutic options.     

Transcranial color-coded duplex sonography

Transcranial color-coded duplex sonography (TCCS) enables the reliable assessment of intracranial stenoses, occlusions, and cross-flow through the circle of Willis without using potentially hazardous compression tests. Transpulmonary ultrasound contrast agents (UCAs) increase the number of conclusive TCCS investigations, which suggests that UCAs may provide the conclusive evaluation of intracranial arteries in most patients with ischemic cerebrovascular disease. Further, contrast-enhanced TCCS may become an important tool both for the management of acute ischemic stroke by assessing intracranial hemodynamics and the displacement and diameter changes in supratentorial ventricles. TCCS is useful for the detection and monitoring of intracranial vasospasm, may visualize larger supratentorial hematomas with subcortical location and hemorrhagic transformation of ischemic infarcts, and provides the incidental detection of cerebral aneurysms and arteriovenous malformations. Second-generation UCAs and new ultrasound machines are very likely to further increase the frequency of conclusive TCCS studies. Power-based three-dimensional, contrast-enhanced TCCS is an important further development, which would make the method much less operator dependent. Site-targeted UCAs appear to provide a new and exciting method for ultrasonic diagnosis and management of patients with ischemic cerebrovascular disease. Received: 21 November 1998 Accepted: 12 December 1998     

Additional predisposing risk factors for atherothrombotic cerebrovascular disease among treated hypertensive volunteers

A 7-year prospective study of a cohort of 107 neurologically normal elderly hypertensive volunteers (mean age, 65.8 +/- 8.3 years) was undertaken to investigate the predictive validities of additional risk factors for atherothrombotic cerebrovascular disease including stroke, transient ischemic attacks, reversible ischemic neurological deficits, and multi-infarct dementia. This longitudinal study has been in progress now for 7 years with a mean follow-up interval of 50.12 +/- 5.76 months. Among 107 formerly symptom-free, normal hypertensive volunteers, 25 (23%) have developed cerebrovascular disease, 7 (6.5%) sustained a stroke, 10 (9.3%) developed multi-infarct dementia, and 18 (16.8%) have transient ischemic attacks. None have suffered intracranial hemorrhage. Mean gray matter cerebral blood flow (CBF) values measured at the initial visit were sensitive predictors of cerebrovascular disease. Eight of 16 hypertensives (50%) with initial CBF values below 60.0 ml/100 g/min now exhibit signs and symptoms of cerebrovascular disease, while 11 of 43 hypertensives (25.6%) with initial CBF values between 60.1 and 69.9 ml/100 g/min and only 6 of 48 (12.5%) with initial CBF levels above 70.0 developed cerebrovascular disease. Incidence of cerebrovascular disease among cigarette smoking hypertensive volunteers (32.5%) was significantly greater than among nonsmokers (17.2%).     

Malformation vasculaire cérébrale découverte dans le bilan pré-thrombolyse d’un infarctus cérébral. Impact sur la décision thérapeutique

Intravenous recombinant tissue plasminogen activator for acute ischemic stroke is contraindicated in patients harboring an asymptomatic intracranial vascular malformation, whether it is incidentally discovered at the time of the initial cerebral imaging or previously known. Because thrombolysis is associated with a risk of serious intracerebral hemorrhage, it is theoretically possible that this treatment increases the risk of bleeding or rupture of these malformations. However, this risk seems very low in clinical practice. We report two cases, one with a probable brainstem cavernous malformation treated with alteplase for a supratentorial ischemic stroke who developed just after treatment a fatal brainstem hemorrhage, and another one with asymptomatic dural arteriovenous fistula, treated by endovascular thrombectomy solely. This approach was safe and effective, and the patient had an endovascular embolization of the fistula one month later as it became symptomatic. Based on the literature, we discuss the bleeding risk of asymptomatic intracranial vascular malformations in acute ischemic stroke patients treated with alteplase, depending on the type of malformation (intracranial aneurysm, arteriovenous and cavernous malformation or fistula), and the alternative therapeutic options.     

Intracranial aneurysms in Ehlers-Danlos syndrome type IV in early childhood.

Ehlers-Danlos syndrome type IV is of special interest to neurologists because of the risk of cerebrovascular complications. We describe a 5-year-old female with Ehlers-Danlos syndrome type IV, demonstrating multiple intracranial aneurysms and right middle cerebral artery stenosis. The diagnosis of Ehlers-Danlos syndrome type IV was confirmed by electron microscopic examination of a skin biopsy. To our knowledge, this is the youngest reported patient with intracranial aneurysms associated with the Ehlers-Danlos syndrome type IV. Ehlers-Danlos syndrome type IV should be considered in the differential diagnosis of cerebrovascular disorder and stroke in early childhood.     

Dual Antiplatelet Therapy after Noncardioembolic Ischemic Stroke or Transient Ischemic Attack: Pros and Cons

Dual antiplatelet therapy simultaneously blocks different platelet activation pathways and might thus be more potent at inhibiting platelet activation and more effective at reducing major ischemic vascular events compared to antiplatelet monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. However, dual antiplatelet therapy carries an increased risk of bleeding. Patients with ischemic stroke or transient ischemic attack (TIA) are generally older and likely to have a fragile cerebrovascular bed, which further increases the risk of systemic major bleeding events and intracranial hemorrhage. Clinical trials and meta-analyses suggest that in comparison to antiplatelet monotherapy, dual antiplatelet therapy initiated early after noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent stroke and major vascular events without significantly increasing the rate of major bleeding events. In contrast, studies of long-term therapy in patients with noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding the benefit of dual antiplatelet therapy over monotherapy. However, the harm associated with major bleeding events, including intracranial hemorrhage, which is generally more disabling and more fatal than ischemic stroke, is likely to increase with dual antiplatelet therapy. Physicians should carefully assess the benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy when managing patients with ischemic stroke or TIA.     

代谢综合征与颅内外动脉粥样硬化性狭窄的相关性研究

目的:探讨代谢综合征(Metabolic syndrome,MS)与颅内外动脉粥样硬化性病变的相关性。方法:连续收集579例因急性脑梗塞或血管性危险因素入院的患者,借助经颅多普勒超声和/或核磁共振血管成像明确有无颅内外动脉粥样硬化性狭窄,分为狭窄组和非狭窄组;采用IDF的MS诊断标准,明确两组MS的发生率;分析颅内外动脉粥样硬化性狭窄的危险因素,并探讨MS与颅内、颅外动脉粥样硬化性狭窄的相关性。结果:1、狭窄组和非狭窄组MS的发生率分别为71.26%,58.43%,两组比较有统计学差异(P=0.0015)。2、与脑动脉粥样硬化性狭窄相关的危险因素依次为:脑梗塞病史、高血糖、高胆固醇血症、高血压、低HDL血症,年龄,MS并非脑动脉粥样硬化性狭窄的独立危险因素,OR0.798。3、MS与颅内动脉粥样硬化性狭窄相关,OR1.736,但其风险依赖于其组分中的高血糖、高血压及低HDL血症;MS与颅外动脉粥样硬化性狭窄不相关,OR1.466。结论:MS不是脑动脉粥样硬化性狭窄的独立危险因素,MS与颅内动脉粥样硬化性狭窄相关,但这种危险性依赖于MS各组分,MS与颅外动脉粥样硬化性狭窄无相关性。     

颅内动脉狭窄与HLA-DQA1、DQB1基因多态性关系研究

目的 探讨白细胞抗原(HLA)-DQA1、DQB1基因多态性与颅内动脉狭窄的关系.方法 运用聚合酶链反应-序列特异性引物(PCR-SSP)方法 对自2006年7月至2007年3月天津医科大学总医院神经内科收治的15例缺血性卒中伴颅内动脉中重度狭窄患者(简称狭窄组)、49例缺血性卒中且无动脉狭窄患者(简称无狭窄组)和52例健康体检者(对照组)进行HLA-DQA1和DQB1基因多态性分型. 结果 狭窄组DQA1*0501和DQB1*0501出现频率增高,与其它2组比较差异有统计学意义(P<0.05);而无狭窄组与对照组相比,DQA1*0301和DQB1*0301频率增高,差异有统计学意义(P<0.05). 结论 DQA1*0501和DQB1*0501是缺血性卒中伴颅内动脉狭窄易感基因,DQA1*0301和DQB1*0301为缺血性卒中易感因素.     

Postpartum RCVS and PRES with normal initial imaging findings

Postpartum angiopathy as clinical presentation of reversible cerebral vasoconstriction syndrome remains an intriguing phenomenon. The diagnosis needs to be considered in women presenting with thunderclap headache with or without associated neurological deficits. Here, we present a patient with thunderclap headache with initial normal laboratory and cerebral imaging findings, including intracranial angiography. Her condition worsened over several days and magnetic resonance imaging revealed changes initially compatible with posterior reversible encephalopathy syndrome, sequentially ischemic stroke and narrowing of the intracranial arteries. Although the patient was in coma for several days, she completely recovered and the focal vasoconstriction fully resolved. This case underscores the complex and variable presentation of postpartum angiopathy and illustrates the diagnosis to be (re)considered even if cerebral vasoconstriction is not documented at the onset of symptoms.     

Large middle cerebral artery dissecting aneurysm mimicking hemorrhagic stroke

Dissection of intracranial arteries is a rare cause of cerebrovascular diseases commonly presenting as an ischemic stroke. We report a patient with middle cerebral artery dissection who developed a large middle cerebral artery dissecting aneurysm mimicking a hemorrhagic stroke.     

Recurrent transient ischemic attacks in a 15-year-old boy with beta-thalassemia minor and thrombophilia. Contribution of perfusion SPECT to clinical diagnosis

beta-Thalassemic patients exhibit an increased frequency of thrombotic events but most patients with heterozygous beta-thalassemia minor are asymptomatic and no single case with beta-thalassemia minor and concurrent stroke was reported. We present a 15-year-old boy with heterozygous beta-thalassemia minor who developed recurrent transient ischemic attacks as documented with repeated brain SPECTs whereas structural neuro-imaging was not contributory. The patient exhibited resistance to activated protein C due to heterozygosity for factor V Leiden as well as slightly decreased plasma levels of protein C and S. This unique association of risk factors might have caused clinically significant thrombophilia resulting in recurrent cerebrovascular events. This case report underlines the thrombogenic risk of heterozygous beta-thalassemia minor in children heterozygous for factor V Leiden mutation. We therefore suggest to screen for thrombophilia in children with beta-thalassemia minor when thromboembolism-related phenomena occur. This case also demonstrates that brain perfusion SPECT is a useful and sensitive tool for detecting cerebrovascular events in patients with hemoglobinopathies.     

Cerebrovascular Involvement in Mucormycosis in COVID-19 Pandemic

BackgroundMany countries have seen an unprecedented rise of cases of coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM). Cerebrovascular involvement in CAM has not been studied so far. We describe clinico-radiological manifestations of cerebrovascular complications observed in CAM.MethodsIn this multicentric retrospective observational study from India, patients with CAM who developed cerebrovascular involvement were studied. Their demographics, risk factors, clinical manifestations, imaging, laboratory profile and outcomes were noted.ResultsOut of 49 subjects with cerebrovascular involvement, 71.4% were males while average age was 52.9 years. Ischemic stroke was commonest (91.8%) followed by intracranial haemorrhage (6.1%) and subarachnoid haemorrhage (2%). The incidence of cerebrovascular complications in CAM was found to be 11.8% in one center. Cerebrovascular symptoms appeared a median of 8.3 days from the onset of mucormycosis. Commonest presentation of mucormycosis was rhino-orbito-cerebral syndrome in 98%. Diabetes mellitus was present in 81.7%. Forty percent developed stroke despite being on antiplatelet agent and/or heparin. Amongst subjects with ischemic strokes, location of stroke was unilateral anterior circulation (62.2%); bilateral anterior circulation (17.8%); posterior circulation (11.1%) and combined anterior and posterior circulation (8.9%). Vascular imaging revealed intracranial occlusion in 62.1%; extracranial occlusion in 3.4% and normal vessels in 34.5%. Mortality was 51% during hospital stay.ConclusionsCerebrovascular involvement was seen in 11.8% patients of CAM. Angio-invasive nature of the fungus, prothrombotic state created by COVID-19, and diabetes were important causative factors. Subjects with CAM should be screened for involvement of the brain as well as its vessel. Antiplatelet agents/heparin did not seem to provide complete protection from this type of stroke.     

单纯颅内动脉狭窄性缺血性脑血管病预后评估

目的 探讨单纯颅内动脉狭窄性缺血性脑血管病1年卒中复发的影响因素。 方法 筛选经数字减影血管造影（digital subtraction angiography,DSA）证实存在单纯颅内动脉粥样硬 化性狭窄的缺血性脑血管病患者86例,随访1年,将卒中事件作为终点事件。分析颅内动脉狭窄的分 布特征,Cox回归模型分析年龄、性别、高血压、高血脂、糖尿病、吸烟、饮酒、超敏C反应蛋白（high sensitive C reactive protein,hsCRP）、动脉狭窄数目、动脉狭窄程度、前后循环狭窄、缺血类型、冠状动 脉粥样硬化性心脏病史、缺血性脑血管病史等对终点事件的影响。 结果 结果显示颅内动脉狭窄好发于大脑中动脉（35.51%）,80例符合入组标准的患者完成1年随访。 多因素Cox回归分析显示：年龄≥60岁[危险比（risk ratio,RR）2.628,95%可信区间（confidence interval, CI）1.066～6.478,P =0.036] 、女性（RR 2.645,95%CI 1.133～6.178,P =0.025）、美国国立卫生研究院 卒中量表（National Institutes of Health Stroke Scale,NIHSS）评分＞1（RR 3.644,95%CI 1.280～10.369, P =0.015）和多发性颅内动脉狭窄（RR 2.712,95%CI 1.048～7.019,P =0.040）是终点事件的危险因素。 结论 年龄、性别、NIHSS评分和颅内动脉狭窄数目可能是颅内动脉狭窄性缺血性脑血管病患者1年 内再发卒中事件的独立危险因素。