The genetics of intracranial aneurysms

The rupture of an intracranial aneurysm (IA) leads to a subarachnoid hemorrhage, a sudden onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension and excessive alcohol intake are associated with subarachnoid hemorrhage. IAs, ruptured or unruptured, can be treated either surgically via a craniotomy (through an opening in the skull) or endovascularly by placing coils through a catheter in the femoral artery. Even though the etiology of IA formation is mostly unknown, several studies support a certain role of genetic factors. In reports so far, genome-wide linkage studies suggest several susceptibility loci that may contain one or more predisposing genes. Studies of several candidate genes report association with IAs. To date, no single gene has been identified as responsible for IA formation or rupture. The identification of susceptible genes may lead to the understanding of the mechanism of formation and rupture and possibly lead to the development of a pharmacological therapy.     

Early fetal development of the human vertebral artery especially at and above the occipitovertebral junction

Little is known about the chronological changes that occur in the topographical anatomy of the fetal vertebral artery (VA), especially at and above the occipitovertebral junction. We histologically examined paraffin-embedded horizontal, sagittal and frontal sections of the heads of 25 human embryos and fetuses of crown-rump length 20–110 mm, corresponding to 6–15 weeks of gestation. At 6 weeks, the VA ran anterosuperiorly through a large intracranial subdural space filled with loose mesenchymal tissue. This intracranial course was distant from the brain stem, suggesting that the developing brain did not “guide” the VA. Before 8–9 weeks, the VA appeared to take an almost straight upward course at the occipitovertebral junction. Later, however, the atlanto-occipital joint growing along the mediolateral axis caused the VA to curve at the junction area. In specimens before 10 weeks, the terminal of the VA, or the origin of the basilar artery, was on the anterior side of the inferior olive and near the jugular foramen. The fetal posterior inferior cerebellar artery originated at the same caudal site distant from the primitive cerebellum. Later, the terminal or origin moved rostrally to the level of the pons. These findings indicate that the basic branching pattern of the VA–basilar artery is independent of the developing brain, whereas the arterial courses are secondarily “corrected” by the growing brain and atlanto-occipital joint.     

Developmental anomalies of the distal vertebral artery and posterior inferior cerebellar artery: diagnosis by CT angiography and literature review

Purpose

The aim of this study was to identify variations in the anatomy of the distal vertebral artery (VA) and posterior inferior cerebellar artery (PICA) with computed tomography (CT) angiography.

Methods

CT angiography was performed at two hospitals. And the results were analyzed for VA anomalies.

Results

Seven of the 3067 patients who received brain CT angiography in first hospital had seven intracranial VA fenestrations. Twelve of 546 patients who received CT angiography of intracranial and extracranial vessels in second hospital had 16 anatomical variations of the V3 segment. Two fenestrations of the V3 segment, three C1 origins of the PICA, seven aberrant VAs with an intradural course at the C2 level without a normal VA, and four aberrant VAs with an intradural course at the C2 level with a normal VA were observed. Seventeen of the 314 patients who received cervical CT angiography in second hospital had 21 anatomical variations of the VA. Two fenestrations of the V3 segment, six C1 origins of the PICA, three C2 origins of the PICA, one VA origin of the occipital artery, one fenestration of the V4 segment, five aberrant VAs with an intradural course at the C2 level without a normal VA, and three aberrant VAs with an intradural course at the C2 level with a normal VA were observed.

Conclusions

A certain number of anatomical variants of the distal VA and PICA may reflect variations in size and connections of the lateral or posterior spinal artery.

     

Traumatic subarachnoid haemorrhage: an alternative source.

Traumatic subarachnoid haemorrhage is known on many occasions to result from a blow on the neck rupturing the vertebral artery within the cervical spine. On some occasions, however, no such damage to the artery in the neck can be found to account for the haemorrhage. Some cases are described in which the source of haemorrhage was rupture of the vertebral artery within the skull close to the basilar artery. The reason why rupture should occur at this site is discussed.     

影响颅内小型动脉瘤破裂的影像解剖特征分析

目的:探讨颅内小型动脉瘤的破裂与其影像解剖特征的关系,建立动脉瘤破裂风险评分的预测模型,为颅内小型动脉瘤破裂高危患者的早期识别干预提供参考。方法:回顾性分析2015年1月—2020年5月郑州大学附属郑州中心医院经头颈CT血管造影或全脑血管造影证实的182例颅内小型动脉瘤(最大径<5 mm)患者的临床资料,其中男62例、...     

闪光视觉诱发电位无创颅内压监测结合头颅CT的临床研究

目的:探讨闪光视觉诱发电位无创颅内压监测与头颅CT之间的相关性.方法:用无创颅内压监测仪对50例颅脑外伤患者进行动态颅内压监测,其中重型颅脑损伤者20例,中型23例,轻型7例;每次检测后行头颅CT检查并计分,分析其CT变化特征,并与颅内压值对照.结果:伤后同一时点,患者的颅内压和头颅CT计分比较,重型＞中型＞轻型(P＜0.05).中、重型颅脑损伤患者保守治疗组和手术治疗组的颅内压与头颅CT计分之间,组内比较具有相关性,计算相关系数分别为r=0.92和r--0.96,差异有统计学意义(P＜0.05).结论:闪光视觉诱发电位无创颅内压监测与头颅CT变化呈正相关,两者结合可以指导治疗并判断预后.     

A clinical analysis of twelve cases of ruptured cerebral de novo aneurysms

Formation of cerebral de novo aneurysms (CDNA) is rare, and the pathogenesis remains obscure. In this study, we investigated the factors that contribute to the formation of CDNA and suggest guidelines for following patients treated for cerebral aneurysms. We retrospectively reviewed 2,887 patients treated for intracranial aneurysm at our institute from January of 1976 to December of 2005. Of those patients, 12 were readmitted due to recurrent rupture of CDNA, which was demonstrated by cerebral angiography. We assessed clinical characteristics, such as gender, size and site of rupture, past history, and the time to CDNA rupture. Of the 12 patients, 11 were female and 1 was male, with a mean age at rupture of the first aneurysm of 44.7 years (range: 30-69 years). The mean time between the first episode of subarachnoid hemorrhage (SAH) and the second was 8.9 years (range: 1.0-16.7 years). The most common site of ruptured CDNA was the internal carotid artery (5 patients, 41.7%), followed by basilar artery bifurcation (3 patients, 25.0%). In the remaining 4 patients, rupture occurred in the anterior communicating, middle cerebral, anterior cerebral (A1), or posterior cerebral (P1) arteries. In 5 cases (41.7%), the CDNA occurred contralateral to the initial aneurysm. Eleven patients (91.7%) had a past history of arterial hypertension. There was no history of habitual smoking or alcohol abuse in any of the patients. Eight patients underwent clipping for CDNA and three patients were treated with coiling. One patient who had multiple aneurysms was treated with clipping following intra-aneurysmal coiling. Assessment according to the Glasgow Outcome Scale (GOS) of the patients after the treatment was good in 10 cases (83.3%) and fair in 2 cases (16.7%). Although formation of CDNA after successful treatment of initial aneurysm is rare, several factors may contribute to recurrence. In our study, female patients with a history of arterial hypertension were at higher risk for ruptured CDNA. We recommend follow-up imaging studies every five years after treatment of the initial aneurysm, especially in women and those with a history of arterial hypertension.     

Mouse Models of Intracranial Aneurysm

Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid hemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarizes current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell‐derived factor‐1, tumor necrosis factor‐α, the renin‐angiotensin system and the β‐estrogen receptor. An agreed clear, precise and reproducible definition of what constitutes an aneurysm in the models would assist in their use to better understand the pathology of intracranial aneurysm and applying findings to patients.     

Ultra-Early Surgery for Poor-Grade Intracranial Aneurysmal Subarachnoid Hemorrhage: A Preliminary Study

Purpose

To describe the therapeutic effect and possibility of the ultra-early surgery for poor-grade aneurysmal subarachnoid hemorrhage (Hunt-Hess grades IV - V).

Materials and Methods

Nine cases with intracranial aneurysms, demonstrated by computed tomographic angiography (CTA), were treated by ultra-early surgery under general anesthesia within 24 hours from subarachnoid hemorrhage (SAH), 5 cases were treated within 6 hours and 4 cases in 6 - 24 hours. Preoperative Hunt-Hess grade: 6 cases were IV and 3 cases were V. The clinical outcome was evaluated by Glasgow Outcome Scores (GOS).

Results

In operation, difficult dissection occurred in 5 cases (55.6%), and rupture of aneurysm occurred and temporary obstructions were performed in 4 cases (44.4%). After clipping of aneurysm, 2 cases underwent V-P shunt because of hydrocephalus, pulmonary infection occurred in 3 cases, hypothalamus reaction accompanied with upper gastrointestinal hemorrhage in 2 cases. The clinical outcome were favorable (GOS 4 - 5) in 4 cases (44.4%), dissatisfied (GOS 2 - 3) in 3 cases (33.3%), and dead (GOS 1) in 2 cases (22.2%) when patients departed from our hospital.

Conclusion

The ultra-early surgery can avoid early rebleeding of intracranial aneurysm, therefore, should be considered in the treatment of Hunt-Hess grade IV-V intracranial aneurysms. The appliance of CTA can make it possible to use of ultra-early surgery and improve the therapeutic effect.     

Rupture of posterior inferior cerebellar artery by single blow to head

Two cases of isolated traumatic subarachnoid hemorrhage from the posterior inferior cerebellar artery are described. The rupture was caused in one instance by a fist blow to the face and in the other by a kick to the head. One patient survived for three days, the other patient for three weeks. In the latter patient, intimal fibrosis was progressing and the brain stem was partly infarcted. Necrosis and fragmentation of the wall adjacent to the rupture suggested both devitalization due to stretching and jarring as pathogenetic mechanisms. These lesions can be distinguished from berry aneurysms by their location along the trunk of the artery instead of in the fork of the bifurcation, by the lack of a fibrous aneurysmal sac, and often by fragmentation of the arterial wall at the edge and also near and opposite the rupture.     

Cerebral vasospasm

Cerebral vasospasm (specifically, intracranial arterial spasm) is variously defined as: (1) an arteriographically evident narrowing of the lumen of one or more of the major intracranial arteries at the base of the brain due to contraction of the smooth muscle within the arterial wall, or due to the morphological changes in the arterial wall and along its endothelial surface that occur in response to vessel injury; (2) the delayed onset of a neurological deficit following subarachnoid hemorrhage, thought to be due to ischemia or infarction of a portion of the brain; or (3) the combination of these two features (symptomatic vasospasm). The arterial contraction of intracranial arterial spasm typically develops a few days after the rupture of an intracranial aneurysm and lasts 2 to 3 weeks. Such arterial spasm can also occur in other conditions such as head trauma. If it is severe enough it can lead to cerebral infarction. The pathogenesis of this condition is still unclear. Many ingenious attempts have been made to prevent or treat cerebral vasospasm, but most have failed. The best current approach is to ensure adequate blood volume, and to elevate the patient's blood pressure (especially if the aneurysm has been secured by an early operation). The continuing investigation of drugs such as calcium channel blocking agents to improve the cerebral circulation has begun to provide additional help.     

Increased brain edema in aqp4-null mice in an experimental model of subarachnoid hemorrhage

We investigated the role of the glial water channel protein aquaporin-4 in brain edema in a mouse model of subarachnoid hemorrhage in which 30 μl of blood was injected into the basal cisterns. Brain water content, intracranial pressure and neurological score were compared in wildtype and aquaporin-4 null mice. We also measured blood-brain barrier permeability, and the osmotic permeability of the glia limitans, one of the routes of edema elimination. Wildtype and aquaporin-4 null mice had comparable baseline brain water content, intracranial pressure and neurological score. At 6 h after blood injection, aquaporin-4 null mice developed more brain swelling than wildtype mice. Brain water content increased by 1.5±0.1% vs. 0.5±0.2% (Mean±Standard Error, P<0.0005) and intracranial pressure by 36±5 vs. 21±3 mm Hg (P<0.05) above pre-injection baseline, and neurological score was worse at 18.0 vs. 24.5 (median, P<0.05), respectively. Although subarachnoid hemorrhage produced comparable increases in blood–brain barrier permeability in wildtype and aquaporin-4 null mice, aquaporin-4 null mice had a twofold reduction in glia limitans osmotic permeability. We conclude that aquaporin-4 null mice manifest increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water.     

脑动脉DSA形态分析及其意义

目的：探讨脑血管造影各主要动脉的投影规律及其分支的显示率，为脑血管疾病的影像诊断和介入治疗提供重要参考。方法：随机抽取140例全脑血管DSA系列图像，选择其中无脑血管疾病的51例进行观察。分别统计颈内动脉和椎动脉造影时正常脑血管各主要分支的显示率；归纳大脑前动脉A1段、大脑中动脉M1段及大脑后动脉P1段在平面上的投影规律并分析总结了脑动脉的正常解剖学特征及其变异。结果：①脑底动脉变异较大；②颈内动脉照影时OA、AChA、ACoA、PCoA、ACA和MCA的显示率分别为96.1％、92．2％、52．9％、69．6％、100％和100％；③椎动脉造影时PICA、AICA、BA、SCA、PCA和PCoA的显示率分别为66．7％、62．7％、100％、70．6％、80．4％和41．2％。结论：①尽管脑底血管实际解剖关系较为复杂，但造影时反映到平面上可简捷的用“水平、上升、下降”等来描述血管的形态和走行；②虽然是平面图像，通过调整投照体位仍可非常逼真的反映血流的动态变化。     

The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites.

BACKGROUND. Stroke is an important cause of death among blacks, and intracerebral and subarachnoid hemorrhages account for nearly half of all early deaths from stroke. The present study investigates whether blacks and whites differ in their risk of having either intracerebral or subarachnoid hemorrhage. METHODS. We reviewed the medical records, autopsy reports, and CT scans of all patients suspected of having had an intracerebral or subarachnoid hemorrhage during 1988 among the nearly 1.3 million people in the Greater Cincinnati metropolitan area. RESULTS. There were 221 cases of first spontaneous intracranial hemorrhage among 1,086,462 whites (159 intracerebral and 62 subarachnoid hemorrhages), and 45 cases among 171,718 blacks (27 intracerebral and 18 subarachnoid hemorrhages). Blacks had 2.1 times the risk of subarachnoid hemorrhage of whites (95 percent confidence interval, 1.3 to 3.6) and 1.4 times the risk of intracerebral hemorrhage (95 percent confidence interval, 0.9 to 2.1). In those under the age of 75, the risk of intracerebral hemorrhage among blacks was 2.3 times that of whites (95 percent confidence interval, 1.5 to 3.6), whereas the risk among blacks 75 or older was one fourth that of whites (95 percent confidence interval, 0.1 to 0.8). Deaths within 30 days of intracerebral or subarachnoid hemorrhage accounted for 1.9 years of life lost per 1000 blacks under 65 years of age, as compared with 0.5 year per 1000 whites. CONCLUSIONS. Young and middle-aged blacks have a substantially higher risk of subarachnoid or intracerebral hemorrhage than whites of similar age. These types of stroke are important causes of excess mortality among young and middle-aged blacks.     

Clinico-anatomical analysis of the causes of death in ruptures of intracranial arterial aneurysms

Causes of lethal outcome in patients after subarachnoid hemorrhage due to cerebral aneurysm rupture were analysed. The major death cause in the operated patients was cerebral edema and dislocation, while in non-operated ones it was the penetration of blood into the ventricles of the brain. Cerebral edema and dislocation syndrome were mainly caused after surgery by ischemic changes in cerebral tissue. A relationship between the aneurysm localization and the extent of subarachnoid hemorrhage was revealed as well as between the hematoma localization and incidence of hemorrhage into the ventricles of the brain.     

The value of radio-anatomical features on non-contrast CT scans in localizing the source in aneurysmal subarachnoid haemorrhage

Identification of the source of subarachnoid haemorrhage (SAH) can be a challenge in the presence of multiple aneurysms. This study was carried out to assess whether radioanatomical features on noncontrast enhanced computerised tomography (CT) scans may be of value in localizing ruptured intracranial aneurysms. The diagnostic CT scans of 56 consecutive patients, investigated for SAH with cerebral angiography, over a period of six months were available for review. Various radioanatomical features were assessed: (1) pattern of subarachnoid blood (e.g. predominant site and location near major vessel bifurcation), (2) presence of intraparenchymal haematoma, (3) presence of aneurysm contour and (4) hydrocephalus. On the basis of the findings an estimation of the anatomical location of the source of bleeding was made and then compared with the angiogram findings to which the reviewer was blinded. The location of the aneurysm was correctly identified in 89.5% of cases. Careful analysis of the pattern of bleeding was essential for the successful localization of the aneurysm in all these cases. The presence of an aneurysm contour was also associated with correct identification of the source of bleeding (chi(2) = 6.067, P = 0.02). Our findings suggest that radioanatomical features on CT scans in SAH can be a valuable aid in the correct identification of the location of the ruptured aneurysm. This would be of particular significance in the presence of multiple intracranial aneurysms.     

Type IV Ehlers-Danlos syndrome presenting as sudden infant death

A previously healthy 5-month-old female infant presented with sudden death due to spontaneous subarachnoid hemorrhage associated with minor multifocal visceral hemorrhages. The clinical diagnosis had been sudden infant death syndrome. Although the family history was noncontributory and other features of type IV Ehlers-Danlos syndrome (EDS) were absent, the pattern of hemorrhage was consistent with this type of connective tissue disorder. The diagnosis was confirmed after postmortem analysis of skin and aorta showed less than 5% type III collagen (normal greater than 15%). Extensive literature review failed to find any other reported cases of sudden death in infancy due to intracranial hemorrhage in patients with previously unsuspected type IV EDS. The authors suggest that collagen analysis should be performed in cases of unexplained multifocal spontaneous hemorrhage in infancy so that this rare diagnosis will not be missed.     

基于CT图像的颅内血肿检测与分割

目的:为提高血肿分割精度,提出一种基于改进Canny算子的颅内类血肿噪声检测方法。方法:首先用区域生长算 法分割出颅脑组织,去掉颅骨等干扰信息。然后使用基于改进Canny边缘检测的方法检测颅脑边缘类血肿噪声,并与原 图像进行与运算消除该噪声。最后,通过使用OTSU适应度函数的遗传算法精准分割出颅内血肿。结果:该方法在随机 抽取的200例颅脑血肿图像中,血肿检测的准确率达到96.3%,Dice相似度达到93.5%。结论:该方法能准确、有效地检测 并分割出颅内血肿。     

新生儿颅内出血危险因素及预防措施研究

目的探讨新生儿颅内出血的类型及其可能的危险因素,研究预防措施。方法选择2004-2009年住院的180例颅内出血新生儿为病例组,同期住院的200例非颅内出血新生儿为对照组进行病例对照研究。单因素分析用卡方检验,多因素分析用多元Logistic回归分析。结果病例组中出血部位发生率由高到低依次为脑室周围-脑室内出血、蛛网膜下腔出血、脑实质出血、硬膜下出血、小脑出血。产程延长、产钳、低出生体重儿、过期产、巨大儿、母亲感染发热、母亲产前出血、脐带绕颈、胎儿宫内窘迫、胎盘老化、胎头吸引、胎位异常、臀位牵引、新生儿呼吸困难、新生儿低血糖、新生儿酸碱失衡、新生儿出血病、新生儿休克、新生儿血小板减少、新生儿窒息、早产儿均是新生儿颅内出血的相关危险因素。结论减少早产,提高产科质量,控制感染,预防出血,维持内环境稳定,可降低新生儿颅内出血的发生率。     

TNF-α and sICAM-1 in intracranial aneurismal rupture

Introduction  Subarachnoidal hemorrhage (SAH) occurring after aneurismal rupture produces an inflammatory response in the cerebral circulation. Tumor necrosis factor (TNF)-α is a major cytokine in this process. Adhesion molecules provide information on inflammatory reactions taking place in the walls of blood vessels. Clinical evidence suggests a role of soluble intercellular adhesion molecule (sICAM)-1 in early hemorrhagic events. This study aimed to evaluate the implementation of early TNF-α and sICAM-1 serum measurement for the prognosis of patient outcome after intracranial aneurismal rupture. Materials and Methods  The study consisted of 27 patients with a diagnosis of intracranial aneurysm. SAH was evaluated on admission according to the Fisher scale, patients’ consciousness with the Glasgow Coma Scale, clinical grading with the Hunt and Hess scale, and clinical outcome with the Glasgow Outcome Scale (GOS). Blood samples were drawn within 72 h after arrival at the emergency room. Serum concentrations of TNF-α and sICAM-1 were assayed with the ELISA method. Results  The initial serum TNF-α concentration in the aneurismal patients was low and did not correlate with radiological and clinical scores. The serum sICAM-1 level positively correlated with the severity of bleeding assessed by the Fisher scale and negatively with the patient’s scoring in the GOS. Conclusions  This study demonstrated the absence of a systemic TNF-α-mediated inflammatory response at the onset of subarachnoid hemorrhage. Early measurement of serum sICAM-1 levels offers a potential prognostic value in the assessment of patients’ outcome after brain aneurismal rupture.