ORIGINAL ARTICLES

RUPTURED INTRACRANIAL ANEURYSM: Clinical Series

The mechanisms by which smoking and hypertension lead to increased incidence of intracranial aneurysm (IA) formation remain poorly understood. The current study investigates the effects of these risk factors on wall shear stress (WSS) and oscillatory shear index (OSI) at the site of IA initiation.

Two (n = 2) IAs from two patients with history of smoking and hypertension were artificially removed with the help of software @neuFuse (Supercomputing Solutions^®, Bologna, Italy) and the vessel geometry reconstructed to mimic the condition prior to IA formation. Two computational fluid dynamics (CFD) analyses were performed on each data-set by using in turn the normal physiological values of blood viscosity (BV), and high BV values specific to smoking and hypertension, obtained from literature.

At normal BV, high WSS (>15 Pa) was observed at the site of IA initiation in both patients. When BV values specific to smoking and hypertension were used, both the areas affected by high WSS (>15 Pa) and the maximum WSS were increased whilst the magnitude and distribution of OSI showed no significant change.

Long-term exposure to high WSS may result in an increased risk of IA development. An incremental increase in areas of high WSS observed secondary to smoking and hypertension may indicate a further increase in the risk of IA initiation. Interestingly, the relationship between BV and the area of increased WSS was not linear, reflecting the need for patient-specific CFD analysis.

BACKGROUND

Intracranial aneurysms and systemic arterial hypertension coexist in a high percentage of patients. The relationship between intracranial aneurysms and hypertension is poorly defined.

METHODS

Therefore, we reviewed the role of hypertension in the pathogenesis of saccular aneurysms as previously reported in clinical, experimental, and autopsy studies.

RESULTS

Among 24 relevant clinical and/or autopsy studies, the mean incidence of pre-existing hypertension was 43.5% in aneurysm patients compared to 24.4% in the normal population. Although definitive evidence is lacking, data from multiple types of investigations indicate that systemic arterial hypertension creates a greater risk for the development of intracranial aneurysms than previously believed. The underlying pathophysiological mechanism(s) are also poorly defined.

CONCLUSIONS

We propose a unifying hypothesis: Endothelial injury, occlusion of the vasa vasorum, and disruption of the synthesis of collagen and elastin are likely the most important factors in initiating the development of aneurysms. Chronic hypertension potentially affects all of these factors. Consequently, chronic hypertension may cause intimal thickening, necrosis of the tunica media, changes in the compositional matrix, and degeneration of the internal elastic lamina to develop in the arterial wall. These structural changes could cause a focal weakening in the arterial wall with resultant bulging. This theory accounts for the high incidence of intracranial aneurysms in the absence of any known associated hereditary or connective-tissue disease. Nor does it exclude the possibility of other etiological factors. From the perspective of prevention, however, it offers clear opportunities for prophylaxis.

Impact of cardiac complications after aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We performed a meta-analysis to assess whether EKG changes, myocardial damage, or echocardiographic wall motion abnormalities (WMAs) are related to death, poor outcome (death or dependency), or delayed cerebral ischemia (DCI) after SAH.

Articles on cardiac abnormalities after aneurysmal SAH that met predefined criteria and were published between 1960 and 2007 were retrieved. We assessed the quality of reports and extracted data on patient characteristics, cardiac abnormalities, and outcome measurements. Poor outcome was defined as death or dependence by the Glasgow Outcome Scale (dichotomized at ≤3) or the modified Rankin scale (dichotomized at >3). If studies used another dichotomy or another outcome scale, we used the numbers of patients with poor outcome provided by the authors. We calculated pooled relative risks (RRs) with corresponding 95% confidence intervals for the relation between cardiac abnormalities and outcome measurements.

We included 25 studies (16 prospective) with a total of 2,690 patients (mean age 53 years; 35% men). Mortality was associated with WMAs (RR 1.9), elevated troponin (RR 2.0) and brain natriuretic peptide (BNP) levels (RR 11.1), tachycardia (RR 3.9), Q waves (RR 2.9), ST-segment depression (RR 2.1), T-wave abnormalities (RR 1.8), and bradycardia (RR 0.6). Poor outcome was associated with elevated troponin (RR 2.3) and creatine kinase MB (CK-MB) levels (RR 2.3) and ST-segment depression (RR 2.4). Occurrence of DCI was associated with WMAs (RR 2.1), elevated troponin (RR 3.2), CK-MB (RR 2.9), and BNP levels (RR 4.5), and ST-segment depression (RR 2.4). All RRs were significant.

Markers for cardiac damage and dysfunction are associated with an increased risk of death, poor outcome, and delayed cerebral ischemia after subarachnoid hemorrhage. Future research should establish whether these cardiac abnormalities are independent prognosticators and should be directed toward pathophysiologic mechanisms and potential treatment options.

AF = atrial fibrillation; BBB = bundle branch block; BNP = brain natriuretic peptide; CI = confidence interval; CK-MB = creatine kinase MB; DCI = delayed cerebral ischemia; GCS = Glasgow Coma Scale; HR = hazard ratio; LVH = left ventricular hypertrophy; NT-proBNP = N-terminal prohormone brain natriuretic peptide; pt = patient; RR = relative risk; SAH = subarachnoid hemorrhage; STROBE = Strengthening the Reporting of Observational Studies in Epidemiology; WFNS = World Federation of Neurosurgical Societies; WMA = echocardiographic wall motion abnormality.