A comprehensive analysis of the relationship between ACA velocities and ACA infarction following aneurysmal subarachnoid hemorrhage.

PURPOSE: To evaluate the relationship between anterior cerebral artery (ACA) velocities (and ancillary parameters) and ACA infarction following aneurysmal subarachnoid hemorrhage (aSAH), and to examine the factors that influence velocities. METHODS: Retrospective investigation of 500 consecutive aSAH patients. ACA mean velocities (Vm) were evaluated by daily transcranial ultrasound during the early (days 1-4) and late (days 5-20) periods posthemorrhage. Presence and timing of acute ACA infarctions were identified by serial retrospective review of cerebral computerized tomography (CT) scans. Predictors of ACA velocities were identified and compared to predictors of vasospasm and infarction from the literature. RESULTS: Decreased velocities on the day of infarction were observed in infarct-positive vessels when compared to infarct-negative vessels. ACA velocity increases, ipsilateral/contralateral ACA velocity ratios, and ACA velocity ranges, were inaccurate in anticipating infarction. Decreased ACA index velocities were moderately accurate in anticipating ACA infarction during the early [Vm<60cms/s], late [Vm<70cms/s] and overall [Vm<70cms/s] time periods. Decreased index velocities also independently predicted infarction during all time periods. ACA velocities were most consistently predicted by age, race, hemorrhage quantity on CT, and ACA/ACom (anterior communicating artery) aneurysm location. CONCLUSIONS: ACA velocity increases and ancillary parameters do not relate to the development of infarction, whereas velocity decreases are moderately accurate in anticipating infarction. Predictors of velocity increases generally coincide with those of vasospasm, whereas predictors of velocity decreases coincide more with those of infarction following aSAH.

Prevalence, timing, risk factors, and mechanisms of anterior cerebral artery infarctions following subarachnoid hemorrhage.

Anterior cerebral artery (ACA) ischemia may be underdiagnosed following subarachnoid hemorrhage (SAH). The purpose of this study is to characterize the prevalence, timing, and risk factors for ACA infarction, following primary spontaneous SAH. This was a retrospective study of consecutive SAH patients. Final admission CT scans were reviewed for the presence of ACA infarction, and prior scans serially reviewed to determine timing of infarct. Infarctions were categorized as any, early (days 0-3), late (days 4-15), or perioperative (2 days after aneurysm treatment). Demographic and clinical variables were statistically interrogated to identify predictors of infarct types. Of the 474 study patients, ACA infarctions occurred in 8 % of patients, with 42 % occurring during the early period. Multivariate logistic regression identified H/H grade 4/5 (p < 0.001), ACA/ACom aneurysm location (p < 0.001), and surgical clipping (p = 0.011) as independent predictors of any ACA infarct. In Cox hazards analysis, H/H grade 4/5 (p < 0.001), CT score 3/4 (p = 0.042), ACA/ACom aneurysm location (p < 0.001), and surgical clipping (p = 0.012) independently predicted any ACA infarct. Bivariate logistic regression identified non-Caucasian race (p = 0.032), H/H grade 3/4 (p < 0.001), CT score 3/4 (p = 0.006), IVH (p = 0.027), and ACA/ACom aneurysm (p = 0.001) as predictors of early infarct (EI). Late infarct (LI) was predicted by H/H grade 4/5 (p = 0.040), ACA/ACom aneurysm (p < 0.001), and vasospasm (p = 0.027), while postoperative infarct (PI) was predicted by surgical clipping (p = 0.044). Log-rank analyses confirmed non-Caucasian race (p = 0.024), H/H grade 3/4 (p < 0.001), CT score 3/4 (p = 0.003), IVH (p = 0.010), and ACA/ACom aneurysm (p < 0.001) as predictors of EI. LI was predicted by ACA/ACom aneurysm (p < 0.001) while surgical clipping (p = 0.046) again predicted PI. Clinical severity/grade and ACA/ACom aneurysm location are the most consistent predictors of ACA infarctions. Vasospastic and non-vasospastic processes may concurrently contribute to ACA infarcts.

VEGF-C, VEGF-D and VEGFR-3 expression in peripheral neuroblastic tumours.

AIMS: More than 50% of neuroblastomas (NBs) present with haematogenous and/or lymphatic metastasis; however, little is known about the clinicopathological significance in NBs of the key lymphangiogenesis growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D and the receptor VEGFR-3. METHODS AND RESULTS: Ninety-three NBs and nine ganglioneuromas (GNs) were immunostained for VEGF-C, VEGF-D and VEGFR-3. VEGF-C and VEGF-D were present in 76% and 82% of the NBs, respectively. There was no significant difference in VEGF-C expression between NBs and GNs. VEGF-D expression was significantly higher in NBs compared with GNs and in MYCN-amplified NBs. VEGFR-3 tumoral cell expression (VEGFR-3c), present in 48% of the NBs, was significantly higher in NBs from children ≥ 18 months at presentation and those belonging to a high-risk group. VEGFR-3 lymphovascular density was increased significantly in NBs compared with GNs and in NBs associated with adverse clinicopathological and biological factors. Lymphovascular invasion, assessed in VEGFR-3-stained vessels, was present in ∼50% of NBs. Cox regression analyses demonstrated that VEGFR-3c expression was associated with a significantly shorter event-free survival and that its effect was independent of the important pathological variable, mitosis-karyorrhexis index. CONCLUSIONS: VEGF-D and VEGFR-3 up-regulation support tumour progression in NB and VEGFR-3c may provide a useful prognostic marker in NBs.