The measuring of substantia nigra hyperechogenicity in an Italian cohort of Parkinson disease patients: a case/control study (NOBIS Study).

Transcranial sonography (TCS) shows an increased echogenic area of the substantia nigra (SN) in patients with Parkinson disease (PD). It has been increasingly used in the diagnosis of PD and its differentiation from atypical parkinsonian syndromes. Here, we studied the diagnostic accuracy of SN TCS in Italian patients. In this blinded cross-sectional study (NOBIS study), two expert neuro-sonologists performed TCS in 25 PD patients and 29 age- and sex-matched controls. The study participants were completely hidden to the TCS investigators using large drapery. One month later, the SN TCS recordings were re-read by the initial investigator, and cross-read by the second reader. Diagnostic accuracy was estimated on the first reading, intra-reader reliability on re-reading, and inter-reader reliability on cross-readings. The mean SN echogenic area was larger in the patients (0.24 cm2) than in the controls (0.15 cm2; Mann-Whitney test, p < 0.001). SN measures did not differ between right and left, or between ipsilateral and contralateral to the clinically more affected side. There was no correlation between SN echogenicity and PD severity or duration. High intra-reader (concordance correlation coefficient 0.93) and inter-reader (0.98) agreement of SN measurements was found. The diagnostic accuracy for the detection of PD was high (area under receiver-operating characteristic curve 0.91; 95% CI 0.83-1.00) with an optimum cut-off value for SN echogenic area of 0.18 cm2 with the device used here (specificity 0.83-0.90; sensitivity 0.72-0.92). This study supports the use of SN TCS in the diagnostic workup of PD if performed by trained readers.

Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events.

BACKGROUND AND PURPOSE: The clinical usefulness of noninvasive measurement of carotid intima media thickness and plaque visualization in the general population is still uncertain. METHODS: We evaluated the age-specific incidence rates of cerebrovascular events in a cohort of 1348 subjects randomly taken from the census list of San Daniele Township and followed for a mean period of 12.7 years. The association among common carotid intima media thickness, measured at baseline, arterial risk factors, and incidence of ischemic cerebrovascular events was modeled using Poisson regression. The predictive ability of common carotid intima media thickness over arterial risk factors (summarized in the Framingham Stroke Risk Score) was evaluated by receiver operating characteristic curve analysis. RESULTS: During the follow-up, 115 subjects developed nonfatal ischemic stroke, transient ischemic attack, or vascular death, which were the predefined study end points. After adjustment for age and sex, hypertension, diabetes, common carotid intima media thickness above 1 mm, and carotid plaques were all independent risk factors for development of vascular events. Inclusion of carotid findings (presence of common carotid intima media thickness above 1 mm or carotid plaques) resulted in a predictive power higher than Framingham Stroke Risk Score alone only on for those subjects with a Framingham Stroke Risk Score over 20%. CONCLUSIONS: Although common carotid intima media thickness and presence of carotid plaques are known to be risk factors for the development of vascular events and to be independent from the conventional risk factors summarized in the Framingham Stroke Risk Score, their contribution to individual risk prediction is limited. Further studies will be required to address the role of carotid ultrasonography in the primary prevention of high-risk subjects.

MicroV Technology to Improve Transcranial Color Coded Doppler Examinations.

The purpose of this review is to provide an update on technology related to Transcranial Color Coded Doppler Examinations. Microvascularization (MicroV) is an emerging Power Doppler technology which can allow visualization of low and weak blood flows even at high depths, thus providing a suitable technique for transcranial ultrasound analysis. With MicroV, reconstruction of the vessel shape can be improved, without any overestimation. Furthermore, by analyzing the Doppler signal, MicroV allows a global image of the Circle of Willis. Transcranial Doppler was originally developed for the velocimetric analysis of intracranial vessels, in particular to detect stenoses and the assessment of collateral circulation. Doppler velocimetric analysis was then compared to other neuroimaging techniques, thus providing a cut-off threshold. Transcranial Color Coded Doppler sonography allowed the characterization of vessel morphology. In both Color Doppler and Power Doppler, the signal overestimated the shape of the intracranial vessels, mostly in the presence of thin vessels and high depths of study. In further neurosonology technology development efforts, attempts have been made to address morphology issues and overcome technical limitations. The use of contrast agents has helped in this regard by introducing harmonics and subtraction software, which allowed better morphological studies of vessels, due to their increased signal-to-noise ratio. Having no limitations in the learning curve, in time and contrast agent techniques, and due to its high signal-to-noise ratio, MicroV has shown great potential to obtain the best morphological definition.

The San Daniele 2 Project: protocol description and population characteristics.

In 1990 we studied the prevalence and determinants of carotid atherosclerosis in an Italian general asymptomatic population (630 males and 718 females aged 18-99 years) living in the San Daniele district of the Friuli-Venezia Giulia Region. The global prevalence of subclinical carotid atherosclerosis was 25.4% in men and 26.4% in women. We considered intima-media thickness, non-stenotic plaque (< 40%), and stenotic plaque (> 40%). In the multiple logistic regression, the cross-sectional analysis of subjects aged 40 years showed a positive significant association between plaques/stenosis and age (p < 0.001), systolic blood pressure (p < 0.01), cigarette smoking (p < 0.0001), and the protective effect of high-density lipoprotein cholesterol (p < 0.037). In 2002 we decided to re-examine the initial cohort with the following objectives: prospectively evaluating the modifications of the previous carotid findings, their relationship with known and less documented cardiovascular risk factors and the predictive power of those variations on incident coronary and cerebrovascular events. We plan to evaluate the association of carotid plaque and carotid intima-media thickness with the genetic polymorphisms involved in atherosclerosis in survivors and finally to study the incidence and the determinants of atrial fibrillation in a general population. In this paper, we will describe the methodology of the screening and the cohort population characteristics. We have compared the San Daniele Project survivor cohort's characteristics to the current general population of the same age living in the Friuli-Venezia Giulia Region so as to extend the study's conclusions to the whole regional population.

HDL-C, triglycerides and carotid IMT: a meta-analysis of 21,000 patients with automated edge detection IMT measurement.

OBJECTIVE: Common carotid artery (CCA) intima-media thickness (IMT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), but not triglyceride levels, are markers of future cardiovascular events. The relationship between these three factors is, however, unclear. METHODS: We included six large observational studies that used the same harmonized, B-mode ultrasound protocol, the same software for IMT measurement by automatic edge detection on CCA in a plaque-free region, following the Mannheim consensus, and certification of all sonographers. Using the best view of the CCA, the sonographer had to confirm that the quality index was ≥ 0.5 on a measurement performed on 10-mm length. We used individual data meta-analysis to estimate the cross-sectional associations of lipids with CCA-IMT. RESULTS: Overall, 21,587 patients with complete information on lipids and CCA-IMT were available. Age- and sex-adjusted CCA-IMT differed by -7.8 µm (95% CI -9.1 to -6.5 µm, P < 0.001) per 1 SD higher HDL-C level. After further adjustment for other atherosclerosis risk factors, the relationship was attenuated, but remained significant (regression coefficient, -3.7 µm; P < 0.001). This was found regardless of LDL-C levels (P for heterogeneity = 0.70). After adjustment for age and sex, triglycerides were positively associated with CCA-IMT, overall and in each LDL-C subgroup, but not after further adjustments for other risk factors. CONCLUSIONS: Relationships between HDL-C and triglyceride levels and CCA-IMT were consistent with that previously observed with clinical events by the Emergency Risk Collaboration group, including at low LDL-C levels. This reinforces the need to verify whether raising HDL-C levels decreases both CCA-IMT and future clinical events.

Association of plasma fibrinogen, C-reactive protein and G-455>A polymorphism with early atherosclerosis in the VITA Project cohort.

While increased fibrinogen is associated with vascular events, only few data are available on its association with preclinical atherosclerosis. We aimed at evaluating the association between fibrinogen levels, fibrinogen polymorphism G-455>A and C-reactive protein and preclinical atherosclerosis in a population-based, cross-sectional study. A cohort of 2,580 subjects was enrolled. Fibrinogen was measured at time of original enrollment and at time of the second visit, when ultrasound examination of both left and right common carotid arteries was performed, together with evaluation of C-reactive protein (CRP) and of the fibrinogen G-455>A polymorphism. CRP and fibrinogen levels at baseline were the two variables mostly influencing fibrinogen levels at the follow-up visit (p<0.0001). Carriers of the H2H2 genotype of the G-455>A polymorphism had increased fibrinogen levels, particularly in association with increased CRP levels. Increased fibrinogen levels were independently associated with presence of carotid plaques, particularly in those subjects having a persistent increase of fibrinogen (odds ratio 1.98, 95% confidence interval 1.47-2.67). An association between the H2H2 genotype and presence of carotid plaques was observed only in a subgroup of subjects with CRP > 0.5 mg/dl. A persistent increase of plasma fibrinogen is associated with an increased risk of early atherosclerosis.

Determinants of carotid plaque occurrence. A long-term prospective population study: the San Daniele Project.

BACKGROUND: Increased carotid intima media thickness (CIMT) is frequently associated with established modifiable and non-modifiable cardiovascular risk factors, and is thought to be an independent predictor of ischemic cerebrovascular and cardiac events. The presence of carotid plaque is considered an established feature of atherosclerosis. There exist few longitudinal data on the predictive role of CIMT in the occurrence of carotid plaque. METHODS: We restudied the survivors of a cohort of the San Daniele Project, a large randomized general population study, investigated in 1990 regarding the prevalence and determinants of carotid atherosclerosis. Using ultrasonography, we determined in 1,193 subjects (548 men and 645 women), the common carotid IMT and the presence of non-stenotic and stenotic plaque. RESULTS: In 795 subjects without plaques or previous ischemic events at baseline, we found in multivariate analysis that CIMT > or =1 mm, age, hypertension and history of smoking are significant predictive elements of the occurrence of a new carotid plaque. The incremental probability of plaque occurrence is greater in midlife. CIMT and age are the most predictive risk factors with ORs of 3.66 (95% CI 1.4-9.4) and 3.02 (95% CI 2.4-3.7), respectively. The ORs for hypertension and smoking account for 1.5 (95% CI 1.1-3.4) and 1.7 (95% CI 1.1-2.8), respectively. CONCLUSIONS: Age, hypertension, history of smoking and B-mode detection of CIMT increases in subjects without carotid atherosclerosis and free of previous vascular events predict the occurrence of carotid atherosclerotic plaque.

Abnormal pressure passive dilatation of cerebral arterioles in the elderly with isolated systolic hypertension.

The aim of this study was to investigate the cerebrovascular adaptability to 2 sequential pressor stimuli in elderly patients with isolated systolic hypertension. Ten healthy elderly normotensive subjects (68 to 82 years), 10 elderly subjects with isolated systolic hypertension (63 to 82 years), and 10 young normotensive subjects (24 to 40 years) took part in the study. A pressor reaction, using sequential cold pressor and handgrip stimulation, was induced. The cerebrovascular response to the pressor stimulation was measured by transcranial Doppler determination of the mean flow velocity in the middle cerebral arteries. In all of the subjects, blood pressure increased during handgrip (+12 mm Hg, P<0.001 in the young; +18 mm Hg, P<0.01 in the elderly normotensive subjects; +19 mm Hg, P<0.001 in the hypertensive patients versus baseline). In the hypertensive subjects, the pressure increase persisted well into the recovery period. The pressure increase caused a significant increase in mean flow velocity in the middle cerebral arteries only in the elderly subjects. Cold pressor test increased blood pressure in all of the subjects during stimulation and the first 2 minutes of the recovery period (at whole-curve ANOVA: F=22.03, P<0.001 in the young participants; F=18.3, P<0.001 in the normotensive elderly; and F=13.04, P<0.001 in the hypertensive elderly). Mean flow velocity in the middle cerebral arteries significantly increased only in the hypertensive subjects. In the elderly hypertensive patients, the cerebrovascular reaction to adrenergic stimuli was more impaired than in the elderly normotensive subjects. This event can amplify the pressure insult on cerebral hemodynamics and increase the predisposition to cerebral damage, such as vascular cognitive impairment or stroke.