Kurt Niederkorn

White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors.

We studied 52 asymptomatic subjects using magnetic resonance imaging, and we compared age-matched groups (51-70 years old) with and without white matter lesions with respect to carotid ultrasonography, cerebral blood flow (xenon-133 injection), and cerebrovascular risk factors. In the group with white matter signal abnormalities, we noted a higher frequency of extracranial carotid artery disease, a lower mean gray matter blood flow (F1), and a significant reduction (p less than 0.05) in blood flow of the slow-flowing (F2) compartment. Hypertension, diabetes mellitus, and cardiac diseases (p less than 0.002) were found more often in this group. Our results indicate that a higher incidence of changes known to be associated with an increased risk for stroke exists in the presence of white matter lesions in normal elderly individuals.

Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis

We reviewed the MRIs of 49 asymptomatic volunteers (age range, 31 to 77 years) and of 50 MS patients (age range, 14 to 63) for areas of increased signal (AIS) and features discriminating MS lesions from lesions seen with normal aging. We obtained optimal specificity of MRI interpretation (100%) if we required at least two of the following three AIS features — size ≥6 mm, abutting ventricular bodies, infratentorial location — for a positive MRI diagnosis of MS. Applying these criteria to the MRIs of elderly patients with suspected MS should significantly improve specificity (p < 0.001) over current quantitative criteria (at least three AIS≥3 mm) without significantly decreasing sensitivity.

Paraoxonase PON1 Polymorphism Leu-Met54 Is Associated With Carotid Atherosclerosis Results of the Austrian Stroke Prevention Study

BACKGROUND AND PURPOSE Genetic polymorphism at the paraoxonase locus is associated with serum concentration and activity of paraoxonase and with increased risk for coronary heart disease. Two frequent polymorphisms present at the paraoxonase gene are the methionine (M allele) leucine (L allele) interchange at position 54 and the arginine (B allele) glutamine (A allele) interchange at position 191. This is the first study to determine the effect of these polymorphisms on carotid atherosclerosis. METHODS The paraoxonase genotypes at positions 54 and 191 of 316 randomly selected individuals aged 44 to 75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Carotid atherosclerosis was assessed by color-coded Duplex scanning and was graded on a 5-point scale ranging from 0 (normal) to 5 (complete luminal obstruction). RESULTS The LL, LM, and MM genotypes at position 54 were noted in 137 (43.4%), 132 (41.8%), and 47 (14.9%) subjects; the AA, AB, and BB genotypes at position 191 occurred in 172 (54.4%), 124 (39.2%), and 20 (6.3%) individuals. The LL genotype was significantly associated with the presence and severity of carotid disease (P=0.022), whereas the 191 polymorphism had no effect. Logistic regression analysis with age and sex forced into the model demonstrated plasma fibrinogen (odds ratio [OR], 1.005 per mg/dL), LDL cholesterol (OR, 1.01 per mg/dL), cardiac disease (OR, 1.75), and the paraoxonase LL genotype to be significant predictors of carotid atherosclerosis. The ORs for the associations with age and sex were 1.09 (P=0.0003) and 1.66 (P=0.052) per year. CONCLUSIONS These data suggest that the paraoxonase LL genotype may represent a genetic risk factor for carotid atherosclerosis.

Apolipoprotein E Polymorphism and Silent Microangiopathy-Related Cerebral Damage Results of the Austrian Stroke Prevention Study

BACKGROUND AND PURPOSE Microangiopathy-related cerebral damage (MARCD) includes white matter abnormalities and lacunar infarctions and represents a common MRI observation in subjects above 50 years of age. The risk factors of such brain abnormalities are not fully determined. The goal of this study was to determine whether the genetic heterogeneity of apolipoprotein E (apoE) contributes to the occurrence of MARCD. METHODS Brain MRI (1.5 T) was performed in 280 individuals (ages 50 to 75 years) without neuropsychiatric disease randomly selected from the official register of residents of the city of Graz, Austria. All study participants underwent apoE genotyping, carotid Doppler sonography, electrocardiography, echocardiography, and a complete blood chemistry panel. MARCD was defined as evidence of early confluent and confluent white matter hyperintensities or lacunes. Carotid atherosclerosis was graded on a five-point scale ranging from not present (0) to complete occlusion (5). RESULTS MARCD occurred in 61 individuals (21%). The distribution of apoE genotypes differed significantly between subjects with and without MARCD (P = .036). Subjects with such findings more commonly had the epsilon 2/epsilon 3 genotype (24.6% versus 10%) at similar frequencies of genotypes containing the epsilon 4 allele. The epsilon 2/epsilon 3 genotype was associated with lower levels of total cholesterol (P = .0009), LDL cholesterol (P = .00001), and apolipoprotein B (P = .00001). Also, there was a nonsignificant trend toward less cardiac disease. Other major vascular risk factors and carotid abnormalities were similar among the various genotypes. Multiple logistic regression analysis created a model of significant MARCD predictors, including age (odds ratio [OR], 1.1 per year), hypertension (OR, 3.4), and the apoE epsilon 2/epsilon 3 genotype (OR, 3.0). CONCLUSIONS These data suggest an association between the apoE epsilon 2/epsilon 3 genotype and MARCD despite favorable effects on the lipid profile and cardiac disease.

Mechanical recanalization in basilar artery occlusion: The ENDOSTROKE study

A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion.

C-Reactive Protein, Carotid Atherosclerosis, and Cerebral Small-Vessel Disease Results of the Austrian Stroke Prevention Study

Background and Purpose— C-reactive protein (CRP) is an inflammatory marker known to be a risk factor for stroke. We examined the associations between CRP, carotid atherosclerosis, white matter lesions, and lacunes as manifestations of cerebral large- and small-vessel disease. Methods— In the community-based Austrian Stroke Prevention Study, CRP concentrations were measured by a highly sensitive assay in 700 participants at baseline. All underwent carotid duplex scanning, and a subset of 505 subjects underwent brain magnetic resonance imaging. Imaging was repeated after 3 and 6 years. We graded carotid atherosclerosis in both common and internal carotid arteries on a 5-point scale and calculated the sum of scores as an index of the severity of carotid atherosclerosis. The volume of white matter lesions and the number of lacunes were considered small vessel disease–related brain abnormalities. Results— After adjustment for vascular risk factors, the severity and progression of extracranial carotid atherosclerosis increased with increasing quintiles of CRP. Only study participants in the fourth and fifth quintile (>2.50 mg/L) had significantly more baseline atherosclerosis and greater progression when we used the first quintile (<0.80 mg/L) as a reference. No interactions were seen between CRP quintiles and vascular risk factors for carotid atherosclerosis. The associations between severity and progression of small vessel disease–related brain abnormalities and CRP were nonsignificant. Conclusions— We found evidence for differential effects of CRP in different beds of the arterial brain supply. CRP was a marker for active carotid atherosclerosis but not for small vessel disease–related brain lesions.

Angiotensinogen Polymorphism M235T, Carotid Atherosclerosis, and Small-Vessel Disease-Related Cerebral Abnormalities

The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. We studied the role of this polymorphism as a risk factor for carotid atherosclerosis and small-vessel disease-related brain abnormalities. A total of 431 randomly selected community-dwelling subjects without clinical evidence for strokes underwent angiotensinogen genotyping and carotid Duplex scanning; 1.5-T brain magnetic resonance imaging (MRI) was done in 396 individuals. At 3-year follow-up, we reexamined 343 and 267 study participants by ultrasound and brain MRI, respectively. Carotid atherosclerosis was graded on a 5-point scale. Small-vessel disease-related brain abnormalities were deep or subcortical white matter lesions or lacunes. Progression of carotid atherosclerosis and MRI findings was rated by direct imaging comparison by 3 independent raters. The M/M, M/T, and T/T genotypes were seen in 20.9%, 52.9%, and 18.1% of subjects, respectively. The M235T polymorphism was neither associated with baseline carotid findings nor with progression of carotid atherosclerosis. There was a trend toward more frequent small-vessel disease-related MRI abnormalities in the T/T than in the other genotypes at the baseline examination. Progression of brain lesions occurred significantly more commonly in T/T than in M/M and M/T carriers (P <0.001). Logistic regression analysis identified the T/T genotype (odds ratio, 3.19;P =0.002) and arterial hypertension (odds ratio, 3.06;P =0.03) as significant independent predictors of lesion progression. These data suggest that the angiotensinogen T/T genotype at position 235 is a genetic marker for brain lesions from and progression of small vessel disease but not for extracranial carotid atherosclerosis.

β-Fibrinogen Gene Polymorphism (C148→T) Is Associated With Carotid Atherosclerosis

Abstract—Polymorphisms at the β-fibrinogen locus have been shown to be associated with plasma concentration of fibrinogen and coronary heart disease. The effect of the genetic heterogeneity of fibr...

Clinical Presentation, Etiology, and Long-Term Prognosis in Patients With Nontraumatic Convexal Subarachnoid Hemorrhage

Background and Purpose— Nontraumatic subarachnoid hemorrhage at the convexity of the brain (cSAH) is an incompletely characterized subtype of nonaneurysmal subarachnoid bleeding. This study sought to systematically describe the clinical presentation, etiology, and long-term outcome in patients with cSAH. Methods— For a 6-year period, we searched our radiological database for patients with nontraumatic nonaneurysmal subarachnoid hemorrhages (n=131) seen on CT or MRI. By subsequent image review, we identified 24 patients with cSAH defined by intrasulcal bleeding restricted to the hemispheric convexities. We reviewed their medical records, analyzed the neuroimaging studies, and followed up patients by telephone or a clinical visit. Results— The 24 patients with cSAH had a mean age of 70 years (range, 37–88 years), 20 (83%) were >60 years, and 13 (54%) were women. Patients often presented with transient sensory and/or motor symptoms (n=10 [42%]) and seizures (n=5 [21%]), whereas headaches typical of subarachnoid hemorrhage were rare (n=4 [17%]). MRI provided evidence for prior bleedings in 11 patients (microbleeds in 10 and parenchymal bleeds in 5) with a bleeding pattern suggestive of cerebral amyloid angiopathy in 5 subjects. At follow-up (after a mean of 33 months), 14 patients (64%) had an unfavorable outcome (modified Rankin scale score 3–6), including 5 deaths. We did not observe recurrent cSAH. Conclusions— Our data suggest that cSAH often presents with features not typical for subarachnoid bleeding. In the elderly, cSAH is frequently associated with bleeding-prone conditions such as cerebral amyloid angiopathy. Recurrence of cSAH is rare but the condition itself is a marker of poor prognosis.

Assessment of Cerebrovascular Risk Profiles in Healthy Persons: Definition of Research Goals and the Austrian Stroke Prevention Study (ASPS)

The advent of new laboratory methods and noninvasive imaging modalities has extended the diagnostic possibilities in normal individuals. This article elaborates the new options for the assessment of stroke risk offered by these techniques. In this context we present the Austrian Stroke Prevention Study, which is the first prospective long-term investigation of normals that includes Doppler sonography, magnetic resonance imaging and single photon emission computed tomography. The design, utility and limitations of this study are discussed.