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An optimized multislice data acquisition scheme for phase acquisition of composite echoes (PACE) imaging is presented. This new scheme uses a repetition time equal to the mixing time and an appropriate phase cycling scheme, which allows for more efficient exploitation of all composite echoes. These modifications provide true multislice capability in parallel to a reduction of the acquisition time by a factor >2 compared with the original PACE method. Moreover, T1 values can be obtained directly from phase images without the use of a lookup table. Because of the symmetrical application of the radio frequency pulses, this method is also well suited for T1sat imaging. Phantom studies showed a significantly better accuracy of the multislice fast PACE technique compared with a conventional two-point method in multislice acquisition mode, although precision was limited at high T1 values. T1 and T1sat measurements in brain tissue of eight healthy volunteers confirmed the stability of the fast PACE technique in a clinical setting. Magn Reson Med 42:1089–1097, 1999. © 1999 Wiley-Liss, Inc.

A previously healthy 28-year-old Caucasian woman experienced a syncope and was referred to our emergency department. On admission, the patient was neurologically normal and alert. Electrocardiogram (ECG) was normal. Peripheral blood count and blood chemistry, including C-reactive protein and cardiac troponin T, were within normal limits. The patient revealed no history of drug or alcohol abuse. Testing for opiates, benzodiazepines, tricyclic antidepressants and metamphetamine in urine was negative. During the initial clinical assessment, the patient suddenly developed dysarthria, nystagmus on bilateral gaze, left hypoglossal paresis and left arm weakness. Head CT and intracranial CT angiography were performed immediately and revealed no pathology. Following the CT scan, the patient developed acute dyspnoea and hypoxia, and required immediate intubation. ECG now showed high T-waves in precordial leads and cardiac troponin T was measured as 0.93 ng/ml (normal range below 0.03 ng/ml). Transthoracic echocardiography revealed a highly reduced left ventricular ejection fraction of 15–20%. Within 2 hours, the ejection fraction recovered to 40–45% with persisted basal hypokinesia. Brain MRI 4 hours following the onset of brain-stem symptoms revealed acute ischaemic lesions in both cerebellar hemispheres (fig 1A) and in the left dorsolateral medulla oblongata. Magnetic resonance angiography showed multifocal narrowing of both vertebral …

Magnetic resonance imaging (MRI) has dramatically increased our ability to detect morphological abnormalities in relation to aging of the brain. Among those changes are alterations of the white matter which display high signal intensity on both proton density and T2-weighted images. They may be seen in the deep and subcortical white matter or in a periventricular location. In clinically asymptomatic individuals the reported prevalence ranges from 20% to 60% for deep and subcortical white matter hyperintensities and from 15% to 94% for periventricular changes. Besides different characteristics of the populations examined these wide ranges are a consequence of quite diverse rating schemes and measurement approaches. Inadequate grading of MRI hyperintensities may also explain some of the inconsistencies in the reported associations of white matter damage with cerebrovascular risk factors or cognitive functions. Therefore development of a commonly accepted rating scheme would be desirable. Histopathologic observations could lay the basis. Hyperintense periventricular capping of the frontal horns and a smooth halo of periventricular hyperintensity have been linked to disruption of the ependymal lining, subependymal gliosis and concomitant loss of myelin. Punctate lesions in the deep and subcortical white matter corresponded to minor perivascular reduction in myelin content possibly because of a lower permeability of thickened arteriolar walls. Larger patchy and confluent hyperintensities, however, appear to indicate more extensive ischemic damage consistent with advanced microangiopathy. In parallel, newer MRI techniques may also contribute to the delineation and separation of these various types of tissue alteration.

Microangiopathy-related cerebral damage (MARCD) represents a common incidental MRI observation in the elderly. The risk factors of such findings are widely unknown. We therefore performed MRI in 349 randomly selected volunteers (ages 50 to 70 years) without neuropsychiatric disease, and evaluated the association of MARCD with conventional and recently suggested cerebrovascular risk factors such as apolipoprotein E genotypes, plasma concentrations of essential antioxidants and anticardiolipin antibody titres. MARCD was defined as evidence of early confluent and confluent deep white matter hyperintensities and lacunes. It was present in 71 (20.3%) subjects. Individuals with MARCD were older than those without such findings (62.7 years vs 59.6 years; P=0.0001). They had a higher rate of arterial hypertension (45.1% vs 28.1%; P=0.006) and cardiac disease (50.7% vs 37.1%; P=0.04), higher systolic blood pressure readings at exam (144.4 mmHg vs 136.7 mmHg; P=0.004), and higher serum fibrinogen concentrations (327.1 mg/dl vs 292.5 mg/dl; P=0.001). Their levels of total cholesterol (217.6 mg/dl vs 231.2; P=0.009), apolipoprotein A-I (167.3 mg/dl vs 177.4 mg/dl, P=0.02), lycopene (0.17 micromol/l vs 0.24 micromol/l; P=0.003), retinol (1.91 micromol/l vs 2.10 micromol/l; P=0.02) and alpha-tocopherol (27.55 micromol/l vs 31.14 micromol/l; P=0.001) were significantly lower. Forward stepwise regression analysis created a model of independent predictors of MARCD with age entering first (odds ratio 2.01/10 years), fibrinogen second (odds ratio 2.45/100 mg/dl), alpha-tocopherol third (odds ratio 0.55/10 micromol/l), and arterial hypertension fourth (odds ratio 1.96). The association of MARCD with various treatable clinical conditions may have preventive implications.

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 ε2/ε3 genotype (24.6% versus 10%) at similar frequencies of genotypes containing the ε4 allele. The ε2/ε3 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 ε2/ε3 genotype (OR, 3.0). Conclusions These data suggest an association between the apoE ε2/ε3 genotype and MARCD despite favorable effects on the lipid profile and cardiac disease.

Recently, the Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study showed patients with relapsing - remitting multiple sclerosis to benefit from repeated administration of intravenous immunoglobulin (IVIg). To provide a more detailed understanding of IV/g's action we performed further analyses on the time course of treatment effects and in regard to the impact of clinical disability at study entry on patients' response to medication. The AIMS trial was a randomized, placebo-controlled, double blind, multicenter trial. It included 148 patients (IVIg : 75; placebo 73) who suffered from relapsing-remitting MS, were 15-65 years old and scored from I -6 on the Expanded Disability Status Score (EDSS). IVIg was given over 2 years in a monthly dosage of 0.15 - 0.2 g/kg body weight. Within the first 6 months of the trial clinical disability of IVIg treated patients improved significantly from a baseline EDSS of 3.33 ± 1.38 to a score of 3.05 ± 1.73 (P=0.002). This improvement was retained over the subsequent 18 months of the trial (final EDSS: 3.09 ± 1.62). In contrast, placebo-treated patients showed a slight trend for deterioration over the study period (baseline EDSS: 3.37± 1.67; final EDSS: 3.49± 1.83). IVIg treatment was associated with a significant reduction of relapses throughout the study which was independent of the patients' disability at baseline. The observation of clinical improvement in the early phase of IVIg medication may suggest the activation of repair mechanisms such as the promotion of remyelination while immunoregulatory effects would be expected as the cause of fewer exacerbations throughout the AIMS study. These hypotheses need to be tested in future trials.

Pyogenic infectious spondylitis (PIS) is an uncommon but serious inflammatory disorder of the discovertebral junction with frequent involvement of neural structures including the spinal cord. We report a series of 41 patients (age range 21-75 years, mean age 59 years) with primary PIS confirmed by signal abnormality of the intervertebral disk and adjacent vertebral bodies on magnetic resonance imaging. The prevailing clinical symptom was focal back pain aggravated by percussion in 90% of patients. Radicular signs or symptoms were present in 59% and spinal cord symptoms in 29% of patients, respectively. Evidence of inflammation consisted of an elevated sedimentation rate in 76%, leukocytosis in 61% and fever in 61% of individuals. Predisposing factors such as diabetes mellitus, previous nonspinal surgery and other sites of infection or inflammation were identified in 17 (41%) patients and 30 (73%) were older than 50 years. The lumbar spine was most often affected and PIS was associated with an epidural abscess in 15 (37%) patients. Increased alertness for PIS in the context of focal back pain with clinical or laboratory signs of inflammation is needed to speed up its detection.

BackgroundTo evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke.MethodsIn 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied.ResultsPlasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3-6) compared to favourable (mRS 0-2) outcomes. MR-proADM levels were entered into a predictive model including the patients' age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (pConclusionsPlasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients' age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients' functional outcome.

To further elucidate the relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease (AD) we performed a case-control comparison between 30 consecutive patients with probable AD (age range 49-76, mean 65 years) and 60 asymptomatic volunteers matched for age, sex, and major cerebrovascular risk factors. We used a 1.5T magnet and determined the extent of morphologic abnormalities both by visual grading and measurement. AD patients showed comparable grades of deep/subcortical white matter hyperintensities (WMH) and a similar extent of the total WMH area as controls (3.3 cm2 +/- 8.8 vs. 2.0 cm2 +/- 4.6). They had significantly more often a "halo' of periventricular hyperintensity (PVH) (p0.0005) and an increased mean PVH thickness (3.0 mm +/- 1.9 vs. 1.3 mm +/- 1.2; p0.001). This PVH thickness correlated significantly with measures of ventricular enlargement. While univariate logistic regression also suggested a significant association of PVH thickness with a diagnosis of AD this association was lost against atrophy measures in a multivariate analysis. Our results confirm a significantly greater extent of PVH in AD patients than controls even when matched for cerebrovascular risk factors. However, this abnormality was not independently related to the disease but rather appears to be an epiphenomenon of brain atrophy.

Background and Purpose MRI of patients with a transient ischemic attack (TIA) may provide more detailed morphological insights than CT. We therefore studied the frequency and type of TIA-related infarcts shown by MRI, examined the utility of intravenous contrast material, and searched for potential predictors of infarct occurrence. Methods We performed 1.5-T MRI of the brain on 62 patients (age range, 28 to 93 years; mean, 61 years) with a hemispheric TIA. Contrast material (Gd-DTPA) was given to 45 individuals. We recorded type, number, size, and location of ischemic brain lesions and related the presence of acute infarction to features of clinical presentation and probable causes for the TIA. Results MRI showed focal ischemic lesions in 50 patients (81%), but an acute TIA-associated infarct was seen in only 19 subjects (31%). In patients with an acute lesion, the infarcts were smaller than 1.5 cm in 13 (68%), purely cortical in 11 (58%), and multiple in 7 (37%) individuals. Contrast enhancement contributed to the delineation of an acute lesion in only 2 of 45 patients (4%). Acute infarction was unpredictable by clinical TIA features, but the frequency of identifiable vascular or cardiac causes was significantly higher in those patients with TIA-related morphological damage (odds ratio, 5.2 [95% confidence interval, 1.6 to 17.3]). Conclusions More than two thirds of TIA patients showed no associated brain lesion even when MRI and contrast material were used, but the overall frequency of ischemic damage was high. TIA-related infarcts on MRI were mostly small and limited to the cortex and tended to consist of multiple lesions. A positive MRI underscores the need for comprehensive diagnostic workup since evidence of infarction appears to be associated with a higher frequency of significant vascular or cardiac disorders.

Kearns Sayre Syndrome (KSS) belongs to the group of so called ‘mitochondrial encephalopathies’. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) may have the potential to noninvasively detect and monitor disease specific cerebral involvement, as we wish to demonstrate in a patient whom we have followed for 3.5 years. At first presentation with incomplete external ophthalmoplegia, ptosis, pigmentary retinopathy and impaired hearing MRI demonstrated ill defined areas of symmetric T2-prolongation in the dorsal parts of the mesencephalon, the pons and in both cerebellar hemispheres. While the patients clinical symptoms deteriorated, including the onset of dysphagia, signal abnormalities spread downwards into the medulla oblongata involving the glossopharyngeal nuclei and supratentorially into the white matter. Proton MRS performed with the PRESS sequence (TR/TE 1500/136 ms) in the area of white matter damage showed a doublet at 1.33 ppm, which is characteristic for the presence of lactate. Our findings suggest MRI abnormalities to increase in parallel with neurologic progression of KSS and confirm the utility of 1H-MRS in supporting mitochondrial respiratory chain insufficiency as the underlying cause of parenchymal alterations.

Objective: To search for a morphologic basis of cognitive impairment possibly associated with arterial hypertension using magnetic resonance imaging and a demanding neuropsychologic test battery. Design: Case-control comparison with age, length of education, presence of diabetes, and presence of cardiac disease as matching criteria. Setting: Austrian Stroke Prevention Study. Subjects: A total of 89 hypertensive subjects and 89 control subjects from a subset of 272 volunteers with no neurologic symptoms undergoing extensive diagnostic workup in a large-scale stroke prevention study among randomly selected elderly community members. Main Outcome Measures: Focal brain abnormalities and size of ventricles and cortical sulci as assessed by magnetic resonance imaging and neuropsychological test scores. Results: Hypertensive subjects more commonly showed areas of white matter hyperintensity and moderately severe ventricular enlargement compared with controls. While no differences were noted between the investigational groups in test results of memory capacity and conceptualization, hypertensive subjects tended to perform worse when assessed for attentional and visuopractical skills. These differences became significant when comparing the brain-damaged subsets of patients and controls with their counterparts without cerebral changes. The pattern and extent of neuropsychologic deficits was similar in hypertensive and normotensive subjects with abnormal magnetic resonance imaging scans. Conclusion: Our data strongly suggest the high rate of brain abnormalities among hypertensive subjects as the cause of their subtle neuropsychological dysfunction.

Background and Purpose Our aim was to assess the association of elevated anticardiolipin antibody (aCL) titers with silent brain damage and cognitive functioning in middle-aged and elderly normal subjects. Methods We determined the IgM and IgG aCL titers from 233 randomly selected clinically normal participants of a population-based stroke prevention study (age range, 44 to 82 years). aCL titers were categorized into negative (0 to 10 U/L), low positive (10 to 20 U/L), and moderately high positive (>20 U/L). All participants underwent 1.5-T MRI and demanding neuropsychological testing. Semiautomated measurements of the total white matter hyperintensity area and the size of ventricles and cortical sulci were conducted. Results There were 180 subjects (77.3%) with negative, 35 (15.0%) with low positive, and 18 (7.7%) with moderately high positive aCL titers. The frequency and extent of focal and diffuse brain abnormalities were not related to the aCL status of those examined. However, subjects with positive aCL results performed worse than those with negative findings on almost all tests administered, and this effect was mainly IgG titer related. When an ANCOVA test and partial correlations to correct for slight group differences in age and for the presence of major vascular risk factors were used, values of P Conclusions Increased aCL titers in normal elderly persons may be associated with subtle neuropsychological dysfunction, but they do not appear to cause any morphological changes as demonstrated by MRI.

Severe white matter hyperintensities (WMH) represent cerebral small vessel disease and predict functional decline in the elderly. We used fMRI to test if severe WMH impact on functional brain network organization even before clinical dysfunction. Thirty healthy right-handed/footed subjects (mean age, 67.8 ± 7.5 years) underwent clinical testing, structural MRI and fMRI at 3.0T involving repetitive right ankle and finger movements. Data were compared between individuals with absent or punctuate (n = 17) and early confluent or confluent (n = 13) WMH. Both groups did not differ in mobility or cognition data. On fMRI, subjects with severe WMH demonstrated excess activation in the pre-supplementary motor area (SMA), frontal, and occipital regions. Activation differences were noted with ankle movements only. Pre-SMA activation correlated with frontal WMH load for ankle but not finger movements. With simple ankle movements and no behavioral deficits, elderly subjects with severe WMH demonstrated pre-SMA activation, usually noted with complex tasks, as a function of frontal WMH load. This suggests compensatory activation related to disturbance of frontosubcortical circuits.

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

To document the occurrence, time course, and predictors of global cognitive impairment following a supratentorial stroke, we prospectively studied 41 consecutive patients with acute cerebral ischemia and no evidence of pre-existing intellectual disturbances. The Graded Neurologic Scale and Mattis Dementia Rating Scale were used to assess neurologic and cognitive deficits within the first week, 3 weeks and 6 months after the onset of symptoms. CT was performed at each examination and semiquantitative measurements of infarct volumes and brain atrophy were obtained. Sixty-one percent of patients were found to be cognitively impaired within the first week. After 6 months this deficit had resolved in 24%, but was still present in 37% of individuals. Initial findings associated with a high risk of long-term intellectual dysfunction were: 1. moderately severe cognitive impairment, 2. diminished alertness in the acute stroke stage, 3. infarction involving the temporal lobe, 4. evidence of multiple brain infarcts and 5. pronounced ventricular enlargement. Logistic regression analysis revealed temporal infarcts and evidence of multiple ischemic lesions as the most powerful predictors of persistent cognitive impairment. By these two factors alone, 85.4% of study participants could be correctly classified regarding their cognitive outcome. These results suggest cognitive dysfunction to be a frequent sequela of supratentorial stroke. Its long-term persistence may be predicted on the basis of certain features.

Bilateral medial medullary infarction is a rare event which clinically presents with flaccid tetraplegia sparing the face, bilateral disturbance of deep sensation, hypoglossal nerve palsy and respiratory failure. We here report a patient with such symptoms in whom magnetic resonance imaging enabled the detection of signal abnormalities in the lower brainstem as soon as 9 h after onset. Results of a control study 3 weeks later correlated well with the extent of infarction that was seen at autopsy. Early lesion detection in the lower medulla by magnetic resonance imaging and the unfavorable prognosis of patients with ischemic damage at that location may provide the rationale for aggressive therapeutic strategies in such a condition.

Background and purpose: These European Federation of Neurological Societies guidelines on neuroimaging of motor neuron diseases (MNDs) are designed to provide practical help for the neurologists to make appropriate use of neuroimaging techniques in patients with MNDs, which ranges from diagnostic and monitoring aspects to the in vivo study of the pathobiology of such conditions. Methods: Literature searches were performed before expert members of the Task Force wrote proposal. Then, consensus was reached by circulating drafts of the manuscript to the Task Force members and by discussion of the classification of evidence and recommendations. Results and conclusions: The use of conventional MRI in patients suspected of having a MND is yet restricted to exclude other causes of signs and symptoms of MN pathology [class IV, level good clinical practice point (GCPP)]. Although the detection of corticospinal tract hyperintensities on conventional MRI and a T2-hypointense rim in the pre-central gyrus can support a pre-existing suspicion of MND, the specific search of these abnormalities for the purpose of making a firm diagnosis of MND is not recommended (class IV, level GCPP). At present, advanced neuroimaging techniques, including diffusion tensor imaging and proton magnetic resonance spectroscopic imaging, do not have a role in the diagnosis or routine monitoring of MNDs yet (class IV, level GCPP). However, it is strongly advisable to incorporate measures derived from these techniques into new clinical trials as exploratory outcomes to gain additional insights into disease pathophysiology and into the value of these techniques in the (longitudinal) assessment of MNDs (class IV, level GCPP).

Repeated bleeding into CSF spaces may cause superficial siderosis with progressive neurologic impairment. The unique physical properties of MRI provide a basis for the in vivo diagnosis of this entity.

To search for a morphologic basis of cognitive impairment possibly associated with essential hypertension, we studied 35 otherwise asymptomatic hypertensive individuals (mean age, 38.7 years; range, 22 to 49 years) and 20 normotensive control subjects (mean age, 37.9 years; range, 26 to 49 years) using neuropsychologic tests and magnetic resonance imaging. Irrespective of drug treatment, hypertensive individuals performed significantly worse than did control subjects when assessed for verbal memory and total learning and memory capacity, while there were no differences in test results of visual memory, attention, vigilance, and reaction time. The hypertensive individuals also described themselves as less active but ranked similar on five other mood subscales. Punctate high-signal intensities of the white matter were found almost twice as often in the hypertensive group (38%) as in the control group (20%). There was no difference in test performance between hypertensive individuals with and those without white matter lesions, however. Our results confirm the presence of subtle neuropsychologic deficits and indicate a higher frequency of white matter signal abnormalities in essential hypertension, as shown on magnetic resonance imaging, but do not indicate a correlation of these findings with each other.

To the Editor. —In an imaging study of Alzheimer's disease and normal aging, Leys et al, 1 using our rating scale, 2 found no difference in magnetic resonance imaging white matter hyperintensities between the two groups, and only a trend toward increased periventricular hyperintensity in patients with Alzheimer's disease. This is in contrast to our initial observation of a hyperintense "halo" in six of 12 cases of Alzheimer's disease. 2 We would like to emphasize, however, that a part of us (F.F., R.S., H.O.) could not replicate this finding in a subsequent study performed under similar conditions. There still remains a trend toward more signal abnormalities in Alzheimer's disease, however. The Table summarizes the current data from subjects without cerebrovascular risk factors in this ongoing project. 3 A disproportionately higher number of patients with more marked ventricular enlargement in our first study appears to be the likeliest explanation for these

MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS.

Objective: To determine the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity evolution over 3 years. Methods: In the setting of the Austrian Stroke Prevention Study, 1.5-T MRI was performed at baseline and at a 3-year follow-up in 273 community-dwelling elderly (mean age, 60 ± 6.1 years) without neuropsychiatric disease. At each visit individuals underwent a structured clinical interview and examination, EKG, echocardiography, extensive laboratory workup, and demanding neuropsychological testing. MR images were read by three independent raters, and the change of white matter hyperintensities from baseline was assessed by direct image comparison. The change was graded as absent, minor, or marked. Minor change was defined as a difference of no more than one to four punctate lesions between both scans. A change was considered to be marked if there was a difference of more than four abnormalities or a transition to early-confluent and confluent lesions. Results: Combined ratings indicated lesion progression in 49 individuals (17.9%). Lesion progression was minor in 27 participants (9.9%) and was marked in 22 (8.1%). Regression of white matter hyperintensities did not occur. Diastolic blood pressure (odds ratio, 1.07/mm Hg) and early-confluent or confluent white matter hyperintensities at baseline (odds ratio, 2.62) were the only significant predictors of white matter hyperintensity progression. Lesion progression had no influence on the course of neuropsychological test performance over the observational period. Conclusions: White matter hyperintensities progress in elderly normal subjects. Our data may be used as a reference for future observational and interventional studies on white matter hyperintensity progression in various CNS diseases. The lack of an association between lesion progression and cognitive functioning needs to be explored further.

Background: Incidental foci of signal loss suggestive of past microbleeds are a frequent finding on gradient-echo T2*-weighted MRI of patients with nontraumatic intracerebral hemorrhage and have been associated with bleeding-prone microangiopathy. If and to what extent such lesions may also occur in the normal population is unclear. Objective: To determine focal hypointensities in asymptomatic elderly individuals and their relation to other clinical and morphologic variables. Methods: T2*-weighted MRI of the brain was performed in a consecutive series of 280 participants (mean age 60 years, range 44 to 79) of the Austrian Stroke Prevention Study. This cohort consisted of randomly selected individuals without history or signs of neuropsychiatric disorder. Results: Past microbleeds ranging from one to five foci of signal loss were seen in 18 (6.4%) individuals. They were strongly associated with higher age, hypertension, and lacunes ( p p = 0.02). Hypertension was present in all individuals with focal hypointensities in the basal ganglia and infratentorially but in only 5 of 10 volunteers with microbleeds limited to cortico-subcortical sites ( p = 0.04). Conclusions: MRI evidence of past microbleeds may be found even in neurologically normal elderly individuals and is related, but not restricted, to other indicators of small vessel disease. The predictive potential of this finding regarding the risk of intracerebral bleeding requires further investigation.