[Consensus statement "Dementia 2010" of the Austrian Alzheimer Society]. / Konsensusstatement "Demenz 2010" der Osterreichischen Alzheimer Gesellschaft.

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.

Discrimination of white matter lesions and multiple sclerosis plaques by short echo quantitative 1H-magnetic resonance spectroscopy.

Multiple sclerosis (MS) plaques and age related white matter lesions (WML) are of similar morphological appearance on T2 weighted MRI. Therefore their differentiation is sometimes crucial. Proton magnetic resonance spectroscopy ((1)H-MRS) adds metabolic information to conventional imaging and may help to distinguish inflammatory MS plaques from vascular related WML. This study was performed to evaluate the metabolite pattern in MS plaques and WML. 15 MS patients, 14 elderly individuals with WML and 16 controls were investigated by conventional MRI and short echo quantitative (1)H-MRS (TE: 30ms, TR: 3000ms). The mean metabolite concentrations in normal control white matter (NCWM), MS plaques and WML were: t-NAA: 8.96 mmol/l (SD: 0.93) vs 6.79 mmol/l (SD: 1.99) vs 7.18 mmol/l (SD: 1.41); Cho:1.66 mmol/l (SD: 0.4) vs 1.49 mmol/l (SD: 0.45) vs 1.46 mmol/l (SD: 0.34); PCr:5.64 mmol/l (SD: 0.83) vs 4.9mmol/l (SD: 1.3) vs 4.95 mmol/l (SD: 0.86); myo-Ins: 4.57 mmol/l (SD:1.05) vs 6.34 mmol/l (SD: 2.03) vs 4.5 mmol/l (SD: 0.96). t-NAA reduction in MS plaques and WML was significant compared with controls (p

Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements.

BACKGROUND AND PURPOSE: To provide further insight into the MRI assessment of age-related white matter changes (ARWMCs) with visual rating scales, 3 raters with different levels of experience tested the interrater agreement and comparability of 3 widely used rating scales in a cross-sectional and follow-up setting. Furthermore, the correlation between visual ratings and quantitative volumetric measurement was assessed. METHODS: Three raters from different sites using 3 established rating scales (Manolio, Fazekas and Schmidt, Scheltens) evaluated 74 baseline and follow-up scans from 5 European centers. One investigator also rated baseline scans in a set of 255 participants of the Austrian Stroke Prevention Study (ASPS) and measured the volume of ARWMCs. RESULTS: The interrater agreement for the baseline investigation was fair to good for all scales (kappa values, 0.59 to 0.78). On the follow-up scans, all 3 raters depicted significant ARWMC progression; however, the direct interrater agreement for this task was poor (kappa, 0.19 to 0.39). Comparison of the interrater reliability between the 3 scales revealed a statistical significant difference between the scale of Manolio and that of Fazekas and Schmidt for the baseline investigation (z value, -2.9676; P=0.003), demonstrating better interrater agreement for the Fazekas and Schmidt scale. The rating results obtained with all 3 scales were highly correlated with each other (Spearman rank correlation, 0.712 to 0.806; P< or =0.01), and there was significant agreement between all 3 visual rating scales and the quantitative volumetric measurement of ARWMC (Kendall W, 0.37, 0.48, and 0.57; P<0.001). CONCLUSIONS: Our data demonstrate that the 3 rating scales studied reflect the actual volume of ARWMCs well. The 2 scales that provide more detailed information on ARWMCs seemed preferential compared with the 1 that yields more global information. The visual assessment of ARWMC progression remains problematic and may require modifications or extensions of existing rating scales.

CT and MRI rating of white matter changes.

The impact of white matter changes (WMC) detectable on CT or MRI on various diseases like ischemic stroke and intracerebral hemorrhage and their association with cognitive impairment was and still is under debate. To assess WMC in a qualitative and/or semiquantitative fashion rating scales have been developed. For MRI most widely used scales are the scales of Manolio, Fazekas, Schmidt, and Scheltens. Most recently a new scale extending earlier suggestions has been introduced by Wahlund et al. applicable for both CT and MRI. This article will review strengths and weaknesses of these rating scales and will discuss further requirements and future perspectives.

Risk factors and progression of small vessel disease-related cerebral abnormalities.

A three year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate and clinical predictors of progression of small vessel disease related cerebral abnormalities including white matter changes and lacunes. White matter hyperintensity progression was found in 17.9% of individuals over the 3 year period. New lacunes occurred in 2.2% of subjects. The overall frequency of progression of small vessel disease related brain changes was 19%. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline predicted lesion progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study described that polymorphisms in the renin angiotensin system (RAS) increase the susceptibility for progression of cerebral small vessel disease. Homozygosity for the T allele of the M235T polymorphism of the angiotensinogen gene was associated with a 3.19-fold increased risk for lesion progression independently of arterial hypertension. These data suggest that drugs influencing the RAS system may allow to intervene with an unfavorable course of cerebral small vessel disease.

Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis.

While much work has concentrated on focal white matter (WM) lesions in multiple sclerosis, there is growing evidence to suggest that normal-appearing WM (NAWM) and grey matter (GM) are also involved in the disease process. This study investigated multiple sclerosis disease effects on NAWM and cortical GM (CGM) metabolite concentrations, and the relationships between these metabolite concentrations and clinical impairment. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) data acquired using point resolved spectroscopic (PRESS) localization (echo time 30 ms, repetition time 3000 ms, nominal voxel volume 2.3 ml) from 27 relapsing-remitting multiple sclerosis and 29 normal control (NC) subjects were processed using LCModel to estimate metabolite concentrations in millimoles per litre. (1)H-MRSI voxel tissue contents were estimated using SPM99 tissue and semi-automatic lesion segmentations of three-dimensional fast spoiled gradient recall scans acquired during the same scanning session. NAWM and CGM metabolite concentrations estimated were: choline-containing compounds (Cho); creatine and phosphocreatine (Cr); myo-inositol (Ins); N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (tNAA); and glutamate plus glutamine (Glx). CGM data came from 24 of the multiple sclerosis (mean age 35.2 years, mean disease duration 1.7 years) and 25 of the NC (mean age 34.9 years) subjects. NAWM data came from 25 of the multiple sclerosis (mean age 35.0 years, mean disease duration 1.7 years) and 28 of the NC (mean age 36.7 years) subjects. Metabolite concentrations were compared between multiple sclerosis and NC subjects using multiple (linear) regression models allowing for age, gender, (1)H-MRSI voxel tissue and CSF contents, and brain parenchymal volume. At a significance level of P < 0.05, CGM Cho, CGM and NAWM tNAA, and CGM Glx were all significantly reduced, and NAWM Ins was significantly elevated. Spearman correlations of multiple sclerosis functional composite scores with tissue metabolite concentrations were significant for the following: CGM Cr (r(s) = 0.524, P = 0.009), CGM Glx (r(s) = 0.580, P = 0.003) and NAWM Ins (r(s) = -0.559, P = 0.004). These results indicate that metabolite changes in NAWM and CGM can be detected early in the clinical course of multiple sclerosis, and that some of these changes relate to clinical status. The correlation of clinical impairment with CGM Cr and Glx but not tNAA suggests that it is more closely associated with neuronal metabolic dysfunction rather than loss in clinically early relapsing-remitting multiple sclerosis. The correlation of clinical impairment with a raised NAWM Ins may indicate that glial proliferation also relates to function at this stage of the disease.

Quantitative 1H MRS imaging 14 years after presenting with a clinically isolated syndrome suggestive of multiple sclerosis.

clinically isolated syndromes (CIS) are events suggestive for emerging multiple sclerosis (MS). A majority of patients develop MS within months or years whilst others remain clinically isolated. The goal of this study was to investigate whether biochemical metabolites detectable by 'H magnetic resonance spectroscopy (MRS) may serve to distinguish between these two groups. We investigated 41 patients 14 years after presentation with a CIS and 21 controls with combined quantitative short echo 'H MRS and magnetic resonance imaging (MRI) and assessed disability according to the Expanded Disability Status Scale (EDSS). At follow-up, 32 had developed MS, and 9 still had CIS. Compared with controls, MS patients demonstrated significantly higher concentrations of myo-inositol (Ins) in normal appearing white matter (NAWM) and lesions. Lesions also demonstrated a reduced N-acetyl-aspartate (NAA) level and an increase in choline-containing compounds (Cho). The NAWM Ins concentration was correlated with EDSS (r = 0.48, p = 0.005). MS normal appearing cortical grey matter (CGM) exhibited a decreased NAA. Patients who remained CIS did not differ significantly from controls in any MRS measure. Metabolite changes in normal appearing white and grey matter in MS indicate diffuse involvement of the entire MS brain, which was not seen in the persisting CIS patients. Elevated Ins in MS NAWM appeared functionally relevant It may indicate glial cell proliferation or gliosis.

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.

Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study.

Neuronal damage and loss is likely to underlie irreversible disability in multiple sclerosis (MS). The time of onset, location and extent of neuronal damage in early disease are all uncertain. To explore this issue 16 patients with short duration, mild relapsing-remitting disease (mean disease duration 1.8 years, median EDSS 1) were studied using short echo time proton magnetic resonance spectroscopic imaging (1H-MRSI) to quantify the concentration of the neuronal marker N-acetyl-aspartate (NAA). The data were compared with those from 12 age-matched controls. 1H-MRSI was obtained from a 1.5-cm-thick slice just above the lateral ventricles. The Linear Combination (LC) Model combined with locally developed software allowed automated measurement of absolute metabolite concentrations from lesions, normal-appearing white matter (NAWM) and cortical grey matter (CGM). MS CGM exhibited significantly lower NAA (P = 0.01) and myo-inositol (P = 0.04) than control CGM. MS NAWM exhibited a lower concentration of NAA (P = 0.01) and increased myo-inositol (P = 0.03) than control white matter. More marked reductions in NAA and increases in myo-inositol were seen in lesions. The reduced NAA in MS CGM and NAWM suggest that mild but widespread neuronal dysfunction or loss occurs early in the course of relapsing-remitting MS. This preliminary finding should be confirmed in a larger cohort, and follow-up studies are also needed to determine the prognostic and pathophysiological significance of these early changes.

Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis.

High-resolution diffusion tensor imaging (DTI) was performed in 14 patients with clinically definite multiple sclerosis (MS) and the trace of the diffusion tensor () and the fractional anisotropy (FA) were determined in normal appearing white matter (NAWM) and in different types of focal MS lesions. A small but significant increase of the in NAWM compared to control white matter ((840 +/- 85) x 10(-6) mm(2)/sec vs. (812 +/- 59) x 10(-6) mm(2)/sec; P < 0.01) was found. In addition, there was a significant decrease in the FA of normal-appearing regions containing well-defined white matter tracts, such as the genu of the internal capsule. In non-acute lesions, the of T(1)-hypointense areas was significantly higher than that of T(1)-isointense lesions ((1198 +/- 248) x 10(-6) mm(2)/sec vs. (1006 +/- 142) x 10(-6) mm(2)/sec; P < 0. 001), and there was a corresponding inverse relation of FA. Diffusion characteristics of active lesions with different enhancement patterns were also significantly different. DTI with a phase navigated interleaved echo planar imaging technique may be used to detect abnormalities of isotropic and anisotropic diffusion in the NAWM and selected fiber tracts of patients with MS throughout the entire brain, and it demonstrates substantial differences between various types of focal lesions.

Longitudinal change of white matter abnormalities.

A three year follow-up of 273 participants (mean age 60+/-6.1 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity in elderly individuals without neuropsychiatric disease. Lesion progression was found in a total of 49 (17.9%) individuals. It was minor in 27 (9.9%) and marked in 22 (8.1%) participants. Diastolic blood pressure (odds ratio 1.07/mmHg) 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 neuropsychologic test performance over the observational period.

Novel imaging technologies in the assessment of cerebral ageing and vascular dementia.

Introduction of magnetic resonance imaging (MRI) has opened new possibilities for detecting age-related brain tissue changes. The majority of these abnormalities consists of hyperintense foci in the deep and subcortical white matter probably related to microvascular disturbances and of signal hyperintensities around the lateral ventricles. It has also been suggested that these abnormalities may contribute to the development of cognitive impairment. The correlation between age-related signal abnormalities on conventional MRI and neuropsychologic dysfunction is limited, however, and a threshold beyond which such a relation may come into existence has not yet been defined. Poor tissue characterisation by conventional MRI may be one explanation. Therefore, new pulse sequences are expected not only to provide a higher lesion contrast such as the fluid attenuated inversion recovery (FLAIR) technique but also to offer new insights concerning the composition of incidental brain lesions. In this context both magnetisation transfer imaging (MTI) and diffusion weighted imaging (DWI) may serve to gain information about the integrity of cell membranes and organelles and the preservation of axons and fibre tracts. We will review the technical background of these recently developed MR sequences and their first applications to age-associated brain abnormalities.

MRI cerebral white matter lesions and paraoxonase PON1 polymorphisms : three-year follow-up of the austrian stroke prevention study.

White matter lesions (WMLs) on magnetic resonance imaging (MRI) scans of older persons are thought to be caused by cerebral small-vessel disease. As they progress, these brain abnormalities frequently result in cognitive decline and gait disturbances, and their predictors are incompletely understood. Genetic risk factors have been implicated but remain undetermined so far. We examined whether 2 common polymorphisms of the paraoxonase (PON1) gene leading to a methionine (M allele)-leucine (L allele) interchange at position 54 and an arginine (B allele)-glutamine (A allele) interchange at position 191 are associated with the presence and progression of WMLs. We studied 264 community-dwelling subjects without neuropsychiatric disease (ages 44 to 75 years). All underwent vascular risk factor assessment, brain MRI, and PON1 genotyping. MRI scanning was repeated after 3 years. The extent and number of WMLs were recorded by 3 independent readers. Progression of WMLs was assessed by direct scan comparison. The final rating relied on the majority judgment of the 3 readers. The LL, LM, and MM genotypes were noted in 111 (42.0%), 118 (44.7%), and 35 (13.3%) subjects, respectively; the AA, AB, and BB genotypes occurred in 146 (55.3%), 98 (37.1%), and 20 (7.8%) individuals, respectively. Carriers of the LL genotype showed a nonsignificant trend toward more extensive WMLs and more frequently demonstrated lesion progression over the 3-year observation period (P=0.03). The polymorphism at position 191 had no effect. Logistic regression analysis yielded age (odds ratio, 1.08/y), diastolic blood pressure (odds ratio, 1.05/mm Hg), and LL paraoxonase genotype (odds ratio, 2. 65) to be significant predictors of WML progression. These data suggest that the LL PON1 genotype at position 54 influences the extent and progression of WMLs in elderly subjects.

Fast multislice T(1) and t(1sat) imaging using a phase acquisition of composite echoes (PACE) technique.

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, T(1) 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 T(1sat) 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 T(1) values. T(1) and T(1sat) 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.

MRI white matter hyperintensities: three-year follow-up of the Austrian Stroke Prevention Study.

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.

Diffusion-weighted imaging with navigated interleaved echo-planar imaging and a conventional gradient system.

PURPOSE: To demonstrate the technical feasibility and precision of a navigated diffusion-weighted (DW) MR imaging method with interleaved echo-planar imaging and test its diagnostic sensitivity for detection of ischemic stroke. MATERIALS AND METHODS: Apparent diffusion coefficient (ADC) measurements were performed in phantoms, and six healthy adult volunteers were examined to determine intrasubject (precision) and intersubject (reference range) variations in absolute ADC and relative ADC (rADC) measurements. DW imaging maps and lesion rADC values were also obtained in 34 consecutive stroke patients to evaluate the sensitivity and reliability of DW-interleaved echo-planar imaging for detection of ischemic brain damage. RESULTS: Phantom and volunteer ADC values were in excellent agreement with published data. The intrasubject variation of rADC was 6.2%. The ADC precision ranged from 6.5% in the subcortical white matter in the frontal lobe to 12.9% in the head of the caudate nucleus. Interleaved echo-planar imaging enabled rapid acquisition of high-quality images of the entire brain without substantial artifacts. Within the 1st week, the sensitivity of DW-interleaved echo-planar imaging for detection of acute infarction was 90% (18 of 20 true-positive studies) and independent of lesion location. CONCLUSION: DW-interleaved echo-planar imaging with phase navigation and cardiac triggering is robust, reliable, and fast. With high sensitivity for detection of early ischemic infarction, it is useful for examining stroke patients by using MR systems with conventional gradient hardware.

Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds.

BACKGROUND AND PURPOSE: Patients with spontaneous intracerebral hemorrhage (ICH) frequently have small areas of signal loss on gradient-echo T2*-weighted MR images, which have been suggested to represent remnants of previous microbleeds. Our aim was to provide histopathologic support for this assumption and to clarify whether the presence and location of microbleeds were associated with microangiopathy. METHODS: We performed MR imaging and correlative histopathologic examination in 11 formalin-fixed brains of patients who had died of an ICH (age range, 45-90 years). RESULTS: Focal areas of signal loss on MR images were noted in seven brains. They were seen in a corticosubcortical location in six brains, in the basal ganglia/thalami in five, and infratentorially in three specimens. Histopathologic examination showed focal hemosiderin deposition in 21 of 34 areas of MR signal loss. No other corresponding abnormalities were found; however, hemosiderin deposits were noted without MR signal changes in two brains. All specimens with MR foci of signal loss showed moderate to severe fibrohyalinosis, and there was additional evidence of amyloid angiopathy in two of those brains. CONCLUSION: Small areas of signal loss on gradient echo T2*-weighted images indicate previous extravasation of blood and are related to bleeding-prone microangiopathy of different origins.

MRI evidence of past cerebral microbleeds in a healthy elderly population.

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 < 0.001), and extensive white matter damage was more frequently noted (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.

[Indications of cerebral micro-hemorrhage in MRI. Comparative histological findings and possible clinical significance]. / Hinweis auf zerebrale Mikroblutungen in der MRT. Vergleichende histologische Befunde und mögliche klinische Bedeutung.

Increased use of gradient echo T2*-weighted gradient echo sequences in magnetic resonance imaging (MRI) of patients suffering from primary ICH called attention to foci of signal loss which were suggested to represent remnants of cerebral microbleeds. In a post mortem correlative MR and histopathological study we provide support for this notion. We found areas of signal loss on gradient echo T2*-weighted sequences in 7 out of 11 brains of patients who had died of intracerebral hematoma. Histopathologically, these areas represented hemosiderin deposits indicating previous extravasation of blood. To provide data about the prevalence of these MRI findings in a healthy elderly population a subgroup of participants of the Austrian Stroke Prevention Study was analyzed. We detected foci of signal loss on gradient echo T2*-weighted sequences in 18 out of 280 volunteers (6.4%). MR-based evidence of previous microbleeds may indicate a potentially higher risk of suffering from intracerebral bleeding which could have therapeutic implications for the treatment of acute stroke and for secondary prevention. This hypothesis will have to be tested in future prospective trials.

The spectrum of age-associated brain abnormalities: their measurement and histopathological correlates.

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.