Vanninen_EU Neurology 10/03/2010 10:16 Page 49
Diffusion- and Perfusion–weighted MRI and MRA in ApoE Polymorpism and Stroke
Figure 1: Relative Haemodynamics (Ischaemic/Contralateral x 100%) in the Hypoperfused Subregions on
Day One of Stroke Onset
200
al)
150
alater
100
50
Percentage (ischaemic/contr
0
CBF CBV MTT CBF CBV MTT CBF CBV MTT
Ischaemic core Infarct growth Oligaemic tissue
Non-carriers Carriers
CBF = central blood flow; CBV = central blood volume; MTT = mean transit time. *Indicates significant difference between ε4 carriers and non-carriers.
26
Under similar ischaemic severity, the brain tissue proceeded to infarction earlier in ε4 carriers than in non-carriers. Data originally published in Liu et al., 2006.
structurally intact tissue in the hypoperfusion area. Three perfusion collateral M1 flow in patients with ICA occlusion may be increased
parameters on PWI – cerebral blood flow (CBF), cerebral blood cholesterol levels, slow narrowing of the cerebral arteries by
volume (CBF) and mean transit time (MTT) – are often used to atherosclerosis and subsequent gradual development of collateral
evaluate the hypoperfusion severity. Reduced relative CBV usually pathways. Well-established collateral circulation in ε4 carriers may
indicates irreversible ischaemic tissue. The brain tissue with support the observation by McCarron et al. that improved survival
reduced CBV at acute stage is believed to have run out of the with increasing ε4 dose was found in the ischaemic group of acute
cerebrovascular reserves.
23
The volume of the lesion on the CBV stroke patients, and that ε4 may also have some favourable effect.
21
map at acute stage is closest to the final infarct volume in the However, this is contradictory to the findings from stroke models in
general population;
24,25
however, it seems that this is not true in ε4 transgenic mice. This contradiction may account for the species
carriers. The study by Liu et al. found that although the volume of difference or the young age of the animal. In young animals, no
lesions with reduced CBV at acute stage was significantly smaller in haemodynamically significant lesions have been observed, even in
ε4 carriers than in non-carriers, the final infarct volumes had no ApoE-deficient mice, despite marked hypercholesterolaemia.
27–29
significant difference between carriers and non-carriers.
20
Semi-
quantitative measurements showed that under similar ischaemic Weir et al.
30
hypothesised that divergent influences of the ApoE ε4
severity, the brain tissue proceeded to infarction earlier in ε4 allele on ischaemic and haemorrhagic stroke survival may result from
carriers than in non-carriers (see Figure 1).
26
The observation that in differences in coagulation profiles. In haemorrhagic stroke patients,
ε4 carriers the CBV viability perfusion threshold is closer to the CBV ε4 carriers had higher partial thromboplastin time ratios than non-ε4
values of normal uninjured brain than in non-carriers
20
provides carriers. Among 529 ischaemic stroke patients, an increasing ε4 allele
imaging evidence that the brain tissue is less tolerant of ischaemia dose was associated with improved survival after adjusting for
in ε4 carriers than in non-carriers. baseline National Institutes of Health Stroke Scale (NIHSS) and partial
thromboplastin time ratio.
An interesting finding of an MR angiographic (MRA) study in a
prospectively selected stroke study population
24,26
was that in spite of In cerebral amyloid angiopathy-related haemorrhage, a less
a more frequent internal carotid artery (ICA) occlusion rate (50%) in frequent cause of ICH, the ApoE ε4 allele is thought to enhance
the subgroup of ε4 carriers, this group had a high frequency of amyloid protein deposition in cortical blood vessels, whereas the ε2
established collateral middle cerebral artery (MCA) flow. Interestingly, allele predisposes amyloid-laden blood vessels to rupture.
31
there was actually a significantly higher frequency in establishing Lemmens et al. obtained brain MRI scans and ApoE genotypes in
MCA flow via collateral circulation in the ε4 carriers than in the 334 transient ischaemic attack or ischaemic stroke patients,
non-carriers on day one of onset. All of those ε4 carriers who had an but found no association between the presence of microbleeds
occlusion of the ICA showed collateral MCA flow, while the remaining and the ApoE ε4 or ApoE ε2 alleles.
32
In the Rotterdam Scan Study
ε4 carriers showed normal appearance on MRA. On the other hand, with individuals from the general population 60 years of age and
among the ε4 non-carriers, one-third had an occlusion of the ICA and over, ApoE ε4 carriers had significantly more strictly lobar
only one of them (20%) showed collateral MCA flow. microbleeds than non-carriers.
33
ApoE ε4 is known to be associated with higher serum cholesterol Clinical Outcome
levels and development of atherosclerosis.
4
From this point of view a Evidence has shown that functional outcomes are not associated
plausible explanation for the higher frequency in establishing with ApoE genotype.
22
In the McCarron study,
22
189 consecutive
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