Spontaneous (non-traumatic) intracerebral haemorrhage accounts for ~10% of all
strokes in Western populations. Investigations may identify intracerebral haemorrhage
(ICH) as ‘secondary’ to underlying causes such as tumours or aneurysms, but ~80% of
ICHs which have no apparent underlying cause (so-called ‘primary’ ICH) tend to be
attributed to small vessel vasculopathies such as arteriolosclerosis or cerebral amyloid
angiopathy (CAA), on the basis of an adult’s risk factors and clinical and radiographic
features of the ICH.
The commonly accepted hypothesis is that CAA contributes to lobar ICH and
arteriolosclerosis causes non-lobar ICH. In the following thesis, I set out to explore
whether (a) the baseline demographic, clinical features and apolipoprotein E genotype
of adults with lobar and non-lobar ICH differ, (b) the prognosis of adults with lobar and
non-lobar ICH differ and (c) the neuroimaging correlates of small vessel disease in
adults with lobar and non-lobar ICH differ since this might provide clues to the
vasculopathies underlying lobar and non-lobar ICH. I explored (d) the strength of the
association between CAA and ICH by systematically reviewing neuropathological case
control studies and (e) the radiological and pathological features of lobar ICH to
examine the nature of CAA in persons with lobar ICH and whether any computed
tomography (CT) features of ICH are associated with CAA-related lobar ICH.
I set up a prospective, community-based inception cohort study of adults with ICH in
South East Scotland. Adults with spontaneous primary definite ICH had the
opportunity to consent to participate in the Lothian Study of IntraCerebral
Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN), an
ethically-approved, prospective community-based research study examining the causes
of ICH using apolipoprotein E genotyping, brain MRI and research autopsy in case of
death.
Of 128 adults with first-ever spontaneous primary definite ICH diagnosed during 2010-
2011, age and pre-morbid hypertension did not differ by ICH location but a history of
dementia was more common in adults with lobar ICH. The proportion of adults with
one or more non-lobar brain microbleed (BMB) was significantly higher in adults with
non-lobar ICH but I did not find any other differences in the severity or distribution of
other neuroimaging correlates of small vessel disease between lobar and non-lobar ICH.
The apolipoprotein e4 allele was more common in participants with lobar ICH in
comparison to those with non-lobar ICH but the frequency of the e2 allele did not
differ by ICH location. Adults with lobar ICH were significantly more likely to survive
one year after their ICH in comparison to those with non-lobar ICH after adjustment
for other known predictors of outcome.
From a systematic review of neuropathological case control studies of CAA and ICH,
stratified by ICH location, I found a significant association between CAA and lobar
ICH but not with ICH in other locations. I examined the radiological and pathological
features of 33 adults with first-ever lobar ICH. The presence of CAA or vasculopathy
and the severity of CAA in a lobe affected by ICH was concordant with that of the
corresponding contralateral unaffected lobe. Capillary CAA was associated with severe
CAA. Subarachnoid extension of the ICH tended to be more frequent in those with
CAA-related strictly lobar ICH.
Having explored the incidence, risk factors and prognosis of lobar and non-lobar ICH,
in future work I would aim to establish the strength of the association between CAA
and ICH in different brain locations in a neuropathological case control study. Future
work should examine the radiopathological features of lobar ICH in a larger cohort and
the coexistence of other small vessel diseases, in particular arteriolosclerosis in persons
with ICH