Salman, Rustam Al-Shahi

Farrall, Andrew

Smith, Colin

Samarasekera, Neshika Erangi

European Research Council

2016-06-01T14:19:03Z

2016-06-01T14:19:03Z

2015-07-04

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.

http://hdl.handle.net/1842/15836

en

The University of Edinburgh

Samarasekera, N., Al-Shahi Salman, R., Huitinga, I., Klioueva, N., McLean, C.A., Kretzchmar, H., Smith, C., Ironside, J.W.I. 2013 Brain banking of neurological disorders. Lancet Neurology, (12) 1096-105

Samarasekera, N., Smith, C., Al-Shahi Salman, R. 2012 The association between cerebral amyloid angiopathy and intracerebral haemorrhage: systematic review and meta-analysis. JNNP, 83(3):275-81.

Fonville, A.F.F., Samarasekera, N., Hutchison, A., Perry, D., Roos, Y.B., Al-Shahi Salman, R. 2013 Eligibility for Randomized Trials of treatments specifically for intracerebral haemorrhage Community-based study. Stroke, Oct; 44(10):2729-34.

Rannikmae, K. Kalaria, R., Greenberg, S.M., Chui, H.C., Schmitt, F.A., Samarasekera, N., Al-Shahi Salman., R., Sudlow, CLM. 2014 ApoE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis. JNNP, Mar; 85(3):300-5.

Rannikmae, K. , Samarasekera, N., Al-Shahi Salman, R., Martinez-Gonzalez, N. , Annan, R. & Sudlow, CLM. 2013 Genetic associations of cerebral amyloid angiopathy: systematic review and meta-analysis. JNNP, Aug; 84(8):901-8

Poorthuis, M., Samarasekera, N., Kontoh, K., Stuart, I., Cope, B., Kitchen, N., Al- Shahi Salman, R. 2013 Comparative studies of the diagnosis and treatment of cerebral cavernous malformations in adults: systematic review. Acta Neurochir (Wien), Apr; 155(4):643-49.

Josephson C.B., Frantzias, J, Samarasekera, N., Al-Shahi Salman, R. 2010 The persisting burden of intracerebral haemorrhage: Can effective treatments be found? PLOS Medicine, Oct 19; 7(10):e1000353. doi:10.1371/journal.pmed.1000353.

Samarasekera, N., Poorthuis, M., Kontoh, K., Stuart, I., Cope, B., Kitchen, N., Al- Shahi Salman, R. 2012 Guidelines for the management of cerebral cavernous malformations in adults. Funded by Genetic Alliance UK and Cavernoma Alliance UK 2.

Samarasekera, N. The association between cerebral amyloid angiopathy and intracerebral haemorrhage. 2012, JNNP podcast.

Samarasekera, N. Case study. Taking action on Stroke. 2011, The Stroke Association Annual Review. 2011

stroke

intracerebral haemorrhage

Does lobar intracerebral haemorrhage differ from non-lobar intracerebral haemorrhage?

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy