Download Brain Research Imaging Centre (School of Clinical

I have included the original proposed thesis chapter breakdown again in this document
for ease of access / reference. A new summary is now found on page 2.
Minutes from meeting 9 January 2013
PhD Thesis Committee - 10 Week Review
The role of peripheral inflammation in cerebral small vessel disease
Student:
Committee:
Stewart Wiseman (PhD student, School of Clinical Sciences)
Dr Will Whiteley (Chair), Professor Wardlaw, Professor Ralston, Dr
Mohini Gray
MG
In reference to the proposed small imaging study, concern was raised
regarding sample size to find anything significant.
WW
Consider RA rather than lupus
JW/SR Lupus has a high vascular risk therefore good cohort for the small study,
consider RA for a larger literature-based review or record linkage study
WW
If we have CHI numbers and the patients are those of RDU we can link to
the Scottish Stroke Care Audit – for example to assess which of ~3,000 RA
patients might have presented with stroke. This might have ethical and
practical difficulties.
MG
Think not only about inflammatory markers but also specific antibodies
WW
Current systematic review of plasma markers should include TNF for
completeness rather than a new review.
All
A review of stroke / CSVD incidence in rheumatic diseases is crucial to help
inform this thesis
MG
WW
St Thomas Hospital has a cohort of lupus and APS patients
Risk of an uncertain collaboration
MG
SW
Need to be clearer with regard to a specific research question(s)
We are interested in the role of inflammation in CSVD and specifically do
specific rheumatic diagnoses (eg RA) show evidence of more white matter
changes (or stroke/lacunar stroke) versus the normal population
WW
To help our understanding of causality, could we image RA patients pre and
post anti-inflammatory treatment?
JW
To consider use of existing study data. Start by collating a record of what
data items we have (including bloods still held).
MG
Consider psoriasis as another ‘inflammatory’ cohort
MG
SW should consider attending rheumatology/immunology lecture seminars.
SW is not a rheumatologist/immunologist/radiologist and several subject
areas might overwhelm. Be clear on the research question.
Summary
It was noted the chapter structure is relevant and a good working outline. The proposal for
the literature reviews (ch2) was supported but we suggested you include analysis of TNFa
with the other markers rather than a new review.
The proposed biomarker analysis of the existing studies was supported (ch3).
We discussed two new clinical studies. Firstly, a study looking at occurrence and
characteristic of stroke in RDU database of 3000+ RA patients by linking Chi number with
ISD data (ch4). Secondly, a small targeted imaging study of patients at very high risk of
vascular disease. Groups discussed for the imaging study were SLE and/or APS and this
cohort received support, with an alternate or additional group of very severe multidrug
resistant RA a possible option too – this to be considered further once literature surveys
available (ch5).
SW to obtain more insight into the types of data routinely collected in the rheumatology
clinic, including initially the RA database. SW to attend rheumatology/immunology
seminars.
Proposed thesis title: The role of inflammation in cerebral small vessel disease and stroke.
Appendix A
Chapter breakdown
Chapter 1: SETTING THE SCENE
Cerebral small vessel disease and lacunar stroke
The Immune system
Chronic inflammatory diseases
Lupus
Define stroke. Prevalence and cost to society. Explain the differences between
stroke subtypes. Define lacunar stroke. Outline the lacunar hypothesis. Magnetic
resonance imaging sequences for lacunar stroke. Who gets a lacunar stroke? Define
cerebral small vessel disease (CSVD). Imaging feature of CSVD. Risk factors.
Overview of the immune system. Chemokines. Cytokines. Innate immunity in the
brain. Adaptive immunity in the brain. The blood brain barrier / small vessel
endothelium.
Overview of rheumatology. What is inflammation and how is it measured? Overview
of chronic inflammatory diseases.
Define lupus, a systemic multi-organ disease. Prevalence in Scotland. What is
antiphopholipid syndrome (‘sticky blood’)?
Chapter 2: LITERATURE REVIEWS
Systematic Review: Plasma and serum markers in stroke subtypes
Systematic Review: TNF-α in stroke subtypes
Literature Review: Lacunar stroke and inflammatory diseases
Chapter 3: Inflammation in the Edinburgh Stroke Study and Mild Stroke Study I
Analysis of blood markers of inflammation in these cohorts: is there a difference
between lacunar and non-lacunar patients? Correlation of inflammatory markers with
white matter lesion volumes.
Chapter 4: IMAGING EXPERIMENT: Investigating CSVD in a cohort of lupus
patients
Rationale for investigating this cohort. Aims. Methods. Results. Discussion.
Chapter 5: Conclusions and suggestions for future research
Summary of findings. Synthesis of what this thesis adds. What’s next?