Title: “Investigation of combined cerebral oximetry and transcranial Doppler cerebral blood flow measurements in the common dementias.”
Location: The University of Manchester (course admin) and Wythenshawe hospital later renamed University Hospital South Manchester (study location).
Area: Department of Academic Surgery and the Vascular Studies Unit (VSU) at UHSM.
Duration: The MSc officially ran from September 2008 and September 2009. This time period also included my clinical study.
Supervisor: Dr Maureen Thorniley
Other people of interest: Numerous helpful associates but a few that I’d like to mention are Professor C. McCollum (Head of academic surgery), Dr V. Sekar (PhD Student), Dr Z. Bashir (Post doc), Miss J. Mercer (Researcher), Mr T. Kelly (Student), Mrs S. Cooper (MSc course administrator), Dr J. Oldham and Dr P. Gardener (Course directors) and finally C. Slinger, D. Anglin and E. Greenwood (fellow 2009 scholarship students).
The techniques/technology used:Transcranial Doppler (TCD) – Measures the cerebral circulation parameters such as speed, direction, resistance, presence of emboli and so on. The middle cerebral artery (MCA) was the prefered vessel for insonation.
Near infrared spectroscopy (NIRS) – Measures the levels of oxygenation in the cerebral circulation.
Cambridge (CANTAB) – A total of 22 computerised cognitive tests that focus on different areas of the brain and aid in the diagnosis of different neurological conditions.
Mini-mental state examinations (MMSE) – A quick cognitive test (usually under 5 minutes) used to test the mental acuity of an individual.
CAMCOG/ CAMDEX – Other types of cognitive testing procedures commonly used in patient assessments.
Atorvastatin – Medication; statin used to break down plaques in arteries used formed from cholesterol.
Clopidogrel – Medication; anticoagulant used to disperse blot clots.
Hypothesis:
Premise – The process of embolisation is thought to be an early indicator for the onset of dementia. Tiny atherosclerotic plaques give rise to tiny break off particles (named emboli) which travel around in the cerebral circulation. In some cases, these tiny emboli can become lodged in narrow vessels thus decreasing the blood flow and oxygen to certain areas. The decline in cerebral parameters is thought to contribute to the memory decline associated with dementia.
Aims and Objectives – Based on the above hypothesis my project had a number of aims and objectives to fulfil, which were as follows;
- 1st – To screen patients and if they were emboli positive, then the participants underwent further testing where cerebral oxygenation levels (NIRS) and blood flow velocities (TCD) were analysed to see if there was a change in parameters associated with the presence of emboli.
- 2nd – Compare the cerebral parameters of the patients with dementia in the study to normal healthy volunteers of a similar age to see if there were any significant differences between the two groups, which may help to answer some of the questions linked to this area.
- 3rd – To evaluate potential therapies for dementia by analysing TCD and NIRS parameters on a monthly basis. Prior to this the patients were randomised to receive each of the following drug phases, Atorvastatin, Clopidogrel or a no treatment phase.
Methods:
My study had two protocols:
Protocol 1 – Testing normal subjects and patients with dementia.
The aim was to recruit 20 normal and 20 patients with dementia. We ended up with a total of 43 participants - 23 normal subjects and 20 patients with dementia. Both groups of participants (normal and dementia) underwent just a single test session with identical testing procedures. The session involved using TCD and NIRS probes to measure the cerebral parameters whilst the participants underwent the CANTAB test method followed by the MMSE and a full medical history. The results from both groups were analysed to see if any differences could be detected. From all the participants tested, 10 normal subjects were age and sex matched to 10 of the patients with dementia and their results were analysed in greater detail to see if age and gender had any affect on the cerebral circulation. The pictures below show the typical output from each of the methods used (TCD, NIRS, CANTAB).
Protocol 2 – Patients analysed from the drug trial.
These patients were selected from an ongoing clinical trial. 10 patients that had completed the trial in full had their results analysed. Each participant underwent a screening test to see if they were emboli positive of negative, If emboli positive, the participants were randomised to receive the different medications on a monthly basis followed by a month long ‘washout’ period between each drug. At the end of each month (and thus at the end of each different drug phase), the participants underwent 2 x one hour long TCD sessions. Each scan last one hour and each phase requires two scans therefore a minimum of 6 scans per person. A total of 10 patients equals a minimum of 60 scans. These 10 patients also had a monthly MMSE test and a blood sample that was analysed for Interleukin 10, an inflammatory marker.
Results and conclusion: Papers are being written for publication so I will post the link online soon.
Taken by one of the VSU staff. Me working through about a 100 scans (Protocol 1 – 43 scans and protocol 2 – minimum of 60 scans. I look cheerful don’t I?
Further work: Things I would further like to investigate (provided I had the funding and time) would be...
1) Larger patient numbers to increase the validity of my results
2) Validation of CANTAB tests to form part of a diagnostic method
3) Assessment of other neurological defects such as Parkinson’s using the CANTAB method
4) Comparison of other cognitive assessments such as the MMSE, CAM ICU and so on
All in all I enjoyed my project immensely. It was a lot of hard work, long nights and I often felt like packing it all in but I guess I have a strong stubborn streak. And I’m grateful it kicked in because it gave me the fantastic opportunity to learn many things about life in the medical world. Aside from the science/ clinical aspect of the project, from my placement I also learnt many other non-medical stuff.
Two major learning points for me were...
1) Patient responsibility – It seems kind of obvious but some people get so caught up in the end result that they forget everything else. It’s essential to keep patients well informed at all times as they often panic and become anxious very quickly. I learnt that theory and practice are very different in real life. It is VERY hard to recruit people as they can often be very sceptical but mostly scared. Sometimes it’s not even the patients but their carers that are reluctant to some extent. I also learnt very quickly that you must always to be very clear with your aims and what you are doing. Furthermore working with vulnerable populations; especially people with dementia that are often scared/confused, requires the utmost care and attention. Old or young, patients need plenty of patience and need to be constantly reassured. Personally I found those who tried to be a friend and not just their doctor/nurse/researcher or whatever were more successful than those who were strict professionals. I’m not saying that the professional boundaries are not required as they are vital working in such an environment and as part of the clinical team we shouldn’t get too attached but at the same time we should try to be a friend as well, as it helps to break down a lot of barriers.
2) Interdisciplinary teams – Communication is key! Bad communication leads to a lot of infighting between staff and placing blame back and forth as I observed in other departments. It’s bad for staff morale and also for junior staff i.e. students such as me etc. Although I didn’t have any clashes myself – it did show me that sometimes medicine isn’t always about saving lives and includes building on skills that maybe aren’t linked to your scientific and clinical knowledge. Those experiences help make you a good all rounder. I’m sure that all teams go through a few rocky patches but unless they work through it, they’re not doing themselves or their patients any favours. I’m pleased to say that the clinical team I worked with are genuine hard working individuals who are dedicated to their work. I couldn’t have asked for a better place to learn :)
So there you have it... the story of my dissertation. Here’s hoping I get good marks for this past year and for my dissertation (iA). The pictures below show the clinic and work areas, my equipment and patients being tested.
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