The Relationship Between Controlling Risk Factors and Cerebral Haemodynamics in Lacunar Stroke

Understanding the Relationship Between Controlling Risk Factors and Cerebral Haemodynamic Changes in Lacunar Stroke, and Its Interaction With Ageing

The goal of this observational study is to look at differences in brain blood flow before and after management of risk factors such as high blood pressure and diabetes in patients with lacunar stroke. Participants will be asked to undergo a simple brain blood flow assessment at their initial appointment, whereby they will be asked to sit and stand twice. The patients will then be asked for a follow-up assessment 4 weeks after, identical to the first. This will allow us to look at any changes in brain blood flow from before management of risk factors and 4 weeks after management of risk factors.

Stroke is the second major cause of death across the world leading to high mortality rates and leaving those who experience stroke with a poor quality of life. Lacunar stroke accounts for a quarter of ischemic stroke events and can occur at any age, but is more frequent in the older generation (>65 years) yet not uncommon in younger patients. Lacunar stroke is caused by small vessel disease, whereby occlusions or thrombi occur in the small vessels found deep in the brain structures, around the circle of Willis. This event leads to a decrease in blood supply to certain areas of the brain and damage to surrounding tissues, leaving the brain in a vulnerable state. Further events are then likely to occur such as recurrent stroke, intracranial haemorrhage, additional ischemic events, prolonging symptoms and increasing the risk of damage to the brain. Even though lacunar infarcts occur only in the small vessels of the brain, cognitive impairment is commonly seen post-lacunar stroke emphasising the importance of understanding the trajectory of cerebral haemodynamics after a lacunar infarction. Common treatments involve the use of anticoagulants, antiplatelet therapies (both to stop further blood clots forming), blood pressure (BP) lowering agents (reducing BP to reduce fluctuations in cerebral blood flow) and the management of hyperglycaemia (to help reduce damage to blood vessels).

Cerebral autoregulation (CA) plays a large part in regulating cerebral blood flow (CBF), through maintaining cerebral perfusion, even with fluctuating BP. It does this by regulating the cerebral vasculature through adjustments in vessel diameter. CA has been assessed at rest and challenged with paradigms in healthy volunteers and lacunar stroke patients, however comparisons between younger and older lacunar events incorporating risk factors has not been looked at. The difference in CA phenotype between those with uncontrolled high-risk cardiometabolic factors (often younger patients) and those with moderate/severe small vessel disease and recurrent lacunar stroke syndromes (often older patients) is unknown. Therefore, exploring different risk factors and the different lacunar disease phenotypes is important to identify any differences in cerebral haemodynamics.

Assessing dynamic CA (dCA) in response to fluctuations in BP represents how CA responds to BP fluctuations in the body, allowing better application to the human vasculature, compared to assessing static CA. Multiple paradigms and manoeuvres have been used to assess dCA by inducing a rapid change in BP, but both patient tolerability and ability to measure dCA accurately need to be considered for this study. The sit-stand manoeuvre is a clinically applicable manoeuvre which can be done both in the ward and laboratory with minimal stress to the patient. This manoeuvre has been evaluated in a published review and compared to a thigh-cuff technique which has been used extensively in previous research. The thigh-cuff technique induces a rapid change in arterial blood pressure (ABP) through the rapid deflation of the thigh cuff. However, this repeated action can be painful for some participants making it difficult to apply clinically to frail patients leading to issues of unsuccessful repeats. The review found that autoregulatory index (ARI) values were similar across both the sit-stand and thigh-cuff manoeuvres, showing sit-stand is an accurate manoeuvre to measure CA. The sit-stand manoeuvre was also better tolerated compared to the thigh-cuff.

Following up patients post-stroke as high-risk factors are controlled will help understand changes in CA and could help guide the timing of interventions to manipulate BP and potentially for the impact of rehabilitation programmes.

Lacunar stroke is one of the most common types of stroke, occurring in both younger and older generations. Some studies have observed impaired brain blood flow regulation (cerebral autoregulation) in a cohort of ~57 years of age (median), which has also been seen in those with small vessel disease. Small vessel disease is often seen in older patients who often present with recurrent lacunar strokes despite earlier management of risk factors.

By targeting a younger cohort with uncontrolled risk factors (hypertension and diabetes), the investigators aim to perform a more comprehensive study to investigate the haemodynamic consequences of lacunar strokes in this group. This would be done by using Transcranial Doppler ultrasound (TDC) to measure CBv in patients who are diagnosed with a lacunar stroke and have undiagnosed diabetes and/or hypertension at their initial appointment. To measure a dCA response, the sit-stand manoeuvre will be used. These patients would then receive management of their risk-factors and would be asked to undergo another TCD assessment 4 weeks after their initial appointment. Data would be collected and analysed to look at any differences in cerebral haemodynamics between before and after management of such risk factors.

Inclusion Criteria:

• Adults aged between 18-120 years.
• Diagnosis of lacunar stroke syndrome.
• New diagnosis or known diagnosis of hypertension and/or diabetes.

Exclusion Criteria:

• Those who lack capacity can have a personal consultee consent to the study if they can still perform study requirements such as the sit-stand manoeuvre. Those who either cannot perform the manoeuvre or do not have a personal consultee to allow them to consent, are not able to take part.
• Those with poorly controlled medical comorbidities affecting cerebral haemodynamics. (eg., heart failure).