Deciphering intracranial atherosclerosis: stroke detection and treatment
Spearheading a landmark medical discovery, Professor Lawrence Wong (Croucher Fellowship 1992 and Croucher Senior Medical Research Fellowship 2011) explored the mechanisms of strokes amongst Asians over two decades ago, and has been working to uncover the mysteries of this relatively unexplored area of research ever since.
Wong has received great recognition for his research on strokes in Asia, in particular, intracranial atherosclerosis, a condition that involves the narrowing of vessels around the brain. His research confirms that this type of stroke is very common in Asia, especially in China, but is rarely observed in Europe or America. Its rarity in other regions of the world initially led to limited understanding of and treatment options for this disease, which has changed since Wong’s pioneering findings.
“We just hosted the 8th Intracranial Atherosclerosis meeting, an endeavour that began at the Chinese University of Hong Kong in 2004. While there have been other meetings that explore different aspects of strokes, for example, lipids or hypertension, this meeting is solely focused on the nuances of this particular condition and has been vital in raising awareness and encouraging further research. Even the current textbooks have a more detailed description of intracranial atherosclerosis than in the past.”
According to Wong, Asia bears more than half of the world’s stroke burden and the means of prevention and treatment differ from those of the West as well as to that of traditional practices, a distinction that his research has contributed to.
He says, “In the old days, we were told to look at the neck vessels whenever a patient suffering from a stroke came in. But after our research findings, we now know that, in Asia, signs of vessel narrowing are more commonly found near the brain, not in the neck vessels.”
If these tests on the brain imaging expose the presence intracranial atherosclerosis, the patient would be likely to suffer from higher stroke severity as well as a higher recurrent rate, so a more aggressive treatment would be recommended by the doctor.
Community-based study in rural China
Wong had initially found himself on this path of medical research during his time as a doctor in the 90s. He recalls that the wards in Hong Kong were often filled with stroke patients while heart attacks were not as common. This phenomenon of stroke cases exceeding heart disease cases was not reflected in western textbooks.
The textbooks also stated that strokes are normally caused by carotid stenosis, another claim that was not reflected in the medical cases he would see. This led to him wondering why Chinese people seemed to suffer from strokes more often – a question that served as the main driver in his investigation for the past 25 years.
On that path of investigation, Wong pioneered the world’s first community-based study in 1999 which revealed that the prevalence of asymptomatic intracranial atherosclerosis was 6-7% amongst the residents screened. Wong and his team carried portable Transcranial Doppler (TCD) machines into villages in rural China and conducted a door-to-door survey that involved screening all people aged 40 and above. The study proved that this condition is very common amongst Chinese people, and also, that patients flagged for the intracranial atherosclerosis were likely to suffer from a stroke at some point of their lives, as recorded in follow-up studies.
Computer field dynamics
“It has already been 17 years since the community-based study took place, and at that time, the TCD machine was the only tool to diagnose intracranial disease. But now, we have a more effective method involving CT and MR angiograms, as the TCD method is not accurate enough anymore”, he says.
The Doppler Effect from the TCD can only detect flow velocity through the vessels without detailing the anatomy. It is imprecise for diagnosis as it makes use of indirect evidence from stenosis.
Wong and his team began exploring computer field dynamics, or the fractional flow of blood, in the study of intracranial atherosclerosis during Wong’s Croucher Senior Medical Research Fellowship in 2011. While this technique is advanced in cardiology, it has been relatively uncommon in cranial research and diagnosis due to the high risks involved in placing a catheter in the brain.
Using an MR angiogram, for example, one can determine whether the lumen is narrow or not before deciphering the blood flow across the narrowing. The hemodynamic change recorded using the computer flow dynamics can reveal an estimate of the various variables involved, whether it is outflow or inflow or the anatomy of the lesion, thus providing a more accurate reading on the symptoms observed in a patient suffering from intracranial atherosclerosis.
“For the brain, we have to change the game a little bit. With the CT or MR angiogram, the finer details of a vessel wall cannot be studied. The structural features of its wall can only be studied by high resolution MRI, which delineate the contents of the atherosclerotic plaque,” Wong says.
Apart from blood flow, these tools have also revealed that components of the vessel wall play a role in the determining the symptoms developed by these patients.
Wong hopes to uncover the characteristics of the vessel wall that will help design a mechanism to decide which patients require a more aggressive treatment and which do not, as well as help narrow down the most appropriate treatment needed for each specific case.
Wong’s interest in stroke research also spans out to include stroke treatment. In order to repair the brain, the process begins with epidemiology, stroke mechanisms, and then drug treatment.
However in many cases, even after drug treatment, patients continue to suffer from disabilities. Wong seeks to hasten the repair of the brain through neuroplasticity, by prompting it to recover quickly through various treatment strategies.
In the case of patients suffering from ischemia, a lack of blood, one mechanism involves augmenting the blood flow to the brain. The lower limbs take up 25% of cardiac output, which is the quota necessary to run a marathon. Since this level of blood flow is not required on a constant basis, Wong suggests redirecting the flow from the legs to the brain. By increasing the flow of blood to ischemic cells and neurons, together with conducting transcranial magnetic stimulation, the damaged brain may be repaired more quickly and the brain’s function returns to work as normal as possible.
International study on genetics
The latest direction of research that Wong is currently undertaking is the advancement of genetics in stroke research. Collaborating with an international team, this multi-centre consortium aims to conduct gene sequencing on tens and thousands of patients in order to work out the genetic features of a stroke patient and the causes of stroke.
Wong says, “We are talking about how genetics change the manifestation of intracranial stenosis, or whether it is the cause for it, or even more specifically, which kind of genes make this lesion more or less progressive. Since there is still so much we do not know, we will hopefully be able to learn much more about genes and the disease, and the interaction between them.”
Professor Lawrence Wong is the Mok Hing Yiu Professor of Medicine, chief of the Division of Neurology, and director of the S.H. Ho Cardiovascular Disease & Stroke Centre at the Chinese University of Hong Kong. He is also currently serving as the Secretary of the World Stroke Organisation as well as the Associate Editor of the journal Stroke. He is a fellow of the Hong Kong College of Physicians, Hong Kong Academy of Medicine and Royal College of Physicians. He has published more than 400 articles in international journals including the New England Journal of Medicine, Nature, Lancet Neurology, Circulation, Annals of Neurology, Stroke, and Neurology. In 2016 he was awarded the World Stroke Organisation President’s Award for Stroke Services for his dedication in this field of research. Professor Wong was awarded a postdoctoral fellowship by the Croucher Foundation in 1992 and a Senior Medical Research Fellowship in 2011.
To view Wong’s personal Croucher profile, please click here.