Thrombosis or embolism originating from large artery atherosclerosis causes 15% of
the ischemic strokes with a transient or permanent functional deficit. Primary stroke
prevention is based on the control of lifestyle-related risk factors and optimal medical
therapy. Patients with a significant atherosclerotic narrowing in their carotid artery
can also benefit from an additional surgical or endovascular intervention to reduce
the risk, having in mind that atherosclerosis is a systemic disease. We all know that
the degree of stenosis is a relevant risk factor of ipsilateral ischemic stroke, and
this criterion has been used to select patients in randomized clinical trials. Several
clinical trials have been performed to find a cut-off for stenosis and classify the
risk of symptomatic and asymptomatic carotid artery disease. However, after the introduction
of the so-called ‘aggressive medical treatment’, there is a lack of long-term results
regarding this new medical approach. On the other hand, some ischemic strokes associated
with carotid artery disease result from hypoperfusion, in addition to a vulnerable
atherosclerotic plaque embolization in which no clinical treatment can solve the issue.
We also know that these two mechanisms may act synergistically, and a more profound
investigation can make the difference in treating this setting. Routine and more advanced
imaging modalities may provide information on the underlying mechanism involved in
the ipsilateral ischemic stroke. New concepts about intracranial hemodynamic status
and the morphology of the plaque have been discussed, in addition to many neuroimaging
modalities to better understand the pathophysiology involved in each situation. Management
is an ongoing debate and, most of the time, treatment to prevent an ischemic or recurrent
stroke involves some individualized decisions[1],[2].
Cerebral ischemia will arise due to reduced oxygen being delivered to the tissue and
can occur because of reduced oxygen delivery with or without arterial steno-occlusion.
Compromised cerebral perfusion pressure (CPP) occurs in phases, where compensatory
mechanisms can be evaluated. When reduced oxygen delivery starts, vasodilation of
pial arterioles will ensue, resulting in decreased vascular resistance and increased
inflow. In some cases, these tissue-level compensations may be sufficient to ensure
the necessary supply of oxygen, but chronic and increased reductions may cause these
vessels to approach their dilation limit or exhaust the cerebrovascular reserve capacity.
The term cerebrovascular reactivity (CVR) reflects the ability of the blood vessels
to dilate to match tissue blood supply to the increased demand and can be investigated
by measuring the change in cerebral blood flow (CBF) or cerebral blood volume (CBV)
induced by vasodilation. This is obviously not new, and several imaging methods can
assess hemodynamic changes to better understand in which stage brain perfusion is
facing extracranial stenosis[3],[4]. In 1998, Grub and colleagues already demonstrated in the St. Louis Carotid Occlusion
study that elevated OEF (oxygen extract fraction) is an independent predictor of stroke
in patients with carotid occlusion with an ipsilateral ischemic stroke rate at two
years of 5.3% in 42 patients with normal OEF and 26.5% in 39 patients with increased
OEF (p=0.004)[5]. Since then, this result has been reproduced in many studies, with several methodologies
and neuroimaging modalities. Nevertheless, although these data are recognized as important,
this approach could not be established in guidelines mainly because of the unavailability
of methods and because of the high cost to screen all patients with carotid stenosis.
More recently, neurovascular coupling has been studied following the same principle
of hemodynamic response after metabolic demand. The relationship between local activity
and subsequent changes in cerebral blood flow can be considered impaired or not[6].
The article published in the April 2022 issue of Arquivos de Neuropsiquiatria shows the response to a motor task protocol as a provocative vasodilatory/vasoreactivity
TCD test comparing patients with unilateral symptomatic carotid stenosis (three groups
according to the stenosis degree) and health subjects[7]. The study was analyzed considering the degree of stenosis and the asymptomatic
and symptomatic sides. They showed an association between impaired CVR and carotid
occlusion when compared with the healthy population, and some additional findings
concerning the pulsatility index and the sides of stenosis. Although the study design
included a small number of patients and did not perform micro embolus monitoring,
the authors offer us a simple and accessible tool to access hemodynamic information
that can improve our decision-making. Despite the completion of several multi-center
trials, the management of carotid stenosis remains in flux and any additional information
can help make more reliable individual decisions. Dr. Aysel Milanlioglu et al.[7] demonstrated that TCD can provide information about cerebral hemodynamic status
in real-time through an easy and affordable process. TCD with stimulus represented
by motor tasks can inform a ‘valid number’ to explore cerebral autoregulation through
the compensatory mechanisms, including vasoreactivity and functional reserve. They
argue that it is possible to more effectively determine who the high-risk patients
are. The authors found a good correlation between a low reserve and a high degree
of stenosis reinforcing this concept. Considering that stenosis is dynamic and includes
other variables, individual hemodynamic status data should be guaranteed when monitoring
in real-time and should be repeated several times during follow-up. An association
with neuroimage markers, like watershed or border zone, can also provide a full understanding
of its relationship in symptomatic patients.
Future validation of these method findings could lead to powerful biomarkers of cerebrovascular
health and create a different way of thinking in a setting of cerebrovascular disease.
