Dr Joutel indicated that there are actually two
characteristics. The passive diameter of the vessel, or its maximum capacity
of dilation, is reduced. That means that there is a greater than normal
rigidity in the vessels, and that they are less able than normal to relax.
This symptom is identical to a state of hypertension. But patients with
CADASIL display this characteristic even if they do not have hypertension.
Furthermore, in the vessel there is pressure. The myogenic tone allows the
vessel to maintain a certain diameter, a certain contraction, in response to
the pressure, in order not to dilate passively. In CADASIL there are two
abnormalities. On the one hand the vessel’s capacity to relax passively is
diminished. On the other hand, for any given pressure the diameter is a bit
too wide. Thus, the capacity of the vessel to dilate is diminished. In the
new murine model (mice with the identical physiological condition as a
human, but without overexpression of the illness) we can see that the
symptom of accumulation of NOTCH3 appears very early (in the first month of
the life of a mouse whose normal life span is 24 months). Cerebrovascular
dysfunction is visible at one year, that is, at the adult age of the mouse.
On the other hand, the reduced capacity of the vessels to relax becomes
apparent at the age of four months.
(2016 General Assembly, France.)