Aims: Natalizumab inhibits adherence of leukocytes to the cerebral endothelium. Leukocytes
play a role in regulating the vascular tone. Natalizumab may thus also affect cerebral
vasoregulation. This observational study investigates whether neurovascular coupling
and cerebral autoregulation are altered after routine clinical infusion of natalizumab
in patients with relapsing remitting multiple sclerosis.
Methods: In eighteen patients receiving a regular infusion of 300mg natalizumab, neurovascular
coupling to visual stimulation (control system approach) and dynamic cerebral autoregulation
(phase and gain of 0.1Hz oscillations) were serially measured by transcranial Doppler
ultrasound (before, 2 hours and 2 days after the infusion). A repeated examination
28 days after infusion served as a control situation.
Results: Neurovascular coupling was altered 2 hours and 2 days after infusion with an overshooting
initial hemodynamic response. After 28 days, neurovascular coupling was similar to
values before the infusion. Dynamic cerebral autoregulation, cerebral blood flow velocity
and pulsatility index in the middle and posterior cerebral artery were unaltered.
Neurovascular coupling was not related to age, sex, disease duration, time since last
relapse, clinical severity, number of previous natalizumab infusions and occurrence
of new headaches after the infusion.
Conclusions: Natalizumab infusion is associated with a temporarily increased initial hyperemia
to functional activation. Such a hyperreactivity suggests an increased bioavailability
of nitric oxide during functional activation. This is perhaps caused by altered leukocyte
concentration in the cerebral microcirculation. Hemodynamic effects of immunosuppressive
agents acting at the cerebral microcirculation should be considered in future research.
Ideally, they could play a role in noninvasively monitoring the direct biological
effects of such drugs at their site of action. A placebo-controlled trial is thus
warranted to confirm the results of this observational study.
