Natalizumab and regulation of cerebral blood flow: results from an observational study.
BACKGROUND
Natalizumab inhibits adherence of leukocytes to the cerebral endothelium. Since leukocytes play a role in regulating vascular tone, natalizumab may also affect cerebral vasoregulation. The aim of this observational study was to investigate whether neurovascular coupling and cerebral autoregulation are altered following routine clinical infusion of natalizumab in patients with relapsing-remitting multiple sclerosis.


METHODS
In 18 patients receiving regular infusion of 300 mg natalizumab, neurovascular coupling to visual stimulation and dynamic cerebral autoregulation (phase and gain of 0.1-Hz oscillations) were measured by transcranial Doppler ultrasound (before, and 2 h and 2 days after the infusion). A repeated examination 28 days after infusion served as a control situation.


RESULTS
Neurovascular coupling was altered 2 h 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.


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.
Reinhard
Matthias
M
Department of Neurology, University of Freiburg, Freiburg, Germany. matthias.reinhard @ uniklinik-freiburg.de
Rosengarten
Bernhard
B
Kirchhoff
Luise
L
Hetzel
Andreas
A
Rauer
Sebastian
S
D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D000069442:Natalizumab; D019370:Observation; D018709:Statistics, Nonparametric; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab