Sativex(®) and clinical-neurophysiological measures of spasticity in progressive multiple sclerosis.
Despite the proven efficacy of Sativex(®) (9-delta-tetrahydrocannabinol plus cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple sclerosis (MS), little is known about the neurophysiological correlates of such effects. The aim of the study was to investigate the effects of Sativex on neurophysiological measures of spasticity (H/M ratio) and corticospinal excitability in patients with progressive MS. This was a randomized, double-blind, placebo-controlled, crossover study. Consecutive subjects with progressive MS and lower limb spasticity referred to our center were randomized to 4 weeks' treatment (including 2 weeks' titration) with Sativex or placebo, with crossover after a 2-week washout. Clinical and neurophysiological measures (H/M ratio and cortical excitability) of spasticity were assessed. The H/M ratio was the primary outcome, with sample size calculation of 40 patients. Of 44 recruited patients, 34 were analyzed due to 6 drop-outs and 4 exclusions, which lowered the power of the study to show differences between treatments. Neurophysiological measures did not differ significantly according to treatment and did not correlate significantly with clinical response. Response on the modified Ashworth scale (at least 20 % improvement) was significantly more frequent after Sativex than placebo (50 vs 23.5 %; p = 0.041; McNemar). Side effects did not differ significantly according to treatment. Our findings confirm the clinical benefit of Sativex on MS spasticity. The lack of corresponding changes in corticospinal excitability and on the monosynaptic component, of the stretch reflex, although in a limited sample size, points to the involvement of other spinal and supraspinal mechanisms in the physiopathology of spasticity in progressive MS.
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy. leocani.letizia@hsr.it.|Vita-Salute University San Raffaele, Milan, Italy. leocani.letizia@hsr.it.
Letizia
L
Leocani
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.|Vita-Salute University San Raffaele, Milan, Italy.
Arturo
A
Nuara
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
Elise
E
Houdayer
Biostatistics Unit, Department of Health Sciences (DISSAL), University of Genova, Genoa, Italy.
Irene
I
Schiavetti
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
Ubaldo
U
Del Carro
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
Stefano
S
Amadio
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
Laura
L
Straffi
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
Paolo
P
Rossi
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
Vittorio
V
Martinelli
Global Medical Affairs, Almirall S.A., Barcelona, Spain.
Carlos
C
Vila
Biostatistics Unit, Department of Health Sciences (DISSAL), University of Genova, Genoa, Italy.
Maria Pia
MP
Sormani
Neurological Department and INSPE-Institute of Experimental Neurology, Scientific Institute Hospital San Raffaele, Via Olgettina 60, 20132, Milan, Italy.|Vita-Salute University San Raffaele, Milan, Italy.
Giancarlo
G
Comi
D000328:Adult; D002185:Cannabidiol; D002540:Cerebral Cortex / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol; D004338:Drug Combinations; D004558:Electric Stimulation; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000188:drug therapy*; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000209:etiology; D017063:Outcome Assessment, Health Care; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012720:Severity of Illness Index; D050781:Transcranial Magnetic Stimulation
D004338:Drug Combinations; D010936:Plant Extracts; D002185:Cannabidiol; D013759:Dronabinol; C587251:nabiximols
H-reflex; Multiple sclerosis; Sativex; Spasticity; Transcranial magnetic stimulation