Botulinum toxin may ease upper limb spasticity after neuro injury

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Injection of abobotulinumtoxinA safely reduces muscle tone after stroke or traumatic brain injury, new research suggests.

"The publication of this study is great news for the field of neurorehabilitation and botulinum toxin use. This is the first study that demonstrates substantial improvements in active range of motion against the injected muscles in the paretic upper limb, together with expected improvements in tone, spasticity per se, and both patient-rated and physician-rated clinical improvement after one injection only," wrote lead author Dr. Jean-Michel Gracies in a press release.

"This study both confirms the therapeutic value of abobotulinum toxin and shows the practicality and value of new assessment methods that should be used as primary outcome in future studies on the product," added Dr. Gracies, who chairs the Department of Physical Medicine and Rehabilitation of the Groupe Hospitalier Albert Chenevier-Henri Mondor in Créteil, France.

In their randomized controlled trial, Dr. Gracies and colleagues enrolled 243 adults from 34 neurology or rehabilitation clinics in Europe and the U.S. who had suffered a stroke or brain trauma at least six months earlier.

Patients received 500 or 1,000 U of abobotulinumtoxinA, or placebo, injected in a single session into the most hypertonic muscle group among the elbow, wrist, or finger flexors (i.e., the primary target muscle group), and into at least two additional muscle groups from the elbow, wrist, or finger flexors or shoulder extensors.

Up to 48% of the patients were receiving concomitant physiotherapy.

The main endpoint was the change in resistance in the primary target muscle group as measured by the Modified Ashworth Scale (MAS). Secondary endpoints included results of the Physician Global Assessment (PGA) and the Disability Assessment Scale (DAS) in one main treatment target chosen by the patient and physician (dressing, hygiene, limb position, or pain).

As reported online August 27 in The Lancet Neurology, after four weeks the MAS score in the PTMG - a measure of resistance during passive soft-tissue stretching - had changed by 0.3 with placebo, 1.2 with abobotulinumtoxinA 500 U, and 1.4 with 1,000 U (both p

The mean PGA score at week four was 0.6 in the placebo group, 1.4 in the 500 U group (p=0.0003 vs placebo), and 1.8 in the 1,000 U group (p

DAS score for the principal treatment target did not improve significantly with treatment vs placebo.

Treatment-related adverse events occurred in two patients (2%) in the placebo group, six (7%) in the 500 U group, and seven (9%) in the 1,000 U group. All were mild or moderate; the most common was mild muscle weakness.

None of the three serious adverse events were treatment-related: two participants died, one in the placebo group from pulmonary edema and one in the 500 U group from an unspecified pre-existing cardiovascular disorder.

Dr. Gert Kwakkel, chair of neurorehabilitation at the VU (Vrije Universiteit) University Medical Center in Amsterdam, the Netherlands, who co-authored an editorial about the study, wrote in an email to Reuters Health, "Spasticity is difficult to measure with simple clinical measurements such as the modified Ashworth Scale, as used in this trial. Preferably, new measurements should distinguish between the neuronal components of spasticity, such as hyperreflexia and increased muscle tone, and increased stiffness due to contracture and progressive spastic muscle shortening."

"In particular, the relation between the neuronal and mechanical components of spasticity is unknown and requires further investigation," Dr. Kwakkel added.

Dr. Tao Xie, associate professor of neurology and director of the Movement Disorder Clinic at University of Chicago Medicine, wrote in an email, "This is a very interesting, properly powered study."

"However," added Dr. Xie, who was not involved in the study, "whether abotulinumtoxinA injection is useful for improving upper limb capacity remains unresolved. Future studies in assessing active function or task-specific improvement, targeting more muscles of important function (such as the commonly affected thumb and pronation-supination function), and focusing on muscles with some preserved strength, might help provide more information on meaningful gain in function recovery."

Drs. Kwakkel and Xie agreed with the authors' recommendations to maximize treatment benefits by involving a support team of professionals, including physical and occupational therapists.

The authors suggested future testing of repeated injections and focusing on active movement, measurement of cocontraction in the injected muscles and function.

Ipsen sponsored the study. The corresponding author did not reply to requests for comment.

SOURCE: https://bit.ly/1i87uP2

Lancet Neurol 2015.