Exploring Advanced Imaging Techniques to Characterize Botulinum Toxin Diffusion in Human Muscle

Over the past decade, botulinum toxins (BT) have been extensively used to treat any number
of diverse disorders, including functionally significant, focal spasticity in the arm and
leg of persons with injury/disease of the central nervous system. Spasticity is an
involuntary muscle stiffness that limits movement of an extremity and often leads to pain,
hygiene problems, difficulty in bed or wheelchair positioning, and functional deficits in
self-care and mobility.

There are three BT products on the market: MyoBloc®, Botox®, and Dysport®. FDA approval for
use of Botox® in spasticity is anticipated sometime during 2010. In the Weill Cornell
Division of Rehabilitation Medicine alone, nearly 50,000 units of Botox® were injected for
the treatment of spasticity during the 2008-2009 academic year. (Note: The vast majority of
the BT market share in the US rests with Botox®.)

There is excellent evidence supporting the effectiveness of BT in decreasing tone and modest
clinical evidence supporting functional improvement. Despite the frequent use, however,
there is astonishingly little evidence delineating the impact on diffusion of dosing,
dilution, approach to muscle localization, or serotype of BT. To better study these
relationships we will be using advanced imaging to develop a model to characterize the
physical characteristics of BT diffusion in human skeletal muscle.

Inclusion Criteria:

- diagnosis of UMN disease

- clinically significant spasticity in the gastrocnemius muscle to warrant Botox®
injection (made at the discretion of Dr. O'Dell)

- naïve to all botulinum toxins in the lower extremity

Exclusion Criteria:

- MR incompatibility with implanted ferromagnetic devices.[Specifically, they may not
participate in this study if they have a pacemaker, an implanted defibrillator or
certain other implanted electronic or metallic devices. They will be screened by the
MRI staff for past surgical procedures to determine the possibility of having an
implanted medical or metallic device, shrapnel, or other metal, such as metal in the
eye.]

- Pregnancy or breast feeding