Quantifying the spread of botulinum toxin through muscle fascia

Botulinum toxin was recently approved for treating several head and neck dystonias. Paralysis of neighboring muscles is the major complication of its use. Spread of toxin from the injected muscle has been suggested as an etiology. This study examines how botulinum toxin crosses muscle fascia by a novel method of quantifying muscular paralysis. Botulinum toxin (0.2 to 10 U) was placed onto the fascia of rat tibialis anterior (TA) muscles (n = 6). Toxin was also placed on dose-matched muscles that had their fascia surgically removed (n = 6). Twenty-four hours later, the nerve to the tibialis anterior was electrically stimulated to deplete the muscle fibers of glycogen. Toxin-paralyzed fibers retained their glycogen and appeared purple on periodic acid-Schiff (PAS) stain. Botulinum toxin easily passed through muscle fascia even at subclinical doses. The presence of fascia reduced the spread of botulinum toxin by 23%. These results suggest that spread of botulinum toxin can be prevented only by delivering small doses to the center of a target muscle.