Doxorubicin chemomyectomy as a treatment for cervical dystonia: histological assessment after direct injection into the sternocleidomastoid muscle.
The sternocleidomastoid muscle (SCM) is one of the major muscles involved in producing abnormal head position in cervical dystonia patients. This study tested whether doxorubicin chemomyectomy, direct injection of doxorubicin into the SCM to permanently remove muscle fibers, has the potential to be a nonsurgical, permanent treatment for cervical dystonia. The right SCM of rabbits was injected with either 1 or 2 mg doxorubicin. Animals were sacrificed 1-2 months postinjection. The SCM was prepared for histological examination of muscle fiber loss and fiber type composition. In all cases, direct injection of doxorubicin resulted in significant decreases in total muscle cross-sectional areas ranging from 75% up to 98%. Individual myofiber cross-sectional areas were smaller than normal after 2 mg doxorubicin treatment, but similar to normal fiber size after 1 mg doxorubicin. There were increased numbers of myofibers that expressed slow and neonatal myosin heavy chain isoforms in these remaining muscle fibers compared to the untreated SCM on the contralateral side. Developmental myosin heavy chain (MHC) was also present in 53% of the remaining myofibers of the treated muscles. The fiber type composition of muscles contralateral to the doxorubicin injections was compared to the fiber type composition of SCM from normal, untreated controls; no difference was seen in the proportions of fast, slow, and neonatal MHC fiber types in these SCM muscles. In summary, the direct injection of doxorubicin into the SCM resulted in significant muscle loss. This supports the use of doxorubicin chemomyectomy as a potential permanent, nonsurgical treatment for cervical dystonia.
Department of Ophthalmology, University of Minnesota, Minneapolis 55455, USA.
L K
LK
McLoon
J H
JH
Falkenberg
D
D
Dykstra
P A
PA
Iaizzo
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001284:Atrophy / Q000139:chemically induced; D004317:Doxorubicin / Q000494:pharmacology*; D004421:Dystonia / Q000188:drug therapy* / Q000473:pathology; D009121:Muscle Denervation / Q000379:methods; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry / Q000473:pathology; D009210:Myofibrils / Q000737:chemistry / Q000473:pathology; D018995:Myosin Heavy Chains / Q000032:analysis; D009334:Neck Muscles / Q000737:chemistry / Q000473:pathology*; D011817:Rabbits; D014103:Torticollis / Q000188:drug therapy* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D018995:Myosin Heavy Chains