LETTERS
Treatment of Spasticity with Botullnwn Toxin
6. Coers C . Contribution 6 I'ktude de la jonction neuromusculaire. 11. Topographie zonal de I'innervation motrice terminale dam les muscles stries. Arch Biol 1953;64:495-505
G. E. Borodic, MD,*§ R. Ferrante,t§ A. W. Wiegner, PhD,t§ and R. R. Young, MD$§
Reply
The report by Snow and colleagues [I] first demonstrated the safety and efficacy of injecting large spastic skeletal muscles with botulinum-A toxin. Small muscles have been similarly injected to treat spastic dysphonia [ 2 ) and detrusorsphincter dyssynergia in spastic patients with spinal cord injuries 131. Locating optimal injection sites within small muscles of the eyes, larynx, and face is not a particular problem; once the muscle itself is located and injected, the toxin presumably diffuses throughout it. However, when larger muscles are to be injected, as during treatment of spastic patients, where should the injections be made? Because botulinum toxin exerts its effect presynaptically at the neuromuscular junction [4],injections should be directed to the innervation zones within muscles if they are to be optimally effective, minimizing complications. Alternative injection sites such as standard locations used for electromyography electrodes [If or motor points [ S } are apt to be remote from most of the neuromuscular junctions that need to be blocked. The problem is to know where the innervation zones are within muscles; methods for localizing them physiologically or otherwise in vivo have not been perfected. More detailed studies of human intramuscular anatomy are needed to supplement the classical investigations of Coers [ b ] . Meanwhile, those using botulinum toxin to weaken large muscles should keep careful records of injection sites (located reproducibly by surface landmarks) and efficacy of botulinum-induced paresis. Optimal injection sites may thereby be discovered clinically.
Joseph K. C. Tsui, MBBS, MRCP, FRCPC, Barry J. Snow, MD, FRACP, and Donald B. Calne, DM, FRCP, FRCPC We thank D r Borodic and colleagues for their suggestions. While their arguments are entirely reasonable, we are not aware of any evidence that a better therapeutic response is achieved by precise identification of the innervation zone for injection. During the initial stages of development of the technique of treating spasmodic torticollis, we did not find any significant difference in the efficacy obtained by (1) dividing the dose into multiple small injections into many sites ( 5 MU per site), ( 2 ) injecting into 1 to 3 sites at 25 M U per site into the main bulk of the muscle, and (3) injecting into an area with the lowest threshold of response to a stimulating electrode. All three methods produced similar effects in the muscles treated. In our study, we employed surface landmarks described in the standard electromyography literature [ 13 to locate the sites of injections for the adductor muscles. In response to the general issue raised by Borodic and colleagues, we agree that it would be useful to study the extent of diffusion of botulinum toxin from the site of injection.
NeurodegenerativeDisorders Centre University Hospital-UBC Site University of British Cohmbia Vancouver, BC, Canada
Reference 1. Delagi EF, Perotto A, Iazzetri J, Morrison D. Anatomic guide for the electromyographer. Springfield: Charles C Thomas, 1980
'Department of Ophthalmology Massachusetts Eye and Ear lnfimavy fDepartnent of Pathology Massachusetts General Hospital Boston, M A $Spinal Cord Injury Service BrocktonlWest Roxbury V A Medical Center 9 Harvard Medical School Boston, M A
References 1. Snow BJ, Tsui JKC, Bhatt MH, et al. Treatment of spasticity with botulinum toxin: a double-blind study. Ann Neurol 1990;28: 512-515 2. Ludlow CL, Naunton RF, Sedory SE, et al. Effects of botulinum toxin on speech in adductor spasmodic dystonia. Neurology 1988;38:1220-1225 3. Dykstra DD, Sidi AA, Scott AB, et al. Effects of botulinum-A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol 1988;139:919-922 4. Kao I, Drachman DB, Price DL. Botulinum toxin: mechanism of presynaptic blockade. Science 1976;193:1256-1258 5. Borodic GE, Cozzolino D, Ferrante R, et al. Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy. Ophthalmic Plast Reconstr Surg 1991;7:54-60
Lack of Changes in Ventricular Cerebrospinal Fluid Concentrations -of Homovanillic Acid Following Acute Challenge with Levodopa Zouheir Moussa, MD," Christian Raftopoulos, MD,? Serge Przedborski, MD,* and Jerzy Hildebrand, MDX In a recent issue of the Annals, Olanow and colleagues 111 reported that cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) remained unchanged in 4 parkinsonian patients after the administration of a single tablet of 251250 carbidopa/levodopa (Sinemet). In an attempt to study levodopa pharmacokinetics, we
Copyright 0 1992 by the American Neurological Association
113
Treatment of Spasticity with Botullnwn Toxin
6. Coers C . Contribution 6 I'ktude de la jonction neuromusculaire. 11. Topographie zonal de I'innervation motrice terminale dam les muscles stries. Arch Biol 1953;64:495-505
G. E. Borodic, MD,*§ R. Ferrante,t§ A. W. Wiegner, PhD,t§ and R. R. Young, MD$§
Reply
The report by Snow and colleagues [I] first demonstrated the safety and efficacy of injecting large spastic skeletal muscles with botulinum-A toxin. Small muscles have been similarly injected to treat spastic dysphonia [ 2 ) and detrusorsphincter dyssynergia in spastic patients with spinal cord injuries 131. Locating optimal injection sites within small muscles of the eyes, larynx, and face is not a particular problem; once the muscle itself is located and injected, the toxin presumably diffuses throughout it. However, when larger muscles are to be injected, as during treatment of spastic patients, where should the injections be made? Because botulinum toxin exerts its effect presynaptically at the neuromuscular junction [4],injections should be directed to the innervation zones within muscles if they are to be optimally effective, minimizing complications. Alternative injection sites such as standard locations used for electromyography electrodes [If or motor points [ S } are apt to be remote from most of the neuromuscular junctions that need to be blocked. The problem is to know where the innervation zones are within muscles; methods for localizing them physiologically or otherwise in vivo have not been perfected. More detailed studies of human intramuscular anatomy are needed to supplement the classical investigations of Coers [ b ] . Meanwhile, those using botulinum toxin to weaken large muscles should keep careful records of injection sites (located reproducibly by surface landmarks) and efficacy of botulinum-induced paresis. Optimal injection sites may thereby be discovered clinically.
Joseph K. C. Tsui, MBBS, MRCP, FRCPC, Barry J. Snow, MD, FRACP, and Donald B. Calne, DM, FRCP, FRCPC We thank D r Borodic and colleagues for their suggestions. While their arguments are entirely reasonable, we are not aware of any evidence that a better therapeutic response is achieved by precise identification of the innervation zone for injection. During the initial stages of development of the technique of treating spasmodic torticollis, we did not find any significant difference in the efficacy obtained by (1) dividing the dose into multiple small injections into many sites ( 5 MU per site), ( 2 ) injecting into 1 to 3 sites at 25 M U per site into the main bulk of the muscle, and (3) injecting into an area with the lowest threshold of response to a stimulating electrode. All three methods produced similar effects in the muscles treated. In our study, we employed surface landmarks described in the standard electromyography literature [ 13 to locate the sites of injections for the adductor muscles. In response to the general issue raised by Borodic and colleagues, we agree that it would be useful to study the extent of diffusion of botulinum toxin from the site of injection.
NeurodegenerativeDisorders Centre University Hospital-UBC Site University of British Cohmbia Vancouver, BC, Canada
Reference 1. Delagi EF, Perotto A, Iazzetri J, Morrison D. Anatomic guide for the electromyographer. Springfield: Charles C Thomas, 1980
'Department of Ophthalmology Massachusetts Eye and Ear lnfimavy fDepartnent of Pathology Massachusetts General Hospital Boston, M A $Spinal Cord Injury Service BrocktonlWest Roxbury V A Medical Center 9 Harvard Medical School Boston, M A
References 1. Snow BJ, Tsui JKC, Bhatt MH, et al. Treatment of spasticity with botulinum toxin: a double-blind study. Ann Neurol 1990;28: 512-515 2. Ludlow CL, Naunton RF, Sedory SE, et al. Effects of botulinum toxin on speech in adductor spasmodic dystonia. Neurology 1988;38:1220-1225 3. Dykstra DD, Sidi AA, Scott AB, et al. Effects of botulinum-A toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol 1988;139:919-922 4. Kao I, Drachman DB, Price DL. Botulinum toxin: mechanism of presynaptic blockade. Science 1976;193:1256-1258 5. Borodic GE, Cozzolino D, Ferrante R, et al. Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy. Ophthalmic Plast Reconstr Surg 1991;7:54-60
Lack of Changes in Ventricular Cerebrospinal Fluid Concentrations -of Homovanillic Acid Following Acute Challenge with Levodopa Zouheir Moussa, MD," Christian Raftopoulos, MD,? Serge Przedborski, MD,* and Jerzy Hildebrand, MDX In a recent issue of the Annals, Olanow and colleagues 111 reported that cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) remained unchanged in 4 parkinsonian patients after the administration of a single tablet of 251250 carbidopa/levodopa (Sinemet). In an attempt to study levodopa pharmacokinetics, we
Copyright 0 1992 by the American Neurological Association
113
