Seven children between 2 and 15 years of age with cerebral palsy and upper extremity dystonia were enrolled in an open-label, dose-escalation pilot clinical trial of botulinum toxin type B (Myobloc), injected into the biceps and brachioradialis muscles of 1 or both arms. The primary outcome measure was the change in maximum speed of hand movement during attempted forward reaching. Escalating doses of 12.5, 25, and 50 U/kg per muscle were injected at each of 3 visits. Reaching speed improved in response to injection, and dystonia scores on the Burke-Fahn-Marsden dystonia scale, the Unified Dystonia Rating Scale, and the Unified Parkinson's Disease Rating Scale improved. There was not a dose-related effect on efficacy. There were no serious adverse events. Two children reported transient weakness. These results support the use of botulinum toxin type B as a safe and effective treatment for upper extremity dystonia in children with cerebral palsy. Larger controlled trials are needed to confirm these results.
Gormley ME, Gaebler-Spira D., Delgado MRUse of botulinum toxin type A in pediatric patients with cerebral palsy: a three-center retrospective chart review. J Child Neurol.2001;16:113-118.
2.
Graham HK, Aoki KR, Autti-Ramo I., et al. Recommendations for the use of botulinum toxin type A in the management of cerebral palsy. Gait Posture. 2000;11:67-79.
3.
Koman LA, Mooney JF III, Smith B., Goodman A., Mulvaney T.Management of cerebral palsy with botulinum-A toxin: preliminary investigation . J Pediatr Orthop.1993;13:489-495.
4.
Koman LA, Mooney JF III, Smith BP, Goodman A., Mulvaney T.Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, double-blind trial. J Pediatr Orthop.1994;14:299-303.
5.
Koman LA, Mooney JF III, Smith BP, Walker F., Leon JMBotulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind, placebo-controlled trial. BOTOX Study Group. J Pediatr Orthop.2000;20:108-115.
6.
Russman BS, Tilton A., Gormley ME Jr. Cerebral palsy: a rational approach to a treatment protocol, and the role of botulinum toxin in treatment. Muscle Nerve Suppl . 1997;6:S181-S193.
7.
Fehlings D., Rang M., Glazier J., Steele C.An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. J Pediatr.2000;137: 331-337.
8.
Fehlings D., Rang M., Glazier J., Steele C.Botulinum toxin type A injections in the spastic upper extremity of children with hemiplegia: child characteristics that predict a positive outcome. Eur J Neurol.2001;8(suppl 5):145-149.
9.
Graham HK, Boyd RN, Fehlings D.Does intramuscular botulinum toxin A injection improve upper-limb function in children with hemiplegic cerebral palsy?Med J Aust.2003; 178:95-96.
10.
Autti-Ramo I., Larsen A., Taimo A., von Wendt L.Management of the upper limb with botulinum toxin type A in children with spastic type cerebral palsy and acquired brain injury: clinical implications. Eur J Neurol.2001;8(suppl 5):136-144.
11.
Dressler D. , Bigalke H., Benecke R.Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure. J Neurol.2003;250:967-969.
12.
Factor SA, Molho ES, Evans S., Feustel PJEfficacy and safety of repeated doses of botulinum toxin type B in type A resistant and responsive cervical dystonia. Mov Disord. 2005;20:1152-1160.
13.
Dolly O.Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins. Headache. 2003;43(suppl 1): S16-S24.
Pellizzari R., Rossetto O., Schiavo G., Montecucco C.Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses. Philos Trans R Soc Lond B Biol Sci.1999;354:259-268.
16.
Turton K., Chaddock JA, Acharya KRBotulinum and tetanus neurotoxins: structure, function and therapeutic utility . Trends Biochem Sci.2002;27:552-558.
17.
Baumann L., Black L.Botulinum toxin type B (Myobloc). Dermatol Surg.2003;29:496-500.
18.
Dressler D. , Adib Saberi F.Botulinum toxin: mechanisms of action . Eur Neurol.2005;53:3-9.
19.
Brashear A. , Lew MF, Dykstra DD, et al. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology . 1999;53:1439-1446.
20.
Brin MF, Lew MF, Adler CH, et al. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology. 1999;53:1431-1438.
21.
Foran PG, Mohammed N., Lisk GO, et al. Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons. J Biol Chem.2003;278:1363-1371.
22.
Purkiss JR, Friis LM, Doward S., Quinn CPClostridium botulinum neurotoxins act with a wide range of potencies on SH-SY5Y human neuroblastoma cells. Neurotoxicology. 2001;22:447-453.
23.
Roger Aoki K.Botulinum neurotoxin serotypes A and B preparations have different safety margins in preclinical models of muscle weakening efficacy and systemic safety. Toxicon. 2002; 40:923-928.
24.
Flynn TC, Clark RE II. Botulinum toxin type B (MYOBLOC) versus botulinum toxin type A (BOTOX) frontalis study: rate of onset and radius of diffusion. Dermatol Surg.2003;29:519-522.
25.
Muthane UB, Panikar JNBotulinum toxins: pharmacology and its current therapeutic evidence for use . Neurology India. 2003;51:455-460.
26.
Lew MF, Adornato BT, Duane DD, et al. Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology . 1997;49:701-707.
27.
Lew MF, Brashear A., Factor S.The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: summary of three controlled clinical trials. Neurology. 2000;55(12 suppl 5):S29-S35.
28.
Truong DD, Cullis PA, O'Brien CF, Koller M., Villegas TP, Wallace JDBotB (botulinum toxin type B): evaluation of safety and tolerability in botulinum toxin type A-resistant cervical dystonia patients (preliminary study). Mov Disord. 1997;12:772-775.
29.
Tsui JK, Hayward M., Mak EK, Schulzer M.Botulinum toxin type B in the treatment of cervical dystonia: a pilot study . Neurology. 199 5 ;45:2109-2110.
30.
Comella CL, Jankovic J., Shannon KM, et al. Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia. Neurology. 2005;65:1423-1429.
31.
Dressler D., Bigalke H.Botulinum toxin type B de novo therapy of cervical dystonia: frequency of antibody induced therapy failure. J Neurol.2005;252:904-907.
32.
Costa J., Espirito-Santo C., Borges A., et al. Botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev.2005(1): CD004315.
33.
Brashear A., McAfee AL, Kuhn ER, Ambrosius WTTreatment with botulinum toxin type B for upper-limb spasticity. Arch Phys Med Rehabil.2003;84:103-107.
34.
Brashear A., McAfee AL, Kuhn ER, Fyffe J.Botulinum toxin type B in upper-limb poststroke spasticity: a double-blind, placebo-controlled trial. Arch Phys Med Rehabil.2004;85:705-709.
35.
Wan XH, Vuong KD, Jankovic J.Clinical application of botulinum toxin type B in movement disorders and autonomic symptoms. Chin Med Sci J. 2005;20:44-47.
36.
Racette BA, Lopate G., Good L., Sagitto S., Perlmutter JSPtosis as a remote effect of therapeutic botulinum toxin B injection. Neurology. 2002; 59:1445-1447.
37.
Tintner R., Gross R., Winzer UF, Smalky KA, Jankovic J.Autonomic function after botulinum toxin type A or B: a double-blind, randomized trial. Neurology. 2005;65:765-767.
38.
Dubow J., Kim A., Leikin J., Cumpston K., Bryant S., Rezak M.Visual system side effects caused by parasympathetic dysfunction after botulinum toxin type B injections. Mov Disord. 2005;20: 877-880.
39.
Dressler D. , Benecke R.Autonomic side effects of botulinum toxin type B therapy. Adv Neurol.2004;94:315-320.
40.
Baumann LS, Halem MLSystemic adverse effects after botulinum toxin type B (myobloc) injections for the treatment of palmar hyperhidrosis. Arch Dermatol.2003;139:226-227.
41.
Comella CL, Leurgans S., Wuu J., Stebbins GT, Chmura T.Rating scales for dystonia: a multicenter assessment. Mov Disord. 2003; 18:303-312.
42.
Martinez-Martin P., Gil-Nagel A., Gracia LM, Gomez JB, Martinez-Sarries J., Bermejo F.Unified Parkinson's Disease Rating Scale characteristics and structure. The Cooperative Multicentric Group. Mov Disord. 1994;9:76-83.
43.
Richards M. , Marder K., Cote L., Mayeux R.Interrater reliability of the Unified Parkinson's Disease Rating Scale motor examination. Mov Disord. 1994;9:89-91.
44.
Burke RE, Fahn S., Marsden CD, Bressman SB, Moskowitz C., Friedman J.Validity and reliability of a rating scale for the primary torsion dystonias . Neurology. 1985;35:73-77.
45.
Haas BM, Bergstrom E., Jamous A., Bennie A.The inter rater reliability of the original and of the modified Ashworth scale for the assessment of spasticity in patients with spinal cord injury. Spinal Cord.1996;34:560-564.
46.
Bohannon RW , Smith MBInterrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther.1987 ;67: 206-207.
47.
Sloan RL, Sinclair E., Thompson J., Taylor S., Pentland B.Interrater reliability of the modified Ashworth Scale for spasticity in hemiplegic patients. Int J Rehabil Res. 1992;15:158-161.
48.
Blackburn M. , van Vliet P., Mockett SPReliability of measurements obtained with the modified Ashworth scale in the lower extremities of people with stroke . Phys Ther.2002;82:25-34.
49.
Varni JW, Seid M., Knight TS, Uzark K., Szer ISThe PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and impact on clinical decision-making. J Behav Med.2002;25:175-193.
50.
Varni JW, Seid M., Kurtin PSPedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care.2001; 39:800-812.
