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Published in: Current Neurology and Neuroscience Reports 8/2014

01-08-2014 | Demyelinating Disorders (DN Bourdette and V Yadav, Section Editors)

Botulinum Toxin for Symptomatic Therapy in Multiple Sclerosis

Authors: Michelle H. Cameron, Francois Bethoux, Nina Davis, Meredith Frederick

Published in: Current Neurology and Neuroscience Reports | Issue 8/2014

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Abstract

Botulinum toxin (BT) is a neurotoxin that paralyzes muscles by inhibiting release of acetylcholine from presynaptic vesicles at the neuromuscular junction. In people with multiple sclerosis (MS), clinical experience and research studies show that local injection of minute quantities of BT can temporarily control skeletal muscle spasticity, bladder detrusor hyperreflexia, and tremor. Specifically, BT injections have been shown to reduce muscle tone and improve passive function, and possibly improve active function, in patients with spasticity. Injection of BT into the bladder wall is a uniquely effective, safe, and durable treatment in patients with neurogenic detrusor hyperreflexia due to MS who have insufficient response or who do not tolerate oral antimuscarinic medications. This procedure has markedly reduced the need for indwelling catheters and bladder surgery. In addition, a recent study suggests BT may be effective for select patients with MS-associated upper extremity tremor. Appropriate use of BT can improve quality of life for many patients with MS.
Literature
1.
go back to reference Chen S. Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins (Basel). 2012;4:913–39.CrossRef Chen S. Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins (Basel). 2012;4:913–39.CrossRef
2.
go back to reference Lance J. Symposium synopsis. In: Feldman RG, Young RR, Koella WP, editors. Spasticity: disordered motor control. Chicago: Year Book Medical Publishers; 1980. p. 485–94. Lance J. Symposium synopsis. In: Feldman RG, Young RR, Koella WP, editors. Spasticity: disordered motor control. Chicago: Year Book Medical Publishers; 1980. p. 485–94.
3.
go back to reference Rizzo MA, Hadjimichael OC, Preiningerova J, Vollmer TL. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler. 2004;10:589–95.PubMedCrossRef Rizzo MA, Hadjimichael OC, Preiningerova J, Vollmer TL. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler. 2004;10:589–95.PubMedCrossRef
4.
go back to reference Barnes MP, Kent RM, Semlyen JK, McMullen KM. Spasticity in multiple sclerosis. Neurorehabil Neural Repair. 2003;17:66–70.PubMedCrossRef Barnes MP, Kent RM, Semlyen JK, McMullen KM. Spasticity in multiple sclerosis. Neurorehabil Neural Repair. 2003;17:66–70.PubMedCrossRef
5.
go back to reference Simpson DM, Gracies JM, Graham HK, Miyasaki JM, Naumann M, Russman B, et al. Assessment: botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70:1691–8.PubMedCrossRef Simpson DM, Gracies JM, Graham HK, Miyasaki JM, Naumann M, Russman B, et al. Assessment: botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70:1691–8.PubMedCrossRef
6.
go back to reference Consortium of Multiple Sclerosis Centers. Spasticity management in multiple sclerosis. Hackensack, NJ; 2003. Consortium of Multiple Sclerosis Centers. Spasticity management in multiple sclerosis. Hackensack, NJ; 2003.
7.
go back to reference Gold R, Oreja-Guevara C. Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines. Expert Rev Neurother. 2013;13:55–9.PubMedCrossRef Gold R, Oreja-Guevara C. Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines. Expert Rev Neurother. 2013;13:55–9.PubMedCrossRef
8.
go back to reference Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003;4, CD001332.PubMed Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003;4, CD001332.PubMed
9.
go back to reference Snow BJ, Tsui JK, Bhatt MH, Varelas M, Hashimoto SA, Calne DB. Treatment of spasticity with botulinum toxin: a double-blind study. Ann Neurol. 1990;28:512–5.PubMedCrossRef Snow BJ, Tsui JK, Bhatt MH, Varelas M, Hashimoto SA, Calne DB. Treatment of spasticity with botulinum toxin: a double-blind study. Ann Neurol. 1990;28:512–5.PubMedCrossRef
10.
go back to reference Grazko MA, Polo KB, Jabbari B. Botulinum toxin A for spasticity, muscle spasms, and rigidity. Neurology. 1995;45:712–7.PubMedCrossRef Grazko MA, Polo KB, Jabbari B. Botulinum toxin A for spasticity, muscle spasms, and rigidity. Neurology. 1995;45:712–7.PubMedCrossRef
11.
go back to reference Hyman N, Barnes M, Bhakta B, Cozens A, Bakheit M, Kreczy-Kleedorfer B, et al. Botulinum toxin (Dysport) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study. J Neurol Neurosurg Psychiatry. 2000;68:707–12.PubMedCentralPubMedCrossRef Hyman N, Barnes M, Bhakta B, Cozens A, Bakheit M, Kreczy-Kleedorfer B, et al. Botulinum toxin (Dysport) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study. J Neurol Neurosurg Psychiatry. 2000;68:707–12.PubMedCentralPubMedCrossRef
12.
go back to reference Sheean G. Botulinum toxin treatment of adult spasticity: a benefit-risk assessment. Drug Saf. 2006;29:31–48.PubMedCrossRef Sheean G. Botulinum toxin treatment of adult spasticity: a benefit-risk assessment. Drug Saf. 2006;29:31–48.PubMedCrossRef
13.••
go back to reference Picelli A, Lobba D, Midiri A, Prandi P, Melotti C, Baldessarelli S, et al. Botulinum toxin injection into the forearm muscles for wrist and fingers spastic overactivity in adults with chronic stroke: a randomized controlled trial comparing three injection techniques. Clin Rehabil. 2014;28:232–42. This study provides evidence regarding the impact of instrumented muscle localization on the efficacy of BT-A injections. Sixty patients with poststroke upper extremity spasticity were randomized into three groups (manual needle placement, electrical stimulation guidance, ultrasonography guidance). The injections were performed in the wrist and finger flexor muscles. At 4 weeks, there was a significantly larger improvement on all outcome measures in the electrical stimulation and ultrasonography placement groups compared with the manual needle placement group. No significant difference was observed between the two instrumented injection guidance techniques.PubMedCrossRef Picelli A, Lobba D, Midiri A, Prandi P, Melotti C, Baldessarelli S, et al. Botulinum toxin injection into the forearm muscles for wrist and fingers spastic overactivity in adults with chronic stroke: a randomized controlled trial comparing three injection techniques. Clin Rehabil. 2014;28:232–42. This study provides evidence regarding the impact of instrumented muscle localization on the efficacy of BT-A injections. Sixty patients with poststroke upper extremity spasticity were randomized into three groups (manual needle placement, electrical stimulation guidance, ultrasonography guidance). The injections were performed in the wrist and finger flexor muscles. At 4 weeks, there was a significantly larger improvement on all outcome measures in the electrical stimulation and ultrasonography placement groups compared with the manual needle placement group. No significant difference was observed between the two instrumented injection guidance techniques.PubMedCrossRef
14.
go back to reference Giovannelli M, Borriello G, Castri P, Prosperini L, Pozzilli C. Early physiotherapy after injection of botulinum toxin increases the beneficial effects on spasticity in patients with multiple sclerosis. Clin Rehabil. 2007;21:331–7.PubMedCrossRef Giovannelli M, Borriello G, Castri P, Prosperini L, Pozzilli C. Early physiotherapy after injection of botulinum toxin increases the beneficial effects on spasticity in patients with multiple sclerosis. Clin Rehabil. 2007;21:331–7.PubMedCrossRef
15.
go back to reference Litwiller SE, Frohman EM, Zimmern PE. Multiple sclerosis and the urologist. J Urol. 1999;161:743–57.PubMedCrossRef Litwiller SE, Frohman EM, Zimmern PE. Multiple sclerosis and the urologist. J Urol. 1999;161:743–57.PubMedCrossRef
16.
go back to reference Kalsi V, Apostolidis A, Popat R, Gonzales G, Fowler CJ, Dasgupta P. Quality of life changes in patients with neurogenic versus idiopathic detrusor overactivity after intradetrusor injections of botulinum neurotoxin type A and correlations with lower urinary tract symptoms and urodynamic changes. Eur Urol. 2006;49:528–35.PubMedCrossRef Kalsi V, Apostolidis A, Popat R, Gonzales G, Fowler CJ, Dasgupta P. Quality of life changes in patients with neurogenic versus idiopathic detrusor overactivity after intradetrusor injections of botulinum neurotoxin type A and correlations with lower urinary tract symptoms and urodynamic changes. Eur Urol. 2006;49:528–35.PubMedCrossRef
17.
go back to reference Schurch B, de Seze M, Denys P, Chartier-Kastler E, Haab F, Everaert K, et al. Botulinum toxin type A is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. J Urol. 2005;174:196–200.PubMedCrossRef Schurch B, de Seze M, Denys P, Chartier-Kastler E, Haab F, Everaert K, et al. Botulinum toxin type A is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. J Urol. 2005;174:196–200.PubMedCrossRef
18.
go back to reference Sussman D, Patel V, Del Popolo G, Lam W, Globe D, Pommerville P. Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity. Neurourol Urodyn. 2013;32:242–9.PubMedCrossRef Sussman D, Patel V, Del Popolo G, Lam W, Globe D, Pommerville P. Treatment satisfaction and improvement in health-related quality of life with onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity. Neurourol Urodyn. 2013;32:242–9.PubMedCrossRef
19.
go back to reference Schurch B, Stohrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000;164:692–7.PubMedCrossRef Schurch B, Stohrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000;164:692–7.PubMedCrossRef
20.
go back to reference Herschorn S, Gajewski J, Ethans K, Corcos J, Carlson K, Bailly G, et al. Efficacy of botulinum toxin A injection for neurogenic detrusor overactivity and urinary incontinence: a randomized, double-blind trial. J Urol. 2011;185:2229–35.PubMedCrossRef Herschorn S, Gajewski J, Ethans K, Corcos J, Carlson K, Bailly G, et al. Efficacy of botulinum toxin A injection for neurogenic detrusor overactivity and urinary incontinence: a randomized, double-blind trial. J Urol. 2011;185:2229–35.PubMedCrossRef
21.••
go back to reference Ginsberg D, Gousse A, Keppenne V, Sievert KD, Thompson C, Lam W, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187:2131–9. This international, multicenter, double-blind, randomized, placebo-controlled study included the largest number of MS subjects, 227, more than all prior efficacy trials combined. The primary outcome was the change from the baseline in number of weekly incontinence episodes. Secondary outcomes included bladder capacity, maximum detrusor pressure at initial involuntary contraction, and quality-of-life summary score on a validated questionnaire. At 2, 6, and 12 weeks of treatment, all subjects receiving BT-A demonstrated a statistically significant decrease in the number of incontinence episodes compared with those receiving placebo. No differences were noted between responses in patients treated with 200 units versus 300 units. Additionally, the dry rates for those treated with 200 units and 300 units were 36% and 42%, respectively. Similar statistically significant decreases in detrusor pressure and bladder capacity in the two treatment arms (200 units and 300 units compared with placebo) were observed as well. Quality of life was significantly improved in all of those receiving BT-A. This is the most comprehensive and rigorous study of the use of BT-A in NDO due to MS, and its findings validate the efficacy, safety, and improvement in well-being that derive from detrusor injection of BT-A.PubMedCrossRef Ginsberg D, Gousse A, Keppenne V, Sievert KD, Thompson C, Lam W, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187:2131–9. This international, multicenter, double-blind, randomized, placebo-controlled study included the largest number of MS subjects, 227, more than all prior efficacy trials combined. The primary outcome was the change from the baseline in number of weekly incontinence episodes. Secondary outcomes included bladder capacity, maximum detrusor pressure at initial involuntary contraction, and quality-of-life summary score on a validated questionnaire. At 2, 6, and 12 weeks of treatment, all subjects receiving BT-A demonstrated a statistically significant decrease in the number of incontinence episodes compared with those receiving placebo. No differences were noted between responses in patients treated with 200 units versus 300 units. Additionally, the dry rates for those treated with 200 units and 300 units were 36% and 42%, respectively. Similar statistically significant decreases in detrusor pressure and bladder capacity in the two treatment arms (200 units and 300 units compared with placebo) were observed as well. Quality of life was significantly improved in all of those receiving BT-A. This is the most comprehensive and rigorous study of the use of BT-A in NDO due to MS, and its findings validate the efficacy, safety, and improvement in well-being that derive from detrusor injection of BT-A.PubMedCrossRef
22.
go back to reference Mehnert U, Birzele J, Reuter K, Schurch B. The effect of botulinum toxin type A on overactive bladder symptoms in patients with multiple sclerosis: a pilot study. J Urol. 2010;184:1011–6.PubMedCrossRef Mehnert U, Birzele J, Reuter K, Schurch B. The effect of botulinum toxin type A on overactive bladder symptoms in patients with multiple sclerosis: a pilot study. J Urol. 2010;184:1011–6.PubMedCrossRef
23.
go back to reference Kuo HC. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn. 2011;30:1242–8.PubMed Kuo HC. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn. 2011;30:1242–8.PubMed
24.
go back to reference Grosse J, Kramer G, Stohrer M. Success of repeat detrusor injections of botulinum a toxin in patients with severe neurogenic detrusor overactivity and incontinence. Eur Urol. 2005;47:653–9.PubMedCrossRef Grosse J, Kramer G, Stohrer M. Success of repeat detrusor injections of botulinum a toxin in patients with severe neurogenic detrusor overactivity and incontinence. Eur Urol. 2005;47:653–9.PubMedCrossRef
25.
go back to reference Gaillet S, Bardot P, Bernuz B, Boissier R, Lenne-Aurier K, Thiry-Escudier I, et al. Five years follow-up study and failures analysis of botulinum toxin repeated injections to treat neurogenic detrusor overactivity. Prog Urol. 2012;22:1064–70.PubMedCrossRef Gaillet S, Bardot P, Bernuz B, Boissier R, Lenne-Aurier K, Thiry-Escudier I, et al. Five years follow-up study and failures analysis of botulinum toxin repeated injections to treat neurogenic detrusor overactivity. Prog Urol. 2012;22:1064–70.PubMedCrossRef
26.
go back to reference Veeratterapillay R, Harding C, Teo L, Vasdev N, Abroaf A, Dorkin T, et al. Discontinuation rates and inter-injection interval for repeated intravesical botulinum toxin type A injections for detrusor overactivity. Int J Urol. 2014;21:175–8.PubMedCrossRef Veeratterapillay R, Harding C, Teo L, Vasdev N, Abroaf A, Dorkin T, et al. Discontinuation rates and inter-injection interval for repeated intravesical botulinum toxin type A injections for detrusor overactivity. Int J Urol. 2014;21:175–8.PubMedCrossRef
27.
go back to reference Apostodolis A, Haferkamp A, Aoki KR. Understanding the role of botulinum toxin A in the treatment of the overactive bladder—more than just muscle relaxation. Eur Urol Suppl. 2006;5:670–8.CrossRef Apostodolis A, Haferkamp A, Aoki KR. Understanding the role of botulinum toxin A in the treatment of the overactive bladder—more than just muscle relaxation. Eur Urol Suppl. 2006;5:670–8.CrossRef
28.
go back to reference Game X, Castel-Lacanal E, Bentaleb Y, Thiry-Escudie I, De Boissezon X, Malavaud B, et al. Botulinum toxin A detrusor injections in patients with neurogenic detrusor overactivity significantly decrease the incidence of symptomatic urinary tract infections. Eur Urol. 2008;53:613–8.PubMedCrossRef Game X, Castel-Lacanal E, Bentaleb Y, Thiry-Escudie I, De Boissezon X, Malavaud B, et al. Botulinum toxin A detrusor injections in patients with neurogenic detrusor overactivity significantly decrease the incidence of symptomatic urinary tract infections. Eur Urol. 2008;53:613–8.PubMedCrossRef
29.
go back to reference Alusi SH, Worthington J, Glickman S, Bain PG. A study of tremor in multiple sclerosis. Brain. 2001;124:720–30.PubMedCrossRef Alusi SH, Worthington J, Glickman S, Bain PG. A study of tremor in multiple sclerosis. Brain. 2001;124:720–30.PubMedCrossRef
30.
go back to reference Labiano-Fontcuberta A, Benito-Leon J. Understanding tremor in multiple sclerosis: prevalence, pathological anatomy, and pharmacological and surgical approaches to treatment. Tremor Other Hyperkinet Mov. 2012;2:1–10. Labiano-Fontcuberta A, Benito-Leon J. Understanding tremor in multiple sclerosis: prevalence, pathological anatomy, and pharmacological and surgical approaches to treatment. Tremor Other Hyperkinet Mov. 2012;2:1–10.
31.
go back to reference Clarke CE. Botulinum toxin type A in cerebellar tremor caused by multiple sclerosis. Eur J Neurol. 1997;4:68–71.PubMedCrossRef Clarke CE. Botulinum toxin type A in cerebellar tremor caused by multiple sclerosis. Eur J Neurol. 1997;4:68–71.PubMedCrossRef
32.
go back to reference Alusi SH, Worthington J, Glickman S, Findley LJ, Bain PG. Evaluation of three different ways of assessing tremor in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2000;68:756–60.PubMedCentralPubMedCrossRef Alusi SH, Worthington J, Glickman S, Findley LJ, Bain PG. Evaluation of three different ways of assessing tremor in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2000;68:756–60.PubMedCentralPubMedCrossRef
33.
go back to reference Brin MF, Lyons KE, Doucette J, Adler CH, Caviness JN, Comella CL, et al. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology. 2001;56:1523–8.PubMedCrossRef Brin MF, Lyons KE, Doucette J, Adler CH, Caviness JN, Comella CL, et al. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology. 2001;56:1523–8.PubMedCrossRef
Metadata
Title
Botulinum Toxin for Symptomatic Therapy in Multiple Sclerosis
Authors
Michelle H. Cameron
Francois Bethoux
Nina Davis
Meredith Frederick
Publication date
01-08-2014
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 8/2014
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-014-0463-7

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