Pharmacologic management of spasticity following stroke.

Spasticity is a pervasive and debilitating condition that frequently occurs following upper motor neuron (UMN) lesions. Although the exact incidence of spasticity is unknown, it is likely that it affects more than half a million people in the United States alone, and more than 12 million people worldwide.1 Following stroke, approximately 65% of individuals develop spasticity.2 The definition of spasticity is variable among health care professionals. To some, spasticity simply refers to a velocity-dependent resistance to movement. For others, spasticity is part of a central motor neuron syndrome that includes hyperactive deep tendon reflexes, increased resistance to passive movement, flexed posturing of the upper extremity and extension of the lower extremity, excessive contraction of antagonist muscles, and synergistic movement patterns.3 In 1980, Lance published this frequently cited definition: “Spasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex, as one component of the upper motoneuron syndrome.”4(p485) This definition emphasizes the fact that spasticity is just one component of a UMN syndrome. Although the strongest association may be made between spasticity and the hyperactive stretch reflex arc, clinicians are acutely aware of abnormal reflexive movements observed in patients with a UMN lesion that are not in response to stretch. The neurophysiologic mechanisms underlying spasticity are complex, but the phenomenon occurs when supraspinal inhibition is lost because of a lesion in the brain or spinal cord,5,6 resulting in a stretch reflex that comes on sooner and stronger than it should.7 Spasticity alone does not cause disability, but it is one component that contributes to functional impairments in people following a brain or spinal cord injury. For the purposes of this review, the term “spasticity” is used as …

[1]  J. Tallman,et al.  The GABA-ergic system: a locus of benzodiazepine action. , 1985, Annual review of neuroscience.

[2]  M. Chaffman,et al.  Dantrolene , 1986, Drugs.

[3]  R. Dengler,et al.  Local botulinum toxin in the treatment of spastic drop foot , 1992, Journal of Neurology.

[4]  W. Wisden,et al.  GABA(A)-receptor subtypes: clinical efficacy and selectivity of benzodiazepine site ligands. , 1997, Annals of medicine.

[5]  P. Sandford,et al.  Clonidine in the treatment of brainstem spasticity. Case report. , 1992, American journal of physical medicine & rehabilitation.

[6]  M. Médici,et al.  A double-blind, long-term study of tizanidine ('Sirdalud') in spasticity due to cerebrovascular lesions. , 1989, Current medical research and opinion.

[7]  The effects of botulinum toxin treatment on associated reactions of the upper limb on hemiplegic gait–a pilot study , 2002, Disability and rehabilitation.

[8]  I. Milanov,et al.  Mechanisms of tizanidine action on spasticity , 1994, Acta neurologica Scandinavica.

[9]  T K Das,et al.  Effect of treatment with botulinum toxin on spasticity. , 1989, Postgraduate medical journal.

[10]  C. Poulos,et al.  Objective assessment of spasticity, strength, and function with early exhibition of dantrolene sodium after cerebrovascular accident: a randomized double-blind study. , 1992, Archives of physical medicine and rehabilitation.

[11]  S. Madi-Jebara,et al.  BLOOD SAVING EFFECTS AFTER CARDIAC SURGERY: LOW DOSE APROTININ VERSUS TRANEXAMIC ACID , 1992 .

[12]  H. Topka,et al.  Management of spasticity associated pain with botulinum toxin A. , 2000, Journal of pain and symptom management.

[13]  A. Wagstaff,et al.  Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. , 1997, Drugs.

[14]  D. Simpson.  Clinical trials of botulinum toxin in the treatment of spasticity , 1997, Muscle & nerve. Supplement.

[15]  L. A. Koman,et al.  Neuromuscular Blockade in the Management of Cerebral Palsy , 1996, Journal of child neurology.

[16]  R. Penn,et al.  Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. , 1993, Journal of neurosurgery.

[17]  W. Rymer,et al.  Spastic hypertonia: mechanisms and measurement. , 1989, Archives of physical medicine and rehabilitation.

[18]  H. J. Hansen,et al.  Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen , 2002, Clinical Neurology and Neurosurgery.

[19]  R. Penn,et al.  The effects of intrathecally administered baclofen on function in patients with spasticity. , 1995, Physical therapy.

[20]  S. Tuel,et al.  CONTINUOUS INTRATHECAL BACLOFEN IN SPINAL CORD SPASTICITY: A Prospective Study , 1992, American journal of physical medicine & rehabilitation.

[21]  C. Clemente.  Neurophysiologic mechanisms and neuroanatomic substrates related to spasticity , 1978, Neurology.

[22]  G. Novack,et al.  A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady state. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[23]  Robert B. Anderson,et al.  The Use of Open Phenol Blocks to the Motor Branches of the Tibial Nerve in Adult Acquired Spasticity , 1991, Foot & ankle.

[24]  D. Dralle,et al.  INTRATHECAL BACLOFEN FOR SPASTICITY , 1985, The Lancet.

[25]  D. Erickson,et al.  Control of intractable spasticity with intrathecal morphine sulfate. , 1989, Neurosurgery.

[26]  Gerry E Conti,et al.  Changes in movement characteristics of the spastic upper extremity after botulinum toxin injection. , 2003, Archives of physical medicine and rehabilitation.

[27]  D M Simpson,et al.  Traditional pharmacological treatments for spasticity part II: General and regional treatments , 1997, Muscle & nerve. Supplement.

[28]  M. Hadley,et al.  Intrathecal Baclofen for Spastic Hypertonia From Stroke , 2001, Stroke.

[29]  A. Dromerick,et al.  Open-Label Dose-Titration Safety and Efficacy Study of Tizanidine Hydrochloride in the Treatment of Spasticity Associated With Chronic Stroke , 2001, Stroke.

[30]  L. Provinciali,et al.  Low-dose botulinum toxin with ankle taping for the treatment of spastic equinovarus foot after stroke. , 1998, Archives of physical medicine and rehabilitation.

[31]  Young Rr,et al.  Drug therapy: spasticity (first of two parts). , 1981, The New England journal of medicine.

[32]  J. Palo,et al.  Dantrolene sodium in chronic spasticity of varying etiology , 1982, Acta neurologica Scandinavica.

[33]  B. Bussel,et al.  Intrathecal baclofen in subjects with spastic hemiplegia: assessment of the antispastic effect during gait. , 2003, Archives of physical medicine and rehabilitation.

[34]  W. B. Ketel,et al.  Long-term treatment with dantrolene sodium of stroke patients with spasticity limiting the return of function. , 1984, Current medical research and opinion.

[35]  S. C. Wang,et al.  Locus of action of centrally acting muscle relaxants, diazepam and tybamate. , 1971, The Journal of pharmacology and experimental therapeutics.

[36]  J. Froger,et al.  Efficacy of botulinum toxin A in upper limb function of hemiplegic patients , 2002, Journal of Neurology.

[37]  L. Seeberger,et al.  Spasticity After Stroke , 1996 .

[38]  E. Elovic,et al.  Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. , 2002, The New England journal of medicine.

[39]  Spasticity: A Rehabilitation Challenge in the Elderly , 2001, Gerontology.

[40]  C. Ciccone.  Pharmacology in Rehabilitation , 1990 .

[41]  R. Katz.  Management of Spasticity , 1988, American journal of physical medicine & rehabilitation.

[42]  B. Bhakta,et al.  Impact of botulinum toxin type A on disability and carer burden due to arm spasticity after stroke: a randomised double blind placebo controlled trial , 2000, Journal of neurology, neurosurgery, and psychiatry.

[43]  J. Lance,et al.  Bacloffen (Lioresal) in the long-term management of spasticity. , 1976, The Medical journal of Australia.

[44]  Y. Kirazlı,et al.  Comparison of phenol block and botulinus toxin type A in the treatment of spastic foot after stroke: a randomized, double-blind trial. , 1998, American journal of physical medicine & rehabilitation.

[45]  K. Follett,et al.  A prospective study of catheter-related complications of intrathecal drug delivery systems. , 2000, Journal of pain and symptom management.

[46]  J. Basmajian,et al.  Ketazolam treatment for spasticity: double-blind study of a new drug. , 1984, Archives of physical medicine and rehabilitation.

[47]  R. Roberts,et al.  Correlations between dose, plasma concentrations, and antispastic action of tizanidine (Sirdalud). , 1994, Journal of neurology, neurosurgery, and psychiatry.

[48]  M. Hadley,et al.  Continuously infused intrathecal baclofen for spastic/dystonic hemiplegia: a preliminary report. , 1999, American journal of physical medicine & rehabilitation.

[49]  S. Otto,et al.  A randomized, double‐blind, placebo‐controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke , 2001, European journal of neurology.

[50]  R. A. Davidoff.  Antispasticity drugs: Mechanisms of action , 1985, Annals of neurology.

[51]  B. Bhakta,et al.  Use of botulinum toxin in stroke patients with severe upper limb spasticity. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[52]  M. Maležič,et al.  Botulinum toxin treatment for lower limb extensor spasticity in chronic hemiparetic patients. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[53]  C. Boake,et al.  Improvement in walking speed in poststroke spastic hemiplegia after intrathecal baclofen therapy: a preliminary study. , 2003, Archives of physical medicine and rehabilitation.

[54]  J. B. Blacklock,et al.  Control of spasticity by implantable continuous flow morphine pump. , 1985, Neurosurgery.

[55]  M. Eyssette,et al.  A multi-centre, double-blind trial of tizanidine, a new antispastic agent, in spasticity associated with hemiplegia. , 1988, Current medical research and opinion.

[56]  Mechanisms of spasticity. , 1974, Archives of physical medicine and rehabilitation.

[57]  M. Brin.  Botulinum toxin: Chemistry, pharmacology, toxicity, and immunology , 1997, Muscle & nerve. Supplement.

[58]  Chyatte Sb,et al.  The effects of dantrolene sodium on spasticity and motor performance in hemiplegia. , 1971 .

[59]  R. Harvey,et al.  The prevention and management of complications after stroke. , 1999, Physical medicine and rehabilitation clinics of North America.

[60]  A. Levin,et al.  Complications associated with infusion pumps implanted for spasticity. , 1995, Stereotactic and functional neurosurgery.

[61]  L. Provinciali,et al.  Post-stroke spasticity management with repeated botulinum toxin injections in the upper limb. , 2000, American journal of physical medicine & rehabilitation.

[62]  E. Spatz,et al.  Chronic intrathecal delivery of baclofen by a programmable pump for the treatment of severe spasticity. , 1996, Journal of neurosurgery.

[63]  Wen-Chou Chi,et al.  Effect of Intramuscular Botulinum Toxin Injection on Upper Limb Spasticity in Stroke Patients , 2002, American journal of physical medicine & rehabilitation.

[64]  Garland De,et al.  Current uses of open phenol nerve block for adult acquired spasticity. , 1982 .

[65]  R. Penn,et al.  Long-term intrathecal baclofen infusion for treatment of spasticity. , 1987, Journal of neurosurgery.

[66]  Y. Kirazlı,et al.  Mechanisms of action of phenol block and botulinus toxin Type A in relieving spasticity: electrophysiologic investigation and follow-up. , 1999, American journal of physical medicine & rehabilitation.

[67]  D. Uebelhart,et al.  Symptoms of recurrent intrathecal baclofen withdrawal resulting from drug delivery failure: a case report. , 1999, American journal of physical medicine & rehabilitation.

[68]  C. O’Brien,et al.  A clinical overview of treatment decisions in the management of spasticity , 1997, Muscle & nerve. Supplement.

[69]  A. Sherwood,et al.  Gabapentin for the treatment of spasticity in patients with spinal cord injury , 1997, Spinal Cord.

[70]  C. Chabal,et al.  Intrathecal fentanyl alleviates spasticity in the presence of tolerance to intrathecal baclofen. , 1992, Anesthesiology.

[71]  D. Tk,et al.  Botulinum toxin in treating spasticity. , 1989 .

[72]  Werner Poewe,et al.  A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Compare the Efficacy and Safety of Three Doses of Botulinum Toxin Type A (Dysport) With Placebo in Upper Limb Spasticity After Stroke , 2000, Stroke.

[73]  D. M. Simpson,et al.  Botulinum toxin type A in the treatment of upper extremity spasticity , 1996, Neurology.

[74]  D M Simpson,et al.  Traditional pharmacological treatments for spasticity part I: Local treatments , 1997, Muscle & nerve. Supplement.

[75]  M. Bullard,et al.  Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose. , 1998, Journal of toxicology. Clinical toxicology.