espasticidade - evidências: tratamento medicamentoso e...

Espasticidade - evidências: tratamento

medicamentoso e não medicamentoso

Jorge Laíns

Serrano S, Ferreira AM, Mendes B, Rocha F, Constantino J, Lopes J, Lucas I

Prevalence

– Post-stroke spasticity incidence – 19-38%*

– Stroke survivors

• 4-9% - severe functional impairment of upper limb due to

spasticity**

Spasticity

* Lundström E. et al. Eur J Neurol 2008.

** Sommerfeld DK et al. Stroke 2004

Non-Pharmacologic Management

– Orthosis

– Kinesiotherapy and physical agents

Pharmacologic Management

– Oral agents

– Intrathecal baclofen

– Botulinum toxin

Spasticity treatment

Non-Pharmacologic Management of Spasticity

Following Stroke

Orthosis

• Spasticity and contracture guides treatment options

• Broadly

– drug interventions - effective at targeting spasticity

– non-drug interventions - greater impact on contracture

Orthosis

Nair KP, Marsden J. The management of spasticity in adults. BMJ 2014

• advantage

– Duration of its effectiveness - can be placed and left for

several hours without the presence of a physiotherapist or

nurse

• disadvantage

– Holds the joint in a fixed position rather than applying a

constant torque

Orthosis

• Robert Teasell MD. Stroke Rehabilitation Clinician Handbook. (4. Motor Rehabilitation), Norhayati Hussein MBBS MRehabMed. 2014

• Nair KP, Marsden J. The management of spasticity in adults. BMJ 2014

Orthosis - Evidence in Favor

• Doucet BM, et al. 2013

– Case series design

– Evidence level: 4

– 12-week dynamic progressive orthotic intervention

(Dynasplint®) in chronic stroke patients exhibiting wrist flexion

contracture

– … beneficial effect: ↑ PROM and ↓ RTPM (resistance to

passive movement) in the wrist of persons with chronic stroke…

• Doucet BM, Mettler JA. Effects of a dynamic progressive orthotic intervention for chronic hemiplegia: a case series. J Hand Ther.

2013 Apr

Orthosis – evidence in favor

• Appasamy M. et al. 2015

– 22 adults with hemiparesis and genu recurvatum

– BTx-A injections alone or in combination with multiple types of

orthotic interventions that included AFO

– Genu recurvatum in hemiparesis can be successfully

controlled by combined medical and orthotic interventions

• Appasamy M, De Witt ME, Patel N, Yeh N, Bloom O, Oreste A, Treatment strategies for genu recurvatum in adult patients with

hemiparesis: a case series. 2015

Orthosis – evidence in favor

• Tyson SF, Kent RM. 2013

– n = 334 post-stroke

– AFO

• improvement in mobility (FAC), walking (speed and step/stride

length), and balance (weight distribution on standing)

• did not affect other aspects of mobility (timed stair climb and

TUG) and balance (postural sway)

Tyson SF, Kent RM. Effects of an ankle-foot orthosis on balance and walking after stroke: a systematic review and pooled meta-analysis.

Arch Phys Med Rehabil. 2013 Jul

Orthosis – evidence in favor

• Gatti MA. et al. 2012– Compare the knee kinematics with an AFO/footwear vs barefoot

– n = 10, post-stroke with plantarflexor spasticity

– benefits with AFO/footwear use in the kinematics of the knee, the step

length of the non-paretic limb, and the gait velocity in hemiplegics after

mild to moderate stroke

– AFO can improve the gait pattern and increase velocity in these

subjects

Gatti MA, Freixes O, Fernández SA, Rivas ME, Crespo M, Waldman SV, Olmos LE-, Effects of ankle foot orthosis in stiff knee gait in

adults with hemiplegia J Biomech. 2012 Oct

Orthosis – evidence in favor

• Pradon D. et al. 2012

– gait analysis before BTx-A, week 3 and 6 (with and without

orthosis)

– n = 8 chronic hemiplegics

– BTx-A injection of the triceps surae and wearing an AFO is

more effective than use of BTx-A only

– BTx-A injection into the triceps surae improves the gait of patients

• stance phase - ↑ ankle dorsiflexion

• swing phase - not proved to ↑ dorsiflexion

Pradon D, Hutin E, Khadir S, Taiar R, Genet F, Roche N. A pilot study to investigate the combined use of Botulinum toxin type-a and

ankle foot orthosis for the treatment of spastic foot in chronic hemiplegic patient Clin Biomech (Bristol, Avon). 2011

Orthosis – evidence in favor

Orthosis - Evidence Against

• VA/DoD clinical practice guideline for the

management of stroke rehabilitation

– Positioning, passive stretching, and ROM may provide relief

and should be done several times daily in persons with

spasticity

– Corrective measures for contractures that interfere with function

include - splinting, serial casting, surgical correction

The management of stroke rehabilitation working group. VA/DoD clinical practice guideline for the

management of stroke rehabilitation. Version 3.0. 2010

Orthosis – no evidence

• Basaran A et al. 2012

– RCT

– n = 39, 5 weeks, home-based exercise program with wrist and

finger flexors stretches with reach and grasp activities +

conventional therapy

– Groups

• experimental - volar or dorsal splint

• control - no splint

– no significant difference in spasticity reduction and PROM

between groups

Basaran A, Emre U, Karadavut KI, Balbaloglu O, Bulmus N. Hand splinting for poststroke spasticity: a randomized controlled trial. Top

Stroke Rehabil 2012 Jul-Aug; 19(4):329-37.

Orthosis – evidence against

• Thibaut A. et al. 2013

– Orthoses efficacy

• recently failed to provide any significant improvement in

spasticity of the wrist flexor or wrist ROM

Thibaut A, Chatelle C, Ziegler E, Bruno MA, Laureys S, Gosseries O. Spasticity after stroke: Physiology, assessment and treatment

Brain Inj. 2013

Orthosis – evidence against

• Ibuki A. et al. 2013

– effect of three tone reducing devices

• dynamic foot orthosis, muscle stretch, and orthokinetic

compression garment

– on soleus muscle reflex excitability while standing; n=13

with spasticity post-stroke

– all - no significant effect on soleus reflex excitability while

standing

Ibuki A, Bach T, Rogers D, Bernhardt J. The effect of tone-reducing orthotic devices on soleus muscle reflex excitability while standing in

patients with spasticity following stroke. Prosthet Orthot Int. 2010 Mar;34(1):46-57.

Orthosis – evidence against

Intercollegiate Stroke Working Party. National clinical guideline for stroke, 4th edition. London: Royal College of Physicians, 2012.

Orthosis – evidence against

• National clinical guideline for stroke. Royal College of

Physicians, 2012

– Splinting after stroke is usually concerned with maintaining or

extending the range of movement around a joint

– Splinting of the arm and hand should not be used routinely

after stroke

• Andringa A. et al. 2012

– n = 11 stroke patients

– telephone interviews - explore the long-term use and

experienced comfort with the orthosis

– patients cannot tolerate a static orthosis for at least 8 h/d,

during a period of ≥ one year

Orthosis – evidence against

Andringa A, van de Port I, Meijer JW. Long-term use of a static hand-wrist orthosis in chronic stroke patients: a pilot study. Stroke Res

Treat. 2013;

Non-Pharmacologic Management of

Spasticity Following Stroke

Kinesiotherapy and Physical

Agents

• Physical Therapy

– limiting muscle contractures and reducing hyperactivity for at

least a short period of time can be helpful

Stretching

Postural management and standing

Strengthening

Other physical modalities

Thibaut, Aurore, et al. "Spasticity after stroke: Physiology, assessment and treatment." Brain Injury 27.10 (2013): 1093-1105.

Kinesiotherapy and Physical Agents

• Stretching

– Cochrane meta-analysis of four trials

• n = 161

• no significant effect on spasticity*

– Systematic review of the effectiveness of stretching in brain

injuries

• stretching does not induce significant changes in joint

mobility, pain, spasticity or activity limitation**

* Katalinic OM, Harvey LA, Herbert RD, Moseley AM, Lannin NA, Schurr K. Stretch for the treatment and prevention of contractures. Cochrane

Database Syst Rev 2010;9:CD007455.

** Katalinic OM, Harvey LA, Herbert RD. Stretch for the treatment and prevention of contractures. Phys Ther 2011;91(1):11–24.

Kinesiotherapy and Physical Agents

• Postural management and standing

– management of postural alignment to prevent or reduce

contracture and spasticity

– systems to maintain alignment when sitting, standing, and in

bed, e.g. standing frames*

• Evidence level **

– early - C

– late - C

* Nair, Krishnan, et al. ”The management of spasticity in adults”, BMJ 2014;349:g4737.

** CANADIAN BEST PRACTICE RECOMMENDATIONS FOR STROKE CARE. Fourth Edition Lindsay MP, Gubitz G, Bayley M, Phillips S (Editors), on

Behalf of the Canadian Stroke Best Practices and Standards Working Group

Kinesiotherapy and Physical Agents

• Strengthening

– Meta-analysis - 15 RCTs

– strengthening exercises improved strength and activity after

stroke

– did not worsen spasticity*

– the presence of spasticity should not limit the use of strength

training of the leg**

• Evidence level **

– early - C

– late - C

* Ada L, Dorsch S, Canning CG. Strengthening interventions increase strength and improve activity after stroke: a systematic review. Aust J

Physiother 2006;52:241-8.

** CANADIAN BEST PRACTICE RECOMMENDATIONS FOR STROKE CARE. Fourth Edition

Kinesiotherapy and Physical Agents

• Constraint Induced Movement Therapy

– n = 10 patients

– reduction in spasticity, using MAS*

* Kagawa S, Koyama T, Hosomi M, Takebayashi T, Hanada K, Hashimoto F, et al. Effects of constraint-induced movement therapy on spasticity in

patients with hemiparesis after stroke. J Stroke Cerebrovasc Dis 2013;22:364-70

Kinesiotherapy and Physical Agents

• Other physical modalities

* Thibaut, Aurore, et al. "Spasticity after stroke: Physiology, assessment and treatment." Brain Injury 27.10 (2013): 1093-1105.

** Nair, Krishnan, et al. ”The management of spasticity in adults”, BMJ 2014;349:g4737

Kinesiotherapy and Physical Agents

• Cryotherapy

• Thermotherapy

• Hydrotherapy

• Ultrasound

• Transcutaneous electrical stimulation

• Extracorporeal shock wave therapy

• Whole body vibration

• Vibratory stimulation

• Neuro-developmental inhibitory

techniques

• Transcranial magnetic stimulation

• Transcranial direct current stimulation

• Electromyography biofeedback

• Acupuncture

Used to relax muscles and reduce the intensity of spasticity*

• Other physical modalities

– require further evidence before they can be recommended for

the treatment of spasticity*

– Future studies should also investigate their effectiveness

* Ada L, Dorsch S, Canning CG. Strengthening interventions increase strength and improve activity after stroke: a systematic review. Aust J

Physiother 2006;52:241-8.

** Kagawa S, Koyama T, Hosomi M, Takebayashi T, Hanada K, Hashimoto F, et al. Effects of constraint-induced movement therapy on spasticity in

patients with hemiparesis after stroke. J Stroke Cerebrovasc Dis 2013;22:364-70

Kinesiotherapy and Physical Agents

• Neuro-developmental inhibitory techniques

– reduction of spasticity

– promote postural reflexes prior to facilitating voluntary activity

– few studies showed that this technique is efficient to reduce

spasticity in stroke patients

* Ansari NN, Naghdi S. The effect of Bobath approach on the excitability of the spinal alpha motor neurons in stroke patients with muscle spasticity.

Electromyography & Clinical Neurophysiology 2007;47:29–36.

Kinesiotherapy and Physical Agents

Pharmacologic Management of

Spasticity Following Stroke

Oral Drug Therapytizanidine, dantrolene, oral baclofen

Baclofen

– most commonly administered oral treatment

– potential adverse effects• sedation, fatigue and drowsiness

– a second treatment line in patients with stroke, especially

during early rehabilitation

– proven efficacy in reducing spasticity on the Ashworth scale*

* Hattab JR Review of European clinical trials with baclofen In: Feldman RG,Young RR, Koella WP, editors. Spasticity: Disordered

Motor Control. Chicago, Year Book; 1980. p. 71-85

Oral Drug Therapy

Baclofen

– Some data support its use in stroke*

– Less impact on spasticity in stroke victims** • appears to be less beneficial**

– Caution in the recovery phase of brain injury

• some evidence of deleterious effects on brain plasticity***

* Milanov IG. Mechanisms of baclofen action on spasticity. Acta Neurol Scand 1992; 85: 305-10

** Pedersen E, Arlien-Soborg P, Mai J. The mode of action of the BAGA derivative baclofen in human spasticity. Acta Neurol Scand 1974;

50: 665-80

*** Simon O, Yelnik AP. Managing spasticity with drugs. Eur J Phys Rehabil Med. 2010;46:401–10.

Oral Drug Therapy

Tizanidine

– When baclofen is ineffective, contra-indicated or produces

adverse effects (professional consensus)

– Efficient in chronic stroke patients

– Improvement in spasticity and pain without loss of motor

strength, in an open label dose titration study*

Oral Drug Therapy

*Gelber DA, Good DC, Dromerick A, et al. Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment

of spasticity associated with chronic stroke. Stroke. 2001;32:1841–1846

Tizanidine should be used specifically for chronic stroke patients [Recommendation: Level B]

Tizanidine vs Baclofen*

– tizanidine (max. 20 mg/d) / baclofen (max. 50 mg/d)

– n = 30, lower limb spasticity; chronic stroke

– tizanidine

• 86.6% - improvement in muscle tone (p < .01)

– baclofen

• 78.6% - improvement in muscle tone (p < .01)

– no statistical difference between the 2 treatment groups

* Medici M, Pebet M, Ciblis D. A double-blind, long-term study of tizanidine in spasticity due to cerebrovascular lesions. Curr Med Res

Opin. 1989;11:398.

Oral Drug Therapy

Tizanidine vs Placebo*

– RCT

– n = 23; lower extremities, severe spastic hypertonia

– tizanidine: improvement in AS scores (p < .0001)

– significant difference between tizanidine and placebo after 4

weeks of treatment (p = .0006)

*Meythaler JM, Guin-Renfroe S, Johnson A, Brunner RM. Prospective assessment of tizanidine for spasticity due to acquired brain

injury. Arch Phys Med Rehabil. 2001;82:1155–1163

Oral Drug Therapy

Tizanidine vs Botulinum Neurotoxin

– RCT (n=60)

– BTx-A into spastic upper limb muscles vs oral tizanidine (TZD),

or placebo

– BTx-A produced greater tone reduction than TZD or placebo

in finger and wrist flexors at

• week 3 (p<.001 vs TZD; p<.02 vs placebo)

• week 6 (p = .001 vs TZD; p = .08 vs placebo)

Simpson DM, Gracies JM, Yablon SA, Barbano R, Brashear A; BoNT/TZD Study Team. J Neurol Neurosurg Psychiatry. 2009

Apr;80(4):380-5. doi: 10.1136/jnnp.2008.159657. Epub 2008 Oct 31. Botulinum neurotoxin versus tizanidine in upper limb spasticity: a

placebo-controlled study.

Oral Drug Therapy

Dantrolene

– Sedative effect in doses > 200 – 300 mg

– limited trial data to support its use in stroke*

– Katrak et al. (1992)• patients on Dantrolene Sodium early after a stroke, before the onset

of disabling spasticity, produced no change in clinical tone or

functional outcome**

*Ketel WB, Kolb ME. Long-term treatment with dantrolene sodium of stroke patients with spasticity limiting the return of function. Curr Med

Res Opin.1984 ;9:161–169

**Katrak PH, Cole AM, Poulos CJ, McCauley JC. Objective assessment of spasticity, strength, and function with early exhibition of

dantrolene sodium after cerebrovascular accident: a randomized double-blind study. Arch Phys Med Rehabil.1992 ;73:4–9

Oral Drug Therapy

Benzodiazepines (Clonazepam, Diazepam)

– no longer recommended

» studies on benzodiazepines in post-stroke rehabilitation

showed some detrimental effects*

*Hesse S, Werner C. Poststroke motor dysfunction and spasticity: Novel pharmacological and physical treatment strategies. CNS Drugs

2003;17:1093–1107.

Oral Drug Therapy

Gabapentin

– anticonvulsant, used for neuropathic pain

– effective for decreasing spasticity at high doses (2400–3600

mg/day)*

*Lapeyre E, Kuks JB, Meijler WJ. Spasticity: Revisiting the role and the individual value of several pharmacological treatments.

NeuroRehabilitation 2010;27:193–200

Oral Drug Therapy

Recommendations

• tizanidine and baclofen if associated with pain or decreased function

• diazepam or other benzodiazepines not recommended - possible deleterious effects on recovery* ** ***

• tizanidine specifically for chronic stroke patients

*Goldstein LB. Common drugs influence motor recovery after stroke. The Sygen In Acute Stroke Study Investigators. Neurology. 1995;45: 865– 871.

**Goldstein LB. Potential effects of common drugs on stroke recovery. Arch Neurol. 1998;55:454 – 456.

***Troisi E, Paolucci S, Silvestrini M, Matteis M, Vernieri F, Grasso MG, Caltagirone C. Prognostic factors in stroke rehabilitation: the possible role of

pharmacological treatment. Acta Neurol Scand. 2002;105: 100 –106.

Oral Drug Therapy

• Tizanidine and baclofene• still missing efficient (“good”) oral drugs for systemic spasticity

• Diazepam or other benzodiazepines• MD’s are not aware of this recommendation

Oral Drug Therapy

Pharmacologic Management of

Spasticity Following Stroke

Intrathecal baclofen

Intrathecal baclofen

• Stroke

• “...reported efficacy in reducing spasticity”

• “significant improvements in FIM...”

• “significant decreases from baseline in AS...”

• but “...limited evidence...” (2b level evidence)

• Systematic Review

• 2 studies with ITB

alone, no RCT

Pharmacologic Management of

Spasticity Following Stroke

Botulinum Toxin Injection

Therapy

BTx-A treatment

Botulinum toxin type A – BTx-A

• BTx-A• management of movement disorders, including upper and

lower limb spasticity *

• BTx-A• has not been as well studied in the lower extremity compared

with the upper

• BTx-A• high safety/efficacy profile - largely demonstrated in the last two

decades **

* Jörg Wissel et al. J Rehabil Med 2009

** Simpson DM. et al, Neurology 2008

Spasticity treatment

* Spasticity in adults: management using botulinum toxin. National guidelines 2009. The Royal College of Physicians

* Spasticity in adults: management using botulinum toxin. National guidelines 2009. The Royal College of Physicians

UPPER LIMB – BTx-A

* Spasticity in adults: management using botulinum toxin. National guidelines 2009. The Royal College of Physicians

UPPER LIMB – BTx-A

LOWER LIMB – BTx-A

* Spasticity in adults: management using botulinum toxin. National guidelines 2009. The Royal College of Physicians

LOWER LIMB – BTx-A

* Spasticity in adults: management using botulinum toxin. National guidelines 2009. The Royal College of Physicians

Simpson DM, 2008 *

BTx-A treatment

* Simpson DM. et al, Neurology 2008

• Kaji et al. (2010)

– n = 120, lower limb spasticity post-stroke > six months

– 300 U Botox® vs placebo

– treatment group - significant ↓ MAS scores at weeks 4, 6 and 8

– no significant differences between groups at weeks 10 and 12

Kaji R, Osako Y, Suyama K, Maeda T, Uechi Y, Iwasaki M; GSK1358820 Spasticity Study Group. Botulinum toxin type A in post-stroke

upper limb spasticity. Curr Med Res Opin. 2010 Aug;26(8):1983-92

BTx-A treatment

• Dunne et al. (2012)

– 85 stroke patients (≥ 6 weeks post stroke)

– 200 U (n=28), 300 U Botox® (n=28) or saline

– two Botox® groups

• significantly greater improvement in Ashworth Scale

scores, pain, spasm frequency and the patients who

experienced ≥ 15% increase in ankle dorsiflexion, week 12

Dunne JW, Gracies JM, Hayes M, Zeman B, Singer BJ; Multicentre Study Group. A prospective, multicentre, randomized, double-blind,

placebo-controlled trial of onabotulinumtoxinA to treat plantarflexor/invertor overactivity after stroke. Clin Rehabil. 2012 Sep;26(9):787-97.

BTx-A treatment

• Turner-Stokes L. et al (2013) – ULIS II

– Observational, prospective study

– 84 secondary care centers in 22 countries

– n = 456 adults, post stroke upper limb spasticity

– one cycle of BTx-A

– primary outcome: achievement of the patient’s primary goal for

treatment using GAS

Turner-Stokes L, Fheodoroff K, Jacinto J, et al. BMJ Open 2013;3:e002771

BTx-A treatment

• Turner-Stokes L. et al (2013) – ULIS II

– 79.6% - (n=363) achieved (or overachieved) their primary goal

– 75.4% - (n=355) achieved their secondary goal

– active function goals - 67% (n=122) achieved

• 40.1% (73) - as expected

• 26.9% (49) - beyond expectation

Turner-Stokes L, Fheodoroff K, Jacinto J, et al. BMJ Open 2013;3:e002771

BTx-A treatment

• Serrano S. et al (2014)

– inferential, retrospective study (3 years) – n=28

– evaluate clinical and functional responses to BTX-A in UL

spasticity

– GAS after treatment - ↑ 10,8 points (p <.001)

– Tonus (MAS)

• elbow - ↓ 0,6 degrees (p <.001)

• wrist - 0,8 (p <.001)

• fingers - 0,6 (p= .001)

Serrano S, Constantino J, Januário F, Amaral C. Upper Limb Spasticity: Efficacy and Safety Evaluation of Botulinum Toxin and GAS

Usefulness – Retrospective Study. Revista da SPMFR Vol 25 I Nº 1 I Ano 22 (2014)

BTx-A treatment

• Serrano S. et al (2014)

Serrano S, Constantino J, Januário F, Amaral C. Upper Limb Spasticity: Efficacy and Safety Evaluation of Botulinum Toxin and GAS

Usefulness – Retrospective Study. Revista da SPMFR Vol 25 I Nº 1 I Ano 22 (2014)

BTx-A treatment

• Dashtipour et al. 2015

– 12 RCTs

– strong evidence base (9/12 studies) exists for the use of Dysport®

to reduce upper limb spasticity (ULS) caused by stroke

– statistical significance in MAS reduction, effects on active

movement and pain

Dashtipour K, Chen JJ, Walker HW, Lee MY. Systematic literature review of abobotulinumtoxinA in clinical trials for adult upper limb

spasticity. Am J Phys Med Rehabil. 2015 Mar;94(3):229-38.

BTx-A treatment

Identifying gaps regarding

comprehensive patient management

Spasticity treatment

BTx-A

• The majority are small, short-term studies

• Improvements at the level of impairment (i.e. reduction of tone and

increased range of movement) are readily demonstrated…

• …it is harder to show that these are translated into changes at

the level of activity or participation

* Jörg Wissel et al. J Rehabil Med 2009

** Simpson DM. et al, Neurology 2008

Stroke Rehabilitation

• Stroke Rehabilitation

repetitive

task specific

intensive

• Stroke Rehab

repetitive

task specific

intensive

• better if patient

high vigilance

actively involved

based on the interests of the patient

Stroke Rehabilitation

jorgelains@sapo.pt

jorgelains@roviscopais.min-saude.pt

Espasticidade - evidências: tratamento

medicamentoso e não medicamentoso

jorgelains@sapo.pt

jorgelains@roviscopais.min-saude.pt