new developments in spasticity...
TRANSCRIPT
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New Developments in Spasticity ManagementIleana Howard, MDCinda Hugos, MS, PT
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DisclosuresThe speakers have no financial interests to disclose
PESG and PVA staff have no interest to disclose.
This continuing education activity is managed and accredited by Professional Education Services Group in cooperation with PVA. PESG, PVA, and all accrediting organization do not support or endorse any product or service mentioned in this activity.
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Learning Objectives1. List two patient‐centered outcome measures that can be used to measure the
burden of spasticity symptoms for Veterans with spinal cord injury or disorders.
2. Name three non‐pharmacologic/conservative treatment interventions for spasticity and explain when they should be implemented for patient care.
3. Explain the indications for spasticity management with botulinum toxin for Veterans with spinal cord injury or disorders.
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Introduction
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Most persons with SCI/D have spasticity.
Chronic SCI (> 1 yr post‐injury): 65% (Holz, 2017)* “Problematic” spasticity 30‐40% 1‐5 years out
MS: up to 84% (Rizzo, 2004) patients with MS report some spasticity
ALS: 84% endorse “muscle stiffness” (Nicholson et al, 2017)
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Spasticity Can Be Good or Really Bad
Uninhibited contraction of muscles
Difficulty with movement
Contractures
Pain
Debility
Immobility
Ulceration
Maintains muscle bulk
Helpful with transfers
Connection to paretic limbs
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Recognizing Spasticity
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Classic definition from 1980 (Lance)Spasticity is a motor disorder characterized by a velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitabilityof the stretch reflex, as one component of the upper motor neuron syndrome.
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Patient‐centered description of spasticityNorth American Research Committee on MS (NARCOMS) registry (Rizzo, 2004)Unusual tightening of muscles that feels like leg stiffness
Jumping of the legs
A repetitive bouncing of the foot
Muscle cramping in legs or arms
Legs going out tight and straight
Legs drawing up
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Quantifying Spasticity
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Spasticity Outcome MeasuresObjectiveH‐reflexTorque
Subjective, Clinician‐RatedNeurological ExamPendulum TestMASTardieu
Subjective, Patient ReportedNRSMS‐88ALS‐SI
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Neurological exam ‐ clinical0 1 2 3 42 to 2+ is ‘normal’ muscle tone1 is less than normal tone3 is more than normal tone4 is sustained clonus
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The Pendulum Test
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Ashworth Scale/Modified Ashworth Scale (MAS) (clinical?/research)0 = no increase in tone1 = a slight increase in tone with a ‘catch’1+ = slight increase in tone with a catch followed by minimal resistance throughout the remaining ROM (omit for original Ashworth scale)2 = marked increase in tone but still easily moved3 = considerable increase in tone making movement difficult4 = the limb is rigid
Bohannon, 1987
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Criticisms of the Ashworth/Modified Ashworth ScalesQuestionable validitySubjective by the examinerOnly passive resistance to movement and/or quick stretchDo not capturePatient experienceLevel of voluntary and reflex activity in the alpha motor neuron of agonist or antagonist muscle groupsViscoelastic properties of joints or soft tissueTime of day, temperature, fatigueFunctional activity
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References for MAS criticismsPandyan, Johnson, Price, et al. A review of the properties and limitations of the ashworth and modified ashworth scales as measures of spasticity. Clin Rehabil. 1999; 13(5):373‐383.Ansari, Naghdi, Moammeri, et al. Ashworth Scales are unreliable for the assessment of muscle spasticity. Physiother Theory Pract. 2006; 22(3):119‐25.Nuyens, De Weerdt, Ketelaer, et al Inter‐rater reliability of the Ashworth scale in multiple sclerosis. Clinical Rehabilitation 1994; 8(4):286–292Fleuren JFM, Voerman GE, Erren‐Wolters CV, et al. Stop using the Ashworth Scale for the assessment of spasticity. J Neurol NeurosurgPsychiatry 2010 81: 46‐53.
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Measuring spasticity – patient subjectiveSpasm Frequency ScalePatient counts and records number of spasms per hour or per day
Visual Analog Scale – Numeric Rating Scale for Spasticity (NRS‐S)Patient subjective score
Multiple Sclerosis Spasticity Scale – 88 (MSSS‐88)Patient subjective score
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Spasm Frequency Scale –clinical?/research0 = No spasms in one hour/day
1 = No spontaneous spasms – except with vigorous stimulation
2 = Occasional spontaneous spasm and easily induced spasms
3 = More than 1 but less than 10 spontaneous spasms per hour/day
4 = More than 10 spontaneous spasms per hour/day
Penn, 1989
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Visual Analog Scale (VAS) –clinical/research
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Numeric Rating Scale for Spasticity (NRS‐S) –Measures the severity of spasticity –clinical/research
Farrar, 2008
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Multiple Sclerosis Spasticity Scale (MSSS‐88) – clinical??/researchMeasures the impact of spasticityScores 88‐352: 1=not at all bothered – 4=extremely bothered8 clinically relevant areas with total score and stand alone subscalesMuscle stiffness – 12 questionsPain and discomfort – 9 questionsMuscle spasms – 14 questionsActivities of daily living – 11 questionsWalking – 10 questionsBody Movements – 11 questionsEmotional health – 13 questionsSocial functioning – 8 questions
Hobart, 2006
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MSSS‐88 – sample questions
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brief and reliable patient reported outcome measure of spasticity 20 items with a simple 4‐level Likert scale valid irrespective of age, sex, disease duration and type measures limb and bulbar spasticity
Spasticity Index‐ALS
Muscle stiffnessSpasms
Bulbar spasms, characterised by sudden laryngeal closure and in the most extreme cases causing interference with breathing
Young et al, 2018
Measuring Spasticity in MND/ALS
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ALS‐Spasticity Index (ALS‐SI)‐ excerpt
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Treating Spasticity: Conservative Interventions
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Stepwise Approach to Spasticity TreatmentRehabilitation/Exercise
Complementary and Integrative Medicine
Oral medications
Injection therapies
Surgical treatments
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Rehabilitation – first line treatmentSkilled physical and occupational therapyStretchingPositioningOrthotics/FESCastingStrengtheningLight pressure/StrokingCold/HeatTENS/Electrical stimulationMagnetic stimulation
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TENS for spasticity4 weeks baclofen (10 mg BID) or self‐applied TENS
26 treated with TENSMAS decreased from 1.77 (0.29) to 0.73 (0.70), (P<0.001)
26 treated with baclofenMAS decreased from 1.73 (0.38) to 1.15 (0.63), (P<0.001)
Mean difference in MAS at 4 weeks significantly lower in TENS than baclofenMean difference ‐0.42; 95% CI, ‐0.79, ‐0.05; P<0.05)
TENS may be preferred with better MAS and side effect profile of baclofen
(Shaygannejad, 2013)
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TENS for spasticitySystematic reviewIncluded the above and one earlier study in MSLevel 1 and 2 evidence for short‐term effectiveness for management of spasticity in various neurologic etiologies
Mills, 2016
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Repetitive Transcranial Magnetic Stimulation (rTMS)/Intermittent Theta Burst Stimulation (iTBS)19 RRMS, primarily single lower limb spasticity15 daily stimulations at 5 Hz with rTMS with figure 8 coil over primary motor cortex lasting 1 weekSingle session 5 Hz (fast) reduced reflex activity and increased motor evoked potential amplitude and 1 Hz (slow) had the opposite effect. (Centonze, 2017)20 RRMS, primarily single lower limb spasticity2 week daily real or sham iTBS over primary motor cortex of LEMAS improved significantly and maintained for 1 month
(Mori, 2010)Encouraging results, unknown availability
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Functional Electrical Stimulation (FES)Bioness L300 Go
WalkAide
No specific evidence for spasticity management found
Reasonably good evidence for walking disability in MS and other conditions
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StretchingWhat is stretching:Elongation via applied tension to the soft‐tissue structures of muscle, tendon, connective, vascular, dermal and neural tissueThis tension and resulting elongation may change viscoelastic, structural and excitability properties in the stretched muscle
Goal of stretching for spasticity:Normalize muscle tone, maintain or increase soft‐tissue extensibility, decrease pain, and improve function
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What Do We Know –MS and Spasticity1992‐93 survey of MS Centers practitioners in North America, 93% (14 of 15) reported stretching was effective and used frequently for MS‐related spasticity without research evidence
Finding of literature review:Minimal evidence exists beyond belief that regular stretching reduces spasticity, improves functional mobility and helps to prevent complications such as contracturesBetter measures of spasticity are needed to capture spasticity from the patient’s perspective Questions endorsed to drive future researchDoes a program of daily stretching result in decreased severity of spasticity? Does a program of daily stretching result in improved functional mobility?”
Chan, 1994
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Spasticity guidelineRecommends stretching at every stage of the disease
Multiple Sclerosis Council for Clinical Practice Guidelines. Spasticity Management and Multiple Sclerosis: Evidence‐based management strategies for spasticity in multiple sclerosis. 2003.Haselkorn J, Loomis S. Multiple sclerosis and spasticity. [Review] [64 refs]. Physical Medicine & Rehabilitation Clinics of North America. 16(2):467‐81, 2005 May
Those more disabled and/or with more spasticity need someone to do it for them (MAS 3 and up, at least)Daily patient burdenAdditional daily caregiver burdenLittle to no evidence to support itLike ‘failing’ medications, if patient worsens, it is blamed on the patient and/or caregiver
Didn’t do itDidn’t do it rightDidn’t do it enough
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Systematic reviewsReviewers found the available evidence was inconclusive on the clinical benefit of stretching for spasticity of any origin
They emphasized that future research in the field of stretching for spasticity provides a clear paradigm for stretching, appropriate outcome measures and clinical importance
Bovend'Eerdt TJ, Newman M, Barker K, et al. The effects of stretching in spasticity: A systematic review. Arch Phys Med Rehabil. 2008;89(7):1395‐1406
Non‐pharmacologic interventions for spasticity in MSLow levels of evidence or no evidence
Amatya B, Khan F, La Mantia L, et al. Non pharmacological interventions for spasticity in multiple sclerosis (Review). The Cochrane Collaboration. 2013
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Cochrane ReviewsStretch for contractures Stretch does not have clinically important effects on joint mobility in people with, or at risk of, contractures if performed for less than seven monthsThe effects of stretch performed for periods longer than seven months have not been investigated
Katalinic OM, Harvey LA, Herbert RD, Moseley AM, Lannin NA, Schurr K. Stretch for the treatment and prevention of contractures. Cochrane Database of Systematic Reviews. 2010Katalinic OM, Harvey LA, Herbert RD. Effectiveness of stretch for the treatment and prevention of contractures in people with neurological conditions: A systematic review. Phys Ther. 2011;91(1):11‐24
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Stretching for MS‐related spasticityEmpirical evidenceMuscles shorten when they contractSeems logical to apply the opposite condition, i. e. stretching or elongating muscle tissue, to counteract the shortening effect of the spasticity contracting stimulus.
Actual evidence30 PwMS and spasticity in the quadricepsSignificant improvement on the MAS with oral baclofen and baclofen combined with stretching exercises compared to placebo or placebo with stretching exercisesAdding stretching exercises to baclofen treatment resulted in a trend for further benefit
Brar SP, Smith MB, Nelson LM, et al. Evaluation of treatment protocols on minimal to moderate spasticity in multiple sclerosis. Arch Phys Med Rehabil. 1991 Mar;72(3):186‐9
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MS Spasticity: Take Control (STC)28‐minute educational DVD information about MS‐related spasticity
20‐minute lower stretching DVD teaches a standardized, yet individualized, program of stretching for MS‐related spasticityAny one of the exercises in each group is sufficient to provide an adequate stretch when applied as instructed, in nearly anyone with MS of any ambulatory ability
Participant manuals Photos with written instructions for all the stretch options
Facilitator manuals
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MS Spasticity: Take Control (STC)
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MSSS Total Score in STC pilot
0
50
100
150
200
250
MSSS Mean (SD)
STC Baseline STC Followup UC Baseline UC Followup
*
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MSSS Subscale Scores in STC pilot
0
5
10
15
20
25
30
35
40
45
50
Muscle stiffness Pain and discomfort Muscle spasms ADL Body movements Walking Emotional health Social functioning
MSSS Mean (SD)
SubscaleSTC Baseline STC Followup UC Baseline UC Followup
**
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Cannabis and spasticity
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AAN Systematic Review – CAM in MSComplementary and alternative medicine (CAM) in MS
Spasticity: Nabiximols (Sativex oral spray), oral cannabis extract (OCE) and synthetic THC are probably effective at reducing patient‐reported symptoms of spasticity (LEVEL 1). However, OCE and synthetic THC were not found to be effective for spasticity when it was measured on tests administered by a physician
Yadav, 2014
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AAN Systematic Review ‐Medical marijuana in selected neurological disorders
Medical marijuana in selected neurological disorders
The only strong evidence was in MS, for reducing patient‐reported spasticity
Koppel, 2014
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JAMA Systematic ReviewEvaluated 11 randomized studies with a total of 2138 patients comparing the effect cannabinoids with placebo on spasticity related to MS.
Although the specific details of the studies vary, most studies suggest that cannabinoids are associated with improvements in self‐reported spasticity.
The improvements in objectively measured spasticity generally do not reach statistical significance
(Whiting, 2015)
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Nabiximols and spasticityNovotna 2011 – the pivotal phase III trial572 people, single blind all active for 4 weeks (phase A), followed by 12 weeks double blind (phase B) for those who had ≥ 20% improvement in NRS spasticity (n=272, with 241 randomized)Many countries in EuropeNabiximols (max 12 sprays/32mg/day) or placeboOutcomes:Primary: Spasticity NRSSecondary: responder analysis, spasm frequency score, sleep disturbance NRS, global impression of change
The group taking nabiximols had significantly improved self‐reported spasticity (p=0.0002 ITT)There was also improvement in sleep disturbances (secondary outcome) (p<0.0001)Mean dose: Phase A: 19mg/day, Phase B: ~23mg/day
(Novotna, 2011)
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Adverse EffectsPrimarily: Dizziness, confusion, somnolence/drowsiness, fatigue, nausea, dry mouth, increased appetite
Can worsen cognitive dysfunction in MSOne study comparing 25 regular cannabis users with 25 non‐users, and another comparing 20 users with 19 non‐users, overall users had:Slower information processing speed (PASAT)Worse working memory (2‐back)Worse executive functionAnd, were twice as likely to be cognitively impaired
Honarmand, 2011; Pavisian, 2014; Romero, 2015)
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Cannabinoids for spasticity in MS conclusionsDEA Schedule 1, not FDA approved in US
Data support that it works (reduces severity) for self‐reported spasticity
All RCT data is from oral or oromucosal spray preparations, not smoked cannabis
~50% seem to keep using, ~ 50% stop due to lack of efficacy or AEs
DoseVariesStart low and allow patients to self‐titrate upMost use ~ 20‐40mg THC/day in divided doses
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Conclusions continuedCannabis is increasingly available to our patients with MS and there is growing interest in its use
Multiple forms and formulations are available
In multiple sclerosis, the best evidence for benefit is for reduction of patient reported spasticity, with ~ 50% of subjects reporting benefit
The risks in this population are likely similar to those in other populations
In addition, the most clearly specific risk in this population is worsening of cognition
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Treating Spasticity: Medications
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Medications used to treat spasticityBaclofen
Tizanidine
Dantrolene
Benzodiazepines (diazepam)
Gabapentin
**Poor adherence to these medications (Halpern, 2013)
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How Effective are these Medications in ALS?Evidence for medications to treat ALS‐related spasticity:
‐No medication trials met threshold criteria for inclusion
Cochrane Review (Ashworth, 2012)
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Baclofen for Spasticity in ALS20 Patients Enrolled and Randomized‐9 baclofen‐11 placebo
Baclofen titrated to 80 mg/day over 2
weeks
5 patients responded
favorably at 5 weeks follow‐
up
“administration of diazepam in doses of 80 to 100 mg/day gave only about 50% of the benefit associated with baclofen administration and at the cost of major sedation.” Norris, 1979
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What’s New in Spasticity Medications?Limitations of traditional baclofen (R‐baclofen):Short half‐lifeOnly absorbed in proximal small intestine, therefore extended release not possible
Arbaclofen: R‐baclofen pro‐drugExtended releaseBid dosingAbsorbed throughout intestine
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Arbaclofen studies in SCI354 patients with MS enrolled in double‐blind RCT comparing baclofen, arbaclofen ER, and placebo (Kaba, 2016)10‐20mg bidbaclofen and arbaclofen= similar effect on spasticityLess drowsiness and dizziness in arbaclofen
37 patients with SCI enrolled in randomized, placebo‐controlled crossover study (Nance, 2011)Doses 10mg, 20mg, 30mg bidSignificant improvement in spasticity at 20mg and 30mgLow prevalence of adverse effects (AE), and no discontinuations due to AE
dizziness (5.4%)somnolence (2.7%) weakness (2.7%
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Levetiracetam (Keppra) for spasticity•Small study performed at UT Southwestern (Dallas) on 12 patients with MS•Levetiracetam was prescribed 250mg per day, titrated up to 3,000mg per day
• Average dose 1,583 mg (+/‐ 633mg) per day
•Penn Spasm Frequency Score decreased 2.7 (+/‐ 0.65) ‐> 0.9 (+/‐ 0.29) with treatment•Modified Ashworth Scale did not change
Hawker et al. 2003
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Levetiracetam (Keppra) for spasticity
Adverse Effects:
Drowsiness: 2/12 (dose decreased)
Nausea: 1/12
Constipation: 1/12
Edema: 1/12 (drug discontinued)
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Treating Spasticity:Botulinum Toxin
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Botulinum toxin: When to refer
Symptoms poorly controlled by conservative means/oral medications
Poor adherence to conservative means/oral medications
Intolerable side effects of oral medications
Focal spasticity symptoms
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Botulinum toxin: FDA approval for Lower Extremities, 2017
Gracies, 2017
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Botulinum Toxin for Lower Extremities28 ambulatory persons with MS
100 units incobotulinum toxin injected into the gastroc/soleus bilaterally
Significant sustained improvement in the 6MWT
Gallien et al, 2017
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Botulinum toxin: Mega dosesEvidence for safety of larger doses 600‐800 units
Concern over safety/long term effects of high‐dose injections
(Pingel, 2017)
(Baricich, 2015)
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Botulinum toxin: Frequent injections Previously, 3‐month intervals between injections recommended
Lower immunogenicity for botulinum toxin produced after 1998 Attributed to lower protein load ~10% (4/42) prevalence of Abs prior to
1998 0% (0/119) prevalence after 1998
New evidence for safety of decreased interval between injections (as low as 1 month)
Trompetto, 2017Jankovic, 2003
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Botulinum Toxin for ALSTraditional contraindications for botulinum toxin: Neuromuscular disorders‐including neuromuscular junction disorders (Myasthenia Gravis) and ALS
Case series describing safe and effective use of botulinum toxin in 7 persons with ALS (Vazquez‐Costa, 2016)
Case series of 44 patients with PLS treated with botulinum toxin for spasticity; 16 patients had motor blocks performed before botulinum toxin injections (Mazevet, 2017)
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Botox for Trismus in ALS Botulinum toxin doses range 25‐100 total units
Target muscles: masseter, lateral pterygoid, temporalis
Winterholler, 2002Clark, 2003
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Intrathecal Baclofen
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ITB vs. Oral Baclofen for SCI
McCormick, 2016
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ITB for the ambulatory person with MS
Lee, 2017
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ITB for the ambulatory person with MS•Reduction in MAS
•Reduction in NRS•Modest, significant improvement in T25FW
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Intrathecal Baclofen for ALS Case Report published in 1999 (Marquardt)
Case series of 8 patients with ALS (McClelland, 2007)
• Goal was pain reduction • 6/8 patients (75%) experienced pain reduction• Average pain reduction 54%• 3/8 with complete relief
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Lanig, 2017
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Summary
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1. Assume your patient with SCI/D has spasticity. ~80% of patients with SCI/D have spasticity
Consider using BOTH a provider subjective and patient subjective measure of spasticity:MAS Penn Spasm Frequency ScaleTardieu VAS/NRS
Consider a disease‐specific tool MS‐88ALS‐SI
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2. Don’t discount the effectiveness of modalities/integrative medicine interventionsTENS
FES
Stretching
Cannabis
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3. Refer for injections or pump trial when neededBotulinum Toxin
Focal spasticity
Inadequate response from other measures
Adverse effects from other treatments
Intrathecal Baclofen
Widespread spasticity
Lower extremity predominant symptoms
Inadequate response from other treatments
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4. ALS is not a contraindication to treatment of spasticity•Don’t be a therapeutic nihilist!
•Limited evidence for medications apart from small baclofen study
•Botulinum toxin and intrathecal baclofen having growing evidence as tools for managing ALS‐related spasticity
•Don’t forget to assess for bulbar spasticity symptoms
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Works ReferencedAshworth NL, Satkunam LE, Deforge D. Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database of Systematic Reviews. 2012(2).Baricich A, Grana E, Carda S et al. “High Doses of onabotulinum toxin A in post‐stroke spasticity: a retrospective analysis.” J Neural Transmission 2015; 1283‐1287Bohannon RW, Smith MB. Inter rater reliability of a modified Ashworth Scale of muscle spasticity. Phys Ther 1987; 67: 206–207Centonze, Koch, Versace, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27;68(13):1045‐50.Chan A, Hugos C, Morrison S, et al. Balance and Spasticity: What We Know and What We Believe. Neurorehabilitation and Neural Repair. 1994; 8(3):119‐130Farrar JT, Troxel AB, Stott C, et al. Validity, reliability, and clinical importance of change in a 0‐10 numeric rating scale measure of spasticity: a post hoc analysis of a randomized, double‐blind, placebo‐controlled trial. Clin Ther. 2008 May;30(5):974‐85
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Works ReferencedGallien P, Leblong E, Fraudet B, Petrilli S, Robineau S, Houedakor J. Therapeutic Benefit of Botulinum Toxin a (Incobotulinum Toxin) for the Treatment of Spasticity of the Triceps Suraein Multiple Sclerosis: An Observational Study. Phys Med Rehabil Int. 2017;4(6):1133.Gracies JM et. al. “Efficacy and Safety of abobotulinum toxin A in spastic lower limb: Randomized trial and extension.” Neurology 2017 2245‐2253Halpern R, Gilliard P, Graham G et al. “Adherence Associated with Oral Medications in the Treatment of Spasticity.” PM&R (5)9: 747‐756Hawker K, Frohman E, Racke M. Levetiracetam for phasic spasticity in multiple sclerosis. Archives of neurology. 2003 Dec 1;60(12):1772‐4.Hobart JC, Riazi A, Thompson AJ, et al. Getting the measure of spasticity in multiple sclerosis: The Multiple Sclerosis Spasticity Scale (MSSS‐88). Brain. 2006 Jan; 129:224‐34Holtz KA, Lipson R, Noonan VK, Kwon BK, Mills PB. Prevalence and effect of problematic spasticity after traumatic spinal cord injury. Archives of physical medicine and rehabilitation. 2017 Jun 1;98(6):1132‐8.
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Works ReferencedHonarmand K, et al. Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology. 2011; (76) 13:1153‐1160.Jankovic J; Vuong KD; Ahsan J. “Comparison of Efficacy and Immunogenecity of Original versus Current Botulinum Toxin in Cervical Dystonia.” Neurology April 8, 2003 60(7) 1186‐1188Kaba S, Kantor D, Tyle P. The Safety and Efficacy of Arbaclofen Extended Release Tablets in the Treatment of Spasticity in Patients with Multiple Sclerosis. Archives of Physical Medicine and Rehabilitation. 2016 Oct 1;97(10):e91.Koppel BS, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Apr 29;82(17):1556‐63.Lanig IS, New PW, Burns AS, Bilsky G, Benito‐Penalva J, Bensmail D, Yochelson M. Optimizing the Management of Spasticity in People With Spinal Cord Damage: A Clinical Care Pathway for Assessment and Treatment Decision Making From the Ability Network, an International Initiative. Archives of physical medicine and rehabilitation. 2018 Feb 8.
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Works ReferencedLance JW. Symposium synopsis. In: Feldman RG, Young RR, Koella WP, eds. Spasticity: disorder of motor control. Chicago: Year Book Medical Publishers; 1980:485‐94Marquardt G, Lorenz R. Intrathecal baclofen for intractable spasticity in amyotrophic lateral sclerosis. Journal of neurology. 1999 Jul 1;246(7):619‐20.Mazevet D; Deffontaines S et al. “Botulinum toxin for treatment of spasticity in patients with primary lateral sclerosis.” Annals Phys Med Rehab 2017 60 e24Mills, Dossa. Transcutaneous Electrical Nerve Stimulation for Management of Limb Spasticity: A Systematic Review. Am J Phys Med Rehabil; 2016, 95(4):309–318McClelland III S, Bethoux FA, Boulis NM, Sutliff MH, Stough DK, Schwetz KM, Gogol DM, Harrison M, Pioro EP. Intrathecal baclofen for spasticity‐related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine. 2008 Mar;37(3):396‐8.
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Works ReferencedMcCormick ZL, Chu SK, Binler D, Neudorf D, Mathur SN, Lee J, Marciniak C. Intrathecal versus oral baclofen: A matched cohort study of spasticity, pain, sleep, fatigue, and quality of life. PM&R. 2016 Jun 1;8(6):553‐62. Mori, Codecà, Kusayanagi. Effects of intermittent theta burst stimulation on spasticity in patients with multiple sclerosis. Eur J Neurol. 2010 Feb;17(2):295‐300Nance PW, Huff FJ, Martinez‐Arizala A, Ayyoub Z, Chen D, Bian A, Stamler D. Efficacy and safety study of arbaclofen placarbil in patients with spasticity due to spinal cord injury. Spinal cord. 2011 Sep;49(9):974.Nicholson K, Murphy A, McDonnell E, Shapiro J, Simpson E, Glass J, Mitsumoto H, Forshew D, Miller R, Atassi N. Improving symptom management for people with amyotrophic lateral sclerosis. Muscle & nerve. 2017 May.Novotna A, et al. A randomized, double‐blind, placebo‐controlled, parallel‐group, enriched‐design study of nabiximols (Sativex(®) ), as add‐on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol. 2011 Sep;18(9):1122‐31.
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Works ReferencedPavisian B, et al. Effects of cannabis on cognition in patients with MS: A psychometric and MRI study. Neurology. 2014 May 27;82(21):1879‐87.Penn RD, Savoy SM, Corcos D, Latash M, Gottlieb G, Parke B, Kroin JS. Intrathecal baclofen for severe spinal spasticity. N Engl J Med. 1989 Jun 8;320(23):1517‐21Pingel J, Nielsen MS, Lauridsen T, Rix K, Bech M, Alkjaer T, Andersen IT, Nielsen JB, Feidenhansl R. Injection of high dose botulinum‐toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non‐fibrilar structures. Scientific reports. 2017 Nov 7;7(1):14746.Rizzo MA, Hadjimichael OC, Preiningerova J, et al. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler. 2004;10(5):589‐595Romero K; Pavisian B; Staines WR; et al. Multiple sclerosis, cannabis, and cognition: A structural MRI study. NeuroImage Clinical. 8:140‐7, 2015.
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