The Management of Spasticity after SCI A Systematic Review of the literature, 2000-2010

Systematic Review – Management of Spasticity Compiled by the Shepherd Center Study Group in Atlanta, GA. Innovative Knowledge Dissemination & Utilization Project for Disability & Professional Stakeholder Organizations/ NIDRR Grant # (H133A050006) at Boston University Center for Psychiatric Rehabilitation.

Systematic Review – Management of Spasticity A review was conducted using a system for rating the rigor and meaning of disability research (Farkas, Rogers and Anthony, 2008). The first instrument in this system is: “Standards for Rating Program Evaluation, Policy or Survey Research, Pre-Post and Correlational Human Subjects” (Rogers, Farkas, Anthony & Kash, 2008) and “Standards for Rating the Meaning of Disability Research” (Farkas & Anthony, 2008).

Shepherd Center Systematic Review Group Leadership Team: Reviewers: Lesley Hudson, MS David Apple, MD Deborah Backus, PhD, PT Rebecca Acevedo Leslie VanHiel, MSPT Jennith Bernstein, PT Amanda Gillot, OT Ashley Kim, PT Elizabeth Sasso, PT Kristen Casperson, PT Anna Berry, PT Liz Randall, SPT Data Coordinator: Editor:

Glossary of Abbreviations General SCI - Spinal cord injury ASIA – American Spinal Injury Association AIS – ASIA Impairment Scale ISNCSCI – International Standards for the Neurological Classification of Spinal Cord Injury Assessment (formerly ASIA exam)

Glossary of Abbreviations Research Studies and Interventions RCT – Randomized control trial LE – Lower extremity ROM – Range of motion TENS – Transcutaneous electrical nerve stimulation rTMS - Repeated transcranial magnetic stimulation eSCS - Spinal cord electrical stimulation FES – Functional electrical stimulation WBV – Whole body vibration

Glossary of Abbreviations Outcome Measures for Research Studies AS – Ashworth Scale MAS – Modified Ashworth Scale CSS - Composite spasticity score (based on several AS scores) VAS – Visual Analog Scale MPSFS – Modified Penn Spasm Frequency Scale SCATS – Spinal Cord Assessment Tool for Spastic Reflexes SCI-SET – Spinal Cord Injury Spasticity Evaluation Tool Hmax/Mmax – Electrophysiological ratio measure of neural excitability EMG - Electromyography

Definitions of Spasticity Involuntary muscle firing Velocity-dependent Increase resistance to stretch Abnormal processing of sensory input within networks of neurons in the spinal cord networks. There are many definitions of spasticity, but the most referenced: Lance, 1980: “Spasticity is a motor disorder characterized by a velocity- dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one component of the upper motor neuron syndrome.”

Other Definitions Decq’s definition, 2003 : “…a symptom of the upper motor neuron syndrome characterized by an exaggeration of the stretch reflex secondary to hyperexcitability of spinal reflexes.” It separates: Intrinsic tonic spasticity: exaggeration of the tonic component of the stretch reflex (hypertonia). Intrinsic phasic spasticity: exaggeration of the phasic component of the stretch reflex (hyper-reflexia, clonus, velocity-dependent resistance). Extrinsic spasticity: exaggeration of extrinsic flexion or extension spinal reflexes (spasms, withdrawal reflex). Adams & Hicks, Spinal Cord, 2005 Don’t think we need this slide for payers

Positive Effects of Spasticity Spasticity may: Be used to help with transfers, standing, walking, and ADLs. Help prevent muscle atrophy. Muscles may appear to be healthier compared to those without spasticity. http://www.dinf.ne.jp/doc/english/global/david/dwe001/dwe001g/dwe00136g06.jpg

Negative Effects of Spasticity However, spasticity may also lead to: Decreased range of motion (ROM) Inability to position the limbs safely Limited mobility Difficulty performing personal hygiene Discomfort and pain andgodlaughs.blogspot.com

Is Treatment Necessary? If mild, wait and see? Questions to ask: Does it cause pain? Interfere with sleep? Make function unsafe? Cause secondary issues of - Poor posture / asymmetric seating? Pressure sores? Make care difficult? Affect hygiene? Will treatment improve quality of life and safety?

Treatment Goals Relieve signs & symptoms Decrease frequency and severity of spasticity Improve function Gait Posture Reach and grasp for ADLs Improve ease of care

Patient Evaluation and Treatment Planning Evaluate Patient: Does spasticity/ overactivity interfere significantly with function? Measures must include all aspects of spasticity Will it lead to musculoskeletal deformity? Patient Evaluation and Treatment Planning No treatment necessary No Yes Patient and Caregiver Objectives Identify patient and caregiver goals Functional Objectives Improve gait, hygiene, ADLs, pain relief, ease of care Decrease spasm frequency & severity Technical Objectives Promote tone reduction, improved range of motion, joint position Decrease spasm frequency Decrease hyper-reflexia Spasticity Management Program MODIFIED from Spasticity Treatment Planning. WEMOVE.org, 2005.

Spasticity is an ongoing problem, despite treatment options. Traditional and surgical treatment options are routinely used to decrease spasticity… Yet, many persons with SCI continue to have problems related to spasticity: More than half of all persons surveyed with chronic SCI report symptoms and sequelae of spasticity (Sköld, et al. 1999; Maynard, et al. 1990). Persons with cervical and motor incomplete injuries seem to have spasticity that is more frequent and more severe.

Conservative Treatment Options Pharmacological Management Baclofen – oral or pump (intrathecal) Adjunct Dantrolene, Zanax, or Valium Physical and Occupational Therapy Range of motion (ROM) exercises & prolonged stretching Casting or splinting Electrical stimulation - transcutaneous nerve stimulation (TENS) Acupuncture Massage

If other options don’t work… Surgery involves cutting pathways in the nervous system thought to be involved in spasticity. However, forms of electrical stimulation to the spinal cord (epidural spinal cord stimulation) and electromagnetic stimulation to the brain (transcutaneous magnetic stimulation - TMS) may mimic the effects of surgical interventions.

Spasticity and its management in SCI is multi-faceted. Spasticity is no longer just an extremity’s resistance to quick movement. It includes spasms, overall hypertonia, hyper- reflexia, and clonus. The optimal treatment for each of these different aspects of spasticity is not yet clear. The literature related to spasticity has not been evaluated in terms of what is meaningful to persons with SCI.

Purpose of Review To evaluate all published research from the past 10 years related to the management of spasticity after spinal cord injury (SCI) to determine which evidence may be: Meaningful to persons with SCI who have spasticity (e.g. includes level and completeness of injury). Related to any type of spasticity a person may experience (velocity-dependent resistance, spasms, hypertonia, clonus).

Definitions of types of spasticity used in this review Velocity-dependent resistance = phasic (quick and short lasting) spasticity of resistance felt when an extremity is moved quickly Hypertonia = tonic (longer lasting, co-contraction) spasticity of increased resistance to movement throughout range Spasms = phasic spasticity of body movement into a flexor or extensor pattern Clonus = phasic spasticity of repeated movement of a body part when positioned with the muscle stretched Hyper-reflexia = increased reflex response (e.g. the knee reflex response)

The Review Conducted by 7 clinicians. Included all articles published between 2000 and 2010 related to the treatment of spasticity in persons with SCI. All articles rated on quality of the science & meaningfulness to persons with SCI, or their caregivers and clinicians, or payers. Any article of high quality that was meaningful was considered for this summary.

Study Designs Accepted for Review Experimental: Employed methods including a random assignment and a control group or a reasonably constructed comparison group. Quasi-experimental: No random assignment, but either with a control group or a reasonably constructed comparison group. Descriptive: Neither a control group, nor randomization, is used. These included case studies and reports, studies employing repeated measures, and pre-post designs.

Search Results Of 49 papers reviewed: Seven papers met criteria of quality and meaningfulness. Only 3 of the 7 papers defined spasticity, and these all differed. Each of the 7 papers used different outcome measures of spasticity. These are ongoing problems with research in this area.

Definition of Spasticity provided Aspect of spasticity measured Study Definition of Spasticity provided Aspect of spasticity measured Bowden & Stokic 2009 Based on Lance, 1980: “…a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one component of upper motor neuron syndrome”; “…include clonus, involuntary muscle contractions or spasms, and muscle co-contraction.” Passive resistance to stretch Spasm frequency & severity Stretch reflex/hyper-reflexia Flexion withdrawal Kumru, et al. 2010 Based on Decq, 2003: “…a symptom of upper motor neuron syndrome, characterized by an exaggeration of the stretch reflex, spasms, and resistance to passive movement across a joint, secondary to hyperexcitability of spinal reflexes.” Velocity-dependent resistance to stretch Clonus Hypertonia Ness & Field-Foté 2009 Own definition: “…spastic hypertonia with increased reflex excitability and disordered motor output (i.e. spasticity, clonus, spastic gait patterns)…” Stretch reflex/quadriceps hyper-reflexia

Definition of Spasticity provided Aspect of spasticity measured Study Definition of Spasticity provided Aspect of spasticity measured Chung & Cheng 2009 none provided Velocity-dependent resistance to stretch Passive resistance Clonus Kakebeeke TH, et al. 2005 Krause P et al. 2008 Passive resistance to stretch Stretch reflex/quadriceps hyper-reflexia Pinter MM, et al 2000 Spasm frequency

Experimental Study Design: Overview 2 of 7 studies used a randomized controlled trial (RCT). Both of these studies used electrical stimulation for the treatment. 2 studies were longitudinal cohort designs. 1 study was a case study. 1 study used a pre-post design. 1 study used a cross-over design.

Experimental Study Design: RCT of TENS Intervention Study Design Outcome Measures Participant Characteristics Chung BPH, Cheng BKK 2009 60 mins active TENS or 60 mins placebo; over the common peroneal nerve RCT, n=18 Composite Spasticity Score Full range passive ankle dorsiflexion Ankle clonus 14 male; 4 female 24-77 y.o. C4-T12 AIS A, B, C, D 4 weeks to 364 weeks (approx. 5.5 years) post-SCI

Results: Reduction in Resistance and Clonus with TENS TENS group showed significant decrease in: Composite Spasticity Score (29.5%, p=0.017) Resistance to full passive range at ankle dorsiflexion (31%, p=0.024) Ankle clonus (29.6%, p=0.023) Notes: Anti-spasticity medications were allowed. No significant differences between groups at baseline. Chung & Cheng 2009

Experimental Study Design: RCT of TMS Intervention Study Design Outcome Measures Participant Characteristics Kumru H, Murillo N, Samso JV, et al. 2010 Repetitive Transcranial Magnetic Stimulation (TMS) RCT with cross- over for sham group, n=15 MAS VAS for pain MPSFS SCAT SCI-SET Hmax/Mmax, Reflex (reflex responses on EMG as indicators of neural excitability) Withdrawal Reflex 12 male; 3 female 15-68 y.o. C4-T12 AIS C, D 2-17 months post-SCI

RCT of TMS: Sample Notes 11 of 15 using Baclofen 4 of 15 on no anti-spasticity meds Not all traumatic SCIs: 4 of 15 etiology = tumor 4 of 15 etiology = myelitis Kumru et al., 2010

Results: Decrease in Some Spasticity, Motor Control Still Disordered Neurophysiological function did not change. TMS group, but not sham group, significantly decreased: MAS score (p<0.006) not significantly different between those with traumatic & non- traumatic SCI MPSFS (p=0.01) SCATS (p<0.04) SCI-SET (p=0.003) MAS, SCATS, & SCI-SET results maintained one week after last session (p=0.049). Kumru et al., 2010

Results (cont.): 14 of 15 reported significant improvement in pain on VAS (p<0.002). Was maintained in 13 of 15 at end of the week after TMS (p=0.004) No significant change in measures when sham only. Kumru et al., 2010

Experimental Study Design: Summary of RCTs In persons with acute or chronic, motor complete or incomplete, paraplegia or tetraplegia, applying electrical stimulation peripherally (i.e. at the common peroneal nerve or the nerve innervating the muscle antagonistic to the spastic muscle, Chung & Cheng, 2009), or electromagnetic stimulation centrally (i.e. over the primary motor cortex, Kumru et al., 2010) for motor incomplete injuries led to a significant reduction in several different aspects of spasticity: Velocity-dependent resistance to stretch Spasms Hypertonia Hyper-reflexia Clonus

Descriptive Study Design: Longitudinal Study, Epidural E-stim Intervention Study Design Outcome Measures Participant Characteristics Pinter et al. 2000 Epidural spinal cord electrical stimulation (eSCS) Longitudinal, n=8 EMG during passive stretch of LE & Pendulum Test Ashworth Scale Clinical rating scale 4 male; 4 female 18-34 y.o. C5-T6 AIS A, B, C 19-94 months post-SCI

Results: Epidural Stim Reduced Some Aspects of Spasticity Significant reduction in: EMG activity in left and right legs (p=0.004, p=0.0035, respectively). Except for quadriceps when analyzed independently Ashworth score (p=0.0117) 7 of 8 participants discontinued anti-spasticity medication. Pinter et al., 2000

Descriptive Study Design: Case Study with Baclofen Intervention Study Design Outcome Measures Participant Characteristics Bowden M, Stokic DS. 2009 Pharma- cologic, intrathecal baclofen Single subject case report Ashworth Scale Lower extremity strength using ISNCSCI EMG H-Reflex & H/M ratio (reflex responses on EMG as indicators of neural excitability) Plantar Withdrawal Reflex Maximal Voluntary Dorsiflexion 1 male 41 y.o. T11, AIS D 8 years post-SCI

Strength Decreased, BUT Spasticity Decreased More Dose-dependent decreases in: Ashworth score (p<0.01) Bilateral lower extremity strength (p<0.001) H/M ratio EMG amplitude and duration of the plantar withdrawal reflex Decrease in strength was less than decrease in spasticity. After withdrawal of medication, the rebound in spasticity was less than increase in strength.

Descriptive Study Design: Pre-Post with Passive LE Cycling Intervention Study Design Outcome Measures Participant Characteristics Kakebeeke et al. 2005 30 mins passive lower extremity ergometry Pre-Post, n=10 Muscle strength testing using isokinetic dynamometry (torque) in sitting & lying; movements of leg at 10°/sec & 120°/sec; taken before, after, & 1 week post passive cycling session 9 male; 1 female 23-60 y.o. C6-T12 AIS A, B 1-25 years post-SCI

Results: Strength Same, BUT Reports of Reduced Spasticity No change in elicited peak torque before, immediately after, or one week after passive cycling. 6 of 10 participants reported reduced spasticity immediately after cycling. Kakebeeke et al., 2005

Descriptive Study Design: Cross-over, FES & Passive Cycling Intervention Study Design Outcome Measures Participant Characteristics Krause P, et al. 2008 Functional electrical stimulation cycling, Passive cycling Cross- over, n=5 Modified AS of quads Pendulum Test of quads. Also during Pendulum Test: Peak Velocity (deg/s) during first swing Relaxation Index (A1/(1.6 x A0), where A1 & A0 = degrees of first swing in flexion, then extension, respectively) 3 male; 2 female 37-66 y.o. T3-T7, AIS A 3-9 years post-SCI

Results: Both Active & Passive Cycling Show Some Effects Greater & significant increase in relaxation index (RI) after FES cycling (68%) than after passive cycling (12%) (p=0.01). Peak velocity (PV) significantly increased after FES cycling, unchanged after passive cycling (p=0.01). MAS decreased significantly for both FES cycling (p<0.001) and passive cycling (p<0.05). * Participants were not on anti-spasticity medications.

Descriptive Study Design: Longitudinal, Whole Body Vibration Intervention Study Design Outcome Measures SCI Participant Characteristics Ness LL, Field-Foté EC, 2009 Whole body vibration on vibrating platform Longitudinal, n=16 Pendulum test 14 male; 3 female 28-65 y.o. C4-T8 AIS C, D > 1 year post-SCI

Results: Long Lasting Effects with WBV Significant reduction in quadriceps spasticity (p=0.005). Significant reduction within session (range p=0.005 to 0.006 for weeks 1, 2, 4). No significant difference between those on anti- spasticity meds and those not. Effects lasted at least 6-8 weeks post-intervention. Ness LL, Field-Foté EC, 2009

Medications Varied 7 of 16 on Baclofen 1 of 16 on Tizanidine 9 of 16 on no spasticity medication Ness LL, Field-Foté EC, 2009

Descriptive Study Design: Summary of Studies These studies provide further support that: stimulating the nervous system (e.g. electrical stimulation), OR altering the excitability in the nervous system (e.g. Baclofen) can lead to a reduction in spasticity in persons with complete or incomplete tetraplegia or paraplegia.

Methodological Considerations Definitions of spasticity differ: A motor disorder characterized by a velocity-dependent increase in tonic stretch reflex, exaggerated tendon jerks; includes clonus, involuntary muscle contractions or spasms, and muscle co-contraction (Lance, 1980) Includes intrinsic tonic spasticity (i.e. the exaggeration of the tonic component of the stretch reflex, hypertonia), intrinsic phasic spasticity (i.e. the exaggeration of the phasic component of the stretch reflex or hyper-reflexia and clonus), and extrinsic spasticity, (i.e., the exaggeration of extrinsic flexion or extension spinal reflexes, spasms) (Adams & Hicks, 2005).

Study Limitations Spasticity syndrome may be worse in people with cervical and incomplete injuries than those with thoracic and complete injuries. (Kirshblum, 1999; Maynard et al, 1990; Sköld et al, 1999). Even though studies included persons with complete and incomplete paraplegia and tetraplegia, as well as acute and chronic injuries, results were averaged and reported as a whole. It remains unknown whether there is a differential response to the interventions.

Study Limitations Studies included persons with chronic SCI, who may have musculoskeletal consequences to chronic spasticity. Chronic spasticity has musculoskeletal effects, namely muscle shortening and contractures (Gracies et al., 1997). Musculoskeletal parameters were not assessed in any of these studies. Improvements may have been neural or musculoskeletal or both. Improving one and not the other may preclude maximal improvements.

Study Limitations There were no functional assessments. Whether reducing spasticity is necessary and sufficient for improving motor control and function remains unclear. There were no studies addressing the cost- effectiveness of treatments for spasticity.

Recommendations Any stakeholder interested in the evidence related to the management of spasticity after SCI should consider: Outcome measures differed across all studies. Different aspects of spasticity may be affected by a given intervention. For instance, if spasms are the worse aspect of spasticity, rTMS, eSCS, or baclofen (all with evidence of reducing spasms in persons with SCI) may be pursued. Those with velocity-dependent resistance to stretch may choose TENS or rTMS, but rTMS may give the best results overall if there are multiple areas related to spasticity.

Recommended Future Research Further study is warranted to determine: the differential responses to interventions in those with varying levels of injury, classifications of injury, and times since injury. the differential effects of interventions on neural and musculoskeletal tissues. the effects of interventions on function. the long-term effects of these interventions. the cost-effectiveness of the various treatments for spasticity.

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