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Non pharmacological interventions for spasticity in multiple sclerosis

  1. Bhasker Amatya1,*,
  2. Fary Khan1,2,3,
  3. Loredana La Mantia4,
  4. Marina Demetrios1,
  5. Derick T Wade5

Editorial Group: Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 19 MAY 2012

DOI: 10.1002/14651858.CD009974.pub2


How to Cite

Amatya B, Khan F, La Mantia L, Demetrios M, Wade DT. Non pharmacological interventions for spasticity in multiple sclerosis. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD009974. DOI: 10.1002/14651858.CD009974.pub2.

Author Information

  1. 1

    Royal Melbourne Hospital, Royal Park Campus, Department of Rehabilitation Medicine, Melbourne, Victoria, Australia

  2. 2

    Monash University, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia

  3. 3

    University of Melbourne, Department of Medicine, Dentistry & Health Sciences, Melbourne, Victoria, Australia

  4. 4

    I.R.C.C.S. Santa Maria Nascente Fondazione Don Gnocchi, Unit of Neurology - Multiple Sclerosis Center, Milano, Italy

  5. 5

    University of Oxford, Oxford Centre for Enablement, Oxford, UK

*Bhasker Amatya, Department of Rehabilitation Medicine, Royal Melbourne Hospital, Royal Park Campus, Poplar Road, Parkville, Melbourne, Victoria, 3052, Australia. Bhasker.Amatya@mh.org.au.

Publication History

  1. Publication Status: New
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Giovannelli 2007

MethodsRCT, Italy


ParticipantsN = 37, Treatment = 20; control = 20 (18 at follow-up)

Inclusion criteria: Secondary progressive MS; age 18-65, stable anti-spastic/epileptic treatment for at least 3 months; MAS score > 3

Exclusion criteria: other form of MS; any other disabling condition interfering with the clinical evaluation; pregnancy or breastfeeding; any psychiatric disorders or severe cognitive disturbances that could preclude safe participation in the study; known history of alcohol or substance abuse; previous botulinum toxin type A (BoNT) injections.


InterventionsTreatment group: BoNT & physiotherapy (daily/15 days after BoNT including weekends; programme: passive or active exercise and a stretching regimen on the injected area (40min for each session), consisting of soft movements of joints with short pauses at the final position and reciprocal movements)

Control group: BoNT alone


Outcomes
  • Modified Ashworth scale (MAS): spasticity/muscle tone
  • Expanded Disability Status Scale (EDSS): function
  • Visual Analogue Scale (VAS): patients self-evaluate evolution of spasticity, satisfaction in relief in spasticity in injected muscles with a score from 0 'not satisfied' to 10 'clearly satisfied'


Notes
  • BoNT – total amount and sites injected in upper limb and lower limb were same in both groups
  • Patient perspective assessed with VAS for spasticity
  • Adverse events not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskStated block randomisation by separate statistician who had no contact with study participants

Allocation concealment (selection bias)Unclear riskAllocation concealment not reported

Blinding of participants and personnel (performance bias)
All outcomes
High riskPatients not blinded and knew which group they were in

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessor was blinded: Neurologist blinded (MAS, BoNT injections) and VAS – patient evaluation (subjective)

Incomplete outcome data (attrition bias)
All outcomes
Low riskTwo control patients lost during the study.

Reasons for loss to follow-up provided – failed to attend assessments and therapy

Attrition rate 10%

Selective reporting (reporting bias)Low riskAll outcomes reported

Other biasUnclear risk
  • Small sample size was small, no sample size/power calculation
  • Single centre
  • No measures of activity level / function (e.g. gait/ mobility)
  • No intention-to-treat (ITT) analysis (per protocol)

Lappin 2003

MethodsRCT (Multisite cross-over design), USA


ParticipantsN = 117 all underwent treatment device alternating with control device and vice versa

Inclusion Criteria: clinically definite MS, age 18-65, at least report 2 (spasticity or bladder control problem) on a 6-point MS Symptom Rating Form

Exclusion criteria: experience of an exacerbation or changed medications in past 2 months, pregnant, had a pace maker, or had other serious or chronic diseases


InterventionsTreatment and control groups: Each participant received 4 weeks of active (pulsed electromagnetic device for up to 24 hours /day) and placebo treatments (device with disconnected coil and no signal), separated by a 2-week washout period.


Outcomes
  • MS Quality of Life Inventory (MSQLI) (fatigue, pain, spasms/spasticity (based on the adapted subscale MSQLI pain scale), bladder control and quality of life).
  • MS Performance scales
  • MS Rating Form and Mobility Index
  • Mobility Index (a two item scale made for this study)


Notes
  • Many outcome measures used with complex analyses- mixed results for spasticity
  • Adverse events reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants randomised using centrally generated random number table (but procedure not described; technician was the person who used it)

Allocation concealment (selection bias)Low riskNeither patient nor assessors knew if in active or inactive treatment phase.

Frequency determined by operator on basis of a test but not knowing if active or inactive

Blinding of participants and personnel (performance bias)
All outcomes
Low riskTreating personnel and participants blinded

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskHigh attrition of 19% dropouts (N = 26), as failed to complete both treatments; 2 dropped out as had no fatigue (but met inclusion criteria)

Selective reporting (reporting bias)Low riskAll pre-specified outcomes reported

Other biasUnclear risk
  • Short term: study duration total of 10 weeks only
  • No ITT analysis (per protocol)
  • Multiple statistics- difficult to follow
  • Measures of quality of life MSQLI showed significant results while others MSPS did not

Miller 2007

MethodsRCT (Single blind cross-over design), UK


ParticipantsN = 32: treatment group = 16 and control group = 16

Inclusion Criteria: clinically definite MS and stable for 3 months, increased tone in at least one lower limb (MAS score 1-3), no previous Transcutaneous Electric Nerve Stimulation (TENS)

Exclusion criteria: other neurological conditions, a pacemaker, poor cognition or other serious illness


InterventionsTreatment and Control groups – 2 weeks of 60 min (period A) and 8 hours daily (Period B) of TENS application (100 Hz, 0.125ms pulse width) followed by 2 weeks break (washout period). Participant in each group then undertook 2 weeks of alternative treatment i.e. 60 minutes or 8 hours of TENS per day.


Outcomes
  • Global Spasticity Scale (includes scores for: Ashworth Scale, Clonus score and Patellar tendon reflex).
  • Penn Spasm scale
  • 10-point linear Visual Analogue Scale for pain and spasms


Notes
  • Adverse events not reported
  • Power calculation performed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomly allocated to treatment or control group, however detail not reported

Allocation concealment (selection bias)High riskAllocation concealment not described, patients obviously knew which group they were in

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding of participants and treating personnel

Blinding of outcome assessment (detection bias)
All outcomes
High riskNot stated that assessors were blinded – no information given

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall 37 participants with 5 dropouts. The time points and group allocation (intervention or control ) not specified

Selective reporting (reporting bias)Low riskAll pre-specified (primary and secondary) outcomes reported;

Scales include several different components.

Other biasUnclear risk
  • Potential source of bias related to the study design
  • Significant difference in the baseline EDSS scores between the 2 groups (mean scores 6.8+/-1.2 and 5.1+/-2.8)
  • Patchy longer-term follow-up for questionnaire results – ranging from 8-20 months after study completion
  • No ITT analysis (per protocol)
  • Small sample size, not representative of all MS populations
  • No information on recruitment
  • No information on whether patients could alter other treatments or did do so
  • No information on compliance
  • Cross-over design does not allow for prolonged or cumulative effects

Mori 2010

MethodsRCT, Italy


ParticipantsN = 20: treatment group = 10  and control group = 10

Inclusion criteria: clinically definite diagnosis Relapsing Remitting MS, remitting phase of disease, EDSS scores of 3-6, lower limb spasticity, absence of lesion enhancement after iv gadolinium in cerebral or spinal MRI imaging (performed between 2 and 30 days before the beginning of the study)

Exclusion criteria: not reported


InterventionsTreatment group - Intermittent Theta Burst Stimulation (iTBS) 10 bursts, each burst composed of three stimuli at 50 Hz, repeated at a theta frequency of 5 Hz every 10 s for a total of 600 stimuli (200 s).

Control group – sham stimulation

All were stimulated once a day for five consecutive days for 2 weeks


Outcomes
  • Modified Ashworth Spasticity scale score
  • compound motor action potentials (M) and H reflex (H) : H/M amplitude ratio


NotesAdverse events not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants pseudo-randomly allocated to treatment or control group, details not reported

Allocation concealment (selection bias)High riskAllocation concealment not described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskIt is not reported if patients were able to distinguish the true  from the sham stimulation, during sham stimulation no current was induced in the brain

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors (two neurologists) blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts

Selective reporting (reporting bias)Unclear riskAll pre-specified (primary and secondary) outcomes reported

Other biasUnclear risk
  • Clinical disability of patients are not reported
  • Data of each patient  (change in spasticity or H/M ratio ) post therapy are not reported
  • Small sample size
  • Clinical and statistical significance of the  H. reflex as measure to test the effects of iTBS of the motor cortex on spinal  are not specified

Mori 2011

MethodsRCT, Italy


ParticipantsN = 30: 3 intervention groups with N = 10 in each group


InterventionsParticipants randomised to three different interventions:

  • iTBS (protocol consisted of ten bursts, with each burst composed of three stimuli at 50 Hz, repeated at a theta frequency of 5 Hz every 10 s, for a total of 600 stimuli (200 s)) plus exercise therapy
  • sham stimulation plus exercise therapy for 2 weeks (passive (stretching, mobilization) and active interventions)
  • iTBS alone


Inclusion criteria: clinically definite diagnosis of Relapsing remitting MS, remitting phase of disease, EDSS scores of 3-6, lower limb spasticity, absence of lesion enhancement after iv gadolinium in cerebral or spinal MRI imaging (performed between 2 and 30 days before the beginning of the study)

Exclusion criteria: not reported


OutcomesPrimary:

  • Modified Ashworth scale (MAS) and Multiple Sclerosis Spasticity Score questionnaire (MSSS-88): spasticity


Secondary:

  • Fatigue Severity Scale (FSS): fatigue
  • Barthel index: daily living activities (ADL)
  • Multiple Sclerosis Quality of life inventory (MSQOL-54): health-related quality of life (HRQOL)


Notes
  • Adverse events not reported
  • No control placebo group


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants randomly allocated to three intervention groups stratified by EDSS scores; randomisation procedure not described

Allocation concealment (selection bias)Unclear riskAllocation concealment not described

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAll participants and treating personnel were blinded for first two groups (iTBS+exercise therapy and sham stimulation+exercise therapy). Third group receiving only iTBS was unblinded.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding of outcome assessors

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts

Selective reporting (reporting bias)Low riskAll pre-specified (primary and secondary) outcomes reported

Other biasUnclear risk
  • No long-term follow-up (2 weeks only)
  • Small sample size, not representative of all Italian people – a convenience sample from single institution
  • 10-week time point – no clear relationship to end of rehabilitation programme given
  • Control group - no placebo control group or control group without any intervention

Nielsen 1996

MethodsRCT, Denmark


ParticipantsN = 38, intervention group = 21; control group = 17

Inclusion Criteria: clinically definite diagnosis of MS, stable neurological condition for at least 6 months, MAS score ≥ 2 of at least one joint in lower limb preserved walking performance for 10m

Exclusion criteria: epilepsy, other neurological disorders,, pregnancy, implanted spinal metal, drug infusion pump, pacemaker


InterventionsTreatment group: Repetitive Transcranial Magnetic Stimulation (rTMS): one session of 16 stimuli of 25Hz over the leg motor area and one session of 5min rTMS twice daily for 7 days

Control group: sham stimulation


OutcomesPatients self-score of ease of daily day activities (related to spasticity)

Clinical spasticity score: combination of Ashworth score (muscle tone) and Achilles tendon reflex grading score

Electrophysiological and biomechanical measurement: Stretch reflex threshold


NotesAdverse events not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandom allocation of the participation mentioned, however randomisation procedure not reported

Allocation concealment (selection bias)Low riskAllocation concealment reported

Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants and treating personnel were blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskUnclear if the outcome assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes
Low risk3 participants from treatment group dropped out

Selective reporting (reporting bias)Low riskAll pre-specified (primary and secondary) outcomes reported

Other biasUnclear risk
  • Small sample size
  • Significant differences of the clinical score of spasticity at baseline between groups
  • No ITT analysis (per protocol)

Richards 1997

MethodsRCT, USA


ParticipantsN = 30: treatment group =15  and control group = 15

Inclusion criteria: clinically definite diagnosis of MS, other details not given

Exclusion criteria: not reported


InterventionsTreatment group - magnetic pulsing device with patient-specific  frequencies, (range 4-13 Hz)

Control group – magnetically inactive device

Duration:10-24 hrs a day for 2 months


Outcomes
  • EDSS
  • Patient-reported  performance  scales  eight symptoms (bladder control, cognitive level, fatigue  level, hand function, mobility, sensation, spasticity, and vision)
  • Brain electric activity (quantitative EEG during a language task)


Notes
  • Disease duration and age of participants are not reported
  • Adverse events reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskDetails of randomisation process not reported

Allocation concealment (selection bias)Low risk“Devices (active and placebo) had the same appearance and programmability."

Blinding of participants and personnel (performance bias)
All outcomes
Low riskThe investigator distributing the devices did not know which patient was given the active device

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts

Selective reporting (reporting bias)Low riskAll pre-specified (primary and secondary) outcomes reported

Other biasUnclear risk
  • Intensity of stimulation was different for each patients and the modality of intervention titration (8 patients wore the device 24 hours a day, the others 4 hours the first day increasing the intensity in the next days)
  • The clinical impact of disability assessed with patients reported performance is unclear

Schyns 2009

MethodsRCT (cross-over design), UK


ParticipantsN = 16, intervention group = 8; control group = 8

Inclusion Criteria: clinically definite diagnosis of MS, disability level between 1and 6 on the Hauser Ambulation Index, at least one of the following symptoms based on previous clinical assessment: abnormal muscle tone, lower limb weakness, altered sensation and/or proprioception

Exclusion criteria:


InterventionsGroup 1: four weeks of whole body vibration (WBV) plus exercise three times per week, two weeks of no intervention and then four weeks of exercise
alone three times per week

Group 2: two treatment interventions in the reverse order to Group 1, with 2 weeks rest in between

Protocol:

A. WBV + exercise (3x/week for 4 weeks)

- frequency and amplitude of the vibrations, and duration of exercises, were chosen according to the manufacturers’ recommendations for stretching and strengthening exercise (i.e. 40 Hz, low amplitude (2 mm) and for 30 seconds).

Each session consisted of:

  1. warm-up massage of the quadriceps, hamstrings and gastrocnemius muscles delivered by the vibrating plate. Each muscle group was treated for 60 seconds at 50 Hz.
  2. 10 different strengthening and stretching exercises for the lower limbs with vibration of 40 Hz, for 30 secs.
  3. cool-down massage similar to the warm-up.


B. 2-week rest period

 

C. Exercises only (3x/week for 4 weeks)

- same protocol of exercises for lower limbs, without WBV
- warm up and cool-down consisted of 3 minutes of slow passive movements on a motorized cycling machine.


Outcomes
  • 10-metre walk: function
  • Timed Up and Go Test, Modified Ashworth Scale: spasticity, muscle ton
  • Multiple Sclerosis Spasticity Scale (MSSS-88): spasticity, muscle tone
  • Lower limb muscle force using dynamometer: muscle force
  • Nottingham sensory Assessment: sensation and proprioception
  • Multiple Sclerosis Impact Scale (MSIS-29): heath related QOL


Notes
  • Adverse events reported
  • *Although the study was of a cross-over design, statistical analysis revealed that there was little evidence of a group or interaction effect for any of the outcome measures (except MSSS-88). Therefore, while appreciating that this may be a result of the small sample size in some cases, the effect of WBV and exercise was compared with that of exercise alone regardless of the order the interventions occurred.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskRandomised by the physiotherapist involved with the treatments drawing a number from an envelope

Allocation concealment (selection bias)Unclear riskAllocation concealment not reported

Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding of patients and treating personnel not reported, however, due to the nature of intervention it seems both were not blinded,

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessor blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskDropouts: 3 from treatment group and 1 from control. This might have influenced the findings due to the small sample size (8 in each group). High attrition rate 25%

Selective reporting (reporting bias)Unclear riskAll pre-specified (primary and secondary) outcomes reported

Other biasUnclear risk
  • Small sample size
  • No sample size/power calculation
  • single centre
  • No ITT analysis (per protocol)
  • Cross-over design and way in which data was analysed* see above. Rationale not likely appropriate given small sample size.
  • Difference in MS duration from 10 months to 23 years (mean 6.7 years) in treatment group and 3.5 to 18 years in control group (mean 11.8 years)

Velkonja 2010

MethodsRCT, Slovenia


ParticipantsN = 20: number of participants in each group not stated

Inclusion criteria: clinically definite diagnosis of MS, aged 26–50 years, EDSS ⋜ 6 and EDSS pyramidal functions score (EDSSpyr) < 2

Exclusion criteria: not reported


InterventionsTreatment group - Sports climbing (Delivered by 2 SC instructors at Training, Occupation and Care Centre; programme - Climbing wall, climbing belt and top rope system, climbing up and down wall with rests as needed)

Control group – Yoga (Delivered by MS specialist nurse trained in yoga at Institute of Rehabilitation; programme - stretching and strengthening exercises, breathing exercises, isometric muscle contraction and relaxation

Duration: once a week for 10 weeks


Outcomes
  • Modified Ashworth Scale (MAS): spasticity scores
  • EDSSpyr :Function:-spasticity and muscle strength
  • Mazes subtest of Executive module from the Neuropsychological assessment battery (NAB), Tower of London Test (TOL), Brickenkamp d2 test: cognition (executive function, attention span)
  • Center for Epidemiologic Studies Depression Scale (CES-D): Mood
  • Modified Fatigue Impact Scale (MFIS): fatigue


Notes
  • Disease duration and age of participants are not reported
  • Adverse events not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation methods not clearly described

Allocation concealment (selection bias)Unclear riskNot reported

Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants/ therapists not blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo mention of whether physiotherapist/ neuropsychologist was blinded.  Neurologist performing EDSS was blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo mention of dropouts or adherence to programme, or ITT analysis

Selective reporting (reporting bias)Low riskAll outcomes reported

Other biasUnclear risk
  • Small sample size, no sample size calculation provided
  • Sample not reflective of Slovenian population
  • Exclusion criteria not stated
  • Number of participants in each group not stated
  • Details of programmes not given i.e. session duration, exercises performed, group setting
  • Not clear if duration and intensity of programmed adequate, basis on which it was determined, rationale
  • No explanation of scoring for MAS and no explanation of how summed MAS score was calculated
  • Exact time point of assessment not clear, stated assessment was done ‘after’ programme, short follow-up period will miss assessment of effects being maintained

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bernhardt 2011Abstract only

Castro-Sanchez 2012Spasticity not used as a specific outcome measure

Chiara 1998Not a RCT

Farenelli 1999Spasticity not used as a specific outcome measure

Huges 2009Spasticity not used as a specific outcome measure

Leocani 2012Abstract only

Livesley 1992Spasticity not used as a specific outcome measure

Shaygannejad 2011Abstract only

Sosnoff 2009Not a RCT

Szecsi 2009Not a RCT

 
Table 1. Levels of quality of individual studies

Judgement of risk of bias

Risk of bias in all domains lowHigh methodological quality = ‘high-quality study’

Unclear or high risk of bias for one or more domainsLow methodological quality = ‘low-quality study’

High risk of bias for most domainsVery low methodological quality = ‘very low-quality study’

 
Table 2. Levels of quality of a body of evidence in the GRADE approach  

Underlying methodologyQuality rating

Randomised trials or double-upgraded observational studiesHigh

Downgraded randomised trials or upgraded observational studiesModerate

Double-downgraded randomised trials or observational studiesLow

Triple-downgraded randomised trials or downgraded observational studies or case series/case reportsVery low

 
Table 3. Summary of the findings

StudyAssessment pointsSummary of resultsResults – outcomes in favour of intervention groupAuthor’s conclusions

Giovannelli 2007Baseline, and weeks 2, 4, and 12
  • Significant decrease in spasticity in treatment group compared to control group in MAS scores at weeks 2, 4, and 12, and in VAS rating scale at weeks 4 and 12
  • Control group MAS showed a transient decrease at week 2 and a slight increase at week 4 and week 12


 
Significant decrease in MAS score in treatment group from baseline at (Mean (SD) change score):

  • Week 2 : treatment group:-0.91 (0.52) ; control group: -0.39 (0.50); P < 0.01
  • Week 4 : treatment group: -1.0 (0.69); control group -0.28 (0.46); P < 0.01
  • Week 12 : treatment group -0.95 (0.78); control group: -0.28 (0.46); P < 0.01


The mean (%) difference in MAS between baseline and the end of follow-up was –0.95 (26.1) in the treatment group and –0.28 (7.7) in the control group (P < 0.01).

 

Significant improvement in spasticity in VAS rating scale (Mean (SD) change):

  • Week 2 to week 4 : treatment group 1.77 (0.87) ; control group: 0 (1.08); P < 0.01
  • Week 4 to week 12: treatment group : 2.68 (1.08); control group: 1.06 (1.16); P < 0.01
Addition of active physiotherapy after intramuscular botulin toxin increases reduction in spasticity even at 12 weeks.

Lappin 2003Before (baseline) and after 4 week treatment spell (week 4 and 10)
  • Significantly greater Improvement in fatigue and overall QOL in the active device compared with control group
  • No significant differences in the treatment effects for bladder control (P = 0.26) (MSQLI) and disability composite (P = 0.77) (MSPS)
  • Mixed result for spasticity: no significant difference in the treatment effects on daily diary ratings but MSQLI measure at the end of each sessions showed statistically significant differences (P = 0.04)
  • The 3 scales (fatigue, pain and spasticity) used to create the QLI showed moderate inter-correlations (r = 0.32 to 0.60), however, bladder control scale showed poor correlation with other MSQLI scales (r = 0.00 to 0.26)
  • Adverse events: headaches, dizziness, numbness, fatigue, severe nausea
Mean change scores between active vs. placebo groups::

  • Bladder- 0.08 ; P = 0.26
  • Spasms - 0.13; P = 0.04
  • Fatigue -0.14  ; P = 0.04
  • 3 item QOL -0.12; P = 0.03
  • Disability level (8-MSPS) – 0.12; P = 0.77


No further data or analysis reported for spasms/spasticity
Although the clinical effects seen in the intervention group were small, exposure of people with MS to pulsing weak electromagnetic fields can alleviate some of their symptoms.

More response on less severely disabled people.

Miller 2007Baseline and after (2 weeks) treatments; and follow-up (8-20 months) for the questionnaires for patient report for symptomsNo statistically significant differences in the Global Spasticity Score following either 60 minutes or 8 hours daily of TENS (P = 0.433 and 0.217 respectively)
  • 8 hour TENS application time compared with the shorter 60 minute application time led to significant reduction in muscle spasm (P = 0.038) and pain (P = 0.008)
  • At the end of the study (8-20 months) patients reported reduction in symptoms: 87.5% for spasm, 73.3% for pain and 73.3% for stiffness
TENS is not effective in reducing spasticity, but longer application time may be useful in treating pain and muscle spasm in people with MS.

Mori 2010Baseline and after treatment (immediately after first sessions, 2 weeks) and follow-up of each week up to 4 weeks post treatment)Significant reduction of H/M amplitude ratio and MAS  scores 1 week after the iTBS and persisting up to 2 weeks after  the  end  of  stimulation 2 weeks post iTBS treatment showed:

  • Significant change in H/M amplitude ratio measured from the stimulated leg (P < 0.01)
  • Significant effect on MAS score measured from the stimulation target limb (P < 0.001)
iTBS is, a safe, non-invasive, well-tolerated and feasible protocol, and  a promising tool for the treatment of spasticity in MS.

Mori 2011Baseline and after treatment (2 weeks)
  • Reduction in MAS, MSSS-88, FSS scores, while in the Barthel index and MSQOL-54, physical composite scores were increased, in iTBS and exercise group.
  • ·iTBS alone group showed a reduction of the MAS score.
  • None of the measured scales showed significant changes in sham iTBS and exercise group


 
Significant improvement in the  iTBS and exercise group but not in the sham stimulation and exercise group in:

  • MAS from the stimulated leg (2.1 ± 0.4 before treatment; 1.3 ± 0.4 after treatment; P < 0.05)
  • MSSS-88 (74.3 ± 11.4 before treatment; 53.2 ± 10.9 after treatment; P < 0.001)
  • FSS (39.5 ± 4.2 before treatment; 31.6 ± 4.6 after treatment; P < 0.05),
  • Barthel index (92.5 ± 2.4 before treatment; 95.0 ± 1.85 after treatment; P < 0.05)
  • MSQOL-54 physical health composite (59.7 ± 2.7 before treatment; 64.8 ± 2.7 after treatment; P < 0.05) scores after treatment
iTBS associated with exercise therapy is a promising tool for motor rehabilitation of MS patients.

Nielsen 1996Baseline  and after treatment (1 day, 8 days, and 16 days)
  • Significant improvement in clinical spasticity score (Ashworth Scale) in intervention group (rTMS) compared to control group
  • Significant improvement in self-score of ease of daily activities in both groups


  • Significant improvement in stretch reflex thresh hold in both groups
At day 1 post treatment:

  • Ashworth Scale score for clinical spasticity improved significantly in treatment group compared to control group ( mean change -3.3 ± 4.7 AU vs. 0.7 ± 2.5 AU, P = 0.003)
  • Self-score of ease of daily day activities improved significantly in both groups (P < 0.05 for both groups), but was no difference between the two groups.
  • Threshold of the stretch reflex significantly increased in treatment group compared to control group (4.3±7.5 deg/s vs. -3.8 ± 9.7 deg/s, P = 0.001)


At day 8 post treatment

  • Threshold of the stretch reflex remain improved significantly in treatment group compared to control group (4.4 ± 7.5 deg/s vs. -1.8 ± 8.5 deg/s, P = 0.028)
  • No statistically significant difference in clinical spasticity score or self-score of ease of daily day activities between two groups


At day 16 post treatment

  • No statistically significant difference in any of the scores between two groups
rTMS has an short-lasting antispastic effect in MS.

Richards 1997Baseline  and after treatment (2 months)
  • No significant  change between  pre-treatment  and  post-treatment  in  the  EDSS  scale
  • Significant  improvement in the performance  scale  (PS) combined  rating for bladder control, cognitive  function, fatigue  level,  mobility,  spasticity,  and vision 
  • Significant  change  between  pre-treatment  and  post-treatment  in  alpha  EEG magnitude  during  the language  task
  • Adverse events: headache, psychological problems, dizziness, increase spasm, skin irritation, nausea, exacerbation of MS
Significant difference between pre-treatment and post treatment within the treatment group in (mean (SD):

  • Spasticity:  -0.80 (0.23); P < 0.005
  • Bladder control: -0.5 (0.23); P < 0.05
  • Cognition: -0.63 (0.37); P < 0.05
  • Fatigue: -0.87 (0.4); P < 0.05
  • Mobility: -0.4 (0.27); P < 0.05
  • Vision: -0.23 (0.21); P < 0.05


No adverse events: 6 in treatment group, 7 in control group.
Beneficial effect  of pulsing magnetic fields on MS patients treated  for a  period of 2 months, which is far too short to assess its effects  on the long-term progression of MS.

Schyns 2009Baseline  and after treatment (4 weeks) twice with 2 weeks cool-off period (final at 12 weeks)
  • Exercise programme had positive effects on muscle force and well being
  • Insufficient evidence that the addition of WBV provided any further benefit
  • No change in MAS scores for either intervention,
  • MSSS-88 showed whole body vibration and exercises reduced muscle spasms in both groups (P = 0.02)
  • 10-m walk and Timed Up and Go Test improved, but was not statistically significant
  • No effects on sensation
  • Adverse event: exacerbate a pre-existing knee condition (N = 1)
  • Tone tended to increase more for exercise alone compared with whole body vibration and exercise
  • MSSS-88 pain: statistically significant difference between the results before and after whole body vibration in treatment group (P = 0.036) and no significant difference for control group
  • MSSS-88 spasm: greater reduction in score was achieved using whole body vibration and exercise compared to exercise alone (P = 0.02, 95% CI = 2.00, 14.50)
  • No statistically significant changes for other MSSS-88 components (ADL, social functioning, stiffness, gait, body movement and emotional health)
  • 10-m walk time: both interventions increased the subjects’ walking speed , however the difference between performance with vibration and exercise, and exercise alone was not statistically significant (P = 0.561). A similar pattern was observed with the results of the Timed Up and Go Test (P = 0.720)
  • MSIS-29: overall well being improved in both groups, however, there was no statistically significant difference between groups
Exercise may be beneficial to those with MS, but there is limited evidence that the addition of WBV provides any additional improvements.

Exercise performed three times a week for four weeks
improved muscle force output, functional ability and general well-being in people with MS and addition of whole body vibration to the exercise programme provided some added benefit to exercise alone in terms of reducing muscle spasm.

In addition there was a trend towards a greater increase in muscle force generation with the addition of WBV.

Velkonja 2010Baseline  and after treatment (10 weeks)
  • No significant improvements in spasticity after both interventions (sports climbing (SC) or yoga)
  • Significant reduction in fatigue in SC group, while yoga had no effect
  • No differences in executive function
  • No significant impact of SC and yoga on mood.
  • Increase in selective attention performance in the yoga group (17% increase; baseline: 151.0 (94.5–175.5); after: 176.5 (116.5–191.3; P = 0.005).


 
  • SC group had 25% reduction (P = 0.046) in EDSSpyr; before  4.0 (3.0–4.0) after 3.0 (2.5–4.0)
  • SC reduced fatigue for 32.5% (P = 0.015)
  • Significant effect of SC on the level of fatigue (P = 0.015) as evaluated with the MFIS
Yoga and SC might improve some of the MS symptoms and should be considered in the future as possible complementary treatments.

 

Unable to prove that SC and yoga have an effect on spasticity or mood in patients with MS. SC did not significantly affect performance on tests of selective attention and executive functions, while in the yoga group there was an improvement in selective attention performance and no effect on executive functions. There was a decrease in the level of everyday fatigue in patients with SC but not in the yoga group.

 ADL = activities of daily living; BoNT = botulinum toxin type A; EDSS = Expanded Disability Status Scale; EDSSpyr = EDSS pyramidal functions score; FSS = Fatigue Severity Scale; HRQOL = health-related quality of life; iTBS = Intermittent Theta Burst Stimulation; MAS = Modified Ashworth Scale; MFIS = Modified Fatigue Impact Scale; MS = Multiple Sclerosis; MSQLI = MS Quality of Life Inventory; MSIS-29 = Multiple Sclerosis Impact Scale; MSSS-88 = Multiple Sclerosis Spasticity Scale; MSPS = MS Performance Scale; QLI = quality of life index; QOL = quality of life; SC = Sports climbing; SD = standard deviation; TENS = Transcutaneous Electric Nerve Stimulation; rTMS = Repetitive Transcranial Magnetic Stimulation; VAS = Visual Analogue Scale; WBV = Whole Body Vibration