Electrical stimulation therapy for children with cerebral palsy

Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To perform a systematic review of randomised and quasi‐randomised controlled trials is needed to determine the best available evidence on ES effectiveness reducing spasticity.

Background

Cerebral palsy (CP) is a common paediatric disorder occurring in about 2 to 2.5 per 1000 live births, as a result from brain injury that occurs before cerebral development is complete Rosen 1992.The actual cause of CP remains unknown in 50% of the cases, but prematurity remains the most commonly associated risk factor Taft 1995.

Children with CP suffer from multiple problems and potential disabilities such as cognitive impairment, epilepsy, feeding difficulties, and ophthalmologic and hearing deficits. Likewise, they can present a wide range of motor disturbances and spasticity  is the most common neurological presentation.

The care for the cerebral palsied patient should be managed by a multidisciplinary team, including a paediatrician, orthopaedic surgeon, child neurologist, pediatrics physiatrist, physiotherapist and occupational therapist. Rehabilitation of children with CP involves the application of different therapeutic modalities and is best cared for with an individualized treatment plan that provides a combination of interventions Brunstrom 2001.

Description of the condition

CP is characterized by the inability to normally control motor functions, and it has the potential to exert an effect on the overall development of an affected child. Effective management can improve the quality of life for the child and family. Motor deficits of CP include negative phenomena such as weakness, fatigue, incoordination and positive phenomena such as spasticity, clonus, rigidity, and spasms. Spasticity, the most common neurological presentation, is a velocity dependent increased muscle tone with hyperreflexia, resulting from hyperexcitability of the stretch reflex Lance 1980. It can lead to muscle stiffness, functional impairment, and atrophy. If untreated, it can progress to muscle fibrosis, contractures, and subsequent musculoskeletal deformities Pierson 1997.

CP can be classified according to the topographic distribution of motor involvement. Motor deficits include monoplegia, diplegia, hemiplegia, triplegia,  quadriplegia, and double hemiplegia. These subtypes can be difficult to define clinically, particularly since the degrees of disability can vary widely within all subtypes.

Spasticity  can generates wide‐ranging and debilitating consequences mainly for the more severely involved children with CP including pain, lack of coordination, muscle spasms, muscle weakness and subsequent contractures. There are a wide variety of treatment options for spasticity that include exercise, physical therapy, orthotic devices, medications, surgical procedures and electrical stimulation therapy.

Description of the intervention

There are various forms of electrical therapy as described by Kerr: Threshold Electrical Stimulation (TES) is described as the delivery of low‐intensity electrical stimulation to targeted spastic muscles during sleep at home. This stimulation is not intended to cause muscle contraction. Neuromuscular Electrical Stimulation (NMES): is the application of an electrical current of sufficient intensity to elicit muscle contraction. The NMES can be applied in a task‐specific manner stimuli the muscle at the moment it should be contracting during a functional activity is referred as Functional Electrical Stimulation (FES) Kerr 2004 .

How the intervention might work

The exact mechanism by which threshold electrical stimulation (TES) and neuromuscular electrical stimulation (NMES) might improve motor function in children with cerebral palsy is unclear. Theories on mechanism of action of ES indicate that both TES and NMES may increase muscle strength by increasing the cross‐sectional muscle area. Pape proposed that the  hormonal secretion increased blood flow during sleep associated to high hormonal secretion results in  muscle bulk Pape 1997 . The specific physiological mechanisms of spasticity modulation are not completely understood, but there is a consensus among researchers and clinicians regarding the merits of an ES trial to reduce interfering spasticity Scheker 1999.

Why it is important to do this review

Validation of therapeutic electrical stimulation requires controlled, randomised studies that can isolate the contribution of the electrical stimulation from the other components of physical therapy. The studies performed to date have mostly been of relatively small groups of children. There are few studies on the use of ES in motor disorders. The results of these studies were inconclusive and lack a consensus.

Objectives

To perform a systematic review of randomised and quasi‐randomised controlled trials is needed to determine the best available evidence on ES effectiveness reducing spasticity.

Methods

Criteria for considering studies for this review

Types of studies

We intend to evaluate all randomised and quasi‐randomised controlled trials.

Types of participants

Children with spastic cerebral palsy (diplegic, hemiplegic and quadriplegic) treated with ES ‐ TES and/or NMES as recommended by the authors of primary studies.

Trials including individuals with other diagnoses will not be included, unless the data for individuals with cerebral palsy can be extracted separately.

Types of interventions

We will include clinical trials that compared ES (NMES or TES) on lower limb muscles (quadriceps, tibialis anterior), abdomen, posterior back muscles and gluteus maximus with any of the following interventions:

• Physical therapy

• Stretching programme

• Placebo stimulator

Types of outcome measures

From a preliminary literature analysis the following outcomes were identified by the authors as potential measures of success on the use of ES (NMES or TES) to control muscle spasticity and improve function.

Primary outcomes

‐ Spasticity as assessed by the modified Ashworth score Bohannon 1987

‐ Range of motion (active and/or passive)

‐ Muscle strength ‐ Manual muscle testing

Secondary outcomes

Parameters of gait analysis

‐ Lower limb function

‐ Radiographic angles measurements

‐ Gross Motor Function Measure (GMFM) ‐ Russel 1989

‐ Peabody Developmental Motor Scales (PDMS) ‐ Folio 1983

‐ Physiological Cost Index (PCI) Butler 1984

‐ Adverse events and Complications

Search methods for identification of studies

We will use the search strategy recommended by the Cochrane Movement Disorders Group to find relevant articles for the review, by using search terms and synonyms for "Electrical Stimulation", "Cerebral Palsy" and filters to recruit clinical trials.

We will search the following bibliographic databases using the search strategies outlined below: Medline via PubMed Appendix 1, Cochrane Central Register of Clinical Trials (CENTRAL)(Appendix 2), EMBASE (Appendix 3), CINAHL, PEDRO and LILACS (Appendix 4). There will be no date or language restrictions in electronic searches for trials.

Electronic searches

We will manually search references of relevant studies and meetings, as well as contacting authors to obtain information on additional non‐published studies. Ongoing trials will be searched in the Current Controlled Trials web site (http://www.controlled‐trials.com/).

Searching other resources

Two independent review authors will screen the titles and abstracts of the citations produced by the literature search to determine if the inclusion criteria are met. Any disagreements will be resolved through discussion with a third review author serving as an arbitrator if necessary. We will classify abstracts as relevant, potentially relevant, or not relevant for this review. We will obtain full article copies for those abstracts that are designated relevant or potentially relevant.

Data collection and analysis

Two independent review authors will screen the titles and abstracts of the citations produced by the literature search to determine if the inclusion criteria are met. Any disagreements will be resolved through discussion with a third review author serving as an arbitrator if necessary. We will classify abstracts as relevant, potentially relevant, or not relevant for this review. We will obtain full article copies for those abstracts that are designated relevant or potentially relevant.

Selection of studies

Two authors will independently screen the titles and abstracts of the citations produced by the literature search to determine if the inclusion criteria are met. Any disagreements will be resolved through discussion with a third review author serving as an arbitrator if necessary. We will classify abstracts as relevant, potentially relevant, or not relevant for this review. We will obtain full article copies for those abstracts that are designated relevant or potentially relevant.

Data extraction and management

The data will be extracted by two authors and, in case of discrepancy, a third author will be consulted for further discussion and reliability.

Data collection will be undertaken according to the following criteria using specially designed data extraction forms (Figure 1).

‐ Study methods: randomisation procedure, method of allocation, blinding, design, duration;

‐ Participants: country of origin, sample size, age, gender, inclusion criteria, motor distribution, GMFCS (Gross Motor Function Classification Level), number of participants after randomisation and proportion of follow‐up losses;

‐ Intervention: electrical stimulation (intensity, dose, time), physical therapy, orthosis, surgery;

‐ Control: placebo, physical therapy, orthosis, no treatment, other;

‐ Outcomes: primary and secondary outcomes as mentioned in the section on outcome measures.

Assessment of risk of bias in included studies

The methodological quality of the selected trials will be assessed by two authors according to the methods set out in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions Higgins 2008. The following criteria will be considered:

Selection bias

Was the allocation sequence adequately generated?

Was allocation adequately concealed?

Were there systematic differences between baseline characteristics of the groups that were compared?

Performance bias

Were there systematic differences between groups in the care that was provided, or in exposure to factors other than the interventions of interest?

Attrition bias

Were there systematic differences between groups in withdrawals from a study?

Detection bias

Were there systematic differences between groups in how outcomes were determined?

For the above five items, studies will be classified according to their risk of systematic error as:

• High risk: when the appropriate method to avoid systematic error (bias) was not met;

• Moderate risk: when the appropriate method to avoid systematic error (bias) was not described or the information was not acquired by contacting the authors of primary studies;

• Low risk: when the appropriate method to avoid systematic error (bias) was met.

Measures of treatment effect

Dichotomous data For binary data, results for each study will be expressed as relative risk (RR) with 95% confidence intervals (95% CI) and pooled in a meta‐analysis with Review Manager software, using a fixed effect model. For all statistically significant differences, data will be available as NNT (number needed to treat), meaning the number of patients needed to be treated to avoid one negative event (inverse of risk difference).

Continuous data For continuous data, the mean post‐treatment/intervention values and standard deviation for each group will be reported and the weighted mean differences (WMD) with 95% CI will be calculated in the meta‐analysis. In case there are different scales measuring the same variable, the standardised mean difference (SMD) with 95% CI will be calculated.

Unit of analysis issues

The patient will be used as the unit of analysis.

Dealing with missing data

We will contact authors to supply any data missing from included studies. The actual percentage of participants lost to follow‐up will be shown under "Notes", in the Characteristics of Included Studies Table. We plan to carry out both treated case analysis and intention‐to‐treat analysis and to compare the results. Continuous data that is missing will not be imputed as the strategies for imputation of data are subjective Higgins 2008.

Assessment of heterogeneity

Heterogeneity will be assessed by examining study characteristics and forest plots of the results. We intend to use the I‐squared test to assess the impact of statistical heterogeneity, interpreting an I‐squared of 50% or more as significant.

Assessment of reporting biases

We intend to assess publication bias by preparing a funnel plot, if sufficient number of studies are available. However, we are aware that assymetry in the funnel plot can be associated with other reasons than publication bias (e.g., chance, real heterogeneity, clinical particularities inherent to each one of included studies, such as patients at high risk for the outcome).

Data synthesis

Qualitative information

Qualitative information pertaining to methods, risk of bias, description of participants and outcomes measures will be synthesized and presented in the Table of "Characteristics of included studies".

Quantitative information

For dichotomous variables, relative risk (risk ratio; RR) will be calculated. When studies report the same continuous outcome variables in the same units, weighted mean difference (WMD) will be calculated. On the other hand, when studies report the same continuous outcome in different and not interchangeable units of measure, they will be pooled using standardised mean difference (SMD). For all statistical methods to pool data, 95% confidence intervals (95% CI) will be reported. Irrespective of the nature of data, random effect model statistics will be used, since we are expecting substantial clinical and methodological heterogeneity, which by themselves could generate substantial statistical heterogeneity.

Subgroup analysis and investigation of heterogeneity

We will group results from studies according to some methodological and clinical aspects, including: age, gender, spasticity graded by modified Ashworth score (Bohannon 1987),  motor distribution and GMFCS, when available.

When substantial heterogeneity is found between studies on the I‐squared test, further analysis will be carried on to investigate its potential sources.

Sensitivity analysis

Sensitivity analyses will be conducted to examine how strongly related our review results are to decisions and assumptions that have been made during the review. We will investigate the impact of quasi‐randomised studies, studies with lower methodological quality and effect of the two types of electrical stimulations.

Appendices

Appendix 1. Search Strategy

1 Search terms and synonymous for Cerebral Palsy (clinical condition) and Electrical Stimulation (intervention)  

#1 CP

#2 Cerebral Palsy Atonic

#3 Atonic Cerebral Palsy

#4 Cerebral Palsy Hypotonic

#5 Hypotonic Cerebral Palsies

#6 Hypotonic Cerebral Palsy

#7 Cerebral Palsy Congenital

#8 Congenital Cerebral Palsy

#9 Cerebral Palsy Diplegic Infantile

#10 Cerebral Palsy Diplegia Infantile

#11 Diplegic Infantile Cerebral Palsy

#12 Diplegia Infantile Cerebral Palsy

#13 Infantile Cerebral Palsy Diplegic

#14 Infantile Cerebral Palsy Diplegia

#15 Cerebral Palsy Dystonic‐Rigid

#16 Cerebral Palsies Dystonic‐Rigid

#17 Cerebral Palsy Dystonic Rigid

#18 Dystonic‐Rigid Cerebral Palsies

#19 Dystonic‐Rigid Cerebral Palsy

#20 Monoplegic Cerebral Palsy

#21 Monoplegia Cerebral Palsy

#22 Cerebral Palsies Monoplegic

#23 Cerebral Palsies Monoplegia

#24 Cerebral Palsy Monoplegic

#25 Cerebral Palsy Monoplegia

#26 Monoplegic Cerebral Palsies

#27 Monoplegia Cerebral Palsies

#28 Cerebral Palsy Monoplegic Infantile

#29 Cerebral Palsy Monoplegia Infantile

#30 Monoplegic Infantile Cerebral Palsy

#31 Monoplegia Infantile Cerebral Palsy

#32 Infantile Cerebral Palsy Monoplegic

#33 Infantile Cerebral Palsy Monoplegia

#34 Cerebral Palsy Quadriplegic Infantile

#35 Cerebral Palsy Quadriplegia Infantile

#36 Quadriplegic Infantile Cerebral Palsy

#37 Quadriplegia Infantile Cerebral Palsy

#38 Infantile Cerebral Palsy Quadriplegic

#39 Infantile Cerebral Palsy Quadriplegia

#40 Cerebral Palsy Rolandic Type

#41 Rolandic Type Cerebral Palsy

#42 Cerebral Palsy Spastic

#43 Spastic Cerebral Palsies

#44 Spastic Cerebral Palsy

#45 Little Disease

#46 Little's Disease

#47 Spastic Diplegia

#48 Diplegias Spastic

#49 Spastic Diplegias

#50 Diplegia Spastic

#51 Cerebral Palsy Athetoid

#52 Athetoid Cerebral Palsy

#53 Cerebral Palsies Athetoid

#54 Cerebral Palsy Dyskinetic

#55 Cerebral Palsies Dyskinetic

#56 Dyskinetic Cerebral Palsy

#57 Cerebral Palsy Mixed

#58 Mixed Cerebral Palsies

#59 Mixed Cerebral Palsy

#60 Cerebral Palsy

#61 Electrical Stimulation

#62 Electrical Stimulations

#63 Stimulation Electrical

#64 Stimulations Electrical

#65 Stimulation Electric

#66 Electric Stimulations

#67 Stimulations Electric

#68 TES

#69 Threshold Electrical Stimulation

#70 Threshold Electric Stimulation

#71Therapeutic Electrical Stimulation

#72 Therapeutic Electric Stimulation

#73 NMES

#74 Neuromuscular Electrical Stimulation

#75 Neuromuscular Electric Stimulation

#76 Electrical Stimulation Transcutaneous

#77 Stimulation Transcutaneous Electrical

#78 Transcutaneous Electrical Stimulation

#79 Percutaneous Electric Nerve Stimulation

#80 Percutaneous Electrical Nerve Stimulation

#81 Transdermal Electrostimulation

#82 Electrostimulation Transdermal

#83 Transcutaneous Electrical Nerve Stimulation

#84 Transcutaneous Nerve Stimulation

#85 Nerve Stimulation Transcutaneous

#86 Stimulation Transcutaneous Nerve

#87 Electric Stimulation Transcutaneous

#88 Stimulation Transcutaneous Electric

#89 Transcutaneous Electric Stimulation

#90 TENS

#91Electroanalgesia

#92 Analgesic Cutaneous Electrostimulation

#93 Cutaneous Electrostimulation Analgesic

#94 Electrostimulation Analgesic Cutaneous

#95 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74 OR #75 OR #76 OR #77 OR #78 OR #79 OR #80 OR #81 OR #82 OR #83 OR #84 OR #85 OR #86 OR #87 OR #88 OR #89 OR #90 OR #91 OR #92 OR #93 OR #94 OR #95.

2 Cochrane sensitivity‐maximizing search strategy for identifying randomised trials in MEDLINE via PUBMED  

#1 randomized controlled trial [pt]

#2 controlled clinical trial [pt]

#3 randomized [tiab]

#4 placebo [tiab]

#5 physical therapy [sh]

#6 randomly [tiab]

#7 trial [tiab]

#8 groups [tiab]

#9 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8

#10 humans [mh]

#11 #9 and #10

3 Search strategy for identifying randomised trials in EMBASE via OVID  

#1 randoms

#2 factorials

#3 crossovers

#4 cross overs

#5 placebos

#6 doubls adj blinds

#7 singls adj blinds

#8 assigns

#9 allocats

#10 volunteers

#11 crossover‐procedure

#12 double‐blind procedure

#13 randomized controlled trial

#14 single‐blind procedure

4 Search strategy for identifying randomised trials in LILACS via BIREME  

#1 pt ensaio controlado aleatorio

#2 pt ensaio clinico controlado

#3 mh ensaios controlados aleatorios

#4 mh distribuicao aleatoria

#5 mh método duplo‐cego

#6 mh método simples‐cego

#7 pt estudo multicentrico

#8 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7

#9 tw ensaio

#10 tw ensayo

#11 tw trial

#12 #9 OR #10 OR #11

#13 tw azar

#14 tw acaso

#15 tw placebo

#16 tw controls

#17 tw aleats

#18 tw randoms

#19 #13 OR #14 OR #15 OR #16 OR #17 OR #18

#20 tw duplo

#21 tw cego

#22 #20 AND #21

#23 tw doble

#24 tw ciego

#25 #23 AND #24

#26 tw double

#27 tw blind

#28 #26 AND #27

#29 #19 OR #22 OR #25 OR #28

#30 tw clinic$

#31 #12 AND #29 AND #30

#32 #8 OR #31

What's new

Last assessed as up‐to‐date: 3 January 2011.

Date	Event	Description
20 January 2017	Amended	Published protocol withdrawn. See Published notes for further information.

Contributions of authors

Conceiving the review: SB, FCB, JAP, AFL

Co‐ordinating the review: SB, FCB

Screening search results: SB, FCB, BNGS

Organizing retrieval of papers: FCB

Screening retrieved papers against inclusion criteria: FCB, BNGS, JAP

Appraising quality of papers: FCB, BNGS, JAP

Abstracting data from papers: FCB, BNGS

Writing to authors of papers for additional information: FCB, ETD

Providing additional data about papers: SB, FCB

Obtaining and screening data on unpublished studies: SB, FCB, BNGS, JAP, AFL

Data management for the review: SB, FCB, BNGS

Entering data into Review Manager (RevMan 5.0): SB, FCB, BNGS

RevMan statistical data: SB, FCB, BNGS

Other statistical analysis not using RevMan: SB, FCB, BNGS

Interpretation of data: SB, FCB, BNGS

Statistical inferences: SB, FCB, BNGS,

Writing the review: SB, FCB, BNGS

Guarantor for the review (one author) SB

Person responsible for reading and checking review before submission: SB, FCB, BNGS, JAP, AFL

Declarations of interest

The authors of this review have none conflict of interest known.

Notes

The Cochrane Developmental, Psychosocial and Learning Problems Editorial Team have withdrawn this protocol as it was published five years ago.

Withdrawn from publication for reasons stated in the review