Effectiveness of temporary deafferentation of the arm on somatosensory and motor functions following stroke: a systematic review protocol

Abstract

Review question/objective 

The primary objective of this systematic review is to present the best available evidence related to the temporary deafferentation of the affected arm on motor function and activity of the upper limb (arm and hand) recovery following stroke. Further, this review aims to assess the effects of temporary deafferentation on sensory function, activities of daily living, impact of stroke and quality of life, the acceptability and safety of the intervention as well as adverse events.

Background 

In industrialized countries, stroke is one of the most common causes of acquired disability in adulthood. Stroke is defined according to the World Health Organization as “a syndrome of rapidly developing symptoms and signs of focal, and at times global, loss of cerebral function lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin”.³⁷ Following stroke, up to 85% of patients have hemiparesis, sensory perception and/or motor function impairments of the upper limb in the acute stage. Six months post-stroke, only 5% to 20% of these patients show a complete functional recovery and 30% to 60% remain with a non-functional paretic arm.¹ These deficiencies limit activities and restrict participation in situations of everyday life. The work of therapists is fully oriented towards the recovery of function or strategy by appropriate therapies;² motor recovery may also reduce the impact of complications such as pain following stroke.^3-4 The initial severity of the stroke is one of the most important predictors but variability remains high, likely influenced by therapeutic interventions. The benefit of the latter was also noted in several brain imaging studies showing cortical reorganization.²

Regaining functional use of the upper limb remains one of the biggest challenges for patients and their therapists after stroke. However, with regard to the rehabilitation of the upper limb, the lack of evidence for the effectiveness of interventions remains prominent.^5-8 Some of the therapeutic interventions aimed at motor recovery after stroke have shown potential benefit for arm function; namely constraint-induced movement therapy (CIMT),⁹ mental practice with motor imagery,¹⁰ virtual reality,¹¹ mirror therapy,¹² and electromechanical and robot-assisted arm training.¹³ For other interventions applicable to the upper limb (electrostimulation, biofeedback with electromyography, repetitive task training, bimanual simultaneous therapy), there is not yet enough reliable data to recommend their routine use in neurorehabilitation.^14-17 Among other recent intervention strategies for the recovery of motor function, non-invasive techniques of brain stimulation, such as transcranial magnetic stimulation (TMS, repetitive TMS), transcranial direct current stimulation (tDCS) or a more invasive approach as epidural cortical stimulation (ECS) have also been used.^18-20 For the recovery of sensory perception at the hemiparetic upper limb, several interventions were also identified but again, there is insufficient evidence to support or refute their effectiveness.¹ Yet, sensory deficits significantly limit the patient's ability to use the upper limb and the quality of movement.

Three therapeutic principles are reported in the literature, namely the inhibition of the contralesional motor cortex (e.g. the constraint-induced movement therapy (CIMT)), activation of the ipsilesional motor cortex (e.g. the mental practice, bimanual therapy, CIMT) and modulation of sensory afferents (e.g. mirror therapy).²¹ For modulation of sensory afferents, different sources of information are available: proprioceptive, tactile, vestibular, visual and to a lesser extent, auditory. In this regard, Kwakkel et al.,²² have noted the dependency between the availability of information provided during sensory and motor activity and the efficiency and speed of the process of motor recovery in patients with stroke. Movements need the support of sensory stimulation and sensory information feeds the movement.²³ The therapeutic interventions available fit into this reciprocity between sensation and movement (i.e. the principle of sensory-motor integration). During learning (relearning), the acquisition of specialized skills relies primarily on sensory feedback; first visual and proprioceptive and the sensory feedback provided by the use, even partial of the paretic limb may play a major role in cortical reorganization after stroke.²⁴

A novel approach, capable of modulating mechanisms of bilateral cortical reorganization, is temporary deafferentation.²⁵ It reduces voluntarily the somatosensory input in a body part by temporary anesthesia. Early studies on deafferentation used a pneumatic tourniquet,²⁶ or nerve block,^25,27,29 to achieve anesthesia. However, these methods have significant disadvantages. Blocking with tourniquet left the patient without motor control of their anesthetized extremity; it is a painful procedure. Nerve block is invasive and often uncomfortable for the patient. Currently, studies focus on the use of an an esthetic cream (such as Emla®) covered with an occlusive bandage.^30-34 This anesthesia is an inexpensive technique with only minimal side-effects and is better tolerated by the patients.³² The rapid changes in somatosensory and motor bilateral cortical representations during and after deafferentation have been demonstrated in several functional brain imaging studies: magnetoencephalography (MEG),^26,28,32,35 functional magnetic resonance imaging (fMRI),^26,30 and transcranial magnetic stimulation (TMS).^28,34,36 These changes occurred in healthy subjects,^28,30,33,34 but also in patients with chronic stroke.^32,33,36

By means of functional brain imaging, two main reactions were found in cortical representations after temporary deafferentation. The first was change in homotopic contralateral area to the deafferented area. This phenomenon is based on interhemispheric competition models of sensorimotor processing. Deafferentation of a cortical area influences the homotopic area in the opposite hemisphere.²⁵ The mechanisms underlying this effect remain unclear, yet neural substrates do exist and seem to be predominantly inhibitory,^25,27,29 and mediated through regulation of the neurotransmitter GABA.²⁷ The second reaction was modifications in neighboring ipsilateral areas to the deafferented area.^{28, 30, 32, 34, 36} Temporary interruption of nerve impulses to the body part anesthesia leads to a decrease in brain activity in the brain area concerned. This anesthesia may enable an ‘invasion' of adjacent intact cortical areas in the deafferented region of the brain.²⁸ Thus, temporary deafferentation, through bilateral cortical reorganization observed above, has been demonstrated to improve motor,^{27, 30-32,36} and sensory,^{25,26,28,29,31,32} functions of the homonym contralateral or neighboring ipsilateral body part. For example, cutaneous anesthesia of the intact hand of chronic stroke patients resulted in improvements in performance of a dynamic finger motor task,²⁷ and in tactile capabilities,²⁹ in the paretic hand. The other approach is cutaneous anesthesia of the affected forearm of chronic post-stroke patients. This induced temporary deafferentation leads to an improvement of motor performance and somatosensory sensitivity in the affected hand.^31,32

In sum, this effect might be used to facilitate “tactile spatial acuity and changes in cortical processing for the left hand during cutaneous anesthesia of the right hand” in healthy people,²⁵ and seems therefore to be a promising option in neurorehabilitation after stroke. Recent research suggests that, in people with stroke, deafferentation of the affected arm combined with simultaneous upper extremity training might lead to improvement of arm motor function, when compared with sham.³² Although there are a few published studies of the clinical efficacy of temporary functional deafferentation on motor recovery and somatosensory sensibility of the affected arm in stroke patients,^26,27,29,36 there is currently no systematic review that synthesizes the available trials. Therefore, a systematic review of trials investigating the effectiveness and acceptability of temporary functional deafferentation is required.

Inclusion criteria

Types of participants

This review will consider all studies that include adult patients aged 18 years and older with a clinical diagnosis of stroke, either hemorrhagic or ischemic, that did not necessarily need to be confirmed using imaging studies, regardless of level of severity and regardless of aetiology,¹ undergoing care starting any time after an acute stroke and in any setting.

Types of intervention(s)/phenomena of interest

This review will consider studies that evaluate a novel approach, capable of modulating mechanisms of bilateral cortical reorganization, which is temporary deafferentation.²⁵ It reduces voluntarily the somatosensory input from a body part by temporary anesthesia.

Early studies on deafferentation used a pneumatic tourniquet,²⁶ regional anesthesia,³⁶ or nerve block,^25,27-29 to achieve anesthesia. Currently, studies focus on the use of an anesthetic cream (such as Emla®) covered with an occlusive bandage.^30-34

The deafferentation can be a stand-alone intervention or serve as an adjunct to a conventional intervention (e.g. usual care, or usual physiotherapy or occupational therapy treatment). Hence, trials will be sought that have the following comparisons: deafferentation alone versus no intervention; deafferentation alone versus conventional intervention; deafferentation alone versus placebo deafferentation (for example using placebo cream); deafferentation with conventional intervention versus conventional intervention alone; deafferentation with conventional intervention versus placebo with conventional intervention; or deafferentation plus other therapeutic or novel intervention versus other therapeutic or novel intervention alone.

Types of outcomes

The primary outcomes are those related to motor function and activity. Specific outcome measures considered include:

• Upper limb function and activity:
• arm function and activity: including assessments such as the Motor Assessment Scale (upper limb), Action Research Arm Test, Wolf Motor Function Test;
• hand function and activity: including assessments such as the Nine Hole Peg Test and Box and Block Test.
• Global motor function: including assessments such as the Motor Assessment Scale.

Secondary outcomes included measures of sensory function of arm and hand (e.g. light touch, mechanical sensation, temperature detection, two-point discrimination), activities of daily living (e.g. Functional Independence Measure, Barthel Index), participation restriction and quality of life (e.g. including assessments such as the SF36, EQ5D, Stroke Impact Scale or other patient-reported outcomes), pain (Visual Analogue Scale or Numeric Rating Scale). We also searched for imaging studies including functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS) and reported adverse effects (e.g. swelling, injury and death).

Types of studies

This review will consider both experimental and epidemiological study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies for inclusion.

This review will also consider descriptive epidemiological study designs including case series, individual case reports and descriptive cross sectional studies for inclusion in the absence of higher level evidence.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of PUBMED and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference lists of all identified reports and articles will be searched for additional studies. Studies published in English, French and German will be considered for inclusion in this review.

Studies published from 1980 to 2013 will be considered for inclusion in this review.

The databases to be searched will include: Australian Clinical Trial Registry (ACTR), Bandolier, Best BETS, BioMed Central, CINAHL, Cochrane Central Register of Controlled Trials, Embase, PubMED, PsiTri, Psychinfo, Mednar, OTSeeker and PEDro.

Individual search strategies will be developed for each database to take into account any differences in thesaurus terminology and indexing.

The search for unpublished studies will include: Dissertation abstracts and Conference proceedings Research and clinical trials register: Clinical Trials, Current Controlled Trials.

Hand searching of relevant journals (e.g. Clinical Rehabilitation, Disability and Rehabilitation, Neurorehabilitation and neural repair, Stroke) and conference proceedings will be performed to reveal additional grey literature and unpublished studies.

Full text articles of studies retrieved in the search will be assessed for relevance against the inclusion and exclusion criteria. Two reviewers will conduct this assessment independently using the JBI web-based assessment tools. Any disagreements that arise between the two reviewers will be resolved through discussion or with a third designated reviewer.

Bibliographic details of the studies will be downloaded or manually entered into an Endnote database (Endnote X5).

The search will be limited to English, but we will consider identified studies in French and German languages where an abstract is available.

Initial keywords to be used for the review will be:

‘stroke' and ‘deafferentation' in the title.

Initial keywords to be used will be:

Cerebrovascular disorder, hemiplegia, stroke, paralysis, paresis, nerve block, anesthesia, pharmacological block

Assessment of methodological quality

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.

Data collection

Data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Authors of primary studies will be contacted for missing information or to clarify unclear data.

Data synthesis

Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratios (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different study designs included in this review. Sub group analysis will also be considered where two or more studies report findings specific to either the immediate acute phase post-stroke or the longer term rehabilitative phase; i.e. studies may be sub grouped based on the stage or status of patients as well as the timing when the intervention is being administered. Sub group analysis will also be considered based on arm and hand (e.g. proximal upper limb - shoulder/elbow; distal upper limb - wrist and hand/fingers) where the data available permits. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

Conflicts of interest

There is no conflict of interest regarding this systematic review.