Finding the balance in complex regional pain syndrome. Expertise, optimism, and evidence

Complex regional pain syndrome (CRPS), perhaps more than any other chronic pain disorder, is perplexing. It is highly disabling, particularly once it has “set in,” and it has a tendency to polarize the community—some view it as a quasidiagnosis to obscure malingering or conceal substandard clinical skills,1 and others as a multiple system overprotective response.2 What is agreed is that its pathophysiology is not completely understood and that it is difficult to treat. In light of this rather murky backdrop, we welcome the new perspectives article in this issue of Neurology® by Birklein et al.3 They describe their own clinical approach to the problem and their impressions of what works, what does not, and where the field might be heading. The lead author is the most prolific and arguably the most important researcher in this field, and the article clearly draws on a wealth of expertise and clinical experience probably unmatched globally. The article reminds us of the remaining substantial challenges that we face: for example, the need for prospective studies, higher quality clinical trials and audits, and a putative model that accounts for the transition from acute CRPS to chronic CRPS, which is arguably characterized by distinct pathophysiology. Anyone who treats a good number of CRPS patients will recognize the clinical patterns to which the authors allude and be comforted by the realization that even this group, at the top of the field, share the same substantial treatment challenges.G.L.M. is supported by a Principal Research Fellowship from the National Health & Medical Research Council of Australia ID 1061279

Exercise interventions for adults and children with cerebral palsy (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: - The primary aim of this systematic review is to evaluate the effect of exercise interventions on activity, participation, and health-related quality of life (HRQoL) in adults and children with CP. - The secondary aim is to evaluate the effect of exercise interventions on body functions and body structures.Jennifer M Ryan is receiving funding from Action Medical Research and the Chartered Society of Physiotherapy Charitable Trust to evaluate the feasibility, acceptability, and efficacy of resistance training in adolescents with cerebral palsy

Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II

Background   Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery. When it occurs, it is associated with significant pain and disability. It is thought to arise and persist as a consequence of a maladaptive pro-inflammatory response and disturbances in sympathetically-mediated vasomotor control, together with maladaptive peripheral and central neuronal plasticity. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified, and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS, although their effectiveness is not known. Objectives   To determine the effectiveness of physiotherapy interventions for treating the pain and disability associated with CRPS types I and II. Search methods   We searched the following databases from inception up to 12 February 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments, without language restrictions, for randomised controlled trials (RCTs) of physiotherapy interventions for treating pain and disability in people CRPS. We also searched additional online sources for unpublished trials and trials in progress. Selection criteria   We included RCTs of physiotherapy interventions (including manual therapy, therapeutic exercise, electrotherapy, physiotherapist-administered education and cortically directed sensory-motor rehabilitation strategies) employed in either a stand-alone fashion or in combination, compared with placebo, no treatment, another intervention or usual care, or of varying physiotherapy interventions compared with each other in adults with CRPS I and II. Our primary outcomes of interest were patient-centred outcomes of pain intensity and functional disability. Data collection and analysis   Two review authors independently evaluated those studies identified through the electronic searches for eligibility and subsequently extracted all relevant data from the included RCTs. Two review authors independently performed 'Risk of bias' assessments and rated the quality of the body of evidence for the main outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results   We included 18 RCTs (739 participants) that tested the effectiveness of a broad range of physiotherapy-based interventions. Overall, there was a paucity of high quality evidence concerning physiotherapy treatment for pain and disability in people with CRPS I. Most included trials were at 'high' risk of bias (15 trials) and the remainder were at 'unclear' risk of bias (three trials). The quality of the evidence was very low or low for all comparisons, according to the GRADE approach. We found very low quality evidence that graded motor imagery (GMI; two trials, 49 participants) may be useful for improving pain (0 to 100 VAS) (mean difference (MD) −21.00, 95% CI −31.17 to −10.83) and functional disability (11-point numerical rating scale) (MD 2.30, 95% CI 1.12 to 3.48), at long-term (six months) follow-up, in people with CRPS I compared to usual care plus physiotherapy; very low quality evidence that multimodal physiotherapy (one trial, 135 participants) may be useful for improving 'impairment' at long-term (12 month) follow-up compared to a minimal 'social work' intervention; and very low quality evidence that mirror therapy (two trials, 72 participants) provides clinically meaningful improvements in pain (0 to 10 VAS) (MD 3.4, 95% CI −4.71 to −2.09) and function (0 to 5 functional ability subscale of the Wolf Motor Function Test) (MD −2.3, 95% CI −2.88 to −1.72) at long-term (six month) follow-up in people with CRPS I post stroke compared to placebo (covered mirror). There was low to very low quality evidence that tactile discrimination training, stellate ganglion block via ultrasound and pulsed electromagnetic field therapy compared to placebo, and manual lymphatic drainage combined with and compared to either anti-inflammatories and physical therapy or exercise are not effective for treating pain in the short-term in people with CRPS I. Laser therapy may provide small clinically insignificant, short-term, improvements in pain compared to interferential current therapy in people with CRPS I. Adverse events were only rarely reported in the included trials. No trials including participants with CRPS II met the inclusion criteria of this review. Authors' conclusions   The best available data show that GMI and mirror therapy may provide clinically meaningful improvements in pain and function in people with CRPS I although the quality of the supporting evidence is very low. Evidence of the effectiveness of multimodal physiotherapy, electrotherapy and manual lymphatic drainage for treating people with CRPS types I and II is generally absent or unclear. Large scale, high quality RCTs are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability of people with CRPS I and II. Implications for clinical practice and future research are considered.Cochrane Review Group funding acknowledgement: the National Institute for Health Research (NIHR) is the largest single funder of the Cochrane PaPaS Group

Clinical guidelines for low back pain. A critical review of consensus and inconsistencies across three major guidelines.

Given the scale and cost of the problem of low back pain, it is imperative that healthcare professionals involved in the care of people with low back pain have access to up-to-date, evidenced based information to assist them in treatment decision making. Clinical guidelines exist to promote consistent best practice, to reduce unwarranted variation and the use of low value interventions in patient care. Recent decades have seen the publication of a number of such guidelines. In this narrative review we consider three selected international interdisciplinary guidelines for the management of low back pain. Guideline development methods, consistent recommendations and inconsistencies between these guidelines are critically discussed

Twin peaks? No evidence of bimodal distribution of outcomes in clinical trials of non-surgical interventions for spinal pain: An exploratory analysis.

The presence of bimodal outcome distributions has been used as a justification for conducting responder analyses, in addition to, or in place of analyses of mean difference, in clinical trials and systematic reviews of interventions for pain. The aim of this study was to investigate the distribution of participants’ pain outcomes for evidence of bimodal distribution. We sourced data on participant outcomes from a convenience sample of 10 trials of non-surgical interventions (exercise, manual therapy, medication) for spinal pain. We assessed normality using the Shapiro-Wilk test. Where the Shapiro-Wilk test suggested non-normality we inspected distribution plots visually and attempted to classify them. To test whether responder analyses detected a meaningful number of additional patients experiencing substantial improvements we also calculated the risk difference and number needed to treat to benefit (NNTB). We found no compelling evidence suggesting that outcomes were bimodally distributed for any of the intervention groups. Responder analysis would not meaningfully alter our interpretation of these data when compared to the mean between group difference. Our findings suggest that bimodal distribution of outcomes should not be assumed in interventions for spinal pain and do not support the automatic prioritisation of responder analysis over the between group difference in the evaluation of treatment effectiveness for pain

Physical activity and education about physical activity for chronic musculoskeletal pain in children and adolescents

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To evaluate the effectiveness of physical activity or education about physical activity, or both, compared to active medical care, waiting list, or usual care in children and adolescents with chronic musculoskeletal pain.National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS)

Transcutaneous electrical nerve stimulation (TENS) for chronic pain - an overview of Cochrane Reviews

Background Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and quality of life. Treatment typically includes pharmacological and non-pharmacological approaches. Transcutaneous electrical nerve stimulation (TENS)is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain.ObjectivesTo provide an overview of evidence from Cochrane Reviews of theeffectiveness of TENS to reduce pain in adults with chronic pain(excluding headache or migraine).To provide an overview of evidence from Cochrane Reviews of the safety of TENS when used to reduce pain in adults with chronic pain (excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting.To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine)with a view to recommending strategies to reduce any uncertainty. Methods Search methods We searched the Cochrane Database of Systematic Reviews(CDSR), in the Cochrane Library, across all years up to Issue 11 of12, 2018. Selection of reviewsTwo authors independently screened the results of the electronic search by title and abstract against inclusion/exclusion criteria. Weincluded all Cochrane Reviews of randomised controlled trials(RCTs) assessing the effectiveness of TENS in people with chronic pain.We included reviews if they investigated the following: TENSversus sham; TENS versus usual care or no treatment/waiting list control;TENS plus active intervention versus active intervention alone; comparisons between different types of TENS; or TENS deliveredusing different stimulation parameters.Data extraction and analysisTwo authors independently extracted relevant data, assessed review quality using the AMSTAR checklist and applied GRADE judge-ments where required to individual reviews. Our primary outcomes included pain intensity and nature/incidence of adverse effects;our secondary outcomes included disability, health-related quality of life, analgesic medication use and participant global impressionof change.Main results We included nine reviews investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain. One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies. We therefore extracted data from eight reviews which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies.The included reviews followed consistent methods and achievedoverall high scores on the AMSTAR checklist. The evidence reportedwithin each review was consistently rated as very low quality.Using review authors’ assessment of risk of bias, there were significant methodological limitations in included studies; and for all reviews, sample sizes were consistently small (the majority of studies included fewer than 50 participants per group).Six of the eight reviews presented a narrative synthesis of included studies. Two reviews reported a pooled analysis.Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale (MD−1.58, 95%CI−2.08 to−1.09, P < 0.001, I² = 29%, P = 0.22, 5 studies, 207 participants).However the quality of the evidence was very low due to significant methodological limitations and imprecision. A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention (SMD−0.85, 95% CI−1.36 to−0.34, P = 0.001, I² = 83%, P < 0.001). This pooled analysis was judged as offering very low quality evidence due to significant methodological limitations, large between-trial heterogeneity and imprecision. We considered the approach of combining sham andno intervention data to be problematic since we would predict these different comparisons may be estimating different trueeffects. All remaining reviews also reported pain intensity as an outcome measure; however the data were presented in narrative review form only.Due to methodological limitation and lack of useable data, we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects, nor for the remaining secondary outcomes: disability, health-related quality of life, analgesic medication use and participant global impression of change for any comparisons.We found the included reviews had a number of inconsistencies when evaluating the evidence from TENS studies. Approaches to assessing risk of bias around the participant, personnel and outcome-assessor blinding were perhaps the most obvious area of difference across included reviews. We also found wide variability in terms of primary and secondary outcome measures, and inclusion/exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions.Authors’ conclusions We found the methodological quality of the reviews was good, but quality of the evidence within them was very low. We were the reforeunable to conclude with any confidence that, in people with chronic pain, TENS is harmful, or beneficial for pain control, disability,health-related quality of life, use of pain relieving medicines, or global impression of change. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic painNational Institute for Health Research,via Cochrane Infrastructure funding to the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS

Non-invasive brain stimulation techniques for chronic pain

Background This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). Objectives To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. Search methods For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. Selection criteria Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. Data collection and analysis Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. Main results We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision. rTMS Meta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence). CES For CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence). tDCS Analysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence). Adverse events All forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. Authors' conclusions There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.Cochrane Pain, Palliative and Supportive Car