Exercise for people with peripheral neuropathy (Review) White CM, Pritchard J, Turner-Stokes L This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 6 http://www.thecochranelibrary.com Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Strengthening exercise versus no exercise, Outcome 1 Change in time taken for 6m comfortable walk (seconds). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 Strengthening exercise versus no exercise, Outcome 2 Change in isokinetic knee extension torque (Nm). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 Strengthening exercise versus no exercise, Outcome 3 Change in endurance at 80% MVC (seconds). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.4. Comparison 1 Strengthening exercise versus no exercise, Outcome 4 Change in isokinetic knee flexion torque (Nm). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Strengthening exercise versus no exercise, Outcome 5 Change in maximal isometric voluntary contraction force (Nm). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.1. Comparison 2 Lower limb strengthening and balance exercise versus upper limb strengthening exercise, Outcome 1 % Change in activities specific balance confidence scale scores. . . . . . . . . . . . . . Analysis 3.1. Comparison 3 Home exercise versus no exercise, Outcome 1 Change in average muscle scores. . . . Analysis 3.2. Comparison 3 Home exercise versus no exercise, Outcome 2 Change in left handgrip force (Kg). . . . Analysis 3.3. Comparison 3 Home exercise versus no exercise, Outcome 3 Change in right handgrip force (Kg). . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1 1 2 2 5 6 6 7 9 11 15 16 17 17 20 27 28 28 29 29 30 30 31 31 32 32 42 42 43 43 43 i [Intervention Review] Exercise for people with peripheral neuropathy Claire Margaret White1 , Jane Pritchard2 , Lynne Turner-Stokes3 1 Applied Biomedical Research Division, King’s College London, London Bridge, UK. 2 Neuromuscular Unit 3 North, Charing Cross Hospital, London, UK. 3 Regional Rehabilitation Unit, King’s College London and Northwick Park Hospital, Harrow, UK Contact address: Claire Margaret White, Applied Biomedical Research Division, King’s College London, Room 3.6, Shepherd’s House, Guy’s Campus, London Bridge, London, SE1 1UL, UK.
[email protected]. Editorial group: Cochrane Neuromuscular Disease Group. Publication status and date: Edited (no change to conclusions), published in Issue 6, 2011. Review content assessed as up-to-date: 23 September 2009. Citation: White CM, Pritchard J, Turner-Stokes L. Exercise for people with peripheral neuropathy. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD003904. DOI: 10.1002/14651858.CD003904.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Peripheral neuropathies are a wide range of diseases affecting the peripheral nerves. Demyelination or axonal degeneration gives rise to a variety of symptoms including reduced or altered sensation, pain, muscle weakness and fatigue. Secondary disability arises and this may result in adjustments to psychological and social function. Exercise therapy, with a view to developing strength and stamina, forms part of the treatment for people with peripheral neuropathy, particularly in the later stages of recovery from acute neuropathy and in chronic neuropathies. Objectives The primary objective was to examine the effect of exercise therapy on functional ability in the treatment of people with peripheral neuropathy. In addition, secondary outcomes of muscle strength, endurance, broader measures of health and well being, as well as unfavourable outcomes were examined. Search methods In September 2009 we updated the searches of the Cochrane Neuromuscular Disease Group register, MEDLINE (from January 1966), EMBASE (from January 1980), CINAHL (from January 1982) and LILACS (from January 1982). Bibliographies of all selected randomised controlled trials were checked and authors contacted to identify additional published or unpublished data. Selection criteria Any randomised or quasi-randomised controlled trial in people with peripheral neuropathy comparing the effect of exercise therapy with no exercise therapy or drugs or an alternative non-drug treatment on functional ability (or disability) for at least eight weeks after randomisation was included. Data collection and analysis Two authors independently selected eligible studies, rated the methodological quality and extracted data. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1 Main results Only one trial fully met the inclusion criteria. An additional two trials assessed outcomes less than eight weeks after randomisation and were also included. Methodological quality was poor for several criteria in each study. Data used in the three studies could not be pooled due to heterogeneity of diagnostic groups and outcome measures. The results of the included trials failed to show any effect of strengthening and endurance exercise programmes on functional ability in people with peripheral neuropathy. However, there is some evidence that strengthening exercise programmes were moderately effective in increasing the strength of tested muscles. Authors’ conclusions There is inadequate evidence to evaluate the effect of exercise on functional ability in people with peripheral neuropathy. The results suggest that progressive resisted exercise may improve muscle strength in affected muscles. PLAIN LANGUAGE SUMMARY Exercise for treating people with diseases of their peripheral nerves (peripheral neuropathy) Peripheral neuropathies are a wide range of diseases (both genetic and acquired) affecting the peripheral nerves. Symptoms can include pain, altered sensation such as tingling or numbness, muscle weakness and fatigue. Exercise therapy, with a view to improving strength and stamina, forms part of many rehabilitation programmes after a peripheral neuropathy. This review found inadequate evidence from randomised controlled trials to evaluate the effect of exercise in disability in peripheral neuropathy. There was evidence that strengthening exercises moderately improve muscle strength in people with a peripheral neuropathy. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 2 3 Newton metres The mean Change in isokinetic knee extension torque (Nm) in the intervention groups was 17.23 to 1.5 seconds The mean Change in endurance at 80% MVC (seconds) in the intervention groups was 0.3 higher (11.11 to 30.17 higher) 26 (1 study) ⊕⊕⊕ moderate1 Change in isokinetic knee extension torque (Nm) Follow-up: 8 weeks The mean change in isokinetic knee extension torque (nm) in the control groups was -5.Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.64 higher) 23 (1 study) ⊕⊕⊕ moderate1 Comments 3 .3 seconds The mean Change in time taken for 6m comfortable walk (seconds) in the intervention groups was 0.7 higher (5. Published by John Wiley & Sons.7 higher (0. S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation] Strengthening exercise versus no exercise for people with peripheral neuropathy Patient or population: patients with people with peripheral neuropathy Settings: Intervention: Strengthening exercise versus no exercise Outcomes Illustrative comparative risks* (95% CI) Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) Assumed risk Corresponding risk Control Strengthening exercise versus no exercise Change in time taken for 6m comfortable walk (seconds) Follow-up: 8 weeks The mean change in time taken for 6m comfortable walk (seconds) in the control groups was 0. Ltd.29 higher) 26 (1 study) ⊕⊕⊕ moderate1 Change in endurance at The mean change in en80% MVC (seconds) durance at 80% mvc Follow-up: 8 weeks (seconds) in the control groups was 1.04 lower to 11. Ltd. 4 .1 Newton metres The mean Change in isokinetic knee flexion torque (Nm) in the intervention groups was 0. Very low quality: We are very uncertain about the estimate. allocation concealment. GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. 1 High risk of bias for sequence generation. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.5 lower (9. the median control group risk across studies) is provided in footnotes. CI: Confidence interval.78 lower to 8. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).78 higher) 26 (1 study) ⊕⊕⊕ moderate1 Change in maximal isometric voluntary contraction force (Nm) Follow-up: 8 weeks The mean change in maximal isometric voluntary contraction force (nm) in the control groups was 4 Newton metres The mean Change in maximal isometric voluntary contraction force (Nm) in the intervention groups was 12.g. Published by John Wiley & Sons.51 lower to 26.Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. blinding and incomplete outcome data.71 higher) 26 (1 study) ⊕⊕⊕ moderate1 *The basis for the assumed risk (e.6 higher (1. Change in isokinetic knee flexion torque (Nm) Follow-up: 8 weeks The mean change in isokinetic knee flexion torque (nm) in the control groups was -1. Specific muscle endurance programmes may also involve the use of low load high repetition muscle contractions. show that exercise interventions are associated with significant improvements in muscle strength. pins and needles). Indeed. Patients with peripheral neuropathy typically develop symptoms of numbness. fitter and experienced less fatigue after a 12 week exercise programme that included aerobic activity. Garssen 2004.g. As in other chronic neurological disorders. These can be isometric (performed against maximal resistance where no associated joint movement is possible). psychological dysfunction and difficulties with poor social adjustment (Lennon 1993. where joint movement and limb excursion is permitted) or isokinetic (performed against variable resistance but where the speed of contraction is constant). 5 . Powell 2001. The peripheral neuropathies are a heterogeneous group of disorders in which one or all of the elements of the peripheral nervous system are damaged.BACKGROUND Peripheral nerves connect the sensory receptors and muscles to the central nervous system. Graham 2007). starting at the extremities and progressing more proximally with advancing disease. Reduced or absent reflexes are a characteristic examination finding. The reduction in fatigue was also associated with an improvement in overall mood and quality of life (Garssen 2004.g. Damage to the myelin sheath. Damage to the nerve axon is repaired by regeneration or sprouting from the intact elements.g. It has been suggested that judicious timing of exercise therapy is necessary because evidence from animal studies suggests that increased neuromuscular activity during reinnervation may be detrimental. or walking. There is some consensus that fatigue may be a common feature in people with peripheral neuropathy (Merkies 1999). Thus graded exercise programmes such as those which have been shown to be effective in improving functional performance. Strengthening programmes typically involve progressive resisted exercise utilising repetitions of specific muscle contractions. functional ability and fatigue (Chetlin 2008. Peripheral neuropathies can be genetic or acquired. and chronic neuropathy. The natural history in any individual case of neuropathy is largely dependent upon the underlying cause. Therefore it is important to examine critically the evidence surrounding the safety. the bulk of studies show either no effect (Gardiner 1986. alcoholrelated neuropathy). Nicholas 2000). primarily affecting either the myelin (the nerve insulating sheath).4% of the population (Martyn 1998). joints may be at a mechanical disadvantage and exercising may result in soft tissue damage. Sebum 1996) or a beneficial effect (Einsiedel 1994. or altered sensation (e. running. which may take many months and recovery is often incomplete. pain. chronic inflammatory demyelinating polyradiculoneuropathy. e. Peripheral nerves are subject to a very wide range of diseases called peripheral neuropathies that collectively affect about 2. or demyelination. Strength is affected when motor nerves are involved. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. two cohort studies of exercise for people with inflammatory neuropathy show that participants were stronger. produces dysfunction which may be quite rapidly reversed in a matter of weeks as the myelin regenerates. such as GuillainBarré syndrome. and participation by people with chronic fatigue syndrome (Fulcher 1997. Pfeiffer 2001. Patients are often unsure as to how much exercise they should undertake in both acute neuropathy. isotonic (performed against a submaximal known resistance. Acute neuropathies. the extent to which individuals with similar residual deficits experience limitations in activity and how they perceive the impact of this on their daily lives varies (Lennon 1993. The cardiorespiratory response to exercise testing has been shown to be reduced in people with CMT (Carter 1995) and subclinical deficits in aerobic capacity and/or muscular strength and endurance are revealed by army physical fitness testing (Burrows 1990) in soldiers after recovery from GBS. the axon (the central nerve fibre). tend to relapse and remit. They can be fearful that excessive exercise might exacerbate their symptoms. in some patients where marked weakness is a feature. Since the previous update. Symptoms during and residual problems after peripheral neuropathy include muscle weakness. Others. Hughes 2005). Ribchester 1988) of exercise during reinnervation on the recovery of function. type. Some may be insidious in onset whilst others are acute. Wearden 1998) in RCTs may be appropriate. The extent of an individual’s physical recovery is not necessarily related to recovery of nerve function (Molenaar 1999). Whilst there is some evidence that intensive exercise carried out early in the reinnervation process is detrimental to nerve sprouting (Tam 2001). whilst others gradually deteriorate over many years (e. which is recovering. timing and effectiveness of exercise in the treatment of people with peripheral neuropathy. this is typically greater than 70% of the maximal load possible. Recent recommendations for exercise prescription for people with peripheral neuropathy include a combination of aerobic and functional exercises as well as strengthening exercises to target specific weak muscle groups (Chetlin 2004. reach their worst and then slowly recover. increased fatigability (Merkies 1999). Padua 2008). Graham 2007). Published by John Wiley & Sons. The extent to which subjective feelings of fatigue are related to objective muscle fatigue is unclear. or a mixture of the two. Endurance programmes typically involve gradually increasing the duration and intensity of aerobic activity for example cycling. Ltd. several uncontrolled studies since the last update of this review. Rehabilitation for people after peripheral neuropathy has focused on symptomatic treatment and exercise therapy with little agreement in the literature regarding whether strengthening (Lindeman 1995) or endurance (Pitetti 1993) programmes are more effective (Herbison 1983). in which their exercise tolerance is reduced. Charcot-Marie-Tooth disease (CMT). sensory deficits. However. was included. Appendix 5. were selected. AMED (from January 1985 to September 2009) and LILACS (January 1982 to September 2009) were searched using the search strategy stated in the Cochrane Neuromuscular Disease Group module in combination with terms used identify potential RCTs (see below for strategy). (4) return to work at least twelve months after the start of the intervention. including sensory. as measured by a validated tool. Types of interventions Trials including any form of exercise therapy including either progressive resisted exercise (isometric. motor and combined sensory and motor neuropathies were selected. preparing food etc. was accepted. 6 . carpal tunnel syndrome etc) were not included. Secondary outcome measures included were those validated outcome measures used to assess: (1) muscle strength at least eight weeks after the start of the intervention (or on completion of the exercise programme). Published by John Wiley & Sons. combined using AND with ’strength training’ or ’endurance’ or ’exercise’ or ’physical therapy’ or ’physiotherapy’ or ’rehabilitation’ as search terms in September 2009. Appendix 2. of analgesics. were not accepted. at least eight weeks after the start of the intervention/ The search strategies used are listed in the Appendices: Appendix 1.OBJECTIVES The objective was to systematically review the evidence from randomised clinical trials concerning the effect of exercise therapy on peripheral neuropathy. or increased use. stair climbing and running. In addition unfavourable secondary outcomes were assessed including: (5) relapse as evidenced by an increase in neurological deficit. Quasi-randomised trials are those in which randomisation was intended but may be biased. cervical radiculopathy. Trials including cases of poliomyelitis were not included. functional use of the affected arm/s and/or independence in activities of daily living such as washing. Types of outcome measures Search methods for electronic databases Primary outcomes Functional ability at a timeframe less than eight weeks after the start of the intervention/control period. dressing. isotonic or isokinetic) and/or endurance training compared with either no exercise or drugs or an alternative form of non-drug treatment. Types of participants Trials including participants (adults or children) with a diagnosis of peripheral neuropathy. Search methods for identification of studies The Cochrane Neuromuscular Disease Group Register was searched using ’neuritis’ or ’neuropathy’ or ’CIDP’ or ’guillain barre’ or ’chronic inflammatory demyelinating polyradiculoneuropathy’ or ’polyradiculoneuritis’ or ’polyneuropathy’ or ’polyneuritis’ . (6) development or increase in pain sufficient to require the use. Secondary outcomes METHODS Criteria for considering studies for this review Types of studies Any randomised controlled trial (RCT) or quasi-randomised controlled trial comparing exercise therapy to treat peripheral neuropathy with no exercise therapy or drugs or an alternative form of non-drug treatment. Ltd. Trials involving cases of local entrapment neuropathies with pain as the primary presenting feature (e. (3) psychological status or quality of life at least eight weeks after the start of the intervention (or on completion of the exercise programme). Data collection and analysis Selection of studies Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. The review aimed to select only trials where the primary outcome measure was a measure of functional ability (sometimes called disability or activity limitation (WHO 2001)). Diagnoses dependent on symptoms suggestive of neuropathy alone or neurophysiological abnormalities in the absence of clinical signs. CINAHL (from January 1982 to September 2009). provided that it stipulated the presence of clinical impairment characteristic of peripheral neuropathy. Functional ability may include measures of mobility such as walking. MEDLINE (from 1966 to September 2009). control period. Appendix 3. EMBASE (from January 1980 to September 2009). The diagnosis of peripheral neuropathy offered by the authors. Bibliographies of all selected RCTs were checked and authors contacted to identify additional published or unpublished data. Appendix 4.g. (2) endurance at least eight weeks after the start of the intervention (or on completion of the exercise programme). explicit diagnostic criteria. Measures of treatment effect Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) and risk differences (RD) with 95% CIs for dichotomous outcomes and mean differences (MD) with 95% CIs for continuous outcomes. (Lindeman 1995) recruited 34 patients with CMT disease: 21 subjects had type I. The trial by Lindeman et al. There were no trials involving patients with acute peripheral neuropathy e. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Only one trial fulfilled all selection criteria (Lindeman 1995) and will be referred to as the primary included trial in the results section. six had type II and in two subjects the type was unknown. Richardson (Richardson 2001) recruited 20 subjects with peripheral neuropathy associated with diabetes mellitus. three with CIDP with central demyelination or possible toxic neuropathy. Any disagreement about inclusion criteria was resolved by discussion between the authors without need for the third author. Ruhland 1997). For the purposes of the review. tandem stance. four with idiopathic axonal degeneration and three with hereditary peripheral neuropathy. The two articles (Lindeman. Richardson 2001. Items considered were allocation concealment. six with CIDP with monoclonal gammopathy. only Lindeman 1995 will be referred to. relapsing or progressive). The items were graded: low risk of bias. One of these included aerobic conditioning exercise alongside progressive resistance exercises (Ruhland 1997). Data extraction and management The assessment of methodological quality of the trials was redone for the 2009 update according to the methods now favoured by the Cochrane Collaboration and published in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). The third trial compared progressive resisted exercise and balance exercises with a non-therapeutic exercise control (Richardson 2001). functional reach and the activities specific balance scale. documentation of therapy input. inflammatory (25 patients) or metabolic (20 patients) aetiology. Characteristics of excluded studies. The non-therapeutic exercises consisted of progressive resisted exercises of muscle groups in the upper limb that were considered unlikely to influence the selected focal lower limb outcome measures of unipedal stance. The two trials assessed outcome on completion of shorter intervention and control periods. Data synthesis Data from clinically homogenous studies were pooled where possible and sensitivity analysis undertaken for methodological quality. Two trials compared progressive resisted exercise with a non-intervention control (Lindeman 1995. Published by John Wiley & Sons. The full texts of all potentially relevant studies were obtained and independently assessed by both authors. Ruhland 1997).g. metabolic or inflammatory. at three weeks (Richardson 2001) and six weeks (Ruhland 1997) after commencement and shall be referred to hereafter as the secondary included trials in the results section. whilst a further two were included as they fulfilled all criteria except the outcome criteria of primary and secondary outcomes at least eight weeks after commencement of the intervention/control period (Richardson 2001. 1994a. Authors CMW and JP selected a total of 29 citations of full-length articles and abstracts describing 28 exercise therapy trials. Ltd. Lindeman 1995) describe only one trial. Subgroup analysis and investigation of heterogeneity Subgroups of interest were identified in advance and were chosen for their prognostic importance. mode of onset: acute. high risk of bias or ’unclear’: unknown risk of bias or the entry was not relevant in the study. three trials reported in four full-length articles were identified as RCTs by the authors (Lindeman 1994a. Assessment of risk of bias in included studies Data extraction was performed independently by two authors using a standardised data extraction form. The three identified trials included 82 patients with peripheral neuropathy of either hereditary (37 patients). (b) patients with less severe disease/disability (walks unaided) compared with patients with severe disease (unable to walk or only able to walk with assistance). participant blinding. 7 . Ruhland and Shields (Ruhland 1997) recruited 28 subjects with chronic peripheral neuropathy including 12 with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Characteristics of studies awaiting classification. Lindeman 1995. The search strategy for the databases resulted in a list of 481 citations. how studies deal with baseline differences of experimental groups and completeness of follow-up. The trials were of similar sizes. JP). RESULTS Description of studies See: Characteristics of included studies. explicit outcome criteria. The authors decided which trials fulfilled the inclusion criteria and graded their methodological quality. The other searches did not add any further references.Titles and abstracts identified by the search were checked by two authors (CMW. Ruhland 1997). Out of these. The subgroups were defined as follows: (a) type and mode of onset of neuropathy (ie type of neuropathy either: hereditary. observer blinding. GuillainBarré syndrome (GBS) or recent drug or toxin exposure. even where the programme was less than eight weeks in duration. follow-up was incomplete due to drop-outs. In one case the primary outcome measure. the mean age of patients in the intervention group (63. Ruhland 1997). intensity and duration of exercise were given in both cases. although this was based on different clinical characteristics in each case. the SF-36. Documentation of therapy input was adequate in two trials (Lindeman 1995.5 years) was significantly higher than the control group (52. was described as a measure of health related quality of life (Ruhland 1997). chronic idiopathic axonal degeneration. The second trial. Published by John Wiley & Sons.6 m with or without assistance or assistive device”’(Ruhland 1997). In the other trial (Richardson 2001) one intervention and three Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.Electronic searches were updated prior to submission of the review and a further potentially relevant study. was identified from the Cochrane Neuromuscular Disease Group Register (Zifko 2003).9 ± 16. Thus. The methods of randomisation were unclear in one trial ( Lindeman 1995) and inadequate in the other two (Richardson 2001. In the third trial (Richardson 2001) the intensity and frequency of exercise was less in the control group than the intervention group exposing the trial to moderate risk of bias. Ruhland 1997) due to matching of subjects in intervention and control groups. showed significant baseline differences in severity of neuropathy as indicated by the Michigan Diabetes Neuropathy Score (MDNS) (Richardson 2001). allocation concealment was not possible. due to knee problems. Clear descriptions of outcome criteria were included in all trials. No included trial had disability as the primary outcome measure. the very different nature of the exercises (upper versus lower limb) and the use of outcome measures reflecting lower limb function.2 years). There was no consistent examination of severity or duration of neuropathy. severity or degree of recovery from neuropathy was not indicated in any of the included trials and baseline comparisons of groups were made on the basis of other characteristics. Duration. In the third trial the criteria were not explicitly stated and subjects were selected on the basis of their clinical diagnosis as recorded in a clinical database. This alteration to the original protocol subsequently retrieved two further suitable studies (Richardson 2001. would be selected. performance and attrition bias. The information from the full publication will be included in the review as an update. In the case of (Lindeman 1995) one control patient was unable to undertake the final 24 week follow-up strength assessments. 8 . However. Richardson (Richardson 2001) included patients with a known history of diabetes mellitus and lower extremity symptoms consistent with peripheral neuropathy. In the second trial Lindeman (Lindeman 1995) included patients diagnosed with CMT disease on the basis of their clinical picture. The first trial matched patients on muscle strength and stair-climbing performance and no obvious baseline differences in age or gender of patients was noted (Lindeman 1995). In this trial there were significant differences in the Short Form-36 questionnaire (SF-36) for role limitation (emotional) and social function scale scores and despite nonrandomised placement of patients. CMT disease or toxic neuropathy as long as the toxin was no longer detectable through blood sampling (Ruhland 1997). The study is included in the studies awaiting assessment since the authors are currently seeking to publish the study in full. In two trials the inclusion criteria included a minimum ambulatory capability of: “must be able to walk household distances without assistance or assistive device indoors” (Richardson 2001) and. Subjects were included if they had a clinical diagnosis of CIDP. once available. the trials are susceptible to bias including detection. could prevent true patient blinding to the intervention. Eight out of the 28 patients in the final trial were non-randomly placed into control and experimen- tal groups to maintain similar baseline characteristics for age and gender (Ruhland 1997).6 ± 10. The authors initially planned that only trials where the outcome measures utilised validated measures of disability at least eight weeks after randomisation. its primary focus is on handicap (participation) and quality of life and it does not provide data which could be combined in any robust way with the commonly used standard measures of disability. However in this case baseline differences were accounted for by using these factors as co-variates in the subsequent data analysis. Even in the trial where participants were randomised into active exercising and control exercising groups. and a “qualification period” for recruited subjects was employed to exclude subjects with motivational problems (Lindeman 1995). Only one of the three trials included explicit diagnostic criteria. In the two other trials. There was no attempt to replace data for intention to treat analyses and the matched pair to which the control patient belonged was removed from the analysis. In one trial follow-up was complete for the intended follow-up period (Ruhland 1997) and an intention-to-treat analysis was possible. “the ability to ambulate 4. electromyography and nerve conduction studies but not genetic testing. In the third trial there was no such requirement but the baseline data included a stair climbing test. published only in abstract form. it appears that only ambulant patients were included in the reviewed studies. Under these circumstances it was decided to include those studies where suitable outcome measures had been utilised on completion of an exercise programme. However this retrieved only one suitable study (Lindeman 1995). peripheral polyneuropathy. Risk of bias in included studies Since blinding of patients and researchers is difficult in exercise trials. Allocation concealment was not described in any trial and in both trials where randomisation with matching was carried out. Ltd. Ruhland 1997). They also required conclusive electrodiagnostic evidence of diffuse. Clear descriptions of type. no explicit details of diagnostic criteria were given. Whilst it might be argued that this instrument includes some items relating to disability. primarily axonal. where group randomisation was performed. All trials considered differences in baseline characteristics. control patients dropped out during the course of the trial. six weeks (Ruhland 1997) and 24 weeks (Lindeman 1995). The scores for each trial for the risk of bias are summarised in Figure 1. The intervention periods varied as follows: three weeks (Richardson 2001). Follow-up was not extended beyond the length of the intervention period in any of the included trials. 9 . preventing completion of the trial. None of the trials fulfilled all of the criteria for methodological quality and all three trials failed to reach adequate methodological quality in a number of items. In addition the criterion for patient blinding was waived in the case of exercise versus nonexercise trials. two control patients dropped out giving no reason and the final control patient developed an unrelated illness. Methodological quality summary: review authors’ judgements about each methodological quality item for each included study. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. The intervention patient dropped out due to exercises aggravating an underlying arthritic condition. Published by John Wiley & Sons. Figure 1. Ltd. However the SF-36 scale. However.3 (95% CI -11. No significant changes in right handgrip MD 1. Summary of findings 3 Home exercise versus no exercise for people with peripheral neuropathy Authors decided by consensus not to pool data because of the differences in presentation of the results as well as the variety of outcome measures used. Summary of findings 2 Lower limb strengthening and balance exercise versus upper limb strengthening exercise for people with peripheral neuropathy. Secondary outcome measures: Muscle strength at follow-up Significant improvements in isokinetic knee extension torque in the exercise group at 24 weeks after starting the programme were reported by Lindeman 1995 with an effect size of 17.1).47) (Analysis 2.7 (95% CI 0. Muscle strength was not assessed in one trial (Richardson 2001). in addition to the majority of items pertaining to an individuals level of participation. in the secondary included trials the follow-up period was less than the stated eight weeks recommended by the review protocol. in addition to mean change scores with standard deviations (Richardson 2001.64) (Analysis 1. mean baseline and follow-up scores with standard deviations were presented. the Activities Specific Balance Confidence (ABC) scale score (Richardson 2001) at three weeks after randomisation.47 to 24. Endurance at follow-up The primary included trial utilised the maximum duration of contraction at 80% maximum voluntary contraction (MVC) as a measure of muscle endurance (Lindeman 1995) but there was no improvement in the duration of a sustained 80% maximal voluntary contraction force following 24 weeks of exercise.00 (95% CI -8.50 (95% CI -9. Ruhland 1997). However. where outcomes were assessed at less than eight weeks after commencement of the intervention/control period.29) (Analysis 1.29 to 0.70 (95% CI -0.00) (Analysis 3.7 (95% CI 5. Primary outcome measure The primary included trial showed a significant reduction in the time taken for a six metre walk (Lindeman 1995) at 24 weeks after starting the exercise with a MD of 0.In the secondary included trials.6 (95% CI -1. However.5). there was no improvement in knee flexion torque.3) or left handgrip.17) (Analysis 1. In the two secondary included trials.04 to 11. MD -0. These items assess functional ability and could therefore more readily be interpreted as relating to activity limitation.4) or maximal isometric voluntary contraction force. In the primary included trial. MD 8. The two secondary included trials did not assess endurance.1). used the SF-36 to assess what the authors stated to be health related quality of life (Ruhland 1997). In the primary included trial (Lindeman 1995) mean change scores with standard deviations were presented. Published by John Wiley & Sons. There were no data available for the stated apparent improvement in aspects of upper-leg strength related functional activities of the modified Western Ontario and McMaster University Osteoarthritis Index (WOMAC) used in this study. also contains items pertaining to physical functioning. Psychological status or quality of life at follow-up The primary included trial (Lindeman 1995) did not assess quality of life.3). no overall effect size may be calculated. in one only three weeks (Richardson 2001) and in the other only six weeks (Ruhland 1997). In the final trial there were no significant changes in the chosen disability outcome measure. It should be noted that this measure also includes items that assess functional ability and mobility.2) were shown. Ltd. follow-up was at eight weekly intervals for 24 weeks. Since.71) (Analysis 1. Standard deviations were estimated from the published paired t test P values with the help of a statistician. No other significant improvements in time scored functional activities were observed.Effects of interventions See: Summary of findings for the main comparison Strengthening exercise versus no exercise for people with peripheral neuropathy. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. One of the two secondary included trials. Only one of the secondary included trials assessed quality of life using the SF-36 (Ruhland 1997). in these trials the duration of the exercise intervention was also less than eight weeks. The study reported no significant improvement in psychological status or quality of life and since no standard deviations were presented in the text. The follow-up duration was different in each trial.11 to 30.60 (95% CI 0.91) (Analysis 3. The MD was 0. 10 .30 (95% CI -2.1). MD 12. The review will present data as mean change scores where possible. Unfortunately.60 to 4.23 to 1. no standard deviations were presented in the text of this study so no overall effect size can be calculated.51 to 26.78 to 8. a fixed effects analysis showed that there was a greater change in average muscle scores (AMS) for the exercise group than the control and significant within group improvements in AMS reported by Ruhland (Ruhland 1997). shorter follow-up periods were permitted. no within or between group differences were found for the physical function scale.2).63) (Analysis 3. MD 0. MD 0.78) (Analysis 1.03 to 2. Therefore no analysis of the subgroups of interest (type of neuropathy and disease severity) was possible. however this was not possible due to differences in outcomes and interventions between studies. In one of the secondary included trials. As a consequence.Return to work at 12 months after randomisation Subgroup analysis This was not measured in any of the included trials. Published by John Wiley & Sons. The information reported in the included trials was insufficient for clearly identifying data for the subgroups of interest. one control patient dropped out due to knee pain prior to final follow-up (Lindeman 1995). Pain This was not consistently reported in the included trials. We had planned to pool data from clinically homogeneous studies for meta-analysis. pooling of data was not appropriate. we did not conduct a sensitivity analysis for methodological quality. The primary included trial included only CMT as a cause of peripheral neuropathy (Lindeman 1995). Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. one exercising patient dropped out during the intervention period due to ankle pain (Richardson 2001). In the primary included trial. In addition. 11 . Unfavourable outcomes Relapse as defined by an increase in neurological deficit This was not measured in any of the included trials. Ltd. due to the variety of outcome measures used. In the two secondary included trials the participants had a diagnosis of diabetes-related diffuse primarily axonal peripheral polyneuropathy in one trial (Richardson 2001) and predominantly presumed inflammatory neuropathies (25 patients) or hereditary neuropathy (three patients) in the other (Ruhland 1997). Very low quality: We are very uncertain about the estimate. Follow-up: 3 weeks Illustrative comparative risks* (95% CI) Assumed risk Corresponding risk Control Lower limb strengthening and balance exercise versus upper limb strengthening exercise The mean % change in activities specific balance confidence scale scores in the control groups was 80 score The mean % Change in activities specific balance confidence scale scores in the intervention groups was 8 higher (8.47 lower to 24. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. A D D I T I O N A L S U M M A R Y O F F I N D I N G S [Explanation] Lower limb strengthening and balance exercise versus upper limb strengthening exercise for people with peripheral neuropathy Patient or population: patients with people with peripheral neuropathy Settings: Intervention: Lower limb strengthening and balance exercise versus upper limb strengthening exercise Outcomes % Change in activities specific balance confidence scale scores ABC scale. Published by John Wiley & Sons. Scale from: 0 to 100. CI: Confidence interval. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). allocation concealment and incomplete outcome data and uncertain risk of bias for blinding .g. 1 12 High risk of bias for sequence generation. GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect.47 higher) Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) 16 (1 study) ⊕⊕⊕ moderate1 Comments *The basis for the assumed risk (e. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Ltd. Home exercise versus no exercise for people with peripheral neuropathy Patient or population: patients with people with peripheral neuropathy Settings: Intervention: Home exercise versus no exercise Outcomes Illustrative comparative risks* (95% CI) Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) Assumed risk Corresponding risk Control Home exercise versus no exercise The mean change in average muscle scores in the control groups was 8.03 lower to 2. CI: Confidence interval. Published by John Wiley & Sons. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).6 score The mean Change in average muscle scores in the intervention groups was 0.29 to 0. Follow-up: 6 weeks Comments *The basis for the assumed risk (e.1 kilograms The mean Change in right handgrip force (Kg) in the intervention groups was 1.63 higher) 28 (1 study) ⊕⊕⊕ moderate1 Change in right handgrip The mean change in right force (Kg) handgrip force (kg) in the Follow-up: 6 weeks control groups was 29.91 higher) 28 (1 study) ⊕⊕⊕ moderate1 Change in left handgrip The mean change in left force (Kg) handgrip force (kg) in the control groups was Follow-up: 6 weeks 28. Scale from: 0 to 10.Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.6 higher (0.7 higher (0. Ltd.9 kilograms The mean Change in left handgrip force (Kg) in the intervention groups was 0.6 lower to 4 higher) 28 (1 study) ⊕⊕⊕ moderate1 Change in average muscle scores AMS. 13 .3 higher (2.g. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. allocation concealment and blinding. 1 High risk of bias for sequence generation. Ltd. Published by John Wiley & Sons. xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 14 . GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. and therefore these criteria for methodological quality are difficult to satisfy.DISCUSSION The main finding of the review is that there is insufficient evidence available from randomised controlled trials to confidently evaluate the effect of exercise on functional ability in patients with peripheral neuropathy. Ruhland 1997) with the greatest improvement in strength observed where the methods for determining load for progressive resisted exercise was clearly described and standardised (Lindeman 1995). it could be argued that neither of these measures unequivocally evaluates functional ability since they include questions to evaluate the impact of deficits in functional ability on general functioning or societal participation. The effect of exercise on cardiovascular fitness was not evaluated in any of the included trials. subscales of the SF-36 (Ruhland 1997) or a modification of the functional component of the WOMAC (Lindeman 1995) to assess functional ability. (Lindeman 1995) did not report improvements in any of the measures of functional ability at either of the earlier time points for assessing outcome (eight and 16 weeks after starting exercising). the response to exercise in patients with different types. Ltd. intensity and duration of exercise and the percentage change in strength of leg extensors in this study is comparable with more recent studies of similar interventions in patient populations and healthy exercising controls (Hakkinen 2001. The authors acknowledge that blinding of patients and to a lesser extent observers is difficult in exercise therapy trials. The severity of disease and the duration since onset was not adequately documented in the three trials. If blinding is carried out. muscle strength. Only Lindeman 1995 utilised a standardised method of determining load for exercise intensity. Reporting of outcome measures A lack of consensus in reporting of outcome measures was evident in the review. However. Lindeman et al. Whilst all trials included exercises to improve muscle strength. it generally remains at least at risk of exposure and hence bias. CMT disease.This suggests that exercise may have a limited effect on functional ability. Valkeinen 2004). Two trials used additional measures. severity and/or duration of peripheral neuropathy may be different and therefore reduce the validity and generalisability of findings. at least in the reviewed trials. Both studies using progressive resistance (Lindeman 1995. Indeed. This is an unfortunate omission since the evidence from RCTs for the benefits of regular exercise on improving cardiovascular fitness (Lemura 2000. Moses 1989) and in patients with neuromuscular disorders (Cedraschi 2004) is growing. All three trials were small with only 82 patients examined in total. 15 . Interpreting the findings from included trials The cause of neuropathy was different in each trial (metabolic. Nevertheless. Ruhland 1997 used progressive strengthening exercises determined by the subjects ease of completion and the final study (Richardson 2001) used a fixed load with increased repetitions during the intervention period. However. mood and mental well-being in the general population (McAuley 2000. namely. No significant changes in the composite measures were demonstrated. only an improvement in the six metre comfortable walking speed at 24 weeks after starting the exercise programme was demonstrated by Lindeman 1995. were also included (Richardson 2001. the intensity of exercise was variable and the muscle groups strengthened were different across the three trials. Nevertheless. McArdle 1996). a further two trials that met all criteria except for the need for studies to examine follow-up at least eight weeks after commencement of the intervention or control period. Indeed. It is also important to note that the intervention period in two of the trials was less than the eight weeks initially identified by the review protocol. Ruhland 1997) demonstrated some significant improvements in muscle strength over the period of the intervention. The only beneficial effects of exercise presented were small but significant changes in muscle force which were demonstrated in two trials (Lindeman 1995. inclusion and exclusion criteria based on functional mobility may have reduced variability of these factors in the reviewed trials. It could be that in these trials (Richardson 2001. the included trials failed to meet several of our other criteria for methodological quality and this inevitably limits the certainty with which any conclusions may be viewed. However the response to strengthening exercise varies due to the type. Interestingly. despite the inclusion of 20 minutes of aerobic cycling in the training programme for one study (Ruhland 1997). Only one trial examining the effect of exercise in 34 patients with CMT met the full inclusion criteria and was initially included in the review (Lindeman 1995). CIDP) and mixed causes were evident in one trial (Ruhland 1997). The authors claim that this change in muscle strength represents only a moderate improvement in response to strengthening exercise compared with healthy people (Hakkinen 1985). Whilst all trials used between one and five time scored functional activities to assess functional ability no single activity was the same across trials. Published by John Wiley & Sons. Secondary outcomes Of the stated secondary outcomes. it is well recognised that whilst there are early increases in muscle strength due to train- Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. However. Subsequently. Ruhland 1997) the exercise was not continued for long enough. Ruhland 1997). the authors suggested that this small change in preferred six metre gait speed may be influenced by motivation since the subjects were not blinded for intervention allocation. endurance and quality of life were evaluated in some of the included trials. This is an important finding for two reasons. Firstly. This highlights the paucity of trials and evidence in this important area of investigation. Adverse effects of exercise Only one participant who was undertaking exercise dropped out of the trial (Richardson 2001) due to pain in the lower limb. Limitations in the methods of the review Whilst two authors were independently involved in checking titles and abstracts identified by the search. In addition whilst a standardised data extraction sheet was devised by two authors (CMW. There was no impact on the level of disability in these patients but this may be related to the duration of the exercise intervention and methodological quality of included trials. of which only one trial fulfilled all the selection criteria and a further two trials met all but one of the criteria. disagreements regarding inclusion criteria and quality were resolved by discussion and it was not deemed necessary to refer these to a third author. However. Secondly. This was attributed to the programme aggravating an underlying arthritic condition.ing (Young 1985) these are largely due to improved neural effectiveness and changes to muscle structure take longer to establish (Moritani 1979). Firstly. No other adverse events were documented. It is possible that these omissions may have introduced some personal bias in interpretation of the studies for inclusion in the review. JP) no wider consultation of experts in the field. altered joint mechanics and muscle imbalance may predispose patients to soft tissue injury during exercise. where motor and/or sensory signs and symptoms are present. No true assessment of the cost and benefits of exercise in the treatment of people with peripheral neuropathy can be made until relevant research evidence is available. Recent evidence from animal studies suggests that during the early reinnervation phase after partial denervation high levels of neuromuscular activity as a result of electrical stimulation or exercise prevents axonal sprouting and increases motor unit loss (Tam 2001). despite the relatively high prevalence of peripheral neuropathy in the population (Martyn 1998) the varied diagnostic types and severity of disease makes recruitment to trials of large numbers of sufficiently similar participants difficult. Published by John Wiley & Sons. Several factors regarding the patient group and type of intervention may be responsible for this. This means that accurate description of exercise therapy in clinical trials is not always documented.Thus improvements in muscle strength may not be sufficient in the shorter trials to have an impact on functional ability. Overall the results of the included trials did not show that strengthening and endurance exercise programmes improve functional ability or reduce disability in patients with peripheral neuropathy. Ruhland 1997). Limitations of the review The search strategy of the review identified 481 citations. 16 . AUTHORS’ CONCLUSIONS Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. regarding the content of the data extraction form was carried out. The included trials did not discuss this or the use of orthotic support to protect affected joints during exercise. The possibility of overwork leading to an increase in neurological signs and symptoms has been investigated in both animal and human studies. However in people with post-poliomyelitis where enlarged motor units are compensating for progressive axonal loss due to partial denervation. This final point is important since the continued lack of high quality evidence regarding the efficacy of exercise in the treatment of people with peripheral neuropathy may influence the availability. moderate intensity exercise was effective in increasing muscle strength with no deleterious effects on motor unit number (Chan 2003). Medical charities (NAlliance 2002) and others (DoH 2004) have identified the needs of people with neurological and/or chronic conditions and service provision is a major concern. there was limited evidence that strengthening exercise programmes were effective in increasing the strength of tested muscles (Lindeman 1995. Secondly. including the effect of exercise treatment on the overall economic burden of care to health service providers. in assessing potentially relevant studies for inclusion and in evaluating the methodological quality of included studies. the current clinical provision for patients with peripheral neuropathy is likely to be predominantly by individualised rehabilitation that may include prescription of exercise in response to patients symptoms and individual needs. In addition many people with stable or chronic peripheral neuropathy may not be in receipt of treatment for their symptoms. Ltd. controversy exists regarding the use of strengthening exercises in conditions where partial denervation and reinnervation may be a feature. accessibility and quality of service provision for this client group. it should be noted that in peripheral neuropathy. The modest evidence from this review supports the view that progressive resisted exercise may be effective in improving muscle strength in people with peripheral neuropathy. the willingness of participants to be randomly allocated into either an exercise or non-intervention control group is particularly important for exercise trials where the motivation and commitment of the individual participants to undertake the exercise component may deter them from agreeing to participate. Finally. Therefore the limited evidence available from this review and others evaluating the effect of exercise in people with similar problems such as in fibromyalgia syndrome (Busch 2004) and physical disability in older people (Latham 2004) suggests that exercise programmes aimed at strengthening muscles are feasible in people with peripheral neuropathy. Rode G. ACKNOWLEDGEMENTS Professor RAC Hughes for advice and comments. 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Muscle & Nerve 2004B. Martyn 1998 Martyn C. Vermeulen M. Higgins 2008 Higgins JPT. Available from www.7(1):1–8. In: Martyn C. Katula J. American Journal of Physical Medicine 1979. Hakkinen 2001 Hakkinen A. Cochrane Handbook for Systematic Reviews of Interventions Version 5. Activity and motor unit size in partially denervated rat medial gastrocnemius. De Visser M. Preventative Medicine 2000. Hahn AF. BMJ 1997. Koblar S. Green S (editors). The effects of physical training of functional capacity in adults: Ages 46 to 90: a meta-analysis. Moses 1989 Moses J. Archives of Neurology 2005. and quality of life in Guillain-Barré syndrome and CIDP. van Doorn PA. Journal of Sports Medicine and Physical Fitness 2000. Blissmer B.CD002759. et al. American Academy of Neurology 1999. Yeater RA.85(8):1217–23. McAuley 2000 McAuley E. The effects of exercise training on mental well-being in the normal population: a controlled trial.2 [updated September 2009]. Anderson C.62(8):1194–8. White PD.254(2):228–35.Physical training and fatigue. Stretton C.gov. van der Meché FGA. Journal of Applied Physiology 1994. Cochrane Database of Systematic Reviews 2004. Bennet D. American Academy of Neurology 1999. Garssen 2004 Garssen MP. Cornblath DR.53 (8):1648–54. Effect of explosive type strength training on isometric force . McArdle 1996 McArdle WD. Moritani 1979 Moritani T. [DOI: 10. et al. ∗ Indicates the major publication for the study Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. BMJ 2001. Pflugers Archiv: European Journal of Physiology 1985. Appleby L. Padua 2008 Padua L. Archives of Physical Medicine and Rehabilitation 1993.Randomised. Powell 2001 Powell P. Sebum 1996 Sebum KL. Nicholas 2000 Nicholas R. Edwards RH. Mullis R. Pearson DJ. ICF: International classification of functioning. Nye FJ. http://www. The effects of two forms of isometric training on the mechanical properties of the triceps surae in man. Schmitt L.70(4):548–50. British Journal of Psychiatry 1998. A retrospective analysis of outcome in severe Guillain-Barré syndrome following combined neurological and rehabilitation management. Davies CT. 21(2):654–57. Playford ED.19:1100–9. 20 . Abbas D. Disability and quality of life in Charcot-Marie-Tooth disease type I. Pareyson D. Strickland PL. Aprile I. Pitetti 1993 Pitetti KH. Quattrone A. Ratusinski T. Properties of sprouted motor units: effect of period of enlargement and activity level. Published by John Wiley & Sons. Neurosurgery and Psychiatry 2001. Changes in knee extension and flexion force. WHO 2001 World Health Organization. Neurological Alliance.322 (7283):387–90.22(10): 451–5.uk/ 2002. Journal of Neurology. Neuromuscular disorders 2008.401: 53–75. Wicklein EM. Alen M. placebocontrolled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Kunze K. Tyreman N. Journal of Physiology 1988. Muscle & Nerve 1996. 1st Edition. EMG and functional capacity during strength training in older females with fibromyalgia and healthy controls. et al. Tam 2001 Tam SL. Airaksinen O. McDonagh MJ.74(7):761–5. Barrett PJ. Hakkinen K. Rizzuto N. Ribchester 1988 Ribchester RR. Gordon T. Valkeinen 2004 Valkeinen H. Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome.NAlliance 2002 Neurological Alliance. Hakkinen A. Increased neuromuscular activity reduces sprouting in partially denervated muscles.43(2):225–28. double-blind. Hannonen P. Archibald V. Geneva: World Health Organization.18 (3):199–203.org. Rheumatology 2004. Levelling Up. Ltd. disability and health. Pfeiffer 2001 Pfeiffer G. Morriss RK. Activity-dependent and -independent synaptic interactions during reinnervation of partially denervated rat muscle. 2001.Natural history of CMT1A including QoL: a 2-year prospective study. Endurance exercise training in Guillain-Barré syndrome.405(4):384–388. Disability and Rehabilitation 2000. Thompson AJ. Young 1985 Young K. Gardiner PF. Wearden 1998 Wearden AJ.172:485–90. Journal of Neuroscience 2001. Jassar B.neurologicalalliance. Bentall RP. Cavallaro T. Method of randomisation not stated. Intervention. 21 . 2. other disabling disorder that may influence scoring in functional tests Interventions Intervention group: knee and hip strengthening exercises progressing at 8 weekly intervals from 60% to 80% of 1 repetition maximum and reducing the repetitions from 75 to 30 for 24 weeks. some may have been due to motivational problems. 1. electromyography and nerve conduction studies and living within 100 km. Exclusion criteria: contraindications to muscle strengthening. Controls. 34 subjects underwent a prior qualification period to exclude subjects not suitable for exercise training. Losses after randomisation 2 of 30 (1 prior to allocation) Participants 29 patients with CMT disease (Type I or Type II). Control group: No exercise Outcomes Follow-up at 8-weekly intervals for 24 weeks after commencing exercise or control period. Inclusion criteria: diagnosis supported by clinical picture. Age 16 . Functional component of Western Ontario McMaster University Osteoarthritis Index (WOMAC) Notes Improvements in isokinetic knee extensor torque and 6 m comfortable speed walk Risk of bias Bias Authors’ judgement Support for judgement Random sequence generation (selection High risk bias) Participants matched for knee extensor muscle strength and performance on stairclimbing test Allocation concealment (selection bias) High risk As above for adequate sequence generation. 3. Muscle strength. Blinding (performance bias and detection High risk bias) All outcomes Outcome assessors were blinded to treatment allocation but participants were not. Ltd. Time-scored functional activities. Matching of patients in intervention and control group on knee extension muscle strength and performance on stair-climbing task.CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Lindeman 1995 Methods Prospective randomised controlled single blind trial. Difficult to blind participants in exercise intervention studies Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. mean age 35 (10) years. Four subjects excluded at this stage. mean age 38 (11) years. Published by John Wiley & Sons.60 years. Age: 50 . Ltd. Tandem stance time. Exercises were performed daily and progressed from 10 repetitions to between 20 . vestibular dysfunction. Controls.0 (6. known history of diabetes mellitus. electrodiagnostic evidence of diffuse.3 (7.80 years of age. Exclusion criteria: significant CNS dysfunction. postural hypotension. axonal peripheral polyneuropathy. Unipedal stance time.3) years. heel raises.64. ability to walk household distances. at least MRC grade 3 muscle strength at ankle.63. The first 10 subjects recruited were placed in the intervention group and the next 10 in the control group Participants 20 patients with peripheral neuropathy associated with diabetes mellitus. significant musculoskeletal deformity. Published by John Wiley & Sons. Inclusion criteria: 50 .6) years.30 repetitions over the 3 week intervention period. 1 dropped out prior to baseline assessment but it was not possible to determine the cause (either medical or social problem) and 1 dropped out prior to final outcome session (28 week follow up) due to knee problems Selective reporting (reporting bias) Low risk All outcomes reported. lower extremity pain limiting standing or weightbearing. 1. mean age . unipedal and bipedal toe raises. Control group: Seated. plantar skin ulcers Interventions Intervention group: upright.Lindeman 1995 (Continued) Incomplete outcome data (attrition bias) All outcomes High risk 6 participants lost to follow up throughout the study. mean age . upper limb strengthening exercise 5 times per week Outcomes Follow-up at 3 weeks after commencing intervention.60 years of age. Neck flexion and rotation. Activities-specific balance and confidence (ABC) scale scores Notes Improvements in unipedal and tandem stance times. Support for judgement 22 . electrodiagnostic evidence of any diagnosis other than peripheral neuropathy. Risk of bias Bias Authors’ judgement Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 2. 4 dropped out prior to allocation in accordance with exclusion criteria. intervention. Functional reach 3. inversion and eversion with no use of upper limbs except where minimal support was required. lower extremity symptoms consistent with peripheral neuropathy. angina. 4. Other bias Low risk Richardson 2001 Methods Prospective quasi-randomised controlled single blind trial. 52. Published by John Wiley & Sons. Ltd. idiopathic axonal degeneration or hereditary peripheral neuropathy. Inclusion criteria: clinical diagnosis of included conditions. one due to developing an illness and 2 gave no reason for withdrawal Selective reporting (reporting bias) Low risk All outcomes reported at follow-up Other bias Low risk Authors reported greater severity of neuropathy at baseline (based on the Michigan diabetes neuropathy score) in the intervention group than control but this was not statistically significant Ruhland 1997 Methods Prospective quasi-randomised controlled trial. Progressive resisted shoulder abduction.5) years. flexion and lateral rotation and resisted elbow flexion 10 times daily using light to strong resistance therapeutic elastic bands for 6 week intervention period. Sixty-eight people were contacted to participate in the trial. Age: control group. ability to ambulate at least 4. “first ten subjects were placed in the intervention group and the next 10 subjects were placed in the control group” Allocation concealment (selection bias) As above High risk Blinding (performance bias and detection Unclear risk bias) All outcomes Not clear if participants blinded but they did receive non-active control exercise. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 23 . mean age . mean age .9 (16.Richardson 2001 (Continued) Random sequence generation (selection High risk bias) Allocation based on rule about date of recruitment. eg age and gender across the two groups Participants 28 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) .6m with or without assistive device.6 (10.63. Unable to evaluate blinding of outcome assessors from information given Incomplete outcome data (attrition bias) All outcomes High risk At 3 week follow-up 1/10 from intervention group dropped out due to “foot-ankle pain” and 3/10 control group dropped out. intervention. 31 were recruited for initial evaluations and 28 completed the study. Twenty out of 28 subjects were randomly assigned to the control or intervention groups and non-randomised placement of the remaining 8 was necessary to balance demographics.2) years. CIDP with monoclonal gammopathy or central demyelination or toxic neuropathy. Lower limb exercise was either by a progressive walking or cycling programme at 60-70% of their age-predicted heart rate maximum of up to 20 minutes duration for 6 weeks. Exclusion criteria: Alteration to drug treatment or current regimen within 1 month of entering the trial Interventions Intervention group: general muscle stretches and free active exercises for trunk and shoulder girdle. Published by John Wiley & Sons. Timed 9.Ruhland 1997 (Continued) Control group: no exercise. 3. 24 . 5. Review of post-acute rehabilitation in 31 patients with acute polyneuritis Benyamine 1991 Not a RCT. FVC. 4. Other bias Low risk Characteristics of excluded studies [ordered by study ID] Study Reason for exclusion Becker 1986 Not a RCT. 1. Study of the effectiveness of a protocol to treat various forms of ataxia in 10 elderly subjects Carter 1995 Prospective survey of impairment and disability in 86 patients with CMT disease Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.1m walk. Average muscle scores (AMS). Medical outcomes study (MOS) Short-Form Health Survey (SF-36) Notes Improvements in AMS only. Retrospective study of rehabilitation procedure in patients with Guillain-Barré syndrome Boccignone 1997 Not a RCT. 2. Risk of bias Bias Authors’ judgement Support for judgement Random sequence generation (selection High risk bias) Non-random allocation of 8/28 participants to allow matching on basis of age and gender Allocation concealment (selection bias) High risk As above for adequate sequence generation Blinding (performance bias and detection High risk bias) All outcomes Not described but “evaluator telephoned each subject at the end of the first week and during week 5 to monitor progress and encourage adherence” Incomplete outcome data (attrition bias) All outcomes Low risk 28/28 participants available at follow-up Selective reporting (reporting bias) Low risk Yes all outcomes reported. Ltd. Outcomes Follow-up at 6 weeks after commencement of intervention or control period. Handgrip force. Florence 1984 Pilot study of 8 patients with neuromuscular disease including two patients with CMT disease Forrest 1999 Non-systematic review of clinical trials examining the efficacy of exercise in patients neuromuscular disease Gutenbrunner 1999 RCT comparing standard physiotherapy rehabilitation (including exercise) with standard physiotherapy plus the provision of a special pillow Haslbeck 1996 Not a RCT. Ltd. Survey of rehabilitation of 24 patients with Guillain-Barré syndrome Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons. Clinical review and comments. Comment only. Comparison of hand strength and fatigue between patients with CMT disease and healthy controls Zelig 1988 Not a RCT. Comparison of knee strength and functional ability between a group of patients with CMT disease and healthy controls LoVecchio 1997 A review of diagnostic characteristics in several case studies of patients with neuromuscular disease Melillo 1999 Study of rehabilitation outcome in 37 patients with Guillain-Barré syndrome Meythaler 1997 Retrospective case review of rehabilitation outcome in 39 patients with Guillain-Barré syndrome Palacios 1996 Not a RCT. Jiang 1997 Retrospective epidemiological survey of 556 patients with Guillain-Barré syndrome including length of rehabilitation Kilmer 2000 Review of response to aerobic exercise training in patients with neuromuscular disease Kingery 1997 Critical review and meta-analysis of RCTs for treatment of peripheral neuropathic pain Koch 2002 Non-systematic review of effect of strength and endurance training in neuromuscular disease Levoska 1993 Quasi RCT including passive and active (dynamic muscle training) physiotherapy for head and neck pain Lindeman 1994b Not a RCT. Study of passive joint mobilization on joint mobility Eldar 2000 Review of studies of the effects of activity and exercise in patients with neurological impairment Estacio 1998 Not a RCT.(Continued) Dijs 2000 Not a RCT. 25 . Study of functional outcome in 58 patients with Guillain-Barré syndrome Persson 2001 RCT including surgical management. cervical collar or individualised physiotherapy treatment for cervical radicular pain Rundcrantz 1991 RCT including psychosomatic and ergonomic approaches to treatment of neck pain Videler 2002 Not a RCT. 26 . Ltd. Published by John Wiley & Sons.Characteristics of studies awaiting assessment [ordered by study ID] Zifko 2003 Methods Participants Interventions Outcomes Notes Available in abstract only .awaiting publication of full study report Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 24. Ltd.60.00] Statistical method Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.29] 1 26 Mean Difference (IV. 95% CI) Effect size 8.60 [0. 95% CI) 12. Published by John Wiley & Sons.47] Comparison 3. Fixed. Fixed. Strengthening exercise versus no exercise Outcome or subgroup title 1 Change in time taken for 6m comfortable walk (seconds) 2 Change in isokinetic knee extension torque (Nm) 3 Change in endurance at 80% MVC (seconds) 4 Change in isokinetic knee flexion torque (Nm) 5 Change in maximal isometric voluntary contraction force (Nm) No. of participants 1 1 28 28 Mean Difference (IV. Home exercise versus no exercise Outcome or subgroup title 1 Change in average muscle scores 2 Change in left handgrip force (Kg) 3 Change in right handgrip force (Kg) No. of studies No. Lower limb strengthening and balance exercise versus upper limb strengthening exercise Outcome or subgroup title 1 % Change in activities specific balance confidence scale scores No.03.63] 1 28 Mean Difference (IV.23.7 [0.60 [-1. Fixed. 95% CI) -0. 95% CI) 1.51. 95% CI) Mean Difference (IV.04. 4.64] 1 26 Mean Difference (IV. Fixed. Fixed. of studies No. 0. 95% CI) 17. 95% CI) 0.DATA AND ANALYSES Comparison 1. Fixed. 95% CI) 0.29. Effect size 27 .78. of participants 1 26 Mean Difference (IV.78] 1 26 Mean Difference (IV.47.91] 0. of studies No. 11.30 [-11.30 [-2.71] Statistical method Effect size Comparison 2.7 [5.70 [-0. Fixed. 1.17] 1 26 Mean Difference (IV. Fixed. of participants 1 16 Statistical method Mean Difference (IV. 30.11. 2. 26. 8.0 [-8. Fixed. 95% CI) 0.5 [-9. Ltd. 30.Fixed.70 [ 0.Analysis 1. Outcome 2 Change in isokinetic knee extension torque (Nm).0 % 0. Comparison 1 Strengthening exercise versus no exercise.Fixed.1.3 (0. 30. Review: Exercise for people with peripheral neuropathy Comparison: 1 Strengthening exercise versus no exercise Outcome: 1 Change in time taken for 6m comfortable walk (seconds) Study or subgroup Exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Lindeman 1995 13 1 (0.11.0059) Test for subgroup differences: Not applicable -50 -25 Favours no exercise Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.95% CI IV.0 % 17.Fixed. Outcome 1 Change in time taken for 6m comfortable walk (seconds).5) 13 0. 1. Published by John Wiley & Sons.17 ] IV.3) Total (95% CI) 13 Weight Mean Difference 100.0 % 0.4 (15. 1. Review: Exercise for people with peripheral neuropathy Comparison: 1 Strengthening exercise versus no exercise Outcome: 2 Change in isokinetic knee extension torque (Nm) Study or subgroup Exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Lindeman 1995 13 12.70 [ 5.23.4) 13 -5.95% CI 13 Heterogeneity: not applicable Test for overall effect: Z = 2.2.95% CI IV.76 (P = 0.29 ] IV.93 (P = 0. 0 25 50 Favours exercise 28 .11.Fixed.3 (17.0 % 17.95% CI 13 Heterogeneity: not applicable Test for overall effect: Z = 2.29 ] 100.70 [ 5.23.0033) Test for subgroup differences: Not applicable -2 -1 0 Favours no exercise 1 2 Favours exercise Analysis 1.17 ] 100.70 [ 0. Comparison 1 Strengthening exercise versus no exercise.7) Total (95% CI) 13 Weight Mean Difference 100. 0 % 0.30 [ -11.8 (4) Total (95% CI) 13 Weight Mean Difference 100. 11.78.95% CI IV.0 % -0.11 (P = 0.78 ] 100.Fixed.95% CI 13 Heterogeneity: not applicable Test for overall effect: Z = 0.64 ] 100.96) Test for subgroup differences: Not applicable -50 -25 0 25 Favours no exercise 50 Favours exercise Analysis 1.Fixed.5 (11.95% CI IV.30 [ -11.3 (16. 0 10 20 Favours exercise 29 .5) Total (95% CI) 13 Weight Mean Difference 100. 8.92) Test for subgroup differences: Not applicable -20 -10 Favours no exercise Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.Analysis 1. 8. Review: Exercise for people with peripheral neuropathy Comparison: 1 Strengthening exercise versus no exercise Outcome: 3 Change in endurance at 80% MVC (seconds) Study or subgroup Exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Lindeman 1995 13 1.50 [ -9. Outcome 4 Change in isokinetic knee flexion torque (Nm). 11.4) 13 1. Review: Exercise for people with peripheral neuropathy Comparison: 1 Strengthening exercise versus no exercise Outcome: 4 Change in isokinetic knee flexion torque (Nm) Study or subgroup Exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Lindeman 1995 13 7.0 % 0. Comparison 1 Strengthening exercise versus no exercise. Outcome 3 Change in endurance at 80% MVC (seconds).4.04. Published by John Wiley & Sons.78.95% CI 13 Heterogeneity: not applicable Test for overall effect: Z = 0.50 [ -9.0 % -0.8 (17.64 ] IV.Fixed.05 (P = 0. Ltd.6) 13 7. Comparison 1 Strengthening exercise versus no exercise.04.Fixed.3.78 ] IV. Fixed.95 (P = 0.95% CI IV. Published by John Wiley & Sons.9) Total (95% CI) 13 Weight Mean Difference 100.1. Ltd. Outcome 1 % Change in activities specific balance confidence scale scores. Review: Exercise for people with peripheral neuropathy Comparison: 1 Strengthening exercise versus no exercise Outcome: 5 Change in maximal isometric voluntary contraction force (Nm) Study or subgroup Exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Lindeman 1995 13 16. 24. 26.60 [ -1.75 (P = 0.95% CI IV.Fixed.Fixed.51.Fixed.Analysis 1. Comparison 2 Lower limb strengthening and balance exercise versus upper limb strengthening exercise.47.47 ] 7 Heterogeneity: not applicable Test for overall effect: Z = 0.0 % 12.95% CI 100.5.34) Test for subgroup differences: Not applicable -50 -25 Upper limb exercise Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.0 % 8.47 ] IV.0 % 8.47.080) Test for subgroup differences: Not applicable -50 -25 0 25 Favours no exercise 50 Favours exercise Analysis 2. 0 25 50 Lower limb exercise 30 .95% CI 13 Heterogeneity: not applicable Test for overall effect: Z = 1. Outcome 5 Change in maximal isometric voluntary contraction force (Nm). Comparison 1 Strengthening exercise versus no exercise.6 (19.60 [ -1. Review: Exercise for people with peripheral neuropathy Comparison: 2 Lower limb strengthening and balance exercise versus upper limb strengthening exercise Outcome: 1 % Change in activities specific balance confidence scale scores Study or subgroup Lower limb exercise Mean Difference Upper limb exercise N Mean(SD) N Mean(SD) Richardson 2001 9 88 (11) 7 80 (20) Total (95% CI) 9 Weight Mean Difference 100. 26.7) 13 4 (16.71 ] IV.00 [ -8.0 % 12.71 ] 100.51. 24.00 [ -8. 60 [ 0.95% CI 14 100.25 (P = 0.95% CI Mean Difference IV.29. Comparison 3 Home exercise versus no exercise.0 % 0. Ltd.0 % 0.29. Outcome 1 Change in average muscle scores.91 ] 100. Review: Exercise for people with peripheral neuropathy Comparison: 3 Home exercise versus no exercise Outcome: 1 Change in average muscle scores Study or subgroup Home exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Ruhland 1997 14 0.03.2.1. Outcome 2 Change in left handgrip force (Kg).91 ] IV.78 (P = 0.03.Fixed. Review: Exercise for people with peripheral neuropathy Comparison: 3 Home exercise versus no exercise Outcome: 2 Change in left handgrip force (Kg) Study or subgroup Exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Ruhland 1997 14 1. 0 10 20 Home exercise 31 .Fixed.Fixed.0 % 0.4) 14 -0.44) Total (95% CI) 14 Weight Mean Difference 100.99) Total (95% CI) 14 Weight IV.00016) Test for subgroup differences: Not applicable -4 -2 0 2 No exercise 4 Home exercise Analysis 3.60 [ 0. 0.30 [ -2.95% CI 14 Heterogeneity: not applicable Test for overall effect: Z = 3.1 (3.8 (2.2 (0.29) 14 0.30 [ -2.63 ] Heterogeneity: not applicable Test for overall effect: Z = 0.63 ] 100. Comparison 3 Home exercise versus no exercise.80) Test for subgroup differences: Not applicable -20 -10 No exercise Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 2.Analysis 3.95% CI IV. 2.4 (0. Published by John Wiley & Sons.0 % 0.Fixed. 0. 00 ] IV. or Polyradiculoneuropathy.5 (2. 32 . Review: Exercise for people with peripheral neuropathy Comparison: 3 Home exercise versus no exercise Outcome: 3 Change in right handgrip force (Kg) Study or subgroup Home exercise Mean Difference No exercise N Mean(SD) N Mean(SD) Ruhland 1997 14 2.95% CI IV. 4. Published by John Wiley & Sons. 6 4 or 5 7 (Inflammatory adj polyradiculoneuropath$).mp. Comparison 3 Home exercise versus no exercise. 15 Peripheral Nervous System Diseases/ 16 Neuropath$.15) Test for subgroup differences: Not applicable -10 -5 No exercise 0 5 10 Home exercise APPENDICES Appendix 1. 10 or/7-9 11 6 and 10 12 CIDP.mp.00 ] 100.mp. or Polyradiculoneuropathy/ 2 (Guillain and Barre).0 % 1.mp. Chronic Inflammatory Demyelinating/ 13 (multifocal and neuropath$).mp. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Ovid MEDLINE Search Strategy 1 Polyradiculoneuritis.60. or Demyelinating Diseases/ 5 demyelin$.46) 14 0.60. Ltd.mp. 14 (paraprot$ adj neuropath$).2 (3.mp.3. Outcome 3 Change in right handgrip force (Kg). 8 (Inflammatory adj polyneuropath$). 22 Amyloid Neuropathies/ 23 (Amyloid adj neuropath$).mp. 17 15 or 16 18 PARAPROTEINEMIAS/ 19 17 and 18 20 POEMS Syndrome/ 21 (Poems adj Syndrome).70 [ -0.69) Total (95% CI) 14 Weight Mean Difference 100.95% CI 14 Heterogeneity: not applicable Test for overall effect: Z = 1.Fixed.45 (P = 0.70 [ -0.mp.Analysis 3.0 % 1.Fixed.mp. 4. 3 1 or 2 4 Demyelinating diseases.mp.mp. 9 (Inflammatory adj mononeuropath$).mp. 65 (lumbosacral adj radiculopath$). 34 30 or 32 or 33 35 ALCOHOLISM/ 36 17 and 35 37 (alcohol adj neuropath$).mp.tw.mp. Published by John Wiley & Sons.mp.mp. 57 (neuralgic and amyotropath$).mp. 70 (nerve$ and graft$).mp.24 “HEREDITARY MOTOR AND SENSORY NEUROPATHIES”/ 25 (Motor and Sensory and Neuropath$ and Heredity).mp. 76 (tarsal adj tunnel).mp. Ltd.mp.mp.mp. 26 “HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES”/ 27 (Hereditary and Sensory and Autonomic and Neuropath$). 59 Brachial Plexus Neuritis/ 60 exp PAIN/ 61 pain$.mp. 44 Herpes Zoster/ 45 (Herpes adj zoster). 32 17 and 31 33 ((Drug or Chemically) and induced and Neuropath$). 51 49 or 50 52 (vasculitic$ and neuropath$).mp.mp. 62 60 or 61 63 17 and 62 64 (cervical adj spondylotic adj radiculopath$).mp.mp. 38 Paraneoplastic Syndromes/ 39 17 and 38 40 BORRELIA/ 41 Borrelia$. 71 Tissue Transplantation/ 72 67 and 71 73 Nerve Compression Syndromes/ 74 (entrapment adj neuropath$).mp. 46 NEURALGIA/ 47 (Herpes or herpetic). 28 (Heredit$ and Neuropath$). 75 (carpal adj tunnel). 53 NEURITIS/ 54 Brachial Plexus/ 55 53 and 54 56 (Brachial adj neuritis). 66 “Wounds and Injuries”/ 67 Peripheral Nerves/ 68 66 and 67 69 (Nerve adj trauma).mp.mp. 29 or/24-28 30 (Toxic adj neuropath$).mp. 58 (radiation and plexopath$).mp. 33 . 31 (chemically or toxicity).mp.mp. 42 LEPROSY/ 43 (leprosy or leper$). 48 46 and 47 49 Diabetic Neuropathies/ 50 (Diabetic adj neuropath$). Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. tw. 106 (isometric$ adj5 (exercise$ or strength$)).mp.mp.tw. 122 (exercise$ adj5 train$). 116 (rowing adj5 (exercise$ or train$)). 129 drug therapy.mp.tw.tw. 121 Kinesiotherap$. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 120 ((weight$ adj5 exercise$) or train$). 126 controlled clinical trial. 81 Facial Paralysis/ 82 pals$. and training. 79 (cubital adj tunnel).mp. 85 80 or 83 or 84 86 Trigeminal Neuralgia/ 87 (trigeminal adj neuralgia$). 118 (runnin$ adj5 (exercise or train$)).tw.tw. 107 (isotonic$ adj5 (exercise$ or strength$)).mp.tw. 105 (strength$ adj5 (exercise$ or train$)). 98 exp Exertion/ 99 exp Physical Therapy Techniques/ 100 Physiotherap$. 93 exp Rehabilitation/ 94 exercise$.tw.mp.tw. 110 (endurance adj5 (exercise$ or train)). 117 (run$ adj5 (exercise$ or train$)).mp.mp. 109 (aerobic$ adj5 (exercise$ or train)). 78 (ulnar adj nerve adj compression).ab. 113 (step up$ adj5 (exercise$ or train$)).tw.77 (thoracic adj outlet). Ltd.fs.mp.mp.mp.tw. 112 (gait adj5 train$). 80 (bell$ adj pals$).tw. 119 (treadmill adj5 (exercise$ or train$)). 34 . 123 or/92-122 124 91 and 123 125 randomized controlled trial.tw. 111 (walk$ adj5 (exercise$ or train$)).ab. 104 strength$.pt.tw. 95 exp Exercise Therapy/ 96 exp SPORTS/ 97 Physical education.mp. 83 81 and 82 84 (cranial adj nerve$ adj pal$).mp. 114 ((stair$ adj5 exercise$) or train$).tw.pt.mp. 101 (physical$ adj5 fit$).tw. 127 randomized. 115 (cycle$ adj5 (exercise$ or train$)). 103 (physical$ adj5 activit$).mp.tw. 128 placebo.mp. Published by John Wiley & Sons. 108 (isokinetic$ adj5 (exercise$ or strength$ or train$)). 102 (physical adj5 train$).mp. 88 Peripheral Nervous System Neoplasms/ 89 3 or 11 or 12 or 13 or 14 or 19 or 20 or 21 or 22 or 23 or 29 or 34 or 36 or 37 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 48 or 51 90 52 or 55 or 56 or 57 or 58 or 59 or 64 or 65 or 68 or 69 or 70 or 72 or 73 or 74 or 75 or 76 or 77 or 78 or 79 (29615) 91 85 or 86 or 87 or 88 or 89 or 90 92 rehabilitat$. mp. 131 trial. 3 1 or 2 4 Demyelinating diseases.mp. 42 LEPROSY/ Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.mp.mp. 24 “HEREDITARY MOTOR AND SENSORY NEUROPATHIES”/ 25 (Motor and Sensory and Neuropath$ and Heredity).tw. 31 (chemically or toxicity). Published by John Wiley & Sons. 29 or/24-28 30 (Toxic adj neuropath$). Ovid EMBASE search strategy 1 Polyradiculoneuritis. or Demyelinating Diseases/ 5 demyelin$. 14 (paraprot$ adj neuropath$). 9 (Inflammatory adj mononeuropath$).mp.sh.mp.mp. 8 (Inflammatory adj polyneuropath$).mp. 32 17 and 31 33 ((Drug or Chemically) and induced and Neuropath$).mp.ab.mp.mp.mp.130 randomly. 17 15 or 16 18 PARAPROTEINEMIAS/ 19 17 and 18 20 POEMS Syndrome/ 21 (Poems adj Syndrome).mp.mp.mp. 34 30 or 32 or 33 35 ALCOHOLISM/ 36 17 and 35 37 (alcohol adj neuropath$). or Polyradiculoneuropathy/ 2 (Guillain and Barre).mp. 38 Paraneoplastic Syndromes/ 39 17 and 38 40 BORRELIA/ 41 Borrelia$. or Polyradiculoneuropathy. 6 4 or 5 7 (Inflammatory adj polyradiculoneuropath$). 10 or/7-9 11 6 and 10 12 CIDP. 133 or/125-132 134 (animals not (animals and humans)).mp.mp. 132 groups.ab.ab. 15 Peripheral Nervous System Diseases/ 16 Neuropath$. 22 Amyloid Neuropathies/ 23 (Amyloid adj neuropath$).mp. 35 . 135 133 not 134 136 124 and 135 Appendix 2. Ltd.mp. 28 (Heredit$ and Neuropath$). Chronic Inflammatory Demyelinating/ 13 (multifocal and neuropath$). 26 “HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES”/ 27 (Hereditary and Sensory and Autonomic and Neuropath$). Ltd.mp.mp. 77 (thoracic adj outlet).mp. 75 (carpal adj tunnel). 83 81 and 82 84 (cranial adj nerve$ adj pal$).mp.mp.mp. 70 (nerve$ and graft$).mp.mp. 85 80 or 83 or 84 86 Trigeminal Neuralgia/ 87 (trigeminal adj neuralgia$). 62 60 or 61 63 17 and 62 64 (cervical adj spondylotic adj radiculopath$). 44 Herpes Zoster/ 45 (Herpes adj zoster).mp. 59 Brachial Plexus Neuritis/ 60 exp PAIN/ 61 pain$.mp. 93 exp Rehabilitation/ 94 exercise$.mp. 46 NEURALGIA/ 47 (Herpes or herpetic). 66 “Wounds and Injuries”/ 67 Peripheral Nerves/ 68 66 and 67 69 (Nerve adj trauma). 48 46 and 47 49 Diabetic Neuropathies/ 50 (Diabetic adj neuropath$).mp.mp. 78 (ulnar adj nerve adj compression).43 (leprosy or leper$). 80 (bell$ adj pals$).mp.mp.mp.mp. 53 NEURITIS/ 54 Brachial Plexus/ 55 53 and 54 56 (Brachial adj neuritis).mp.mp.mp. 76 (tarsal adj tunnel).mp. 57 (neuralgic and amyotropath$).mp. 79 (cubital adj tunnel). Published by John Wiley & Sons. 58 (radiation and plexopath$).mp. 88 Peripheral Nervous System Neoplasms/ 89 3 or 11 or 12 or 13 or 14 or 19 or 20 or 21 or 22 or 23 or 29 or 34 or 36 or 37 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 48 or 51 90 52 or 55 or 56 or 57 or 58 or 59 or 64 or 65 or 68 or 69 or 70 or 72 or 73 or 74 or 75 or 76 or 77 or 78 or 79 91 85 or 86 or 87 or 88 or 89 or 90 92 rehabilitat$. 81 Facial Paralysis/ 82 pals$. 71 Tissue Transplantation/ 72 67 and 71 73 Nerve Compression Syndromes/ 74 (entrapment adj neuropath$). 51 49 or 50 52 (vasculitic$ and neuropath$). 95 exp Exercise Therapy/ Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 65 (lumbosacral adj radiculopath$).mp.mp. 36 . Ltd.tw.tw.tw. 107 (isotonic$ adj5 (exercise$ or strength$)).mp.tw. 103 (physical$ adj5 activit$). 37 .tw. 119 (treadmill adj5 (exercise$ or train$)). 98 exp Exertion/ 99 exp Physical Therapy Techniques/ 100 Physiotherap$. 101 (physical$ adj5 fit$).96 exp SPORTS/ 97 Physical education.tw.tw.tw.tw. 109 (aerobic$ adj5 (exercise$ or train)). 123 or/92-122 124 91 and 123 125 crossover-procedure/ 126 double-blind procedure/ 127 randomized controlled trial/ 128 single-blind procedure/ 129 (random$ or factorial$ or crossover$ or cross over$ or cross-over$ or placebo$ or (doubl$ adj blind$) or (singl$ adj blind$) or assign$ or allocat$ or volunteer$). 117 (run$ adj5 (exercise$ or train$)). 113 (step up$ adj5 (exercise$ or train$)).tw.tw. 106 (isometric$ adj5 (exercise$ or strength$)).mp.mp.mp. 110 (endurance adj5 (exercise$ or train)). 120 ((weight$ adj5 exercise$) or train$).mp. 104 strength$. 115 (cycle$ adj5 (exercise$ or train$)).tw. 122 (exercise$ adj5 train$). 105 (strength$ adj5 (exercise$ or train$)).mp. 102 (physical adj5 train$). 130 or/125-129 131 human/ 132 130 and 131 133 nonhuman/ or human/ 134 130 not 133 135 132 or 134 136 124 and 135 Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 118 (runnin$ adj5 (exercise or train$)). and training.tw. 121 Kinesiotherap$. 112 (gait adj5 train$). 116 (rowing adj5 (exercise$ or train$)).tw.mp.mp. 114 ((stair$ adj5 exercise$) or train$). 108 (isokinetic$ adj5 (exercise$ or strength$ or train$)).tw.tw. 111 (walk$ adj5 (exercise$ or train$)).tw.tw. Published by John Wiley & Sons. 34 (paraneoplastic and neuropath$). 36 35 and 17 37 neuroborreliosis. Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 4 1 or 2 or 3 5 Demyelinating Disease/ 6 demyelin$. 39 38 and 17 40 Herpes Zoster/ or Herpes zoster. and 17 29 (neurotoxicity and syndrome$). Ovid AMED search strategy 1 Polyradiculoneuritis/ 2 (Polyradiculoneuritis or Polyradiculoneuropath$ or Polyradiculopath$).mp.mp. 24 20 or 21 or 22 or 23 25 (Toxic adj neuropath$). 14 (paraprot$ and neuropath$).mp. 20 “neuropathies. 41 NEURALGIA/ 42 (Herpes or herpetic or posther$ or post-herp$).mp. 48 NEURITIS/ 49 Brachial Plexus/ 50 48 and 49 51 (Brachial adj neuritis).tw.mp.mp. 38 .mp. Published by John Wiley & Sons.mp.mp.Appendix 3.mp. 7 5 or 6 8 (Inflammatory and polyneuropath$). 30 25 or 27 or 28 or 29 31 ALCOHOLISM/ 32 17 and 31 33 (alcohol and neuropath$). 43 41 and 42 44 Diabetic Neuropathies/ 45 (Diabetic adj neuropath$). 19 (Amyloid and neuropath$).mp.mp.mp. 13 (multifocal and neuropath$). 46 44 or 45 47 (vasculit$ and neuropath$). HEREDITARY MOTOR AND SENSORY”/ 21 (motor and sensory and heredit$ and Neuropath$).mp.mp. 10 8 or 9 11 7 and 10 12 CIDP. Ltd.mp. 9 ((inflammatory adj polyneuropath$) or (inflammatory adj mononeuropath$)).mp.mp. or leper$.mp. 15 Peripheral Nervous System Disease/ 16 Neuropath$. 17 15 or 16 18 (Poems adj Syndrome). 26 (chemically or toxicity).mp.mp.mp. 27 17 and 26 28 ((Drug or Chemically) and induced and Neuropath$). 23 (heredit$ and neuropath$).mp.mp.mp 22 (hereditary and sensory and autonomic and neuropath$).mp.mp.mp. 38 leprosy/ or leprosy. 3 (Guillain and Barre). 35 borrelia/ or Borrelia$. mp.mp.mp.mp.mp. 71 (cubital adj tunnel).mp. 93 (paraneoplastic and (polyneuropath$ or nervous)).mp. 96 (alcohol induced and disorder and nerv$).mp. 94 bulbar palsy. 72 (bell$ adj pals$).43 99 or/46-47. 56 54 or 55 57 17 and 56 58 (cervical adj spondylotic adj radiculopath$).62-64 100 or/65-71.mp. 82 iodopathic dysautonomia$.78-81 101 or/82-91 102 or/92-101 103 rehabilitat$.mp. 89 charcot marie tooth. 39 . 86 gustatory sweating. 65 Nerve Compression Syndromes/ 66 (entrapment adj neuropath$). 64 (nerve$ and graft$).mp. 104 Rehabilitation/ Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration.mp.mp. 97 or/4.11-14. 69 (thoracic adj outlet).mp. 70 (ulnar adj nerve adj compression).mp.mp.mp. 59 (lumbosacral adj radiculopath$). 84 foot ulcer$.mp. 90 (heredit$ and (demyelinat$ or neuropath$)). 68 (tarsal adj tunnel).mp.mp. 53 ((neuralg$ and amyotropath$) or (radiation and plexopath$)). Ltd.24 98 or/30. 85 gastroparesis.18-19.50-53. 73 Facial Paralysis/ 74 pals$.mp. 95 stiff man syndrome$. 77 facial nerve injur$. 92 complex regional pain syndrome$. 91 ((peroneal or median or femoral) and neuropath$).mp. 81 peripheral neuropath$.mp. 54 exp PAIN/ 55 pain$.mp. 75 73 and 74 76 (cranial adj nerve$ adj pal$).mp.mp.mp.mp.mp.mp.mp.mp.57-59. 67 (carpal adj tunnel). 83 glossopharyngeal neuralgia.mp.mp. 60 “Wounds and Injuries”/ 61 Peripheral Nerves/ 62 60 and 61 63 (Nerve adj trauma).mp.32-40. Published by John Wiley & Sons. 87 postural hypotension. 78 72 or 75 or 76 or 77 79 Trigeminal Neuralgia/ 80 (trigeminal adj neuralgia$). 88 (mononeuropath$ or polyneuropath$).52 brachial neuropath$. tw. 144 random$.tw. and training.mp.tw. 121 (endurance adj5 (exercise$ or train)). 132 Kinesiotherap$. 130 (treadmill adj5 (exercise$ or train$)).mp.mp. 134 or/103-133 135 Randomized controlled trials/ 136 Random allocation/ 137 Double blind method/ 138 Single-Blind Method/ 139 exp Clinical Trials/ 140 (clin$ adj25 trial$). 127 (rowing adj5 (exercise$ or train$)). 122 (walk$ adj5 (exercise$ or train$)). 142 placebos/ 143 placebo$.tw.tw.mp. 129 (runnin$ adj5 (exercise or train$)). 106 exp Exercise Therapy/ 107 exp SPORTS/ 108 Physical education.tw. 123 (gait adj5 train$).tw. Published by John Wiley & Sons.105 exercise$. 114 (physical$ adj5 activit$).tw. 151 (multicenter or multicentre). 125 ((stair$ adj5 exercise$) or train$). 150 control$. 126 (cycle$ adj5 (exercise$ or train$)).tw. 116 (strength$ adj5 (exercise$ or train$)).tw. 131 ((weight$ adj5 exercise$) or train$).tw.tw.tw. 145 research design/ 146 Prospective Studies/ 147 cross over studies/ 148 meta analysis/ 149 (meta?analys$ or systematic review$). 119 (isokinetic$ adj5 (exercise$ or strength$ or train$)).tw. 128 (run$ adj5 (exercise$ or train$)).tw. 113 (physical adj5 train$). 153 or/135-152 154 102 and 134 and 153 Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. 152 ((study or studies or design$) adj25 (factorial or prospective or intervention or crossover or cross-over or quasi-experiment$)).tw. 133 (exercise$ adj5 train$). 40 .tw.mp. 141 ((singl$ or doubl$ or treb$ or trip$) adj25 (blind$ or mask$ or dummy)).tw. 120 (aerobic$ adj5 (exercise$ or train)). Ltd. 115 strength$. 112 (physical$ adj5 fit$). 118 (isotonic$ adj5 (exercise$ or strength$)).tw. 124 (step up$ adj5 (exercise$ or train$)).tw.tw.tw.mp.mp.mp.mp.tw.tw. 117 (isometric$ adj5 (exercise$ or strength$)). 109 exp Exertion/ 110 physiotherapy/ 111 Physiotherap$.tw. EBSCOhost CINAHL search strategy S41 S40 and S12 S40 S39 or S38 or S37 or S36 or S35 or S34 or S33 or S32 or S31 or S30 or S29 or S28 or S27 or S26 or S25 or S24 or S23 or S22 or S21 or S20 or S19 or S18 or S17 or S16 or S15 or S14 or S13 S39 (cycl*) or (MH “Cycling”) S38 (physical fit*) or (MH “Physical Fitness”) S37 Kinesiotherap* S36 weight* S35 (treadmill) or (MH “Treadmills”) S34 (row*) or (MH “Rowing”) S33 (run*) or (MH “Running”) S32 (stair*) or (MH “Stair Climbing”) S31 step* S30 (gait) or (MH “Gait”) S S29 (walk*) or (MH “Walking”) S28 endurance S27 (aerobic*) or (MH “Aerobic Exercises”) S26 (isokinetic*) or (MH “Isokinetic Exercises”) S25 (isotonic*) or (MH “Isotonic Exercises”) S24 (isometric*) or (MH “Isometric Exercises”) S23 (strength*) or (MH “Muscle Strengthening”) S22 physical activit* S21 physical train* S20 Physiotherap* S19 (Physical Therapy Techniques) or (MH “Physical Therapy”) S18 (Exertion) or (MH “Exertion”) S17 ((Physical education AND training)) or (MH “Physical Education and Training”) S16 (sport*) or (MH “Sports”) S15 (exercise*) or (MH “Exercise”) S14 (MH “Rehabilitation”) S13 rehabilitat* S12 S11 or S10 or S9 or S8 or S7 or S6 or S5 or S4 or S3 or S2 or S1 S11 (polyneuritis) or (MH “Polyneuritis”) S10 (polyradiculoneuritis) or (MH “Polyradiculoneuritis”) S9 chronic inflammatory demyelinating polyradiculoneuropathy S8 guillain barre Search modes S7 CIDP S6 (neuritis) or (MH “Neuritis”) S5 (peripheral nerves) or (MH “Peripheral Nerves”) S4 polyneuropath* S3 peripheral* nervous* system* disease* S2 (MH “Peripheral Nervous System Diseases”) S1 peripheral neuropath* Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons. Ltd. 41 .Appendix 4. Searches updated to September 2009.535$ OR (Tw clin$ AND (Tw trial$ OR Tw ensa$ OR Tw estud$ OR Tw experim$ OR Tw investiga$)) OR ((Tw singl$ OR Tw simple$ OR Tw doubl$ OR Tw doble$ OR Tw duplo$ OR Tw trebl$ OR Tw trip$) AND (Tw blind$ OR Tw cego$ OR Tw ciego$ OR Tw mask$ OR Tw mascar$)) OR Mh placebos OR Tw placebo$ OR (Tw random$ OR Tw randon$ OR Tw casual$ OR Tw acaso$ OR Tw azar OR Tw aleator$) OR Mh research design) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Ct comparative study OR Ex E05.Appendix 5. 42 . no new studies 4 August 2008 Amended Converted to new review format. Published by John Wiley & Sons. LILACS search strategy (peripheral neuropath$ OR Mh Peripheral Nervous system diseases OR peripheral$ nervous$ system$ disease$ OR polyneuropath$ OR Mh peripheral nerves OR peripheral nerves OR Mh neuritis OR neuritis OR CIDP OR guillain barre OR chronic inflammatory demyelinating polyradiculoneuropathy OR Mh polyradiculoneuritis OR polyradiculoneuritis OR Mh polyneuritis OR polyneuritis) AND (rehabilitat$ OR Mh Rehabilitation OR exercise$ OR Mh exercise OR sport$ OR Mh sport OR (Physical education AND training) OR Exertion OR Mh exertion OR Physical Therapy Techniques OR Mh Physical Therapy OR Physiotherap$ OR physical fit$ OR physical train$ OR physical activit$ OR strength$ OR Mh Muscle Strengthening OR isometric$ OR Mh Isometric Exercises OR isotonic$ OR Mh Isotonic Exercises OR isokinetic$ OR Mh Isokinetic Exercises OR aerobic$ OR Mh Aerobic Exercises OR endurance OR walk$ OR Mh Walking OR gait OR Mh gait OR step$ OR stair$ OR Mh stair climbing OR cycle$ OR Mh cycling OR row$ OR Mh rowing OR run$ OR Mh running OR treadmill Mh treadmills OR weight$ OR Kinesiotherap$) AND ((Pt randomized controlled trial OR Pt controlled clinical trial OR Mh randomized controlled trials OR Mh random allocation OR Mh double-blind method OR Mh single-blind method) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Pt clinical trial OR Ex E05. Ltd.760. 2002 Review first published: Issue 4. 2004 Date Event Description 14 September 2009 New search has been performed Changes to background text. references.337$ OR Mh follow-up studies OR Mh prospective studies OR Tw control$ OR Tw prospectiv$ OR Tw volunt$ OR Tw volunteer$) AND NOT (Ct animal AND NOT (Ct human and Ct animal))) WHAT’S NEW Last assessed as up-to-date: 23 September 2009. MEDLINE (January 1966 to August 2005). ’Risk of bias’. Date Event Description 11 May 2011 Amended Added additional acknowledgement HISTORY Protocol first published: Issue 4. EMBASE (January 1980 to August 2005).318. 1 April 2006 New search has been performed We updated the searches of the Cochrane Neuromuscular Disease Group Register (September 2005) . ’Summary of findings’ tables added. CINAHL (Jan- Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. (Continued) uary 1982 to October 2005) and AMED (January 1985 to October 2005). Ltd. Randomized Controlled Trials as Topic. ii) to identify the most appropriate exercise programme and iii) to provide data for appropriate power calculations. The aims of the study are i) to determine the suitability and sensitivity of outcome measures. INDEX TERMS Medical Subject Headings (MeSH) ∗ Exercise Therapy. Peripheral Nervous System Diseases [∗ rehabilitation]. LTS) have been involved in a pilot study examining the effects of exercise on disability in peripheral neuropathy. No new relevant randomised controlled trials were found 14 July 2004 New citation required and conclusions have changed Substantive amendment CONTRIBUTIONS OF AUTHORS CW developed and wrote the first draft of the protocol and incorporated comments from JP and LTS and Cochrane peer reviewers into the final version. Treatment Outcome MeSH check words Humans Exercise for people with peripheral neuropathy (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons. DECLARATIONS OF INTEREST Two of the authors (CW. 43 . for a subsequent randomised controlled trial.