Durham E-Theses. Grip strength, forearm muscle fatigue and the response to handgrip exercise in rheumatoid arthritis. Speed, Catherine A.

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1 Durham E-Theses Grip strength, frearm muscle fatigue and the respnse t handgrip exercise in rheumatid arthritis Speed, Catherine A. Hw t cite: Speed, Catherine A. (1998) Grip strength, frearm muscle fatigue and the respnse t handgrip exercise in rheumatid arthritis, Durham theses, Durham University. Available at Durham E-Theses Online: Use plicy The full-text may be used and/r reprduced, and given t third parties in any frmat r medium, withut prir permissin r charge, fr persnal research r study, educatinal, r nt-fr-prt purpses prvided that: a full bibligraphic reference is made t the riginal surce a link is made t the metadata recrd in Durham E-Theses the full-text is nt changed in any way The full-text must nt be sld in any frmat r medium withut the frmal permissin f the cpyright hlders. Please cnsult the full Durham E-Theses plicy fr further details.

2 Academic Supprt Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP Tel:

3 ARIA W^mmM mit verscbiedenen Verandcrunfjen fflr Cembal mil 2 Mannalen (Gldberg - Variatinen)

4 Grip strength, frearm muscle fatigue and the respnse t hand grip exercise in rheumatid arthritis. The cpyright f this thesis rests with tlie autlir. N qutatin frm it shuld be published witliut the written cnsent f the authr and infrmatin derived frm it shuld be acknwledged. Catherine A. Speed. B Med Sci, BMBS (University f Nttingham), MRCP (UK), DSMSA. A Thesis submitted fr the Degree f Dctr f Philsphy at the University f Durham. f 3 m 1999

5 T my parents, fr teaching me the imprtance f "always getting my sums right" and fr instilling in me the faith that ver the brw f mst hills gd things usually lie in wait - "et le sleil brillait dans un ciel sans nuage "

6 Acknwledgements The experiences f my three year fellwship has reinfrced the knwledge that in research, as in life, the help and supprt f thers is vital. I wuld like t express my gratitude t all thse wh assisted me in this wrk. My supervisrs, Prfessr Tny Unswrth, Dr Patrick Jnes and Prfessr Ian Haslck fr their advice and assistance. Mr Rbert Ryali and the staff f the Reginal Medical Physics Department at Suth Cleveland Hspital, fr technical advice and supprt. Dr Peter Kelly fr his gd humur and statistical advice. Dr Rbert Campbell, whse dedicatin made the MRI studies pssible. The patients f the Rheumatlgy Department, Suth Cleveland Hspital, fr their wnderful enthusiasm and cmmitment t the prject. The staff in the Rheumatlgy Department, Suth Cleveland Hspital, particularly Jackie Bates and Olwynne Pitcher fr their assistance with the bne densitmetry wrk. Finally, my new friends and clleagues in Cambridge, wh helped t keep me mving in the directin f the finishing line during the final 3 mnths f writing up.

7 ABSTRACT Weakness and subjective fatigue are cmmn features f rheumatid arthritis (RA). Hwever, whether there is a true increase in the fatigability f rheumatid skeletal muscle, in which fibre atrphy has been frequently reprted, is unclear. Such factrs may influence the ability t respnd t exercise prgrammes. In this wrk, a reliable and sensitive technique fr the bjective measurement f frearm muscle fatigue during sustained grip was develped, using pwer spectral analysis f the surface myelectric signal (SMES). The inter-relatinships between grip frce (hand functin) and the activity and severity f the rheumatid disease prcess with muscle fatigue (defined as the decline in the median frequency f the SMES with wrk, (MDFG)) and the initial median frequency f the SMES (IMF) were examined. It has been previusly suggested that the IMF f the SMES may reflect the fibre type f the underlying muscle. The respnse t a 12-week prgressive right hand grip strengthening prgramme in healthy females and thse with RA was als evaluated. Ptential predictrs f utcme and the mechanisms f strength gain were examined. Frearm muscle fatigue in RA was nt significantly greater than in healthy cntrls. Hwever, higher levels f fatigue were assciated with greater systemic disease activity and greater disease severity. The IMF f the SMES was shwn t be stable ver a wide range f grip frces fr a given individual. It was significantly elevated in rheumatid subjects, and shwed a direct assciatin with greater disease severity. Handgrip exercise was highly effective in imprving hand fiinctin in females with RA. Strength gains were als demnstrated in healthy cntrls. Subjects with mre severe disease and greater IMF f the SMES shwed the greatest imprvement in hand functin. Greater systemic and lcal disease activity during the 12-week prgramme were limiting factrs t imprvement in grip. Lcal (right hand) disease activity remained stable r imprved in the RA grup verall, in spite f a trend twards deterirating systemic and left handed disease activity. The tw main ptential mechanisms f strength gain (neural adaptatin and gains in muscle mass) were assessed in bth rheumatid and healthy grups. The frmer was assessed by evaluatin f the neurmuscular efficiency, derived frm the relatinship f the rt mean square f the SMES at a given grip frce. Gains in muscle mass were als assessed using this technique and by vlumetric analysis f frearm musculature using magnetic resnance imaging. Althugh significant gains in muscle mass were demnstrated in the cntrl grup, n such gains were seen in the rheumatid subjects. This indicates that neural adaptatin was an effective methd f strength gain in the rheumatid grup. ni

8 Cntents. Page Acknwledgements Abstract Cntents Abbreviatins List f Figures List f Tables ii iii iv x xi XVllI Chapter One. Intrductin. 1 Chapter Tw: Literature Review Rheumatid muscle L Intrductin Histlgical changes in muscle in rheumatid arthritis Weakness in RA Weakness in RA Arthrgenus weakness and muscle fibre atrphy in RA: a summary Fatigue Intrductin Defining fatigue Fatigue in RA Mechanisms f fatigue in RA The descriptin f the myelectric signal Myelectric manifestatins f fatigue The RMS f the SMES as an indicatr f fatigue Pwer spectral analysis f the surface myelectric signal The descriptin f the pwer spectrum: pwer spectral parameters The frequency spectrum in relatin t EMG measures, Pwer spectral cmpressin during muscle fatigue The descriptin f pwer spectral cmpressin Mechanisms f pwer spectral cmpressin during muscle fatigue. 21 IV

9 2.4 Mtr Unit cntrl and the relatinship between frce and the SMES Intrductin Mtr unit cntrl and the generatin f frce The relatinship between the SMES and frce Neurmuscular efficiency (NME) The relatinship between frce and spectral parameters The relatinship between pwer spectral cmpressin and frce The relatinship between the signal amplitude and spectral parameters during fatigue Changes in the SMES and the frequency spectrum in disease The EMG in rheumatid arthritis Recvery f myelectric parameters after wrk Strength training in rheumatid arthritis Intrductin Mechanisms f strength gain in healthy individuals Imprtant features f strength training prgrammes Assessing the mechanisms f strength gain Strength training and disuse weakness Strength training in RA Grip strength in rheumatid arthritis Intrductin The rheumatid hand Factrs affecting grip strength in RA The assessment f grip strength. 45 Chapter 3: Materials and methds The apparatus The grip bag Surface electrmygraphy: signal acquisitin and prcessing. 48

10 3.2. The SMES acquisitin and analysis system: calibratin and electrde placement System descriptin and calibratin The placement f electrdes n the frearm fr the recrding f the SMES The assessment f grip strength Subject psitining and grip testing The assessment f frearm muscle crss-sectinal area (CSA) and vlume The assessment f the crss-sectinal area f the frearm Vlumetric analysis f the musculature f the frearm The assessment f rheumatid disease The test prtcl The grip strength exercise prgramme. 62 Chapter Fur. Pilt Studies Pilt studies I: The develpment f study techniques and prtcls Intrductin Skin preparatin Grip tests Chice f bandwidth Interelectrde studies Manning windws The effect f smthing cycles n pwer spectral parameters Pilt studies II: The repeatability f the technique f SMES analysis f the frearm Intrductin The restitutin study The lng term repeatability f the technique f SMES analysis f the frearm The repeatability f frearm myelectric parameters generated during sustained submaximal grip: discussins and cnclusins. 90 VI

11 4.3. Pilt studies III The relatinship f grip frce with SMES parameters Summary and discussin: the relatinship f grip frce with SMES parameters Pilt studies TV. The inter-relatinship between frearm myelectric parameters derived frm the SMES during sustained submaximal grip Intrductin Results Discussin. 101 Chapter Five. The assessment f the muscle mass in the right frearm. Pilt studies Intrductin Crss sectinal area (CSA) f the right frearm using magnetic resnance imaging Vlumetric analysis f the musculature f the right frearm The repeatability f vlumetric analysis f the right frearm musculature Selectin f the ptimal MR scanning technique in vlumetric analysis f frearm musculature A cmparisn f frearm muscle vlume with prximal frearm crss-sectinal area (CSA) as measured using magnetic resnance (MR) imaging The analysis f frearm muscle mass in the right frearm: a summary. 107 Chapter Six. Results Grip strength in RA Intrductin Factrs affecting grip strength in RA Summary Frearm myelectric parameters during sustained grip in rheumatid arthritis Intrductin. 116 Vll

12 Grip strength and myelectric parameters in RA: a cmparisn with healthy female cntrls The effect f the activity and severity f rheumatid disease upn frearm myelectric parameters during grip Intrductin Factrs influencing frearm myelectric parameters during grip in healthy cntrls Factrs influencing frearm myelectric parameters during grip in females with rheumatid arthritis Summary: Frearm myelectric parameters during grip in rheumatid arthritis. 121 Chapter Seven. Grip Strength Training in Rheumatid Arthritis The respnse t grip strength training in rheumatid arthritis Intrductin The effects f handgrip exercise upn hand functin in health and rheumatid disease The effect f handgrip exercise n the IMF f the frearm SMES The effect f handgrip exercise n lcal disease activity in RA Predictrs f the utcme f a handgrip exercise prgramme in RA Summary: Handgrip exercise in Rheumatid Arthritis. 131 Chapter Eight. Mechanisms f grip strength gain in a hand exercise prgramme Intrductin The assessment f the mechanisms f strength gain during a hand exercise prgramme using crss-sectinal analysis f frearm musculature by magnetic resnance imaging The assessment f the mechanisms f strength gain during a hand exercise prgramme using vlumetric analysis f the frearm musculature Summary. 146 vin

13 Chapter Nine: Discussin Intrductin The use f grip in the assessment f the myelectric characteristics during wrk The initial median frequency f the frearm myelectric signal as an indicatr f muscle characteristics in RA Other factrs assciated with hand functin in RA Fatigue in rheumatid arthritis The respnse t a handgrip exercise prgramme in RA Mechanisms f strength gain in the hand exercise prgramme Implicatins fr exercise prgrammes in rheumatid disease Further wrk Summary. 161 Chapter Ten. Cnclusins. 163 Chapter Eleven. References. 165 Chapter Twelve: Appendices Disease scres Keital Hand Functinal Index Fuchs Jint Scre The hand exercise prgramme infrmatin sheet. 200 IX

14 Cntents. Page Acknwledgements Abstract Cntents Abbreviatins List f Figures List f Tables ii HI iv x xi xviii Chapter One. Intrductin. 1 Chapter Tw: Literature Review Rheumatid muscle Intrductin Histlgical changes in muscle in rheumatid arthritis Weakness in RA Weakness in RA Arthrgenus weakness and muscle fibre atrphy in RA: a summary Fatigue Intrductin Defining fatigue Fatigue in RA Mechanisms f fatigue in RA The descriptin f the myelectric signal Myelectric manifestatins f fatigue The RMS f the SMES as an indicatr f fatigue Pwer spectral analysis f the surface myelectric signal The descriptin f the pwer spectrum: pwer spectral parameters The frequency spectrum in relatin t EMG measures Pwer spectral cmpressin during muscle fatigue The descriptin f pwer spectral cmpressin Mechanisms f pwer spectral cmpressin during muscle fatigue. 21 IV

15 2.4 Mtr Unit cntrl and the relatinship between frce and the SMES Intrductin Mtr unit cntrl and the generatin f frce The relatinship between the SMES and frce Neurmuscular efficiency (NME) The relatinship between frce and spectral parameters The relatinship between pwer spectral cmpressin and frce The relatinship between the signal amplitude and spectral parameters during fatigue Changes in the SMES and the frequency spectrum in disease The EMG in rheumatid arthritis Recvery f myelectric parameters after wrk Strength training in rheumatid arthritis Intrductin Mechanisms f strength gain in healthy individuals Imprtant features f strength training prgrammes Assessing the mechanisms f strength gain Strength training and disuse weakness Strength training in RA Grip strength in rheumatid arthritis Intrductin The rheumatid hand Factrs affecting grip strength in RA The assessment f grip strength. 45 Chapter 3: Materials and methds The apparatus The grip bag Surface electrmygraphy: signal acquisitin and prcessing. 48

16 3.2. The SMES acquisitin and analysis system: calibratin and electrde placement System descriptin and calibratin The placement f electrdes n the frearm fr the recrding f the SMES The assessment f grip strength Subject psitining and grip testing The assessment f frearm muscle crss-sectinal area (CSA) and vlume The assessment f the crss-sectinal area f the frearm Vlumetric analysis f the musculature f the frearm The assessment f rheumatid disease The test prtcl The grip strength exercise prgramme. 62 Chapter Fur. Pilt Studies Pilt studies I: The develpment f study techniques and prtcls Intrductin Skin preparatin Grip tests Chice f bandwidth Interelectrde studies Manning windws The effect f smthing cycles n pwer spectral parameters Pilt studies II: The repeatability f the technique f SMES analysis f the frearm Intrductin The restitutin study The lng term repeatability f the technique f SMES analysis f the frearm The repeatability f frearm myelectric parameters generated during sustained submaximal grip: discussins and cnclusins. 90 VI

17 4.3. Pilt studies III The relatinship f grip frce with SMES parameters Summary and discussin: the relatinship f grip frce with SMES parameters Pilt studies IV. The inter-relatinship between frearm myelectric parameters derived frm the SMES during sustained submaximal grip Intrductin Results Discussin. 101 Chapter Five. The assessment f the muscle mass in the right frearm. Pilt studies Intrductin Crss sectinal area (CSA) f the right frearm using magnetic resnance imaging Vlumetric analysis f the musculature f the right frearm The repeatability f vlumetric analysis f the right frearm musculature Selectin f the ptimal MR scanning technique in vlumetric analysis f frearm musculature A cmparisn f frearm muscle vlume with prximal frearm crss-sectinal area (CSA) as measured using magnetic resnance (MR) imaging The analysis f frearm muscle mass in the right frearm: a summary. 107 Chapter Six. Results Grip strength in RA Intrductin Factrs affecting grip strength in RA Summary Frearm myelectric parameters during sustained grip in rheumatid arthritis Intrductin. 116 Vll

18 Grip strength and myelectric parameters in RA: a cmparisn with healthy female cntrls The effect f the activity and severity f rheumatid disease upn frearm myelectric parameters during grip Intrductin Factrs influencing frearm myelectric parameters during grip in healthy cntrls Factrs influencing frearm myelectric parameters during grip in females with rheumatid arthritis Summary: Frearm myelectric parameters during grip in rheumatid arthritis. 121 Chapter Seven. Grip Strength Training in Rheumatid Arthritis The respnse t grip strength training in rheumatid arthritis Intrductin The effects f handgrip exercise upn hand functin in health and rheumatid disease The effect f handgrip exercise n the IMF f the frearm SMES The effect f handgrip exercise n lcal disease activity in RA Predictrs f the utcme f a handgrip exercise prgramme in RA Summary: Handgrip exercise in Rheumatid Arthritis. 131 Chapter Eight. Mechanisms f grip strength gain in a hand exercise prgramme Intrductin The assessment f the mechanisms f strength gain during a hand exercise prgramme using crss-sectinal analysis f frearm musculature by magnetic resnance imaging The assessment f the mechanisms f strength gain during a hand exercise prgramme using vlumetric analysis f the frearm musculature Summary. 146 VllI

19 Chapter Nine: Discussin Intrductin The use f grip in the assessment f the myelectric characteristics during wrk The initial median frequency f the frearm myelectric signal as an indicatr f muscle characteristics in RA Other factrs assciated with hand functin in RA Fatigue in rheumatid arthritis The respnse t a handgrip exercise prgramme in RA Mechanisms f strength gain in the hand exercise prgramme Implicatins fr exercise prgrammes in rheumatid disease Further wrk Summary. 161 Chapter Ten. Cnclusins. 163 Chapter Eleven. References. 165 Chapter Twelve: Appendices Disease scres Keital Hand Functinal Index Fuchs Jint Scre The hand exercise prgramme infrmatin sheet. 201 IX

20 Abbreviatins. ESR: CRP: MDF: MDFG: MNF: IMF: SMES: mg: I^V: Hz: BMI: BMD: MGS: MRI: CSA: RA: Erythrcyte sedimentatin rate. C-reactive prtein. Median Frequency. Median Frequency Gradient Mean frequency. Initial Median Frequency. Surface Myelectric Signal. milligrams. micrvlts. Hertz. Bdy Mass Index. Bne Mineral Density. Maximum Grip Strength Magnetic Resnance Imaging. Crss Sectinal Area. Rheumatid Arthritis.

21 Figures The frequency spectrum f the SMES The change in the median frequency f the SMES with time The Hand Assessment System. 47f The pressure readings versus the ADC utput (micrvlts) frm the grip 48f bag cmpared with the sphygmmanmeter (mmhg) The grip frce: RMS gradient (FRMSQ). 49f The SMES Analysis System Calibratin f the SMES acquisitin and analysis system Psitin f extensr electrdes and arm in rig fr frearm SMES 53 analysis during grip Psitin f flexr electrdes and arm in rig fr frearm SMES analysis 53 during grip Subject psitining fr grip testing Patient psitining fr bne densitmetry f the right hand using a Lunar 59 DPX-L Scanner Clse-up view f the psitin f the right hand n perspex bard fr 59 hand bne densitmetry An example f a right hand and wrist subluxatin scre in a female with 60 RA The testing prtcl Prtcl: The repeatability f maximum grip strength (MGS) ver 3 66f tests perfrmed 20 secnds apart by 12 female subjects with RA and 12 cntrls The repeatability f maximum grip strength (MGS) ver 3 tests 66 perfrmed 20 secnds apart by 12 female subjects with RA and 12 cntrls Prtcl: Maintenance f the target grip. 66f Prtcl: The repeatability f the chsen angle f wrist extensin during 67f standard 30-secnd grip tests perfrmed at 2/3MGs, by 12 females with RA and 12 female cntrls The repeatability f the chsen angle f wrist extensin during standard secnd grip tests perfrmed at 2/3 MGS by 12 female subjects and 12 female cntrls Prtcl: The effect f interelectrde separatin (les) distance upn 68f SMES parameters in 10 female cntrls. XI

22 4.1.7 The effect f the les distance upn spectral parameters (expressed as 68 mean (SD)) recrded frm the extensr and flexr frearm musculature during standard grip tests at 2/3 MGS by 10 right handed female cntrls The effect f the les distance upn the spectral peak and the RMS f the 69 SMES (expressed as mean (SD)) recrded frm the extensr and flexr frearm musculature during standard grip tests at 2/3 MGS by 10 right handed female cntrls The effect f smthing cycles upn spectral parameters: data frm the 71 extensr channel frm ne standard grip test perfrmed at 2/3 MGS by ne subject with RA. Spectra befre and after 10 smthing cycles The effect f smthing cycles upn spectral parameters: data frm the 72 extensr channel frm ne standard grip test perfrmed at 2/3 MGS by ne subject with RA Prtcl: The shrt-term repeatability f SMES parameters frm 74f standard grip tests at 2/3MGS perfrmed by 40 females with RA and 16 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard 75f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard 75f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the RMS f the SMES (extensr channel) frm standard 75 grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the RMS f the SMES (extensr channel) frm standard 75 grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the MDFG f the SMES (flexr channel) frm standard 76f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the MDFQ f the SMES (flexr channel) frm standard 76f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability fthemdffthe SMES (extensr channel) frm 76 standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability fthe MDFG fthe SMES (extensr channel) frm 76 standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability fthe IMF fthe SMES (flexr channel) frm standard 77f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability fthe IMF fthe SMES (flexr channel) frm standard 77f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability fthe IMF fthe SMES (extensr channel) frm standard 77 grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls. Xll

23 Repeatability f the IMF f the SMES (extensr channel) frm standard 77 grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Prtcl: The lng-term repeatability f SMES parameters frm 80f standard grip tests at 1/3MGS perfrmed 3 weeks apart by 19 females with RA and 18 female cntrls Prtcl: The lng-term repeatability f SMES parameters frm 80f standard grip tests perfrmed at 1/2 MGS weeks apart by 24 females with RA and 30 female cntrls Prtcl: The lng-term repeatability f SMES parameters frm 81 f standard grip tests at 2/3MGS perfrmed 3 weeks apart by 18 females with RA and 21 female cntrls Repeatability f the RMS f the SMES (extensr channel) frm standard 8 If grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the RMS f the SMES (extensr channel) frm standard 81 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard, 82 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard 82 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the MDFG f the SMES (extensr channel) frm 83f standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability fthe MDFG fthe SMES (extensr channel) frm 83 standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe MDFG fthe SMES (flexr channel) frm standard 84 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe MDFG fthe SMES (flexr channel) frm standard 84 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability fthe IMF fthe SMES (flexr channel) frm standard 86f grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe IMF fthe SMES (flexr channel) frm standard 86f grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the IMF f the SMES (extensr channel) frm standard 86 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the IMF f the SMES (extensr channel) frm standard 86 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA The surface myelectric parameters vs grip frce levels prtcl. 93 xni

24 4.3.2 Mean RMS fthe SMES (A) and linear regressin lines (B) frm 94 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean RMS fthe SMES (A) and linear regressin lines (B) frm flexr 94 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean MDFG fthe SMES (A) and linear regressin lines (B) frm 94 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean MDFG fthe SMES (A) and linear regressin lines (B) frm 95 flexr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean IMF f the SMES (A) and linear regressin lines (B) frm 95 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean IMF f the SMES (A) and linear regressin lines (B) frm flexr 95 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean spectral width (A) and linear regressin lines (B) frm extensr 96 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean spectral width (A) and linear regressin lines (B) frm flexr 96 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Test prtcl: SMES acquisitin and analysis frm frearm surface 99f electrdes during the fllwing grip tests in 161 females with RA and 114 female cntrls The MDFG f the SMES recrded frm the right frearm flexr channel loof versus that frm the extensr channel during a standard right hand grip test perfrmed at 2/3 MGS by 161 females with RA The IMF f the SMES recrded frm the right frearm flexr channel 1 OOf versus that frm the extensr channel during a standard right hand grip test perfrmed at 2/3 MGS by 161 females with RA The relatinship between the spectral width and the IMF f the extensr 100 (A) and the Flexr (B) SMES in 161 females with RA and 114 healthy female cntrls The repeatability f the vlumetric analysis f the right frearm using 105 Tl-W and prtn scanning techniques ver three testing sessins in ten subjects (mean(sd)) Cmparisn f T1 -W and Prtn imaging techniques in vlumetric 106 analysis f right frearm musculature in 10 subjects Mean frearm muscle vlume vs mean frearm CSA as measured using 106 Prtn and TI-W MR imaging in 10 subjects. XIV

25 6.1.1 The relatinship between MGS f the right hand and age in 161 right 111 f hand dminant females with RA and 114 female cntrls MGS f the right hand vs the duratin f disease in 161 right hand 111 dminant females with RA The relatinship between the MGS f the right hand and the flexr IMF 112 f the SMES in 161 females with RA and 114 cntrls MGS f the right hand versus the right hand and wrist subluxatin scre 112 in 161 right hand dminant females with RA The relatinship between the right hand MGS and right hand BMD in f right hand dminant females with RA and 21 female cntrls The relatinship between the vlume f the right frearm musculature 114f and the MGS f the right hand in 27 right hand dminant females with RA and 14 female cntrls Themean(SD)righthandMGS, IMF and spectral widths fthe SMES 117 derived frm extensr and flexr frearm musculature during sustained grip at 2/3 MGS in 161 females with RA and 114 cntrls The relatinship between right hand MGS and MDFG f the 117f extensr (A) and flexr (B) frearm musculature in 161 females with RA and 114 female cntrls The relatinship between right hand MGS and MDFG f the extensr 119f (A) and flexr (B) frearm musculature in 161 females with RA and 114 female cntrls The relatinship between the extensr MDFG and the C-reactive prtein 119 (CRP) f 161 females with RA The relatinship between the extensr MDFG and ulnar deviatin f the 119 right hand and wrist in 161 females with RA The relatinship between the disease duratin and the frearm flexr 120 IMF in 161 females with RA The mean (SD) right hand MGS in the RA and cntrl grups ver the 124f 12 week exercise prgramme The mean percentage change (SD) frm baseline in the right hand MGS 124 in the RA and cntrl grups ver the 12 week exercise prgramme The mean percentage change (SD) in the right hand MGS cmpared t 124 the previus test in the RA and cntrl grups ver the 12 week exercise prgramme The IMF fthe SMES recrded frm the extensr (A) and flexr (B) 125f frearm channels in RA and cntrl grups ver the 12 week hand exercise prgramme (mean (SD)) Right and left hand disease parameters measured during a 12 week right 127 hand exercise prgramme in 79 females with RA (mean (SD)). XV

26 7.4.1 The relatinship between the change in the MGS f the right hand 129 during a handgrip exercise prgramme and extensr IMF in 79 females with RA The relatinship between the change in the MGS f the right hand 129 during a handgrip exercise prgramme and the disease duratin in 79 females with RA The relatinship between the change in the MGS fthe right hand 130 during a handgrip exercise prgramme and the right hand and wrist subluxatin scre in 79 females with RA The relatinship between the crss-sectinal area f the right frearm 134 and the maximum grip strength f the right hand in 27 females with RA prir t cmmencing a hand grip exercise prgramme The mean (SD) MGS fthe right hand in 27 females with RA during a week hand exercise prgramme The percentage changes in the CSA f the right frearm and in the MGS 135f f the right hand in 27 females with RA after a 12 week handgrip exercise prgramme The percentage change in the F:RMS gradients at the extensr and flexr 135f channels vs that in right frearm CSA in 27 females with RA after a 12 week handgrip exercise prgramme The relatinship between changes nted in grip frce : RMS f the 135 SMES gradient (extensr channel) and MGS f the right hand after a 12 week handgrip exercise prgramme in 27 females with RA The relatinship between changes nted in grip frce : RMS f the 135 SMES gradient (flexr channel) and MGS f the right hand after a 12 week handgrip exercise prgramme in 27 females with RA The percentage change in the F:RMS gradients at the flexr channel 136 versus that f the extensr channel in 27 females with RA after a 12 week handgrip exercise prgramme The right frearm muscle vlume and grip strength f the RA and 137f cntrl grups at baseline and after 12 weeks f a handgrip exercise prgramme (mean (SD)) The change in the vlume f the right frearm musculature versus 138f change in the MGS f the right hand in 14 female cntrls (A) and 14 females with RA (B) after a 12 week handgrip exercise prgramme The change in the vlume fthe right frearm and the F:RMS gradients 138 derived frm the extensr (A) and flexr (B) channels after a 12 week hand exercise prgramme in females with RA The relatinship between the change in frearm muscle vlume and the 139f F:RMS gradients derived frm extensr and flexr channels after a 12 week exercise prgramme in 14 female cntrls Grip strength vs RMS f the SMES fr extensr and flexr channels in female cntrls ver a 12 week exercise prgramme. The assciated changes in slpe f the regressin lines, MGS and frearm muscle vlume are given in the assciated tables. xvi

27 8.3.6 Grip strength vs RMS f the SMES fr extensr and flexr channels in females with RA ver a 12 week exercise prgramme. The % changes in slpe f the given regressin lines, MGS and frearm muscle vlume are given in the assciated tables. xvii

28 Figures The frequency spectrum f the SMES The change in the median frequency f the SMES with time The Hand Assessment System. 47f The pressure readings versus the ADC utput (micrvlts) frm the grip 48f bag cmpared with the sphygmmanmeter (mmhg) The grip frce: RMS gradient (FRMSG). 49f The SMES Analysis System Calibratin f the SMES acquisitin and analysis system Psitin f extensr electrdes and arm in rig fr frearm SMES 53 analysis during grip Psitin f flexr electrdes and arm in rig fr frearm SMES analysis 53 during grip Subject psitin ing fr grip testing Patient psitining fr bne densitmetry f the right hand using a Lunar 59 DPX-L Scanner Clse-up view f the psitin f the right hand n perspex bard fr 59 hand bne densitmetry An example f a right hand and wrist subluxatin scre in a female with 60 RA The testing prtcl Prtcl: The repeatability f maximum grip strength (MGS) ver 3 66f tests perfrmed 20 secnds apart by 12 female subjects with RA and 12 cntrls The repeatability f maximum grip strength (MGS) ver 3 tests 66 perfrmed 20 secnds apart by 12 female subjects with RA and 12 cntrls Prtcl: Maintenance f the target grip. 66f Prtcl: The repeatability f the chsen angle f wrist extensin during. 67f standard 30-secnd grip tests perfrmed at 2/3MGs, by 12 females with RA and 12 female cntrls The repeatability f the chsen angle f wrist extensin during standard secnd grip tests perfrmed at 2/3 MGS by 12 female subjects and 12 female cntrls Prtcl: The effect f interelectrde separatin (les) distance upn 68f SMES parameters in 10 female cntrls. XI

29 4.1.7 The effect f the les distance upn spectral parameters (expressed as 68 mean (SD)) recrded frm the extensr and flexr frearm musculature during standard grip tests at 2/3 MGS by 10 right handed female cntrls The effect f the les distance upn the spectral peak and the RMS f the 69 SMES (expressed as mean (SD)) recrded frm the extensr and flexr frearm musculature during standard grip tests at 2/3 MGS by 10 right handed female cntrls The effect f smthing cycles upn spectral parameters: data frm the 71 extensr channel frm ne standard grip test perfrmed at 2/3 MGS by ne subject with RA. Spectra befre and after 10 smthing cycles The effect f smthing cycles upn spectral parameters: data frm the 72 extensr channel frm ne standard grip test perfrmed at 2/3 MGS by ne subject with RA Prtcl: The shrt-term repeatability f SMES parameters frm 74f standard grip tests at 2/3MGS perfrmed by 40 females with RA and 16 female cntrls Repeatability fthe RMS fthe SMES (flexr channel) frm standard 75f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability fthe RMS fthe SMES (flexr channel) frm standard 75f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the RMS f the SMES (extensr channel) frm standard 75 grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the RMS f the SMES (extensr channel) frm standard 75 grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the MDFG f the SMES (flexr channel) frm standard 76f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability fthe MDFG fthe SMES (flexr channel) frm standard 76f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the MDFG f the SMES (extensr channel) frm 76 standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the MDFQ f the SMES (extensr channel) frm 76 standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the IMF f the SMES (flexr channel) frm standard 77f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability fthe IMF fthe SMES (flexr channel) frm standard 77f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the IMF f the SMES (extensr channel) frm standard 77 grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls. Xll

30 Repeatability fthe IMF fthe SMES (extensr channel) frm standard 77 grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Prtcl: The lng-term repeatability f SMES parameters frm 80f standard grip tests at 1/3MGS perfrmed 3 weeks apart by 19 females with RA and 18 female cntrls Prtcl: The lng-term repeatability f SMES parameters frm 80f standard grip tests perfrmed at 1/2 MGS weeks apart by 24 females with RA and 30 female cntrls Prtcl: The lng-term repeatability f SMES parameters frm 81f standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA and 21 female cntrls Repeatability f the RMS f the SMES (extensr channel) frm standard 81 f grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the RMS f the SMES (extensr channel) frm standard 81 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe RMS fthe SMES (flexr channel) frm standard 82 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe RMS fthe SMES (flexr channel) frm standard 82 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability fthe MDFG fthe SMES (extensr channel) frm 83f standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability fthe MDFG fthe SMES (extensr channel) frm 83 standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe MDFG f the SMES (flexr channel) frm standard 84 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe MDFG f the SMES (flexr channel) frm standard 84 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability fthe IMF fthe SMES (flexr channel) frm standard 86f grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability fthe IMF fthe SMES (flexr channel) frm standard 86f grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the IMF f the SMES (extensr channel) frm standard 86 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the IMF f the SMES (extensr channel) frm standard 86 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA The surface myelectric parameters vs grip frce levels prtcl. 93 xni

31 4.3.2 Mean RMS f the SMES (A) and linear regressin lines (B) frm 94 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean RMS f the SMES (A) and linear regressin lines (B) frm flexr 94 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean MDFG fthe SMES (A) and linear regressin lines (B) frm 94 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean MDFG f the SMES (A) and linear regressin lines (B) frm 95 flexr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean IMF f the SMES (A) and linear regressin lines (B) frm 95 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean IMF f the SMES (A) and linear regressin lines (B) frm flexr 95 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean spectral width (A) and linear regressin lines (B) frm extensr 96 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean spectral width (A) and linear regressin lines (B) frm flexr 96 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Test prtcl: SMES acquisitin and analysis frm frearm surface 99f electrdes during the fllwing grip tests in 161 females with RA and 114 female cntrls The MDFG f the SMES recrded frm the right frearm flexr channel loof versus that frm the extensr channel during a standard right hand grip test perfrmed at 2/3 MGS by 161 females with RA The IMF f the SMES recrded frm the right frearm flexr channel 1 OOf versus that frm the extensr channel during a standard right hand grip test perfrmed at 2/3 MGS by 161 females with RA The relatinship between the spectral width and the IMF f the extensr 100 (A) and the Flexr (B) SMES in 161 females with RA and 114 healthy female cntrls The repeatability f the vlumetric analysis f the right frearm using 105 Tl-W and prtn scanning techniques ver three testing sessins in ten subjects (mean(sd)) Cmparisn f Tl-W and Prtn imaging techniques in vlumefric 106 analysis f right frearm musculature in 10 subjects Mean frearm muscle vlume vs mean frearm CSA as measured using 106 Prtn and Tl-W MR imaging in 10 subjects. xiv

32 6.1.1 The relatinship between MGS f the right hand and age in 161 right 111 f hand dminant females with RA and 114 female cntrls MGS f the right hand vs the duratin f disease in 161 right hand 111 dminant females with RA The relatinship between the MGS f the right hand and the flexr IMF 112 f the SMES in 161 females with RA and 114 cntrls MGS f the right hand versus the right hand and wrist subluxatin scre 112 in 161 right hand dminant females with RA The relatinship between the right hand MGS and right hand BMD in f right hand dminant females with RA and 21 female cntrls The relatinship between the vlume f the right frearm musculature 114f and the MGS f the right hand in 27 right hand dminant females with RA and 14 female cntrls The mean (SD) right hand MGS, IMF and spectral widths fthe SMES 117 derived frm extensr and flexr frearm musculature during sustained grip at 2/3 MGS in 161 females with RA and 114 cntrls The relatinship between right hand MGS and MDFG f the 117f extensr (A) and flexr (B) frearm musculature in 161 females with RA and 114 female cntrls The relatinship between right hand MGS and MDFG f the extensr 119f (A) and flexr (B) frearm musculature in 161 females with RA and 114 female cntrls The relatinship between the extensr MDFG and the C-reactive prtein 119 (CRP) f 161 females with RA The relatinship between the extensr MDFG and ulnar deviatin f the 119 right hand and wrist in 161 females with RA The relatinship between the disease duratin and the frearm flexr 120 IMF in 161 females with RA The mean (SD) right hand MGS in the RA and cntrl grups ver the 124f 12 week exercise prgramme The mean percentage change (SD) frm baseline in the right hand MGS 124 in the RA and cntrl grups ver the 12 week exercise prgramme The mean percentage change (SD) in the right hand MGS cmpared t 124 the previus test in the RA and cntrl grups ver the 12 week exercise prgramme. 7.2,1 The IMF f the SMES recrded frm the extensr (A) and flexr (B) 125f frearm channels in RA and cntrl grups ver the 12 week hand exercise prgramme (mean (SD)) Right and left hand disease parameters measured during a 12 week right 127 hand exercise prgramme in 79 females with RA (mean (SD)). XV

33 7.4.1 The relatinship between the change in the MGS f the right hand 129 during a handgrip exercise prgramme and extensr IMF in 79 females with RA The relatinship between the change in the MGS f the right hand 129 during a handgrip exercise prgramme and the disease duratin in 79 females with RA The relatinship between the change in the MGS f the right hand 130 during a handgrip exercise prgramme and the right hand and wrist subluxatin scre in 79 females with RA The relatinship between the crss-sectinal area f the right frearm 134 and the maximum grip strength f the right hand in 27 females with RA prir t cmmencing a hand grip exercise prgramme The mean (SD) MGS fthe right hand in 27 females with RA during a week hand exercise prgramme The percentage changes in the CSA f the right frearm and in the MGS 135f f the right hand in 27 females with RA after a 12 week handgrip exercise prgramme The percentage change in the F:RMS gradients at the extensr and flexr 135f channels vs that in right frearm CSA in 27 females with RA after a 12 week handgrip exercise prgramme The relatinship between changes nted in grip frce : RMS f the 135 SMES gradient (extensr channel) and MGS f the right hand after a 12 week handgrip exercise prgramme in 27 females with RA The relatinship between changes nted in grip frce : RMS f the 135 SMES gradient (flexr channel) and MGS f the right hand after a 12 week handgrip exercise prgramme in 27 females with RA The percentage change in the F:RMS gradients at the flexr channel 136 versus that fthe extensr channel in 27 females with RA after a 12 week handgrip exercise prgramme The right frearm muscle vlume and grip strength f the RA and 137f cntrl grups at baseline and after 12 weeks f a handgrip exercise prgramme (mean (SD)) The change in the vlume f the right frearm musculature versus 138f change in the MGS f the right hand in 14 female cntrls (A) and 14 females with RA (B) after a 12 week handgrip exercise prgramme The change in the vlume f the right frearm and the F:RMS gradients 138 derived frm the extensr (A) and flexr (B) channels after a 12 week hand exercise prgramme in females with RA The relatinship between the change in frearm muscle vlume and the 139f F:RMS gradients derived frm extensr and flexr channels after a 12 week exercise prgramme in 14 female cntrls Grip strength vs RMS f the SMES fr extensr and flexr channels in female cntrls ver a 12 week exercise prgramme. The assciated changes in slpe f the regressin lines, MGS and frearm muscle vlume are given in the assciated tables. xvi

34 8.3.6 Grip strength vs RMS f the SMES fr extensr and flexr channels in females with RA ver a 12 week exercise prgramme. The % changes in slpe f the given regressin lines, MGS and frearm muscle vlume are given in the assciated tables. xvii

35 Figures The frequency spectrum f the SMES The change in the median frequency f the SMES with time The Hand Assessment System. 47f The pressure readings versus the ADC utput (micrvlts) frm the grip 48f bag cmpared with the sphygmmanmeter (mmhg) The grip frce: RMS gradient (FRMSG). 49f The SMES Analysis System Calibratin f the SMES acquisitin and analysis system Psitin f extensr electrdes and arm in rig fr frearm SMES 53 analysis during grip Psitin f flexr electrdes and arm in rig fr frearm SMES analysis 53 during grip Subject psitining fr grip testing Patient psitining fr bne densitmetry f the right hand using a Lunar 59 DPX-L Scanner Clse-up view f the psitin f the right hand n perspex bard fr 59 hand bne densitmetry An example f a right hand and wrist subluxatin scre in a female with 60 RA The testing prtcl Prtcl: The repeatability f maximum grip strength (MGS) ver 3 66f tests perfrmed 20 secnds apart by 12 female subjects with RA and 12 cntrls The repeatability f maximum grip strength (MGS) ver 3 tests 66 perfrmed 20 secnds apart by 12 female subjects with RA and 12 cntrls Prtcl: Maintenance f the target grip. 66f Prtcl: The repeatability f the chsen angle f wrist extensin during 67f standard 30-secnd grip tests perfrmed at 2/3MGs, by 12 females with RA and 12 female cntrls The repeatability f the chsen angle f wrist extensin during standard secnd grip tests perfrmed at 2/3 MGS by 12 female subjects and 12 female cntrls Prtcl: The effect f interelectrde separatin (les) distance upn. 68f SMES parameters in 10 female cntrls. XI

36 4.1.7 The effect f the les distance upn spectral parameters (expressed as 68 mean (SD)) recrded frm the extensr and flexr frearm musculature during standard grip tests at 2/3 MGS by 10 right handed female cntrls The effect f the les distance upn the spectral peak and the RMS f the 69 SMES (expressed as mean (SD)) recrded frm the extensr and flexr frearm musculature during standard grip tests at 2/3 MGS by 10 right handed female cntrls The effect f smthing cycles upn spectral parameters: data frm the 71 extensr channel frm ne standard grip test perfrmed at 2/3 MGS by ne subject with RA. Spectra befre and after 10 smthing cycles The effect f smthing cycles upn spectral parameters: data frm the 72 extensr channel frm ne standard grip test perfrmed at 2/3 MGS by ne subject with RA Prtcl: The shrt-term repeatability f SMES parameters frm 74f standard grip tests at 2/3MGS perfrmed by 40 females with RA and 16 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard 75f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard 75f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the RMS f the SMES (extensr channel) frm standard 75 grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the RMS f the SMES (extensr channel) frm standard 75 grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the MDFG f the SMES (flexr channel) frm standard 76f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the MDFG f the SMES (flexr channel) frm standard 76f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability fthe MDFG fthe SMES (extensr channel) frm 76 standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability fthe MDFG fthe SMES (extensr channel) frm 76 standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability fthe IMF fthe SMES (flexr channel) frm standard 77f grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f the IMF fthe SMES (flexr channel) frm standard 77f grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f the IMF f the SMES (extensr channel) frm standard 77 grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls. Xll

37 Repeatability f the IMF f the SMES (extensr channel) frm standard 77 grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Prtcl: The lng-term repeatability f SMES parameters frm 80f standard grip tests at 1/3MGS perfrmed 3 weeks apart by 19 females with RA and 18 female cntrls Prtcl: The lng-term repeatability f SMES parameters frm 80f standard grip tests perfrmed at 1/2 MGS weeks apart by 24 females with RA and 30 female cntrls Prtcl: The lng-term repeatability f SMES parameters frm 81f standard grip tests at 2/3MGS perfrmed 3 weeks apart by 18 females with RA and 21 female cntrls Repeatability f the RMS f the SMES (extensr channel) frm standard 8 If grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the RMS f the SMES (extensr channel) frm standard 81 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard. 82 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the RMS f the SMES (flexr channel) frm standard 82 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability fthemdfcfthe SMES (extensr channel) frm 83f standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability fthemdffthe SMES (extensr channel) frm 83 standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the MDFG f the SMES (flexr channel) frm standard 84 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the MDFG f the SMES (flexr channel) frm standard 84 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the IMF f the SMES (flexr channel) frm standard 86f grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the IMF f the SMES (flexr channel) frm standard 86f grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f the IMF f the SMES (extensr channel) frm standard 86 grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f the IMF f the SMES (extensr channel) frm standard 86 grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA The surface myelectric parameters vs grip frce levels prtcl. 93 xin

38 4.3.2 Mean RMS fthe SMES (A) and linear regressin lines (B) frm 94 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean RMS f the SMES (A) and linear regressin lines (B) frm flexr 94 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean MDFG fthe SMES (A) and linear regressin lines (B) frm 94 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean MDFG f the SMES (A) and linear regressin lines (B) frm 95 flexr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean IMF f the SMES (A) and linear regressin lines (B) frm 95 extensr frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean IMF f the SMES (A) and linear regressin lines (B) frm flexr 95 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean spectral width (A) and linear regressin lines (B) frm extensr 96 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Mean spectral width (A) and linear regressin lines (B) frm flexr 96 frearm musculature during standard grip tests versus percentage maximal grip pressure in 17 female cntrls Test prtcl: SMES acquisitin and analysis frm frearm surface 99f electrdes during the fllwing grip tests in 161 females with RA and 114 female cntrls The MDFG f the SMES recrded frm the right frearm flexr channel loof versus that frm the extensr channel during a standard right hand grip test perfrmed at 2/3 MGS by 161 females with RA The IMF f the SMES recrded frm the right frearm flexr channel 1 OOf versus that frm the extensr channel during a standard right hand grip test perfrmed at 2/3 MGS by 161 females with RA The relatinship between the spectral width and the IMF f the extensr 100 (A) and the Flexr (B) SMES in 161 females with RA and 114 healthy female cntrls The repeatability f the vlumetric analysis f the right frearm using 105 Tl-W and prtn scanning techniques ver three testing sessins in ten subjects (mean(sd)) Cmparisn f Tl-W and Prtn imaging techniques in vlumetric 106 analysis f right frearm musculature in 10 subjects Mean frearm muscle vlume vs mean frearm CSA as measured using 106 Prtn and Tl-W MR imaging in 10 subjects. xiv

39 6.1.1 The relatinship between MGS f the right hand and age in 161 right 111 f hand dminant females with RA and 114 female cntrls MGS f the right hand vs the duratin f disease in 161 right hand 111 dminant females with RA The relatinship between the MGS f the right hand and the flexr IMF 112 f the SMES in 161 females with RA and 114 cntrls MGS f the right hand versus the right hand and wrist subluxatin scre 112 in 161 right hand dminant females with RA The relatinship between the right hand MGS and right hand BMD in f right hand dminant females with RA and 21 female cntrls The relatinship between the vlume f the right frearm musculature 114f and the MGS f the right hand in 27 right hand dminant females with RA and 14 female cntrls The mean (SD) right hand MGS, IMF and spectral widths f the SMES 117 derived frm extensr and flexr frearm musculature during sustained grip at 2/3 MGS in 161 females with RA and 114 cntrls The relatinship between right hand MGS and MDFG f the 117f extensr (A) and flexr (B) frearm musculature in 161 females with RA and 114 female cntrls The relatinship between right hand MGS and MDFG f the extensr 119f (A) and flexr (B) frearm musculature in 161 females with RA and 114 female cntrls The relatinship between the extensr MDFG and the C-reactive prtein 119 (CRP) f 161 females with RA The relatinship between the extensr MDFG and ulnar deviatin f the 119 right hand and wrist in 161 females with RA The relatinship between the disease duratin and the frearm flexr 120 IMF in 161 females with RA The mean (SD) right hand MGS in the RA and cntrl grups ver the 124f 12 week exercise prgramme The mean percentage change (SD) frm baseline in the right hand MGS 124 in the RA and cntrl grups ver the 12 week exercise prgramme The mean percentage change (SD) in the right hand MGS cmpared t 124 the previus test in the RA and cntrl grups ver the 12 week exercise prgramme The IMF fthe SMES recrded frm the extensr (A) and flexr (B) 125f frearm channels in RA and cntrl grups ver the 12 week hand exercise prgramme (mean (SD)) Right and left hand disease parameters measured during a 12 week right 127 hand exercise prgramme in 79 females with RA (mean (SD)). XV

40 7.4.1 The relatinship between the change in the MGS f the right hand 129 during a handgrip exercise prgramme and extensr IMF in 79 females with RA The relatinship between the change in the MGS f the right hand 129 during a handgrip exercise prgramme and the disease duratin in 79 females with RA The relatinship between the change in the MGS f the right hand 130 during a handgrip exercise prgramme and the right hand and wrist subluxatin scre in 79 females with RA The relatinship between the crss-sectinal area f the right frearm 134 and the maximum grip strength f the right hand in 27 females with RA prir t cmmencing a hand grip exercise prgramme The mean (SD) MGS f the right hand in 27 females with RA during a week hand exercise prgramme The percentage changes in the CSA f the right frearm and in the MGS 135f f the right hand in 27 females with RA after a 12 week handgrip exercise prgramme The percentage change in the F:RMS gradients at the extensr and flexr 135f channels vs that in right frearm CSA in 27 females with RA after a 12 week handgrip exercise prgramme The relatinship between changes nted in grip frce : RMS f the 135 SMES gradient (extensr channel) and MGS f the right hand after a 12 week handgrip exercise prgramme in 27 females with RA The relatinship between changes nted in grip frce : RMS f the. 135 SMES gradient (flexr channel) and MGS f the right hand after a 12 week handgrip exercise prgramme in 27 females with RA The percentage change in the F:RMS gradients at the flexr channel 136 versus that f the extensr channel in 27 females with RA after a 12 week handgrip exercise prgramme The right frearm muscle vlume and grip strength f the RA and 137f cntrl grups at baseline and after 12 weeks f a handgrip exercise prgramme (mean (SD)) The change in the vlume f the right frearm musculature versus 138f change in the MGS f the right hand in 14 female cntrls (A) and 14 females with RA (B) after a 12 week handgrip exercise prgramme The change in the vlume f the right frearm and the F:RMS gradients 138 derived frm the extensr (A) and flexr (B) channels after a 12 week hand exercise prgramme in females with RA The relatinship between the change in frearm muscle vlume and the 139f F:RMS gradients derived frm extensr and flexr channels after a 12 week exercise prgramme in 14 female cntrls Grip strength vs RMS f the SMES fr extensr and flexr channels in female cntrls ver a 12 week exercise prgramme. The assciated changes in slpe f the regressin lines, MGS and frearm muscle vlume are given in the assciated tables. XVI

41 8.3.6 Grip strength vs RMS f the SMES fr extensr and flexr channels in females with RA ver a 12 week exercise prgramme. The % changes in slpe f the given regressin lines, MGS and frearm muscle vlume are given in the assciated tables. xvii

42 List f Tables SMES acquisitin and analysis calibratin Pilt studies I: Details f the study grups invlved in initial pilt 64 studies Cmparisn between the pwer spectral parameters f the SMES 70 frm the frearm extensr channel during a 30 secnd grip test perfrmed at 2/3 MGS befre and after the applicatin f Manning windw (n=29). Mean (SD) Cmparisn between the pwer spectral parameters f the SMES 70 frm the frearm flexr channel during a 30 secnd grip test perfrmed at 2/3 MGS befre and after the applicatin f Manning windw (n=29). Mean (SD) Cmparisn f 0, 3 and 10 smthing cycles n frearm EMG 72 spectral parameters in 16 female subjects with RA. Extensr channel (Mean (SD) Cmparisn f 0, 3 and 10 smthing cycles n frearm EMG 73 spectral parameters in 16 female subjects with RA. Flexr channel (Mean (SD)) Details f the subject grups in the restitutin study Repeatability f myelectric parameters (extensr channel) 79f frm standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f myelectric parameters (flexr channel) frm 79f standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 16 female cntrls Repeatability f myelectric parameters (extensr channel) 79 frm standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA Repeatability f myelectric parameters (flexr channel) frm 79 standard grip tests at 2/3 MGS perfrmed 5 minutes apart by 40 females with RA The study grups in the assessment f the repeatability f the 80 technique f SMES analysis f the frearm Repeatability f myelectric parameters (extensr channel) frm 87f standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f myelectric parameters (flexr channel) frm 87f standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 21 female cntrls Repeatability f myelectric parameters (extensr channel) frm 87 standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA. xvin

43 Repeatability f myelectric parameters (flexr channel) frm 87 standard grip tests at 2/3 MGS perfrmed 3 weeks apart by 18 females with RA Repeatability f myelectric parameters (extensr channel) frm 88f standard grip tests at 1/2 MGS perfrmed 3 weeks apart by 30 female cntrls Repeatability f myelectric parameters (flexr channel) frm 88f standard grip tests at 1/2 MGS perfrmed 3 weeks apart by 30 female cntrls Repeatability f myelectric parameters (extensr channel) frm 88 standard grip tests at 1/2 MGS perfrmed 3 weeks apart by 24 females with RA Repeatability f myelectric parameters (flexr channel) frm 88 standard grip tests at 1/2 MGS perfrmed 3 weeks apart by 24 females with RA Repeatability f myelectric parameters (extensr channel) frm 89f standard grip tests at 1/3 MGS perfrmed 3 weeks apart by 18 female cntrls Repeatability f myelectric parameters (flexr channel) frm 89f standard grip tests at 1/3 MGS perfrmed 3 weeks apart by 18 female cntrls Repeatability f myelectric parameters (extensr channel) frm 89 standard grip tests at 1/3 MGS perfrmed 3 weeks apart by 19 females with RA Repeatability f myelectric parameters (flexr channel) frm 89 standard grip tests at 1/3 MGS perfrmed 3 weeks apart by 19 females with RA Characteristics f the tw study grups. 99f The repeatability f the assessment f CSA f the right frearm 103 using single slice magnetic resnance imaging in ten healthy subjects The repeatability f vlumetric analysis f the frearm f ten 104 subjects ver three testing ccasins using prtn imaging The repeatability f the adjusted vlume f the right frearm frm 105 Tl-W imaging technique ver three testing sessins (mean (SD); 95 % CI (vxels)) Characteristics f the tw study grups. 109f Right hand and general disease parameters at baseline in the RA 109f grup cnsisting f 161 right hand dminant females with RA Right hand disease parameters at baseline in the RA grup 11 Of cnsisting f 161 right hand dminant females with RA. XIX

44 6.1.4 Left hand disease parameters at baseline in the RA grup cnsisting 11 Of f 161 right hand dminant females with RA The multiple regressin analysis fr the factrs affecting grip 112f strength in female healthy cntrls The results f the multiple regressin fr grip strength (dependent 112f variable) in females with rheumatid arthritis Subject characteristics f the main study grup and subgrup in 113 which right hand BMD was measured Characteristics f the RA subgrup assessed in the study f the 114 CSA f the right frearm Characteristics f subgrups included in the study f the vlumetric 114 analysis f the right frearm musculature Myelectric parameters measured frm the right frearm in the tw 116f study grups during a standard right hand grip test perfrmed at 2/3 MGS The multiple regressin analysis fr the factrs affecting the 118f extensr MDFG in female healthy cntrls The multiple regressin analysis fr the factrs affecting the 118f flexr MDFG in female healthy cntrls The muhiple regressin analysis fr the factrs affecting the 118f flexr IMF in female healthy cntrls The multiple regressin analysis fr the factrs affecting the 120f extensr MDFG in females with RA The multiple regressin analysis fr the factrs affecting the flexr 120f MDFG in females with RA The multiple regressin analysis fr the factrs affecting the 120f extensr IMF in females with RA Basic characteristics f the tw exercise grups. 123f Maximum grip strength f the right hand in RA and cntrl grups 123 during the 12 week handgrip exercise prgramme The extensr and flexr frearm IMF in RA and cntrl grups 125 during the 12 week handgrip exercise prgramme Right and left hand disease parameters measured during a 12 week 126 right hand exercise prgramme in 79 females with RA The results f the multiple regressin fr the percentage gain in grip 128f strength (dependent variable) in females with rheumatid arthritis. XX

45 7.4.2 Details f the subgrup f females with RA taking part in the 130 handgrip exercise prgramme in whm BMD f the right hand was measured Details f the study grup cnsisting f 27 right hand dminant 133f females with RA Details f the RA and cntrl grups in the analysis f mechanisms 139 f strength gain in the handgrip exercise prgramme using vlumetric analysis f the frearm. xxi

46 Chapter One. Intrductin. Weakness, subjective fatigue and diminished functin are significant prblems in rheumatid arthritis. These prblems are multifactrial in rigin, with ptential cntributing factrs including pain, inflammatin, defrmity, reflex inhibitin f muscle and decnditining. Histlgical abnrmalities, including muscle fibre atrphy, have been nted in several studies f rheimiatid skeletal muscle and have been suggested t be secndary t disuse atrphy, denervatin, r bth f these prcesses. The significance f such findings with respect t fatigue and fiinctinal capacity are unclear. In spite f the high prevalence f subjective fatigue in rheumatid disease, the issue f whether there is increased fatiguability within the muscle has nt been addressed. Pwer spectral analysis f the surface myelectric signal during sustained muscular wrk is an established technique in the assessment f muscle fatigue. The decrease in the median frequency with time has been shwn t reflect metablic and electrphysilgical changes ccurring within the muscle and is a useful indicatr f muscle fatigue (Kmi & Tesch, 1979; Sadyama et al, 1988). Other myelectric parameters which may be derived frm the frequency spectnmi have been shwn t be ahered in neurmuscular disrders, specifically primary mypathies and mypathies secndary t neurpathic lesins, including denervatin. Such measures may therefre be useful in the assessment f the functinal significance f netirmuscular abnrmalities in subjects with rheumatid disease and their relatinship with disease measures. The issue f therapeutic strengthening exercise in rheumatid arthritis is an area f cnfusin. Much f the lack f a cnsensus f pinin is related t a lack f well designed, scientifically based research n the subject, a lack f functinally based prgrammes, difficulties with defining thse subjects wh will benefit, and cncerns that such prgrammes will have adverse effects upn the disease. This study addressed the inter-related issues f the significance f neurmuscular abnrmalities and the respnse t a simple strengthening exercise prgramme in rheumatid arthritis. Specific issues were addressed using the technique f pwer spectral analysis f the surface myelectric signal during ismetric cntractins. Evidence f specific neurmuscular abnrmalities in skeletal muscle f subjects with

47 RA was sught. The nature f these changes was examined, specifically whether they resembled changes typical f a primary mypathy r thse f a mypathy secndary t denervatin, in additin t whether there was abnrmal fatiguability f the muscle during ismetric cntractins. The relatinship between these neurmuscular abnrmalities and disease characteristics (that is the severity and activity f the disease) was als assessed. It is nt knwn whether the changes which have been nted within rheumatid muscle affect the respnse t strengthening exercise in rheumatid disease. Indeed, the mechanisms f strength gain in RA have als received little attentin in spite f these being the basis fr the develpment f exercise prgrammes in healthy individuals. These areas were als investigated in this study. Grip strength was chsen as the functinal task in this study fr a number f reasns. Grip strength is the crnerstne f hand functinal analysis and reflects disease severity and disease activity in rheumatid disease. The frearm muscles, which are imprtant in the perfrmance f a gripping task, have the advantage f easy accessibility fr surface electrmygraphy. Hence, the assessment f myelectric characteristics during a task that is knwn t reflect nt nly strength, but als many aspects f the rheumatid disease prcess, was pssible. The ability t grip is vital in daily functin and is a task with which mst individuals are familiar, which imprves the reliability f measurements f strength and myelectric characteristics. Perfrming a handgrip strengthening exercise prgramme has the ptential advantage f imprving functin rather than simply the strength f a single muscle and allwed easy mnitring f disease status and myelectric characteristics ver the curse fthe prgramme.

48 Chapter Tw. Grip strength, muscle fatigue and hand grip strength training in rheumatid arthritis: a literature review Intrductin Diminished functin in rheumatid arthritis is mtiltifactrial in rigin, with ptential cntributing factrs including pain, stiffness, defrmity, psychlgical elements, muscle weakness and dysfunctin and fatigue. Histlgical abnrmalities exist within the skeletal muscle in RA, the ptential significance f which - in particular in relatin t weakness and fatigue - frm the basis f the first three sectins f the literature review. The effect f exercise upn hand functin, measured as grip strength, in the presence f these factrs in RA is unclear. This will be reviewed in the latter tw sectins f this chapter. Firstly, the literature t date n the subject f the characteristics f rheumatid muscle will be addressed Histlgical changes in muscle in rheumatid arthritis. Muscle has a relatively limited range f histlgical changes in reactin t disease and mst f these changes are nn-specific (CuUen and Mastaglia, 1982; Neville, 1973). Mypathic changes have been nted in RA; hwever there are n histlgical changes in muscle which are specific t the disease (Magyar et al, 1977). A cmbinatin f features may suggest the diagnsis (Magyar et al, 1977; Halla et al, 1984). Mypathies can be classified as primary, due t a defect in the muscle itself, r secndary t a defect within the nerves supplying the muscle, in which case the mypathy is neurgenic in rigin (Jnes and Rund, 1990). Primary mypathies can be further subdivided int atrphic and destructive mypathies. Atrphic mypathies are assciated with disuse and invlve the reductin in fibre size with little, if any, reductin in ttal number. In destructive mypathies muscle fibres are lst. Althugh atrphic mypathies are ften cnsidered t preferentially affect type II fibres (Jnes and Rund, 1990), this is dependent upn the presence f factrs such as arthrgenus inhibitin and the nature f the disuse.

49 Disuse can be regarded as lcalised (when ne jint is inflamed and held immbile) r generalised (secndary t systemic illness r changes in lifestyle). Hwever, many wrkers fail t differentiate between the tw (Russell and Hanna, 1988; Nrdemar et al, 1976b). In the situatin f general disuse, but n jint immbilisatin. Type II fibre atrphy predminates, prbably because the patient des nt make cntractins strng enugh t recruit high threshld mtr trnits cntaining Type II muscle fibres (Grimby and Thmee, 1988). Preferential Type II fibre atrphy als ccurs in relatin t upper mtr neurne lesins and spinal crd transectin (Magyar et al, 1977). Brke and Kaplan (1972) suggested that in mild RA, atrphy f Type II fibres ccurs due t limitatin f rapid, frceful mvements. In severe RA, they prpsed that Type II fibres actively 'splint' the jint, preventing atrphy f these fibres, but allwing Type I fibre atrphy, since the latter are inactive. Between these tw extremes, varius mixtures f atrphy in the respnse t injiuy r disease may exist (Herbisn et al, 1987; Yung, 1993), pssibly due t a cexistence f general disuse and lcal immbilisatin, which may vary with time. Althugh mst histlgical studies f muscle in RA have indicated preferential atrphy f type II fibres, as has been discussed (Haslck et al 1970; Magyar et al, 1977; Edstrm and Nrdemar, 1974), this may be related t the characteristics f the subjects assessed, the muscle studied (Herbisn et al, 1978) and the limitatins f sme f the techniques used in assessment in the earlier studies (Wrblewski and Nrdemar, 1975). Nrdemar et al (1976a; 1976b) demnstrated atrphy f bth fibre types in the quadriceps f subjects with functinal class I and II RA. Histlgical studies have shwn that muscle fibres d nt atrphy unifrmly (Magyar et al, 1977). The length f a muscle during a perid f immbilisatin influences the final length, the additin f new sarcmeres increasing the lngitudinal length f a muscle if it is immbilised in a lengthened psitin (Haggmark et al, 1979). Cnversely, if the muscle is held in a shrtened psitin, shrtening will ccur due t the lss f sarcmeres (Grdn andpatuiil, 1993). In an immbilised jint at a fixed angle, the pattern f atrphy is dependent upn the relative length f the muscle, which in turn influences the type and amunt f impulses

50 fi-m stretch receptrs. In muscles immbilised in a relaxed state, type I fibre atrphy predminates (Grimby and Thmee, 1988). It has been suggested that the bserved histlgical changes are due t fibre type transfrmatin rather than a specific fibre atrphy pssibly related t altered lading and changes in muscle length (Kilmer, 1996; Appell, 1990), althugh there is little evidence t supprt this. Muscle fibre atrphy and alteratins in muscle length may have significant effects upn functin, the fi-equency spectrum f the SMES and spectral parameters in fatiguing cntractins, as will be described later. Neurgenic mypathy can als give rise t atrphic fibres and usually affects bth fibre types, which is a distinguishing feature frm atrphic mypathy (Kilmer, 1996; Jnes and Rimd, 1990). If the cnditin is chrnic, then reinnervatin ften cmmences. Reinnervatin ccurs by the grwth f nearby mtneurnes, which frm cntact with the atrphic fibres and supply them. The muscle fibres then adpt the characteristics f the mtneurne supplying them; if the neurne is f the same type then the fibre characteristics remain the same (self-reinnervatin) and if nt, they change (Jnes and Rund, 1990; Milner-Brwn et al, 1974; Thmas et al, 1987). Milner-Brwn et al (1974) and Thmas et al (1987) studied MU recruitment in human muscles reinnervated by surgical reunin after cmplete sectin. Sme mtr units shwed nrmal frce threshld and twitch tensin; thers did nt. Thmas et al (1987) cncluded that the predictive factr in recvery f nrmal MU functin was whether self-reinnervatin ccurred. Over a perid f time, after a perid f multiple innervatin, the prcess f denervatin-reinnervatin cntinues, the end result f which may be fibres f a unifrm type, r at least an increase in the relative amunts f ne fibre type (Jnes and Rund, 1990; Engel, 1970) Hence, in diseases f muscle f neurgenic rigin, the successive denervatin and reinnervatin may give rise t fibres with their riginal characteristics r may result in fibres f a unifrm type. The mst cmmn histlgical findings in RA are muscle fibre ati-phy and ndular mysitis (Halla et al, 1984; Magyar et al, 1977). The latter invlves ndular accumulatins f mnnuclear cells and althugh riginally thught t be specific t RA (Curtis and Pllard, 1940; Steiner et al, 1946) it has since been nted in ther cnnective tissue disrders (Sklfif et al, 1950; Pearsn, 1959). It is, hwever, a cmmn finding

51 in RA; Sklff et al (1950) nted it t be present in apprximately 56% f rheumatid subjects. Haslck et al (1970) described a wide variety f neurmuscular changes in RA, including fibre atrphy, peripheral neurpathy and mysitis. Their prpsal that denervatin is an imprtant assciatin with fibre atrphy has been reprted by many wrkers (Magyar et al, 1977; Curtis and Pllard 1940; Sklfif et al, 1950; Halla et al 1984). Magyar et al (1977) in a study f muscle bipsies frm 100 cases f RA, fund atrphy f type II muscle fibres t be a cmmn finding with the appearances f Type I fibres being "within nrmal limits". They agreed with thers (Mrrisn et al, 1947; Yates, 1963; Haslck et al, 1970) that the type II fibre atrphy was neurgenic in rigin, based n the small diameter, angular arrangement and enzyme activity f the fibres. This is indicated fiirther by the findings f abnrmalities within intramuscular nerves. In further bipsy and EMG studies in RA, Wrblewski and Nrdemar (1975) cnfirmed the abve findings, demnstrating muscle fibre atrphy and degenerative changes. Brke and Kaplan (1972) fund Types I and II fibre atrphy in severe and mild RA respectively. Russell and Hanna (1988) emphasised the imprtance f histchemical studies t the demnstratin f islated atrphy f Type II muscle fibres in RA. The mechanisms which may be invlved in fibre atrphy will be discussed further in relatin t weakness in RA. Other nn-specific changes have been nted in rheumatid muscle; their significance is unclear and will be nly briefly utlined here. Changes include degenerative changes in the sarcplasm and interstitial changes such as perivascular ndular mysitis, lymphcytic accumulatins, abnrmalities within the muscle spindles and different stages f vasculitis (Magyar et al, 1977; Wrblewski and Nrdemar (1975), Engel 1966a, 1966b; Cape et al, 1970; Jerusalem et al, 1971). Fcal muscle fibre necrsis and rheumatid mysitis (which is rare as a distinct entity) have als been demnstrated particularly when there is an inapprpriately elevated ESR cmpared t the degree f synvitis (SERD) r a large increase in the level f creatine phsphkinase (Halla et al, 1984; Brke et al, 1972; Reza and Verity, 1977). The mde f selectin f subjects fr histlgical studies f rheumatid muscle varied between thse in which bipsies were taken during unrelated surgical prcedures and thse in which subjects had clinical symptms such as weakness and muscle pain, necessitating

52 muscle bipsy. This adds t the difficulty in interpreting the relevance f the findings f such studies. The main disease parameter assciated with histlgical abnrmalities f rheumatid muscle has been reprted t be independent f bth the activity and duratin f the disease (Magyar et al, 1977) Weakness in RA. Weakness and dysfunctin may be related t extrinsic factrs such as altered jint mechanics and psychlgical elements (Stenstrm, 1994; Clugh, 1991; Wlfe and Cathey, 1991) and t intrinsic factrs assciated with histlgical changes in muscle and arthrgenus muscle weakness. This latter term describes the inability t vluntarily generate the active tensin in rested muscle that is necessary fr the perfrmance f everyday mtr tasks, as result f jint disease (Stkes and Yung, 1984). Functinally significant muscle weakness is a cmmn prblem in RA. Ekdahl and Brman (1992) demnstrated the existence f diminished functinal capacity, ismetric and iskinetic strength and iskinetic endurance in the lwer limbs f subjects with class II RA. Ismetric strength was fund t be 75% f cntrl values, iskinetic strength 65-75% and iskinetic endurance reduced t 45 % f the cntrl level. These fmdings cnfirm earlier fmdings by thers (Tiselius 1969; Ekblm et al, 1974; Nrdesj et al, 1983; Danneskild-Samse and Grimby, 1986; Hsieh et al, 1987). Ismetric and iskinetic weakness has als been reprted in relatin t the upper limbs (Ekblm et al 1974, Beals et al 1985; Danneskild- Samse and Grimby, 1986; Hsieh et al, 1987) with upper limb endurance being reprted as nrmal (Hsieh et al, 1987) r reduced (Nrdesj et al, 1983). Arthrgenus muscle weakness, is multifactrial in rigin (Lee et al, 1974; Helliwell et al, 1987; Yung, 1993). Cntributing factrs include reflex inhibitin and intrinsic changes within the muscle in the frm f muscle fibre atrphy and ther less specific changes. As lng ag as 1873, Sir James Paget recgnised muscle wasting and weakness as a 'clinical sign f muscle atrphy assciated with chrnic inflammatin f the jints' (Magyar et al, 1977). Such findings ccur early and may be the initial manifestatin f the disease (Rpes et al, 1959). Disuse, active rheumatid disease with systemic manifestatins, lcal jint disease, drugs, neurlgical, muscular, skeletal and sft tissue structural abnrmalities, trauma and pr nutritin may all ptentially play rles (Herbisn et al, 1987; Stkes and Yung, 1984; Haslck et al, 1970).

53 Primary muscle atrphy in injury r disease may be selective t the fibre type, the specific regin f a muscle r muscle grup r t agnists r antagnists. It will vary accrding t the disease and with disuse, immbilisatin and reflex inhibitin (Grimby and Thmee, 1988). The effects f disuse upn muscle fibres have been described. Disuse (the term being used nn-specifically) has been suggested t be the cause f muscle weakness in rheumatid arthritis (Hllander and M'^Carty, 1972) and mst wrkers agree that it des cntribute (Haslck et al 1970; Magyar et al, 1977). Hwever, as Hsieh et al (1987) demnstrated, weakness des ccur in patients wh are very active and functinal. True (painless) arthrgenic reflex inhibitin is the vluntary inhibitin f alpha mtr neurnes in the anterir hrn cell f the spinal crd by afferent stimuli fi-m the jint regin (Yung, 1993; de Andrade et al; 1965). This must be differentiated frm pain inhibitin, which is partly invluntary - invlving lng lp reflex pathways - and partly vluntary (Grimby and Thmee, 1988). Studies invlving pst-perative inhibitin f muscle during painful and pain free perids have indicated that pain des nt seem t be assciated with reflex inhibitin (Shakespeare et al, 1985). Ptential mechanisms f reflex inhibitin are the presence f jint effusin, the jint psitin and muscle grup invlved. The aspiratin f jint eftusins reduces the inhibitin f vluntary muscle cntractins and reflex inhibitin is mre marked if the effusin is large (Stkes and Yung, 1984). Hwever, aspiratin des nt ablish the inhibitin cmpletely, implying that ther factrs are invlved (Stkes and Yung, 1984). Reflex inhibitin alters with jint angle, as demnstrated in pst menisectmy patients in whm inhibitin was less when the knee was exercised ismetrically in flexin (Shakespeare et al 1983; Stkes and Yung, 1984). There are bvius implicatins t this, since it will be mre effective t increase strength and prevent atrphy by exercising the jint at an angle at which the reflex inhibitin is at a minimum. In jint disease, it is likely that reflex inhibitin ccurs in all muscles assciated with a particular jint and may persist fr years with pssible dysfunctin as a result (Yung, 1993). Hwever, different grups may be affected t different extents. Jint damage results in greater weakness f tiie extensr muscles than the flexrs (Arvidssn and

54 Erikssn, 1986; Sargeant et al, 1977). The cause f this is nt clear: reflex extensr inhibitin and flexr facilitatin have been prpsed as ptential mechanisms (Yung, 1993). There are ther imprtant factrs assciated with weakness in rheumatid disease. These include disease duratin, the use f specific drugs and disease activity. On the basis f the findings described abve, the mechanism f weakness assciated with the latter seems likely be due t reflex r pain inhibitin. Hsieh et al (1987) studied the ismetric quadriceps and hamstrings strength in patients with early rheumatid arthritis and minimal knee invlvement. They fund that the strengths f these muscles were apprximately 80% f nrmal values, with the quadriceps being the weaker grup. In a study f patients with RA awaiting knee surgery, with lnger disease duratin and mre severe disease, the knee strength was fund t be apprximately 40% f nrmal (Nrdesj et al, 1983). These studies indicate the imprtance f disease duratin t the extent f muscle weakness in RA, cnfirming the histlgical fmdings f mre marked changes in such patients (Magyar 1977; Haslck et al, 1970) Athrgenus weakness and muscle fibre atrphy in RA: a summary. Frm the abve descriptin f rheumatid muscle and related weakness, it is evident that there are tw ptential mechanisms f muscle atrphy in RA: denervatin and disuse. Different fibre types may be affected accrding t the relative imprtance f the tw mechanisms which may ccur alne r in cmbinatin. In additin the effects upn fibre type will depend upn the nature f the immbilisatin in the case f disuse and the pattern f reinnervatin in the case f denervatin. This, in additin t the wide variety f subjects studied, may help t explain the differences in the findings in different studies f muscle in RA. 2.3 Fatigue Intrductin Like weakness, fatigue is a phenmenn with many definitins and is a cmmn feature f rheumatid disease (Belza, 1995; Finals et al, 1981). Hwever, althugh subjective fatigue 9

55 is a cmmn cmplaint, the prevalence f bjective fatigue in RA is unknwn. This is partly a result f the many definitins f the phenmenn and the difficulties in its measurement, in additin t a lack f research in the area. The cntributin f muscle abnrmalities t fatigue in RA is als unknwn. This sectin reviews the cncept f fatigue, the phenmenn f fatigue in RA and its measurement Defining Fatigue. Fatigue is an extremely cmplex phenmenn. It can be described and measured in terms f subjective,fianctinaland physilgical aspects (Edwards, 1981). These definitins d nt necessarily reflect the same phenmena and different terminlgy is ften used by different wrkers, adding t the cnfusin in the interpretatin f the literature in relatin t the cncept f fatigue. Subjective Fatigue is a cnglmerate f symptms related t physical and subjective exhaustin. It can be assessed by rating scales, including thse f Brg (1982). Althugh it may reflect cardivascular respnses t wrk and is imprtant in relatin t functin and perfrmance, it may be prly crrelated with specific changes ccurring at the level f the muscle (McArdle et al, 1991). Functinal fatigue may be defined as a failure t maintain the required r expected frce (Edwards, 1981), r as a decrease in the frce generating ability f a muscle resulting frm recent activity (Bigland-Ritchie et al, 1984). It can be measured in terms f the lss (abslute r rate) f a given frce, such as grip. Sme wrkers call this physilgical fatigue; hwever, fatigue begins the mment a muscle begins t cntract and must be regarded as a prcess rather than a single event (Bigland Ritchie et al, 1986). Measuring and describing fatigue must invlve assessing the changes which ccur frm the initiatin f wrk. The abve definitins f functinal and subjective fatigue d nt reflect this fact and a mre sensitive definitin is needed t better describe and measure muscle fatigue. True physilgical fatigue is a term that reflects the many metablic changes and alteratins at the level f the muscle fibre which ccur during cntractin. Ultimately, these are majr factrs which will predict the degree f fatigue an individual experiences (Windhrst and Mmmaerts, 1996; Westerblad et al, 1991). 10

56 In the investigatin f muscle fatigue, it is useful t fcus upn the unit f muscle cntractin, the mtr unit, defined as an individual mtr nerve cell and the muscle fibres it activates. Prcesses which ccur during fatigue can affect the functin f the mtr unit, resulting in the changes which are cmmnly bserved: a decline in perfrmance, eventually subjective changes and if extreme, injury Fatigue in RA Subjective fatigue in RA is extremely cmmn, with a reprted prevalence f 80 t 93% (Belza, 1995; Pinals et al, 1981). Belza (1995) reprted that 61% f the variatin in subjective fatigue in RA culd be explained by pain, gender, pr sleep, reduced activity levels, cmrbid cnditins and functinal status. Unlike self-reprted fatigue and in spite f the decline in functinal capacity nted in RA (Ekdahl and Brman, 1992), physilgical fatigue in this disease has nt been investigated. Subjective scres cannt be assumed t represent functinal r physilgical fatigue, since subjective fatigue des nt cnsistently crrelate with bjective measures f fatigue (Oberg, 1994). Subjects with RA are recgnised as being decnditined and at an increased risk f cardivascular and peripheral vascular disease (Myllykangas-Lusujarvi et al, 1995), in additin t having the histlgical abnrmalities within skeletal muscles which have been described. These factrs may result in a reduced ability t cpe with the metablic by-prducts which accumulate with muscular wrk, which in turn will result in early muscle fatigue (Jnes and Rund, 1990; Edwards, 1981). Physilgical fatigue in RA is fiirther investigated in this study using analysis f thefi-equencyspectrum f the surface myelectric signal Mechanisms f Fatigue. Numerus bilgical and mtivatinal factrs may ptentially cntribute t muscular fatigue, ccurring anywhere alng the 'chain f cmmand' pathway invlved in mtr unit activity, fi-m the higher centres in the CNS t crss bridge cycling within the muscle (Bigland Ritchie, 1981a, 1981b; Edwards, 1981). Metablic influences upn muscle fatigue with exercise with time prgressively include phsphcreatine depletin, lactate 11

57 and prtn accumulatin, glycgen depletin, reductin in bld glucse and an increase in the bld tryptphan:amin acid rati. The frmer tw features are particularly imprtant limiting factrs in exercise f higher intensities (Edwards et al, 1977). Changes in the myelectiic signal have been nted t ccur with fatigue and have been utilised in its assessment. These myelectric manifestatins f fatigue in relatin t the surface myelectric signal (SMES) during vluntary wrk will be described after a shrt descriptin f the terminlgy used in electrmygraphy The descriptin f the myelectric signal. The myelectric signal (MES) can be described and quantified in many ways. The interference pattern describes the pattern f the MES during a vluntary cntractin, where many MU ptentials are superimpsed upn ne anther, making it impssible t define each MUAP individually. The MES may be quantified by the measurement f its pwer at different frequencies (by the prcess f frequency spectral analysis) r the vltage f the signal, expressed as the rt mean square (RMS) vltage f the MES, r the integrated emg (lemg). This can be further evaluated by the examinatin f the relatinship between this measure and the frce exerted. This relatinship is termed the neurmuscular efficiency (NME) and will be described fiirther in a later sectin. The use f such parameters in the assessment f muscle perfrmance and fatigue m health and disease will nw be detailed Myelectric Manifestatins f Fatigue. During sustained muscular cntractins, physilgical and bichemical mdificatins ccur. These include an elevated level f metablites, resulting in an alteratin f the ph f intra and extracellular fluid and mdificatin f the electrical prperties f muscle fibre membranes (Lindsti-m and Petersen, 1981). As a result, changes ccur in the amplitude, shape, spatial width and prpagatin velcity f the mtr unit ptential - and therefre in the myelectric signal. Since Edwards and Lippld described changes in the myelectric signal during cntractin in 1956, several changes in the myelectric signal during wrk have been advcated as 12

58 indicatrs f muscle fatigue. These include a rise in signal vltage during a sustained submaximal cntractin, a decrease in vltage during a sustained maximal vluntary cntractin and a decrease in frce if a given level f SMES amplitude is maintained (Lindstrm, 1970; Lindstrm et al, 1977; Edwards and Lippld, 1956). Changes in the frequency spectrum f the SMES als ccur with fatigue (Lindstrm et al, 1977) and will be described further belw The RMS f the SMES as an indicatr f fatigue. The increase in the SMES amplitude as a fimctin f time during sustained submaximal cntractins has been used as an indicatr f muscular fatigue fr ver 4 decades. Stephens and Taylr (1972) studied the smthed rectified integrated EMG (lemg) frm the first drsal intersseus muscle in three subjects during cntractins at 70-80% MVC sustained fr 30 secnds. They nted that whilst frce is maintained the lemg increases, and declmes nce mechanical fatigue in the frm f a reductin in cntractin frce ccurs. A nn linear rise in the amplitude f the SMES has been nted by West et al (1995) and thers (Fugelvand et al 1993; Lind and Petrfsky, 1979). The increase in the lemg and the rt mean square (RMS) f the SMES with fatigue during sustained submaximal cntractins (Kurda et al, 1970) has been pstulated as being related t a prgressive increase in muscle fibre recruitment, impaired excitatin-cntractin cupling and/r an increase in firing frequency as cntractile element failure f the initial muscle fibres invlved cmmences (Edwards, 1981). Hwever, althugh a rise in the RMS f the SMES and in the lemg cntinue t be accepted as indicatrs f muscle fatigue (Stulen and DeLuca, 1978; Cper et al 1993, Trup and Chapman, 1972), sme wrkers have reprted n change r a decline in this parameter with sustained wrk (Chapman et al 1970; Seidel et al 1987). Findings differ accrding t the muscle studied, and the intensity f the wrk invlved. It is likely that this is related t the differences which exist between muscles in relatin t their mtr unit cntrl schemes, as will be described in sectin 2.4. It is fr these reasns that DeLuca (1985) and Edwards (1981) stated that the change in the signal amplitude is f little use as an indicatr f fatigue. Mre recentiy, analysis f the SMES in the frequency dmain (pwer spectral analysis) has been utilised in the mnitring f muscle fatigue. 13

59 2.3.8 Pwer spectral analysis (PSA) f the surface myelectric signal. The pwer spectiim describes tiie relatinship between the signal amplitude and frequency (Lindstrm, 1970). Richardsn (1951) was the first t use pwer spectral analysis, in dividing the EMG spectrum int tw parts using a filter, t measure the spectral cntent. Waltn (1952) and ther wrkers (Fex and Krakau, 1957; Sctt, 1967) further develped the technique fr clinical use and the technique has been applied in a wide variety f settings (Lindstrm et al, 1970; Mur et al 1982; Lindsti-m 1970; Kadefrs et al, 1976). Varius methds exist in the determinatin f the pwer spectrum f a signal (Duhamel and Vetterli 1990). Hwever, subjecting the raw MES t a Fast Furier Transfrm (FFT) algrithm is the mst cmmnly accepted methd in PSA (Petrfsky and Lind, 1980; Basan and Ottnell, 1986) The descriptin f the pwer spectrum and pwer spectral parameters. The numerus parameters used t describe the pwer spectrum and changes which ccur in respnse t activity include the mean, median and mde frequencies, the rati parameter, peak frequency and spectral width. The frequency spectrum f the MES is mst cmmnly described in relatin t the median (MDF), mean (MNF) r mde (MF) frequencies (Stulen and DeLuca, 1981; Merletti et al, 1992). The MDF is the frequency at which the pwer spectrum is divided int tw regins f equal pwer. The mde frequency, is the frequency f the peak amplitude f the spectrum. The mde frequency is nt suitable fr use in pwer spectral analysis, as it has a high cefficient f variatin (Schweitzer et al, 1979). The median frequency (MDF) is generally the preferred parameter, being superir t the thers particularly in the estimatin f changes in cnductin velcity and it is less sensitive t nise (Stulen and DeLuca, 1981). The gradient f the median frequency f the SMES (MDFG) describes the gradient f the regressin line fitted t the median frequency versus time plt and has becme a ppular index f muscle fatigue during sustained submaximal ismetric cnti-actins. This is related t physilgical changes that ccur during tiie prcess f fatigue, as will be described further. The initial median frequency (IMF) describes the value btained frm the intercept f the f the regressin line n tiie y axis (time = 0). The IMF represents the median frequency f the SMES prir t the nset f 14

60 fatigue. Spectral parameters are shwn in relatin t the pwer spectrum in figures and Figure 2.3.1: The frequency spectrum f the SMES. SpedRii) Median frequency > Spectral width Frequency (Hz) Figure 2.3.2: The change in the median frequency f the SMES with time. I Initial median frequency (t=) Regressin line (red) f the relatinship betwei the MDF and time, the gradient f which is termed the MDFQ. Time (secnds) The spectral width (SW) describes the wddth f the pwer spectrum at half the peak amplitude. This parameter has nt been fcused upn in the literature t date, pssibly because its' physilgical basis is unclear and it may add n additinal infrmatin t that supplied by the MDF in relatin t the behaviur f the underlying wrking muscle. Althugh the rati parameter, which expresses the rati f lw frequency cmpnents t high frequency cmpnents (Schweitzer et al, 1979), is mst sensitive t cnductin velcity, the relatin is nn linear and it displays a high cvariance (Stulen and DeLuca, 1981). 15

61 The frequency spectrum in relatin t EMG measures. The frequency spectrum f the myelectric signal depends upn the actin ptentials f individual muscle fibres within the pick-up zne f the recrding electrdes, the cnductin velcity f the actin ptentials, the thickness and length f the muscle, the distance between the muscle fibres and the detectin surface f the electrdes, the electide cnfiguratin, the duratin f the actin ptential, the number f phases, turns and zers, fibre type and the level f frce (Lindstim et al, 1977). The relatinship f the pwer spectrum with frce will be described later. In signal thery, the influence f the cnductin velcity f a single fibre actin ptential will persist thrugh all mathematical manipulatins in the mdelling f varius prcesses. In all expressins describing the pwer spectrum, the velcity always appears tgether with the frequency as a qutient (frequency/velcity), thus any velcity change can be seen as a shift f the spectrum alng the frequency axis (Lindstrm, 1970; Lindstrm and Magnussn, 1977). Furier transfrmatin f a ptential f fixed gemetrical shape als shws that the pwer spectrum density is inversely prprtinal t the squared value f the velcity (Lindstrm et al, 1970). When the cnductin velcity decreases, a signal increase, in additin t a spectral shift, ccurs. Such changes are imprtant in the mnitring f muscle fatigue and will be utlined in the sectin The pwer spectrum btained with surface electrdes will differ frm that btained using intramuscular elecfrdes, having a maximum in the frequency regin between 10 and loohz, using surface electrdes cmpared with between apprximately 100 Hz (r lwer) and 200 Hz witii inframuscular electides (Krivickas et al, 1996). The MES (and therefre the frequency spectrum) is strngly influenced by the inter-electrde separatin distance (EES), which affects the bandwidth and amplitude f the EMG signal. A smaller distance prduces higher frequencies and lwer amplitudes than a large les. The duratin f a myelectric signal is cmmnly used as a signal characteristic. It plays a large part in the determinatin f the distributin f pwer ver the frequency interval; pulses f shrt duratin cntain mre high frequency energy than pulses f lnger duratin. The pwer spectrum is strngly influenced by the number f phases f a mtr unit, which in turn is strngly assciated with the duratin f the signal. When 16

62 the duratin is cnstant, an increase in phase number causes a spectral shift twards higher frequencies. When the duratin increases in prprtin t the number f phases, a mre prnunced peak is seen in the lwer regin f the pwer spectrum (Lindstrm and Petersen, 1981). The fibre type cmpsitin f the muscle has been linked with the initial median frequency (IMF) and the change in the MDF with time during a fatiguing cntractin (termed tiie MDF gradient, tiie MDFG) (Linssen et al, 1991; Arendt-Nielsen et al, 1988; Prter et al, 1989; Merletti et al, 1990). Type II fibres have been shwn t have higher MDFs than type I in cntiactin (Milner Brwn et al, 1986) and display higher cnductin velcities alng the muscle fibre membrane (Linssen et al, 1991). The higher cnductin velcity may be due t the generally larger diameters f Type II fibres (Brman et al, 1985; Kereshi et al, 1983), altiiugh Sadyama et al (1988) fund that tiie cnductin velcity crrelates with the crss-sectinal area f the fibres, rather than the diameter. Many wrkers have prpsed that the MFCV is related t fibre diameter: larger fibres with faster MFCVs will have greater mean pwer frequencies (MNFs) (Basmajian and DeLuca, 1985). Hwever, the prpsal that muscle fibre diameter is the imprtant factr in determining the MDF must be brught int questin when the muscle fibre type is cnsidered. In studies f lwer limb musculature, Gerdle et al (1988b) and Mritani et al (1985a) reprted a strng relatinship between the MNF f the EMG and the percentage f type II fibres. Westbury and Shaughnessy (1987) als dcumented this relatinship in the masseter muscles f females. Many f the studies relating the MDF t fibre diameter have been perfrmed upn men, in whm type II muscle fibres are larger than type I fibres in mst muscles. Hence the increase in MDF with frce may be due t either the fibre type r diameter. Hwever, in wmen the size difference between fibre types is much less: many authrs have reprted type I fibres t be larger than type II fibres (Gerdle et al, 1991; Simneau and Buchard, 1989; Frese and Hustn, 1985). Gerdle et al (1991) used this finding t examine the influence f the fibre type cmpsitin n the MNF, by studying a gradually increasing static knee extensin in 10 wmen. The vastus lateralis and medialis and the rectus femris muscles were studied; bipsies f the frmer shwed larger type I fibres than type II in 8 subjects. Tw imprtant fmdings were reprted: significant psitive crrelatins between the MNF and trque were demnstrated fr all 3 muscles and negative crrelatins between type I fibres and the MNF. 17

63 Althugh the Type II fibres in mst muscles are larger than type I fibres, this is nt true fr a small number f muscles, including the erectr spinae, tempralis and ilipsas (Plgar et al, 1973). This may explain the atypical changes in the frequency spectrum f the SMES that has been bserved in sme f these muscles (Ry et al, 1989). Hence, in rder t interpret the frequency spectrum f the MES frm frearm muscles, it is imprtant t establish the relative size and prprtins f fibre types in the frearms f healthy individuals. Jhnsn et al (1973) demnstrated the extensr digitrum cmmunis (EDC) t cnsist f a slight predminance f Type II fibres (51.3 %), which are slightly larger than Type I fibres. Althugh n infrmatin n the flexr carpi radialis (FCR) is available in the literature, the flexr digitrum prfundus als shws a predmmance f Type II fibres (60.9 %), which were significantiy larger than Type I fibres. It is evident that fibre diameter is nt the sle factr influencing the muscle fibre cnductin velcity. As has been discussed, it has been demnstrated t be related t the metablic state f the fibre. Cnductin velcities have been demnstrated t be higher in type II fibres than type I (Mrtimer et al, 1970); this may be related t physilgical characteristics such as greater ATPase activity, Ca^"^ flux and shrter actin ptentials and twitch times (Mritani et al, 1985b). Muscle length has been fund t have an effect n the pwer spectrum (Gerdle et al, 1988a; Inbar et al, 1987; Bazzy et al, 1986). Mst studies indicate that with the muscle in a lengthened state the lw frequency part f the spectrum is mre prminent than when at shrter lengths (Inbar et al, 1987; Bazzy et al, 1986; Duchene and Gubel, 1993). In sme studies which are presumed t be nn-fatiguing, part f the bserved spectral shift culd be attributed t the change in muscle frce with length. Hwever, in studies at each muscle length where frces were expressed in terms f the percentage f the maximal vluntary cntractin (MVC), similar results were btained (Okada, 1987). Several pssible mechanisms fr these bservatins have been suggested (Kssev et al, 1992; Duchene and Gubel, 1993). A decline in cnductin velcity with increasing muscle length can be explained in terms f mdificatin f fibre diameter and/r reductin in the distance frm the deeper, smaller diameter (lw MFCV) fibres t the detectin surface f the electrde (Bazzy et al, 1986). Cnversely, it is pssible that the distance frm the detectin surface t the active MUs increases 18

64 when the muscle is lengthened, resulting in an increase in high-frequency filtering and the bserved spectral shift (Lindstrm and Petersen, 1983a, 1983b). Lindstrm (1974) fund that reducing muscle thickness increases the pwer f high frequency cmpnents. Hwever the ppsite was fund by Bazzy et al (1986). This is ne factr which causes variatins in myelectric characteristics between different muscles. The SMES is affected by changes in muscle temperature (Petifsky, 1979), pssibly due t the effects n resistance f the sarclemma (Fink and Luttgau, 1976). The temperature rise during an ismetric cntractin is linearly related t the frce f cnfractin (Edwards et al, 1975). An increase in muscle temperature results in a reductin in signal amplitude, tiie RMS f tiie SMES and an increase in MNF (Peti-fsky, 1979) Pwer spectral cmpressin during muscle fatigue. Altiiugh Piper first described a reductin in tiie frequency f the MES witii wrk in 1921 (the Piper rhythm) (Stulen and DeLuca, 1981), it was fur decades befre cntiactininduced changes in the frequency cntent f tiie myelectric signal were quantified by, amngst thers, Kgi and Hakamada (1962) and Kaiser and Petersen (1962). These wrkers demnstiated a decline f pwer density in the high frequency regin and an increase in the lw frequency regin during wrk, using ctave band filtering. This was termed the "pwer spectral shift" and was subsequently cnfirmed by ther wrkers (DeLuca, 1984; Lindstim et al, 1977). Lindsfrm (1970) pinted ut that the cnductin velcity f muscle fibres scales the pwer density f the myelectric signal, implying that the pwer specfral "shift" t a lwer frequency is actually a pwer spectial "cmpressin". Different time dependent phenmena take place witiiin tiie muscle during an ismetiic cntractin, including myelectric and pwer spectial density changes as a result f alteratins f amplitude, shape, width and prpagatin velcity f MUAPs, recruitinent alteratins f mtr imits, changes in the firing rates f individual mtr units and changes in tiie frce twitch f individual mtr units (DeLuca, 1984). These have all been utilised as myelectiic manifestatins f muscular fatigue and can be expressed in terms f the changes in mean and median frequencies, cnductin velcity and amplitude (the 19

65 average rectified value and rt mean square f the signal). Changes in the signal amplitude with fatigue have been discussed. Pwer spectral cmpressin has been advcated as a sensitive measure f muscle fatigue and will be fijrther described belw The Descriptin f Pwer Spectral Cmpressin. As utiined earlier, the MFCV has been shwn t be clsely assciated with the frequency spectrum f the SMES. Lindstrm et al (1970) demnstrated that theretically the pwer spectral shift twards lwer frequencies and the increase in the myelectric signal witii fatigue culd be accunted fr by a single elecfrphysilgical crrelate, the cnductin velcity. They fiirther prpsed that, since changes in the frequency can be used t determine changes in the cnductin velcity, they culd als be used t assess fatigue. Hwever, in a review f ptential myelectric indicatrs f fatigue, Merletti et al (1990) cncluded that certain spectral variables (mean and median frequencies - see belw) are mre sensitive t fatigue than the cnductin velcity. The mean and median frequencies are bth apprpriate indicatrs f pwer spectral cmpressin and have been demnstrated in several studies t crrelate with cnductin velcity and muscle fibre type distributin as discussed in Sectin (Linssen et al, 1991; Hakkinen and Kmi, 1983; Viitasal and Kmi, 1978; Van Bxtel et al, 1983). Changes in the MNF have been used t describe alteratins in the pwer spectrum during fatiguing cntractins (Hagberg, 1979; Brman and Kadefrs, 1979; Ortengren et al, 1979; Lynne-Davies, 1979). Variability is small cmpared with its change with muscle fatigue, and it is stable and reliable (Daanen et al, 1990). Hwever, the median frequency (MDF) is the preferred parameter (Stiilen and De Luca, 1978, 1979; Sabbahi et al, 1979; Petrfsky and Lind, 1975). It is superir t the MNF fr estimating changes in cnductin velcity and is less sensitive t nise (Stulen and DeLuca, 1981). Sme wrkers have analysed the spectral changes which ccur during muscle cntractin by dividing the frequency spectra int a set f individual frequency bands (arbitrarily chsen) and als by examining the frequency cntents (Dlan et al 1995; Mxham et al, 1982; Bigland-Ritchie et al, 1981a; Anderssn et al, 1976; Hary et al, 1982; Schweitzer et al, 1979). Sme studies have fund that the high/lw frequency rati reflected fatigue- 20

66 induced changes in the muscle (Mxham et al, 1982; Bigland-Ritchie et al, 1981a; Anderssn et al, 1976; Dlan et al, 1995). Hwever thers have fund this methd t be less reliable than the MDF as an index f fatigue (Hary et al, 1982; Schweitzer et al, 1979). This may be due t the arbitiary nature f the banding and the number f bands chsen. Dlan et al (1995) pinted ut that 2 t 3 bands may nt be adequate and used 10 bands with sme success in reflecting fatigue Mechanisms f Pwer Spectral Cmpressin during Muscle Fatigue. Varius verlapping theries fr the main mechanism f spectial mdificatin exist (StiUen and DeLuca, 1981; Fex and Krakau, 1957; Lindstim et al, 1970, 1977; Duchene and Gubel, 1993; Mrtimer et al, 1970; Mills, 1982). The phenmenn is likely t be assciated with many inter-related factrs, including altered muscle fibre cnductin velcity, the synchrnisatin f mtr unit firing, accumulatin f metablic by-prducts, ischaemia, and the muscle fibre type(s). The muscle fibre cnductin velcity (MFCV) is a basic physilgical parameter that affects the myelectric signal spectial density and cntributes t its cmpressin during fatigue (Merletti et al, 1990). The cnductin velcity declines as vluntary muscular cntiactins prgressively fatigue t exhaustin (Stalberg, 1966). Mrtimer et al (1970) and thers have suggested that that a reductin in cnductin velcity is the mst likely cause f pwer spectral cmpressin (Lindstrm and Petersen, 1983a; Lindstim, 1970; Kranz et al, 1983; Stulen and DeLuca, 1982). Hwever, tiiers pinted ut tiiat a decline in cnductin velcity alne des nt explain the pwer spectial changes seen (Bigland- Ritchie et al, 1981a; Merietti et al, 1990) and spectial mdificatins can ccur independentiy f changes in MFCV (Brdy et al, 1991). The mechanisms by which tiie decline in cnductin velcity ccurs remain unclear (Bigland-Ritchie et al, 1981a, 1981c). The intiamuscular accumulatin f metablic by-prducts during ismetric cntiactins may be due t an increased prductin (Ahlbrg, 1972) and/r reduced remval as a result f reduced bld flw during cntractins (Cuch et al, 1971; Mrtimer et al, 1971). The accumulatin f prtns and lactic acid and tiie resulting reductin in ph (Dawsn et al, 1977) is assciated with functinal fatigue (Sahlin et al, 1975; Karlssn, 1971) and has been suggested t cause pwer spectial shift in fatigue (Mrtimer et al, 1970). This is 21

67 related t the decline in muscle fibre membrane excitability with decreasing ph (Tasaki et al, 1967), particularly intracellular ph (Terakawa et al, 1978). In additin, when ph drps, less calcium ins are available t prduce a muscle cntractin (Nakamuru et al, 1972). A decline in membrane excitability leads t a reductin in cnductin velcity, which in turn has been shwn t be related t pwer spectral cmpressin (Mrtimer et al, 1970). Such findings have led many wrkers t cnclude that the rate f decline in the MNF may be dependent upn the metablic state f the fatiguing muscle (Nagata et al, 1981; Kmi and Tesch, 1979; Mritani et al, 1985a). Other studies have nt been cnsistent with this hypthesis, suggesting that lactate accumulatin is unlikely t be the sle cause f pwer spectral shift (Buissu et al, 1989; Beliveau et al, 1991; Brdy et al, 1991). Karlssn et al (1975) prpsed that lactate influences the pwer spectral shift nly fr given intensities f ismetric cntractin. Buissu et al (1989) demnstrated a crrelatin between MNF and lactate cncentratin, but fund n relatin with muscle ph - pssibly due t difficulties in measuring cytslic ph. Brdy et al (1991) demnstrated an initial relatinship between cnductin velcity, ph and MDF, but MDF and cnductin velcity altered differently in sustained stimulated cntractins. Beliveau et al (1991) reprted that MNF but nt frce generating capacity had cmpletely recvered within a few minutes, despite persistence f acidsis indicating ther prcesses are invlved. In further wrk, Beliveau (1992) cncluded that changes in pwer spectral frequency cmpnents in exercise are nt uniquely determined by changes in muscle ph and cnductin velcity and suggested that ther metablites such as inrganic phsphate and its diprprinated frm may have a rle. Hwever, a study f simultaneus surface electrmygraphy and ^'P NMR spectrscpy by Bendahan et al (1996) fund n verall crrelatin between the high/lw frequency band rati and changes in metablism during fatiguing static cntractins f frearm musculature. Bld flw in cntracting muscle is restricted r arrested (Naess and Strm-Mathiesen, 1955; Mttram, 1963). Stephens and Taylr (1972) and Fx and Kenmre (1967) suggested that impulse transmissin in the neurmuscular system is mst sensitive t ischaemia. In the evaluatin f the recvery frm fatigue by vluntary test cntractins, Hara (1980) cnfirmed that ischaemia is invlved in muscle fatigue; this is prbably related t the accumulatin f metablites. Humphreys and Lind (1963) reprted that the bld flw in the frearm is near t ttal cclusin during handgrip at 70% f the 22

68 maximum grip strength (70% MGS). During grips perfrmed at levels between 30 and 60 % MGS, the bld flw is increased. Studies have als been perfrmed assessing the affect f muscle length n the pwer spectrum during fatiguing activity. Huijing et al (1986), assessing the triceps surae and gastrcnemius, fund that changes in MNF with the muscle in the lengthened state were significantly greater than at shrter lengths. Hwever, endurance at lnger muscle lengths was greater. When this was allwed fr in further assessments, n significant length-related effect was shwn. Much f the early wrk n the mechanism f pwer spectral shift cncentrated n the synchrnisatin f mtr unit firing. Lippld et al (1957) and thers (Fex and Krakau 1957; Lag and Jnes 1977; Bigland-Ritchie, 1983) suggested that the switch frm the nrmal, desynchrnised firing pattem t a synchrnised frm causes the spectral shift. Mrtimer et al (1970) cncluded that the phenmenn is nt slely due t the synchrnisatin f MUAP's, but is largely due t the decline in cnductin velcity, which has been detailed abve. There is evidence that muscle fibres f different types have different prperties during fatiguing exercise. Larssn (1978) and Viitasal and Kmi (1978) were the first t prpse that the MDF declines mre rapidly during a sustained ismetric cntractin t exhaustin in subjects with a high prprtin f Type II fibres than thse with a high percentage f Type I fibres. Hakkinen and Kmi (1983) fund a relatinship between the relative decrease in mean pwer frequency during a 50% MVC and the relative area f Type II fibres f the vastus lateralis muscle. Kurinka (1988) cmpared the fatiguability in the human biceps (which cntain a predminance f slw twitch fibres) and the triceps (which have a majrity f fast twitch fibres) (Jhnsn et al, 1973, Fallentin et al, 1985) and demnstrated different pwer spectra and restitutin patterns between the tw muscle grups. Linssen et al (1991) identified the relative rles f types I and II muscle fibres in fatigue by assessing the muscle fibre and surface EMG studies in patients with cngenital mypathies, cmparing thse wh had % type I fibre predminance with thse patients with 80% type I fibres and with nrmal cntrls. They cncluded that type II fibres have a greater frce generating capacity and are mre fatiguable than type I fibres, as reflected by almst n decline in signal cnductin velcity and nly a slight increase in surface EMG amputude during wrk in subjects 23

69 with mypathy. Overall, studies indicate that muscles with relatively high prprtins f type II fibres have faster spectral shifts than d muscles with high prprtins f type I fibres (Mritani et al, 1986; Van Bxtel et al, 1983; Arendt-Nielsen and Mills, 1988; Prter et al, 1989; Merietti et al, 1990; Huijing et al, 1986). On the basis f these studies, pwer spectral shift has been prpsed t be related t the relative rles f different fibre types (Milner Brwn et al, 1986; Braakhekke et al, 1989). This seems likely but ther factrs are als likely t be significant. Duchene and Gubel (1993) emphasised the difficulties in interpreting the results relating t muscle fibre type and pwer spectral shift, in the light f ther physilgical changes that are ccurring. These include altered MU recruitment and firing rates and alternatins in activity between synergists (Duchene and Gubel, 1990). A descriptin f the relatin f the SMES t frce and mtr unit cntrl pattems will nw fllw Mtr unit cntrl and the relatinship between frce and the SMES Intrductin Changes in neurmuscular cntrl are invlved in spectral mdificatins, as emphasised by Stulen and DeLuca (1981) and DeLuca and Creigh (1985). Changes in mtr unit recruitment alter the fi-equency spectrum f the MES, whereas alteratins in the MU firing rates have little effect (DeLuca et al, 1983; Slmnw et al, 1990). In rder t interpret the alteratins which ccur in the SMES during muscular cntractins and the inter-relatinships between the myelectric parameters and frce, a review f the mechanisms f the mdulatin f MU activity is apprpriate. Studies f the relatinship between the SEMG and frce will als be reviewed Mtr unit cntrl and the generatin f frce. Mtr unit (MU) cntrl, thrugh the recruitment f new mtr units and mdulatin f MU firing rates, frms the basis f the maintenance f a given frce during a sustained muscular cntractin and in increasing levels f frce utput (Milner-Brwn et al, 1972). Numerus wrkers have addressed the interactin between these tw frms f MU 24

70 cntrl with cntradicting results. Much f the cntrversy relates t the examinatin f different muscles and the type and intensity f cntractins perfrmed. Since each muscle has unique anatmical and physilgical characteristics, it is likely that they als differ in their mtr cntrl schemes (DeLuca et al, 1982a, 1982b; Lawrence and DeLuca, 1983). Henneman and c-wrkers first described the rderly recruitment accrding t mtr neurne size (the size principle) in a series f studies n MUs during reflex cntractins f muscle m cats (Heimeman et al, 1974; Bawa et al, 1984), smaller mtr neurnes being recruited earlier than larger nes. Milner-Brwn et al (1973a) cnfumed this pattern f rderly recruitment in vluntary cntractins f the first drsal intersseus muscle f the hand in humans. Other wrkers (Desmedt and Gdaux, 1981; Nardne et al, 1989) have shwn that MU recruitment accrding t the size principle des nt ccur universally in all muscles, raising the prspect f differences between muscles and during different types f wrk. This may in part be explained by the fact that the initial studies were perfrmed using cntractins f single muscles nly, which des nt f necessity reflect the situatin in thefianctinalsetting. The ther mechanism f mtr unit cntrl m increasing levels f frce is the mdulatin f mtr unit firing rates, rate cding. The behaviur f MUs with respect t firing rates ver a range f frce remains an area f cnftasin. MU firing rates have been reprted as varying mntnically wdth frce (Milner-Brwn et al, 1973b), as plateauing at submaximal frce levels (Bigland and Lippld, 1954a,b; Mnster and Chan, 1977) and as firing at cnstant rates, independent f frce (Bracchi et al, 1966). Lw threshld MUs have been reprted t exhibit lw firing rates by sme wrkers (Burke, 1981; Kemell D, 1965) whereas thers have reprted them t fire at higher rates than higher threshld units (Persn and Kudina, 1972; DeLuca and Erim, 1994; Erim et al, 1996). Althugh the relative influence f the MU recruitment and firing frequency n the generatin f frce has been widely investigated (Milner Brwn et al, 1973a, 1973b; Clamann, 1970; Bracchi et al, 1966; Erim et al, 1996; Bigland and Lippld, 1954a), there remains a lack f cnsensus f pinin, which is likely t be due t differences in the muscles studied and prtcls used (Edstrm and Grimby, 1986). The mechanical prperties f a muscle are dependent upn its cmpsitin with respect t the fibre type, which may in turn be expected t play a rle in determining the specific mdulatin f mtr units and recruitment strategies. Muscles with similar fibre cmpsitins have been 25

71 shwn t differ in their mechanisms f the maintenance and increase in frce utput. The relative rles f recruitment and rate cding may depend upn the size f the muscle and its functinal requirements (Fugelvand et al, 1993). Recruitment f MUs has been shwn t be the mst imprtant strategy in the generatin f frce in large muscles ver a wide range f frce (0-90% MVC), whereas rate cding is imprtant in smaller muscles invlved in finely cntrlled mvements, with recruitment being imprtant within the frce range f 0-50%MVC (DeLuca et al, 1982a, 1982b). There is n available infrmatin relating t the number f mtr units in the extensr digitrum cmmunis (EDC) and flexr carpi radialis (FCR) muscles. Hwever, in muscles such as thse f the frearm which are medium sized and perfrm bth pwerful mvements and finely cntrlled mvements f the fmgers and wrist, it seems likely that recruitment is the mre imprtant factr in the generatin f increasing levels f frce, since the rate f firing f mtr units can vary n demand but nly within a limited range f frequencies (Basmajian, 1963). Recruitment is especially imprtant at lw tensins, with frequency f firing cntributing increasingly t strnger tensins (Milner-Brwn et al, 1973b, 1973c). In relatin t the frearm musculature, this has been cnfirmed in the EDC by Mnster and Chan (1977). Hwever, even at high tensins, recruitment has been fund t be imprtant in sme muscles (Clamann, 1970; Hannerz, 1974). Riek and Bawa (1992) assessed MU recruitment in tw frearm muscles, extensr digitrum cmmunis (EDC) and extensr carpi radialis (ECR), during sustained ismetric wrist extensin and radial deviatin tasks at prgressive unspecified frce levels. They demnstiated size-rdered recruitment f MUs in bth muscles during bth tasks. Mnster and Chan (1977) studied the behaviur f MUs in the EDC during vluntary ismetric cntractins, cnfirming that the size principle held true fr this muscle under these circumstances. Jnes et al (1993) shwed that the size principle als applied t the recruitment f MUs in tiie flexr carpi ubiaris (FCU) during ismetric wrist flexin and ulnar deviatin. Althugh these tasks differ frm the grip task used in this study, it is evident that the size principle des hld true fr extensr and flexr frearm muscles during ismetiic cntractins. Mnster and Chan (1977) fund mtneurne firing rates in the EDC during ismetric cntractins t increase with increasing frce levels, plateauing at submaximal frce levels. Anther imprtant cnsideratin in relatin t MU activity in the clinical setting during a functinal task, such as grip, is inter subject variatin in MU activity, which in tum will 26

72 affect SMES parameters. Fleckenstein et al (1994) demnstrated large inter-individual variatin in MU recruitment patterns in frearm flexr muscles during wrist flexin at a standard lad. Althugh the use f a standard lad rather than a percentage f maximum was a limitatin f the study, it des indicate the need t cnsider inter-subject variatin in MU recruitment in the perfrmance f a functinal task which may nt be demnstrated in studies invlving islated muscle cntractin. Having described the mechanisms f MU mdulatin in the generatin f frce, the relatinship between frce and the SMES and between the RMS and spectral parameters will nw be described The relatinship between the SMES and frce. Since Lippld reprted a linear relatinship between the lemg measured frm the gastrcnemius and sleus muscles during plantar flexin f the ft in 1952, numerus reprts have been published n lemg-frce relatinships in human muscles. Reviews by Buisset (1973), Bigland-Ritchie (1981b), Perry and Bekey (1981), Basmajian and De Luca (1985) and mre recently Hf et al (1987) and Clancy and Hgan (1991) are amngst thse t cnfirm that there is a clse relatinship between the tw parameters fr a range f muscles studied. The nature f the relatinship varies between different studies, with disagreements as t whether the relatinship is linear r nn-linear (Perry and Bekey, 1981). Surces f variatin include differences in the structural and physilgical prperties f the muscle(s) being assessed, as has been discussed in relatin t MU cntrl, the relative amunts f Types I and II fibres and their rientatin, accmpanying synergist/antagnist inter-relatinships, wrk intensity and cntractin type, viscelastic prperties and methdlgical aspects such as electrde type and cnfiguratin (Mritani and DeVries, 1978; Lawrence and DeLuca 1983; Perry and Bekey, 1981). Overall, it appears that the linear relatinships btained at lw t mderate frce levels are related t recruitment, whereas quadratic relatinships bserved at higher frce levels are related t rate cding. The frce levels at which the linear relatinship becmes quadratic will vary accrding t the muscle invlved (Perry and Bekey, 1981). The presence f muscle synergism may help t explain the discrepancy between linear and parablic relatinships. Hf and van den Berg (1977) cmpared the lemg- 27

73 ismetric frce relatinship in the sleus whilst sitting and whilst standing, the latter als invlving bth heads f gastrcnemius. Althugh the relatinship fr the individual muscles were nn-linear, nce summed the relatinship became linear. Hence when the muscle being studied is ne f a grup f synergists, the relatinship is likely t be deceptively linear, particularly if biplar electides are being used (Perry and Bekey, 1981). Perry and Bekey (1981) als emphasised the imprtance f muscle length n the nature f the lemg-frce relatinship. This has been cnfirmed by thers wh have demnstrated that the differences between the lemg-frce relatinship btained at different jint angles disappears when the frce is expressed as the percentage f the maximum vluntary cntractin (Vredenbregt and Rau, 1973; Hf and van den Berg, 1977; Cnckaert et al, 1975). With regard t the frearm musculature, West et al (1995) reprted the lemg recrded frm frearm flexr muscles t increase linearly with grip frce ver the range 30-75%. Since there is a wide variatin between muscles in their relatinship between frce and the MES, Lawrence and De Luca (1983) cncluded that there is "n physilgical mdel t describe accurately the relatinship between the amplitude f the surface recrded MES and measured frce utput f different muscles in varius cntractin mdes" Neurmuscular efficiency (NME) Fischer and Merhautva (1961) first prpsed the cncept f the 'efficiency f electrical activity' (EE A) when they suggested pltting the lemg as a functin f the frce f an ismetric cntractin. This later became knwn as neurmuscular efficiency (NME). DeVries (1968) recmmended that it was mre lgical t invert this rati (frce : lemg) such that the 'efficiency' wuld vary directly with functin and mst wrkers have expressed NME in this way (Lindeman and Drukker, 1994; Milner- Brwn et al, 1986; Wds and Bigland-Ritchie, 1983). 28

74 2.4.5 The relatinship between frce and spectral parameters. Studies f the inter-relatinship between frce and the mean r median pwer frequencies f the pwer spectrum have invlved the use f step cntractins (Petrfsky and Lind, 1980; Hagberg and Hagberg, 1988, 1989; Duchene and Gubel, 1990) and ramp cntractins (Gerdle et al 1991; Bildeau et al 1990; Gerdle et al 1990; Hagberg and Hagberg, 1989). Initial studies using step cntractins (the maintenance f frce fr a few secnds f different percentages f the MVC, withut apparent fatigue) suggested that mean pwer frequency was independent f cntractin intensity (Petrfsky and Lind, 1980). Mre recent studies have suggested that the MNF increases with increasing wrk intensity at lw levels f frce (up t 25 t 30 %). An increase in the high frequency part f the spectrum when the level f cntractin increased has been described fr different muscles, such as elbw flexrs (Hagberg and Ericsn, 1982), plantar flexrs (Hagberg and Hagberg, 1988) and masticatry muscles (Duchene and Gubel, 1990). Fr higher levels f frce, cnflicting results have been reprted. Sme wrkers have fund an absence f an increase in MNF with increasing frce level (Hagberg and Hagberg, 1988; Hagberg and Ericsn, 1982; Bazzy et al, 1986; Van Bxtel and Schmaker, 1984; Merietti et al, 1984). Other wrkers have reprted an increase MNF (Brman et al, 1985; Bildeau et al, 1991), r a decrease (Westbury and Shaughnessy, 1987) with higher frces. In studies using ramp cntractins (fr example, varying the frce frm 0 t 100 % f maximum fr 5 secnds) results have als been cnflicting. An increase in spectral parameters with increasing frce has been nted (Gerdle et al 1991; Bildeau et al 1990), but ther studies have shwn n significant increase (Gerdle et al 1990; Hagberg and Hagberg, 1989). When ramp and step cntractins are cmpared, the increase in spectral parameters with the frmer is mre prnunced (Bildeau et al, 1991). The incnsistency f findings in the study f MNF-frce relatinships may be related t differences between individual muscles, their fibre type cmpsitin and distributin 29

75 and their patterns f recruitment, in additin t the vast differences in study prtcls. The ther bvius limitatin f bth appraches t the assessment f the SMES: frce relatinship is the pssibility that fatigue is taking place in the tests, particularly the ramp prtcl The relatinship between pwer spectral cmpressin and frce. At very lw levels f ismetric cntractins (apprximately 10 % MVC), even in the presence f cnsiderable subjective fatigue, there is generally n decrease in MDF r MNF with time. In fact, a rise has been nted fr sme muscles (Arendt-Nielsen et al, 1989; Hagberg and Hagberg, 1989), whilst n change has been nted fr thers (Fallentin et al, 1985; Christensen et al, 1988). In additin, since the muscle fibre cnductin velcity (MFCV) is generally reprted as increasing with frce levels, the rise in the MDF r MNF which has been reprted in studies f sme muscles has been explained by the predminance f recruitment f new MUs - specifically type II fibres (Brman et al, 1985; Sadyama, 1988) - ver any ther events (Duchene and Gubel, 1993). Fr ismetric cntractins ranging frm 15 t 30 % MVC, decreases in the median and mean frequencies have been reprted fr mst muscles (Duchene and Gubel, 1990; Hagberg and Ericsn, 1982). At this level f frce, spectral parameters are prbably affected by tw mechanisms having ppsite effects: the decline in muscle fibre cnductin velcity in active mtr units (due t lcal fatigue) and the recruitment f 'fresh' (large) mtr units (Krgh-Lund and Jrgenssn, 1991; Duchene and Gubel, 1993). Fr ismetric cntractins greater than 40 t 50%, declines in the MFCV and MDF are cnsistently nted (Linssen et al, 1990; Arendt-Nielsen and Mills, 1988; Duchene and Gubel, 1993). It can be cncluded frm the available literature that spectial mdificatin with fatigue is likely t be multifactrial in rigin. At high levels f frce, prgressive recruitment f mre MUs is less likely and the effect f factrs such as accumulatin f metablites and reductin in cnductin velcity predminates, causing specfral cmpressin t lwer frequencies. 30

76 Many studies assess fatigue up t the 'endurance pint' - the pint where the frce begins t fall. Thse studies that last beynd this pint indicate a fall in SEMG amplitude and reinfrcement in the decline in spectral variables and MFCV (Arendt-Nielsen and Mills, 1988). This may indicate that, after the endurance pint, the slw fibres dminate in the recruitment pattem since they are less fatiguable (Duchene and Gubel, 1993) The relatinship between the signal amplitude and spectral parameters during fatigue. Althugh the alteratins in the signal amplitude and frequency spectrum cmpressin are bth cnsidered t be myelectric manifestatins f fatigue, their reprted interrelatinship varies. Chan and Chuang (1996) reprted an increase in the amplitude and decline in the MNF f the SMES recrded frm the EDC during ismetric cntiactins ver a range f frce frm 25 t 100 % in 39 healthy subjects. In a cmbined intramuscular and surface EMG study f the mean pwer frequency (MNF) and RMS f the MES measured during sustained maximal and submaximal (50% MVC) cntractins f the biceps brachii muscle, Mritani et al (1986) cnfirmed an increase in the RMS during submaximal cntractins, with an accmpanying decline in the MNF. During maximal wrk bth the RMS and MNF prgressively decreased with time, the decline in MNF being greater during the maximal than the submaximal test. This wrk emphasises the imprtance f cnsidering the intensity f the muscular wrk invlved when using the change in the RMS f the SMES with time as an indicatr f fatigue. The authrs cncluded that the underlying mechanisms f spectral shift and thse invlved in the alteratin f signal amplitude differ, with the spectral shift partly reflecting the underlying metablic state f the muscle and the amplitude dependent upn characteristics f MU activity Changes in the SMES and the frequency spectrum in disease. Fr decades, attempts have been made t define specific characteristics f the SMES which represent neurmuscular disrders (Waltn, 1952). The interference pattem was first fcused upn in this respect. In a neurgenic lesin, it is nt pssible t recruit the maximum number f mtr units in a vluntary cntractin and the interference pattem is reduced (Lenman and Ritchie, 1987). Actin ptentials are nrmal r slightly 31

77 increased in duratin and are nrmal r slightly decreased in dimensin (Buchthal and Pinelli, 1953). Plyphasic ptentials are cmmn and can result in an increase in the frequency f the signal and result in cnfusin in the differentiatin frm a mypathy (see belw). In primary mypathic disrders, since there is n significant reductin in the number f MUs activated during a vluntary cntractin, recruitment is nrmal and a full interference pattern is btained (Lenman and Ritchie, 1987), althugh there may be a slight reductin in signal amplitude and abnrmal spikes may be apparent (Kugelberg, 1949). Mur et al (1982) reprted the lemg per unit frce recrded frm the surface f the biceps during ismetric cntractin t be significantly higher in subjects with neurmuscular disrders, particularly thse f neurgenic rigin, in cmparisn with thse with 'mygenic disrders' and healthy cntrls. That is, subjects with neurmuscular disrders shw lwer neurmuscular efficiencies than healthy subjects. This was cnfirmed by Lindeman and Drukker (1994). Examinatin f the interference pattern f the SMES may give an indicatin f the presence f a neurmuscular disrder (Larssn, 1975). Hwever this measure lacks specificity and sensitivity, leading wrkers t examine the frequency cntent f the signal (Waltn, 1952; Larssn, 1975). Lwer spectral frequencies in neurgenic disrders (Blanchi and Vila, 1985; Lindstrm et al, 1985, Mur et al, 1982; Herberts et al, 1973; Larssn, 1975) and higher spectral frequencies in subjects with mygenic disrders (Waltn, 1952; Gersten et al, 1965; Lindstrm et al, 1985) have cnsistently been reprted. In patients with primary mypathies, Lindstrm (1970) fund the spectral peak t be displaced t frequencies as high as Hz, whereas in patients with neurpathy, the high frequency cntent was lwer than nrmal. Lindeman and Drukker (1994) nted the IMF f the SMES recrded frm the quadriceps during ismetric knee extensin at 80% MVC t be raised in 33 patients with mytnic dysfrphy (a mygenic disrder) and reduced in thse with hereditary sensry and mtr neurpathy (HSMN; a neurgenic disrder, n=29). Greater MDF gradients were nted in the mygenic grup but nt the neurgenic grup cmpared t cntrls. The higher spectral frequencies bserved in primary mypathies have been suggested t be related t plyphasic, shrt ptentials (Waltn, 1952; Kugelberg, 1949). Wrkers wh have reprted the alteratins seen in the frequency spectrum f the SMES in mypathies give little attentin t the ptential influence f fibre type t these changes. 32

78 Fr example, Lindeman and Drukker (1994) studied subjects with mytnic dystrphy, which is assciated with the degeneratin f type I fibres; there may be sme increase in the size f type II fibres (Gilry, 1990). This may help t explain the increased MDF and greater fatiguability in the grup with primary mypathy, since these are characteristics f type II fibres (Mritani et al, 1986; Merietti et al, 1990). Tw mechanisms have been prpsed t explain the lwer spectral frequencies nted in neurgenic disrders; reduced muscle fibre cnductin velcities (Hermens et al, 1984; Lindstrm et al, 1985) and increased synchrnisatin f MU firing (Hermens et al 1984; Latash, 1988). Larssn (1975) nted the shift twards higher frequencies in neurgenic lesins t crrelate with the duratin f symptms f the disrder and described this as "functinal evidence f the scar frm the disease". He als nted shifts t higher frequencies in thse subjects in whm the disrder was f shrter duratin and suggested this t be related t a relative increase f actin ptentials with thin cmpnents, characteristic f reinnervatin. This wuld explain the high frequencies in subjects with neurgenic lesins reprted by ther wrkers (Engel, 1975; Cruz Martinez et al, 1984; Latash, 1988). Desynchrnisatin f muscle fibre cntractins secndary t prlnged inactivity has als been suggested t play a rle in the phenmenn f raised spectral frequencies in sme subjects with neurgenic disrders (Latash, 1988). The pssibility f a return t nrmal frequency spectral characteristics f the SMES if full reinnervatin ccurs has nt been addressed. Hwever, this may explain why sme wrkers reprted nrmal frequency spectra in subjects with previusly dcumented neurgenic lesins (Waltn, 1952) The EMG in rheumatid arthritis. Few EMG studies f patients with rheumatid arthritis have been published in the literature, particularly ver the last 2 decades and thse reprts available utilised needle electrdes. Analysis f the frequency spectrum during muscle cntractin has nt been investigated in rheumatid disease. In a study f the deltid, biceps brachii, abductr puicis brevis and quadriceps muscles f 93 patients with RA, Steinberg and WynnParry (1961) nted changes 33

79 suggestive f a cmbinatin f denervatin and a primary mypathy, with a fiill interference pattern (small amplitude, brken up shrt duratin plyphasic actin ptentials), suggestive f mypathic lesins and abnrmal intensity-duratin curves with lng duratin plyphasic ptentials - suggestive f denervatin. The EMG findings did nt crrelate with the degree f weakness nr wasting, nr were they related t sterid therapy. There was sme relatin t disease activity. Seventy-nine patients were fund t have EMG findings suggestive f plymysitis, mstly in prximal muscles - as fund by Hrwitz (1949). Lenman and Ptter (1966) reprted a reductin in neurmuscular efficiency in subjects with RA. There seems little agreement abut the presence f spntaneus EMG ptentials, suggestive f denervatin, in RA (Amick, 1960). Mueller and Mead (1952) demnstrated lw amplitude actin ptentials and a disrganised pattern n the EMG, with n spntaneus activity in 25 patients with RA. Mrrisn et al (1947) shwed spntaneus activity in 50% f 34 rheumatid subjects, but nrmal EMGs n cntractin. Wramner (1950) fund spntaneus activity n the EMGs f 76% f 50 rheumatids, whereas Newman et al (1953) fund n such activity. The variatin in findings is nt surprising, since Lenman and Ritchie (1987) pint ut that the finding f abnrmal activity in neurgenic lesins is highly variable and that fibrillatin ptentials can als ccur in mygenic lesins. Graudal and Hvid (1959) fund inflammatry changes in the first drsal intersseus muscles f 60% f 31 patients with RA; 18 ther muscles were nrmal. In 17 ther patients n changes were seen. Amick (1960) fund n significant EMG changes in 25 patients with RA and muscle wasting. They cncluded that wasting was due t disuse Recvery f the myelectric parameters after wrk. The intrasessin repeatability f SMES analysis is cncerned with the allwance f adequate rest intervals between the perfrmance f each task, in rder, that the myelectric parameters will be restred t their resting values. Such studies have been termed restitutin studies (Kurinka, 1988). Larssn et al (1965) and Jhanssn et al (1970) shwed rapid changes t ccur in the pwer spectrum after fatiguing exercise. Mechanical and physilgical recvery times seem t be lnger than that f the frequency spectrum f the SMES (Funderburgh et al, 1974; Hara, 1980; Peti-fsky, 1981). Mrtimer 34

80 et al (1970) demnstrated that muscle fibre cnductin velcity (which is clsely related t the frequency spectrum) returns t nrmal within 2 minutes after ischaemic exercise, in parallel with the restitutin f bld flw. Restitutin f the pwer spectrum fllws a lgarithmic curse with time (Kurinka, 1988; Kadefrs et al, 1968; Petrfsky, 1981). Mst studies published t date using SMES analysis during wrk use rest intervals which seem t be chsen empirically, with n reference made t the assessment f adequate restitutin f myelectric parameters after these intervals. There is little infrmatin available in the literature as t the repeatability f frearm myelectric parameters specifically during grip. In a study f the SMES amplitude measured frm 'medial and lateral frearm' musculature during sustained ismetric grip at up t 70% MGS, Lind and Pefrfsky (1979) nted the average half wave SMES amplitude t have retumed t clse t initial values within 3 minutes and cmpletely by 7 minutes pst exercise, in parallel with the MGS. Petrfsky and Lind (1980) reprted the centre frequency f the SMES recrded frm the FCR during grip ver a range f 25-90% MGS t return t baseline levels within a rest interval f 1 minute. Althugh mst studies indicate that the repeatability f bth same day and between-day testing f the RMS f the SMES is gd fr a variety f muscles (Lind and Petrfsky, 1979; Kadefrs et al, 1968), sme wrkers have shwn pr recvery rates f this parameter after shrt rest perids. Fr example. Miller et al (1987) examined the recvery f the MVC, NME (frce/rectified integrated EMG), and the metablic state f the adductr pllicis muscle (phsphcreatine and ph) after thumb adductin at maximum frce fr 4 minutes. Whilst the MVC and metablic parameters had recvered within 20 minutes f recvery, the NME had nt recvered after 60 minutes, indicating the rectified lemg was nt fully restred. Studies which aim t assess the restitutin f the pwer spectral variables after exercise are mre apparent in the literature than thse f the signal amplitude. Mst studies have indicated that the median and mean frequencies f the SMES recver significantly mre quickly than muscle frce and myelectric parameters such as the RMS. Kadefrs et al (1968) studied the frequency spectra f varius muscles after ismetric cnttactins and fund that recvery f the MES varied accrdmg t the muscle assessed. They shwed that 69% f extensr carpi radialis, 69 % f extensr carpi ulnaris and 42 % f extensr digitrum superficialis t have recvered within 90 secnds f terminating the 35

81 exercise. An early restratin f the MDF in advance f mechanical variables is cnfirmed by ther wrkers (Funderburgh 1974; Petrfsky, 1981; Larssn et al, 1965; Jhanssn et al, 1970). Since the change f the MDF with time during muscular wrk is mst cmmnly used as the indicatr f fatigue, the restitutin f the gradient f the MDF f the SMES ver time (the MDFG) is an imprtant feature t examine when assessing recvery intervals. Althugh there is little infrmatin available n the repeatability f this feature in frearm musculature, this issue has been addressed in studies f ther muscles. Dlan et al (1995) examined the restitutin f the MDFG in back muscles in the study described abve. They reprted crrelatin cefficients f 0.92 (TIO) and 0.50 (L3) n within day testing (after a rest interval apprximately 1 hur). Krivickas et al (1996) reprted an intraclass crrelatin cefficient f 0.43 (p=0.006) fr the repeatability f the MDFG f the SMES recrded frm the biceps during ismetric cntractins sustained fr 100 secnds repeated after a 5 minute rest interval. It is evident frm the literature that the frequency spectrum is highly repeatable n same day testing, after shrt rest perids. Many studies indicate that this is als true fr the RMS f the SMES. The repeatability f the change in the RMS with time (expressed as the RMS gradient) is unclear Strength training in rheumatid arthritis Intrductin. The use f therapeutic exercise in rheumatid arthritis is an area f cnfusin and cntrversy. This is largely a result f the lack f well-structured research in the field, the large number f publicatins based upn anecdtal evidence and tiie cncern tiiat exercise will result in deteriratin in disease (Mapp et al, 1995; Farrell et al, 1992). The fllwdng sectin will review the literature t date n sttength training in relatin t disuse weakness and rheumatid arthritis. Handgrip strength training will be specifically fcused upn, althugh where necessary studies in relatin t ismetric exercise f ther muscles will be described. Firstiy, the mechanisms f stiength training will be detailed. 36

82 2.5.2 Mechanisms f strength gain in healthy individuals. In healthy individuals, tw main mechanisms f strength gain in a prgressive strength training prgramme have been identified. Initially strength gains are related t neural factrs; later, gains in muscle mass becme imprtant. Neural factrs The nervus system is f paramunt imprtance fr the expressin and develpment f strength. Indeed, it is prbable that increases in strength can ccur withut mrphlgical changes in muscle, but nt withut neural adaptatins (Enka, 1988). The cncept f neurmuscular efficiency (Mur et al, 1982) has been described earlier (2.4.4). Imprved levels f neural activity and a mtr learning effect have been bserved with strength training (Mritani and DeVries, 1979). Ikai et al (1968) suggested that mst peple nrmally perate at a level f neural inhibitin, as a prtective mechanism, preventing them frm demnstrating their true strength capacity. With training r in cmpetitin this inhibitin may be remved. With training, subjects learn t recruit mtr units - r t utilise the tensins the muscles can prduce - mre effectively (Mritani and DeVries, 1979; Kmi, 1986; Enka, 1988; Hakkinen, 1989). Psychlgical factrs, increased arusal and neural facilitatin (disinhibitin) may lead t flill activatin f muscle grups (Hakkinen et al, 1988). This neural facilitatin (r neural adaptatin) has been prpsed t be the mechanism underlying the initial rapid strength gain in training prgrammes (Edstrm and Grimby, 1986; Sale, 1987). The phenmenn has been illustrated in varius reprts, including the demnstratin f a fraining effect n the nn-exercised cnfralateral Iknb f subjects wh underg unilateral arm r leg exercise (Enka, 1988). In additin, specific training respnses are mre likely t be due t neural mechanisms than purely adaptatins f muscle (Enka, 1988). The phenmenn f neural adaptatin is mst imprtant in the first 2-3 weeks f strength training (Mritani and DeVries, 1979), but is maintained during subsequent training, when hypertrphy becmes the predminant factr in the further gain f strength. Gains in muscle mass with strength training. In 1935, Fenn and Marsh fund muscle crss-sectinal area (CSA) t be an imprtant determinant f the maximum ismetric frce which culd be prduced by an islated 37

83 skeletal muscle preparatin. Since then it has been established that the strength f a muscle is in prprtin t the physilgical crss sectinal area f the muscle (Arkin, 1938; Asmussen et al, 1965). Muscular grwth in respnse t verlad training ccurs primarily frm hypertrphy f individual muscle fibres (Hakkinen and Kmi, 1983; McDnagh and Davies, 1984). The prcess f hypertrphy is related t the synthesis f cellular material, particularly prtein myfilaments. Myfibrils thicken and increase in number and additinal sarcmeres are frmed by an acceleratin f prtein synthesis and decreases in prtein breakdwn (Edstrm and Grimby, 1986; McDnagh and Davies, 1984). Althugh muscle fibre hyperplasia has been reprted with particular strength training regimes (Tesch, 1988; Larssn and Tesch, 1986), the literature supprts hypertrphy as the greatest cntributin t increased muscle size in respnse t strength training (McArdle et al, 1991; MacDugall et al, 1984). In additin t changes in muscle fibre size, the evidence suggests that the cntractile prperties, metablic capacity and assciated enzymes can change with training (Gllnick et al, 1972), but the fibre type and twitch characteristics remain stable (Brks and Fahey, 1985). Hwever, there is sme evidence that a fast twitch fibre wul be transfrmed int a slw twitch fibre, but nly if their nerve supplies are experimentally interchanged (Edgertn et al, 1980; Kilmer, 1996). The subject f fibre type transfrmatin in healthy individuals in respnse t training remains highly cntrversial. Hwever, as described earlier, it may be an imprtant result f the prcess f reiimervatin (Jnes and Rund, 1990) Imprtant features f strength trammg prgrammes. In designing a strength training prgramme, it is imprtant t establish the specificity f the exercise invlved in relatin t the required task, the training threshld abve which imprvements in strength will ccur, and the ptimal intensity needed t prduce the greatest strength gains within the shrtest perid f time. This is extensively reviewed by numerus wrkers (McDnagh and Davies, 1984; Atha, 1981). It has been demnstrated that the ptimal training intensity fr bth ismetric and dynamic exercise invlves 38

84 submaximal but high intensity, fatiguing cntractins (Szet et al, 1989). This is termed the verlad principle (MacDugall et al, 1980). Training threshld is a functin f strength (Enka, 1988). As strength increases in a training prgramme, the required muscle tensins fr training must increase accrdingly. Thus an effective training prgramme must utilise prgressively higher resistance lads. McDnagh and Davies (1984) cncluded that a threshld lad f 25-30% MVC must be utilised in rder t achieve increases in ismetric strength. The respnse f a muscle t training is specific t the type f exercise and the jint angle used and the speed f cntractin (Maiming et al, 1990). It will als be influenced by the cause(s) f the muscle weakness, where present. The best training fr a task invlves task specific muscle cntractin, that is, the perfrmance f the task itself (Carr and Shepherd, 1987; Rutherfrd, 1988). Cntemprary appraches t strength training ften invlve the identificatin f which muscle grups t train frm bservatin f task perfrmance. Hwever, it can be difficult t defme accurately the muscle grups by this means, particularly when jint defrmity and altered jint angles are present. By training task perfrmance rather than cncentrating n simple strength regimes fr islated muscle grups, it is likely that this can be avided (Carr and Shepherd, 1987). Hwever, it may cntribute t abnrmal muscle cntractin r the utilisatin f a cmpensatry strategy, particularly in patients with jint diseases, such as RA (Wynn Parry, 1983) Assessing the mechanisms f strength gain. De Vries (1968) and Mritani and DeVries (1979) utilised the measurement f the NME in the assessment f the mechanisms f strength gain in a strength training prgramme. They mnitred the NME ver the curse f the prgramme and suggested that, if the strength gain were due t neural adaptatin, the rati f frce t signal amplitude wuld be expected t remain the same. If this were due t gains in muscle mass, the rati wuld increase. 39

85 Figure 2.5.1: Schema fr the evaluatin f mechanisms f strength gain, using the cncept f neurmuscular efficiency, after Mritani and De Vries (1979). Neural adaptatin Muscle hypertrphy (2 Signal amplitude Signal amplitude ( iv) 0 Test 1 B Test 2 Since the strength f a muscle is in prprtin t its crss-sectinal area (CSA) (Arkin, 1938; Asmussen et al, 1965), changes in muscle size in limbs have been examined by the assessment f the limb CSA using skin fld caupers and, mre recently, by imaging techniques such as ultrasund and magnetic resnance imaging (MRI). The frmer technique invlves the measurement f the skinfld thickness at tw r mre sites f the limb, and the CSA calculated. Helliwell and Jacksn (1994) applied this technique t the assessment f frearm muscle mass, as shwn in the fllwing equatin: -] 2 CSA (cm2) = n FOG STd + STv) R - U where FOC = frearm circumference (cm) STd = drsal skin thickness (mm) (NB: duble fld f skin thickness was measured) STv = ventral skin thickness (mm) R = area f radius (cm^) U = area f uba (cm^) R and U taken ft'm tables f bne diameter (Virtama and Helela, 1969), assuming circular crss-sectin (Hrsman and Leach, 1974). 40

86 It has been shvm that the estimatin f muscle mass by this methd is inaccurate (Yung et al, 1980), althugh there may be sme crrelatin between the tw measures. Helliwell and Jacksn (1994) reprted this methd f frearm CSA measurement t crrelate clsely with that btained using cmputed tmgraphy in six subjects with RA and ne nrmal subject. These wrkers suggest that assessment f the CSA by skinfld callipers is a usefial methd fr the mnitring f change in the muscle CSA. Hwever, the repeatability f the technique was nt reprted. Ultrasngraphy has been used t mnitr changes in muscle CSA (Yung et al, 1980). Hwever, significant inter-bserver variatin has been reprted (Hwe and Oldham, 1996) and the sensitivity t change is unclear. In the study by Helliwell and Jacksn (1994) described abve, CT scaiming was used in a single measurement f frearm crsssectinal area in 7 subjects, 6 f these with RA. The repeatability f scanning was nt reprted. The radiatin assciated with CT scanning limits its suitability fr research. Engstrm et al (1991) demnstrated that magnetic resnance imaging (MRI) accurately measures the CSA f skeletal muscle. MRI has als been shwn t identify small changes in skeletal muscle induced by resistanceti-aining (Treutii et al, 1994). MRI has been used t assess lwer limb muscle vlume changes in healthy individuals ver a 17-week perid f bed rest, demnstrating declines in muscle mass ver this perid. The cefficient f variatin ver 1 week in a grup f healthy cntrls was 1.1%. Vlumetiic analysis f frearm musculature has nt been described in the literature Strength training and disuse weakness. Cnsiderable discrepancy exists between animal studies and thse f humans in relatin t strength training and disuse weakness. Animal studies have shwn a very rapid retum t nrmal strength with training after a perid f disuse (McDnagh and Davies, 1984), whereas human studies have varied. Humans with lng standing disuse weakness can experience large sti-engtii gains with tiaining (Hakkinen, 1994). Hwever, studies invlving strength training after a shrt perid f immbilisatin are less clear and have failed t shw any difference between a wide variety f strength tiaining regimes, including everyday mtr tasks (Hakkinen, 1994). 41

87 The mechanisms f strength gain in such cases are als unclear. It is pssible that neural adaptatin and gains in muscle mass may be disrupted. Skeletal muscle fibres - like neurnes - are permanent cells which d nt divide after birth. Pst-natal grwth cnsists purely f the additin f cytplasmic mass with n increase in muscle fibre number. The regeneratin f muscle fibres after injury des ccur t a limited degree, but is limited t a cytplasmic respnse (i.e. a regrwth f sarcplasm); lst muscle mass can nly be replaced by hypertrphy f surviving fibres (Taussig, 1984) Strength training in RA Specific prblems in relatin t exercise t be cnsidered in the patient with RA are related t the fluctuatin in the activity f the disease (and therefre in pain and stif&iess), the mter-subject variatin in the cnditin f jints and ensuring that the jint cnditin is nt wrsened by the exercise. Other factrs include the presence f jint defrmity - which may make sme strengthening regimes difficult - and the presence f cmplicatins assciated with the systemic nature f rheumatid disease, fr example peripheral neurpathy and active clinical mysitis (Herbisn et al, 1987). Ismetric strengthening exercises are frequentiy recmmended fr patients with RA. Machver and Sapecky (1966) fund a strength gain f 23% in the exercised limb and 18%) in the cntralateral (unexercised) limb, after a 7-week prgramme f daily ismetric quadriceps exercises in 11 patients with RA. The latter indicates that the prcess f neural adaptatin ccurred. Handgrip exercise has been demnstrated t imprve grip strength in RA (Dellhag et al, 1992). Fr example, Henig et al (1993) demnstrated imprved grip stiength in RA with 12 weeks f balanced resistive hand exercise perfrmed fr minutes, twice daily. Brightn et al (1993) als reprted imprvements in grip strength with daily active hand exercise in subjects with class I RA. In all f the studies abve, n adverse effects f the prgrammes were fund. Lyngberg et al (1988) reprted a reductin in the number f swllen jints by %>, including thse jints which were stressed during a hme exercise prgramme f bicycle ergmetry, dynamic strength exercises and stretching in subjects with class I and II RA. 42

88 The issue f cmpliance in hme exercise prgrammes was als examined by Ekdahl et al (1990), wh fund 4 initial training sessins t be as effective as 12, and Treusch and Krusen (1943) wh fund 2 supervisry sessins t imprve cmpliance. Parker and Bender (1957) recmmended a hme therapy prgramme be reinfrced every 2 mnths. Since RA is a fluctuating disease, the educatin f the patient with respect t exercise regimes and hw t adapt them accrding t disease variatins has been recmmended (Mahwald et al, 1988,1990). Lyngberg et al (1988), in the stiidy described abve, als emphasised the need fr an initial perid f supervisin prir t the cmmencement f the hme prgramme t ensure cmpliance. In a rare study f the physilgical changes assciated with stiength tiaining in RA, Nrdemar et al (1976a) perfrmed a study f muscle fibre size (assessed n bipsy) and physical perfrmance after physical training (invlving aerbic and stiength tiaining -the type nt clearly stated - predminantiy f the lwer limbs) in patients with RA f fijnctinal class I r II. Atrphic type I and II fibres were nted in mst subjects. Stiength gains were demnstiated in mst subjects and an increase in muscle fibre size, f bth Types I and II was nted, being mre marked in the latter. N fibre type tiansfrmatin with training was nted, nr was there extensive frmatin f new fibres Grip strength in rheumatid arthritis Intrductin. Grip strength is a significant measurement in rheumatid disease, reflecting hand functin and disease activity and severity (Lansbury, 1958; Nrdenskld and Grimby, 1997). Indeed, Nrdenskld and Grimby (1997) fimd grip frce t be a mre accurate assessment f actual glbal disability than the widely used Health Assessment Questinnaire (HAQ) scre. Pincus et al (1987) reprted grip strength t be a predictr f increased mrtality in rheumatid disease. The assessment f frearm muscle fatigue and ther myelectric characteristics during grip and the investigatin f the respnse t handgrip strength training has many advantages. Grip is a task that is familiar t mst individuals, is a vital task in daily activity and reflects the fiinctinal impact f rheumatid disease upn an individual (Pincus et al, 1987; Nrdenskld and Grimby, 1997). Lcal disease activity, defrmity and bne mineral density (a measure f disease 43

89 severity, particularly in early disease) can all be measured. The frearm musculature is actively invlved in grip and is easily accessible fr measurement f the SMES during wrk The rheumatid hand. In early rheumatid disease, active inflammatin f the jint and periarticular structures can result in diminished hand functin thrugh pain, swelling, stiffness, muscle weakness and triggering f tendns. As the disease prgresses, the relative cntributins f these features in additin t permanent defrmity fluctuates (Myers et al, 1980; Hart and Huskissn, 1972; Wright and Jhns, 1960). Numerus defrmities can ccur either alne r in cmbinatin in the rheumatid hand. The tw which are mst characteristic f the disease, uhiar deviatin and anterir subluxatin at the metacarp-phalangeal (MCP) and wrist jints, can be explained by the change in frces seen in flexr tendns in this disease (Smith et al, 1964). The ther mechanisms which have been prpsed include cntracture f the ulnar interssei, ulnar dislcatin f the extensr tendns (Brewertn, 1957), hand use, unilateral capsular damage, gravity, jint shape and pull frm the ulnar deviated little finger (Sti-aub, 1962). Nne can be cnsidered as a primary cause since they are nt cnsistently present r d nt wrk cnsistentiy in the directin f the defrmity (Flatt, 1963), but each may play a part in accentuating r fixing the defrmity (Buimell, 1955). The theries described lead t ther cnclusins in terms f the treatment and preventin f rheumatid defrmities f the hand. The exercise regime f squeezing a rubber ball has been prpsed by sme t be unsuitable (McGregr andwright, 1967), since it is exercising the flexr tendns. The rle f the frearm extensr muscles in grip is frequentiy nt appreciated, althugh sme wrkers have emphasised that the extensrs are at least as imprtant as the flexrs t grip strength (Snijders et al, 1987; Hagg and Milerad, 1997). If the wrist is pulled int extensin, then the extensrs are exercised t a greater extent (Snijders et al, 1987; Hagg and Milerad, 1997). This shuld be beneficial, since grip is strnger with the wrist in sme degree f extensin (Simmns et al, 1981). Such a regime reflects a functinal task and the acquisitin f mtr skills is an ften neglected thugh highly imprtant aspect f therapeutic exercise (Hakkinen, 1994). In injury r disease, the lss f strength in the flexr and extensr muscle grups can ccur. This 44

90 emphasises the need t cnsider bth grups in devising a suitable fiinctinally rientated rehabilitatin prgramme Factrs AfTecting Grip Strength in RA. In RA, grip strength is reduced cmpared t the nrmal ppulatin (Mathiesen et al, 1991). This can be slely due t reflex inhibitin, true muscle weakness, effusin, jint stiffness, pain (r related factrs such as synvitis) r defrmity (including bny defrmity and sft tissue alteratins wdth altered jint mechanics). Spiegel et al (1987) fund grip strength t crrelate with walk time, wrist and hand tenderness, defrmity, ttal jint tenderness, swelling, ESR and wrist and hand swelling. There was n crrelatin between subjective nr bjective mrning stif&iess but ther studies have disputed this (Myers et al, 1981). Grip stiength demnstrates circadian variatin (Wright, 1959; Harkness et al, 1982) in bth healthy and rheumatid subjects. A decline ccurs in early mrning and evening. Nwuga (1975) fund a psitive crrelatin between grip stiength and bdy weight in healthy females, as did Thmgren and Werner (1979), althugh the latter wrkers fund n crrelatin with the rate f develpment f a MVC. N significant relatinship was fund between the bdy weight and endurance f grip (Nwuga, 1975). Schmidt and Tews (1970) fund grip strength t decline after the age f 30 years in males and 40 years in females The assessment f grip strength. The measurement f grip stiength remains the fundatin f hand assessment (Cantiell, 1976; Myers et al, 1980; Mathiesen et al, 1991). One f the mst ppular methds f grip strength measurement utilises the air filled bag. This is cmfrtable and easy t use and prvides sme tactile feedback t the subject during gripping. They allw a grip test f lnger duratin t be perfrmed, which is ften t uncmfrtable with ther devices (Pearsn et al, 1982). There are drawbacks t these devices, as highlighted by Unswrth et al (1990) and Lee et al (1974). Since pneumatic devices are filled with air, (which is cmpressible), the system 45

91 is nn-linear in respnse and this is likely t lead t a very small errr nly. The pressure within the system is dependent upn the frce divided by the area ver which it is applied. The measured grip pressure is ptentially influenced by hand size and alteratin f hand psitin during and between measurements. It is therefre imprtant t ensure all subjects maintain a standard hand psitin. Varius bag sizes are available t suit different hand dimensins. It has been fund that, fr a given frce, with larger bag and/r hand sizes, lwer pressures are recrded. Als, fr a given frce applied at different starting pressures, different readings are btained (Unswrth et al, 1990). It has als been demnstrated that different techniques f squeezing the cuff r bag will give rise t variatins in pressure readings (Carus et al, 1985). Fr example, when the bag is gripped with the fmgers "digging in", a greater pressure is recrded than when gripped with the fingers lying flat. On the basis f these ptential surces f errr, it is recmmended that the vlume, size and initial pressure f the bag is recrded with every measurement and subjects advised apprpriately n their use (Unswrth et al, 1990). The Durham gripper als prvides measurement f grip strength which are sensitive and repeatable and can measure a wide range f frces (Jnes, 1984). This is a 4-channel, stainless steel, strain gauge dynammeter, which can be used t measure grip and individual finger frces. The mst apprpriate index f grip strength, fr example tiie maximal vluntary cntractin (MVC), the time t attain the MVC, etc. remains cnti-versial. Varius parameters have been used in the descriptin f grip sti-engtii (Myers et al, 1980; Grindulis and Calverley, 1983). These include the maximum grip strength, the time taken t reach peak grip, tiie rate f lss f grip frce fi-m the maximum value (MVC) t tiie pint f release ('fatigue rate'), the rate f lss f grip frm the release pint t the baseline value ('release rate') and the integral f the frce-time curve, which reflects tiie ttal amunt f wrk dne. There are few studies examining the inter-relatinship between the functinal parameters and their assciatin witii aspects f jint disease. Helliwell et al (1987) fund tiiat neither the area under the frce-time curve, the fatigue rate nr the release rate prvided additinal infrmatin t the MVC. The time t reach peak grip was independent f the MVC and pssibly being partly a reflectin f jint stiffness. 46

92 r = C Si I IrpD -LJD

93 Chapter 3: Materials and Methds 3.1 The apparatus. The apparatus cnsisted f a grip bag, pressure transducer, EMG amplifier, preamplifiers, filters and electrdes, a data acquisitin (DAQ) card and laptp cmputer, as displayed in figure The Grip Bag This was a 14.5 cm x 9.5 cm, clth cvered, air filled bag, which was cnnected t a pressure gauge, displaying the grip pressures n a dial. The bag was als cnnected t a pressure transducer, the signal frm which was amplified, digitised and relayed t the cmputer. The pressure inside the bag was altered using a rubber bulb and valve. A feedback bar gauge n the cmputer display gave the subject a target pressure at which t aim; this target pressure was a given fractin f the individual's maximum grip strength: 1/3, 1/2 r 2/3 MGS, accrding t the specific test being perfrmed. The starting pressure in the bag was 40 mmhg in all tests. The grip bag and pressure transducer were calibrated against a mercury sphygmmanmeter at the beginning f every week, using a specifically designed calibratin prgramme. The bag was cnnected via a three-way tap t the pressure transducer and a mercury sphygm - manmeter, the latter giving the true pressure reading frm the bag. The utput frm tiie pressure tiansducer was digitised by the DAQ card. Using the baseline value f 40mmHg, the ADC utput was recrded fr steps f lommhg. Figure shws the resultant graph f ADC utput against bag pressure. The slpe f this line gave the calibratin factr which was multiplied by the ADC reading btained frm the tests. 47

94 Figure 3.1.2: The pressure readings versus the ADC utput (micrvus) frm the grip bag cmpared with the sphygmmanmeter (mmhg). =3 a 150 -r ADC utput (nv)

95 3.1.2 Surface Electrmygraphy: Signal Acquisitin and Prcessing. The signal acquisitin hardware included a Medelec MS92a EMG machine and preamplifiers fr amplificatin f the myelectric signals. These were then filtered by a set f filters, with a bandwidth f Hz. The signals were then digitised by a DAQCard-1200 (Natinal Instruments), a multifunctin analgue, digital and cunter-timing 10 PCMCIA card, with a fast 12-bit ADC with 8 analgue inputs. It cnverted the analgue pressure and surface myelectric signals t digital signals fr further prcessing by a laptp cmputer (a Viglen 486MHz Dssier). See Figure The system sftware, develped by Dr P Jnes (Reginal Medical Physics Dept., Suth Cleveland Hspital), cnsisted f calibratin, data acquisitin and analysis prgrammes. The data acquisitin prgram initially cleared the input bxes fr subject details and pened a file fr the EMG and gripper/bag data. It then wrte the patient details int an individual file. Calibratin cnstants frm the grip bag were read in and a reading was taken frm the grip bag (the starting pressure f 40mmHg) t act as a baseline. Bth the surface myelectric signal (SMES) and grip pressure readings were sampled at 1024 samples per secnd (twice the Nyquist rate), in rder t prevent high frequency aliasing f the SMES. Althugh such high sampling rates f the grip pressure were unnecessary, a unifrm sampling rate fr all signals simplified the acquisitin prgramme. The pressure readings frm the grip bag were displayed as a bar chart; the SMES was als displayed n the cmputer screen just prir t cmmencing the test, but prcessing limitatins did nt allw simultaneus display during the test. All data frm each test (the SMES frm bth EMG channels and the grip pressure) were written t a file. The sftware used t analyse the SMES frm each EMG channel read the data in nesecnd epchs, each epch cnsisting f 1024 samples. A fast Furier transfrm algrithm was applied t each epch t btain a frequency amplitude spectrum fr each epch and the spectral peak and median frequency (MDF) were lcated. Fr each test, the mean MDF and spectral peak fr the specific channel was calculated by averaging the values calculated frm the 30, ne-secnd epchs. The MDF fr each 1-secnd epch ver the 30-secnd test 48

96 Figure 3.1.3: the grip frce: RMS vltage gradient (F:RMSG) Grip frce (N) regressin line RMS(nV)

97 was pltted against time and a linear regressin line fitted t the 30 sample pints. The initial median frequency (IMF) was calculated frm the intercept (t=0) f the regressin line, in keeping with the findings f ther wrkers that this is mre reliable than using the MDF f the first ne secnd epch (Mannin & Dlan, 1994). The gradient f the regressin line represented the MDF gradient (MDFG). The spectral width was determined by averaging the 30 amplitude spectra, applying a three pint mving average with three passes t the cmpsite spectrum and calculating the width f the spectrum at half the peak amplitude. The ptin fr data windwing was available, the effects f which were assessed in a pilt study (4.1.6). Data windwing was nt used in the main study. The rt mean square vltage f the SMES (RMS) was calculated fr each ne secnd epch by squaring each f the 1024 vltage samples scaled t EMG amplitude gain and taking the square rt f the mean f these values. The initial RMS (IRMS) and the RMS vltage gradient (RMSG) were determined frm the intercept and slpe respectively f a least squares regressin fit t the RMS value fr each epch pltted against time. The cmpsite spectrum f each channel fr each test was visually appraised, specifically t assess fr the presence f significant interference spikes (e.g. 50 Hz mains pickup). The grip pressure readings ver the test perid were assessed t ensure that a cnstant frce (within 5% f the target value) was maintained. The grip frce : RMS vltage gradient (FRMSG). The target grip frce was pltted against the mean extensr and flexr RMS vltages frm each grip test and linear regressin lines fitted. The slpes f the regressin lines were termed the grip frce : RMS gradients (F:RMSG) fr each channel. This was used in assessing the mechanisms f strength gain during the handgrip exercise prgramme (Chapter 8). See Figure

98 CD CM CD U-> U-1 t r rsi LO CD n in 1 ^ Ln C8 > Q. < LU ID 5 u 50

99 3.2. The SMES acquisitin and analysis system: calibratin and electrde placement System descriptin and calibratin. The SMES acquisitin and analysis system was calibrated using a signal generatr. The frequency and amplitude f the generated signal were measured with an scillscpe and a frequency cunter. Signals f knwn frequencies were fed thrugh the preamplifiers int the system and the centre frequency and RMS vltage f the SMES were then calculated using the analysis sftware. Signal acquisitin was perfrmed with the EMG amplifier set t a gain f 500 ^V/div and 200 j,v/div, since these were the gains used in SMES recrding. The resuhs are shwn in Table 3.2.1, shwing n difference in the generated signal frequency and the system resuhs. A maximum f less than 0.5% difference in the RMS f the SMES calculated by the system at a gain f 500 iv/div and 2.7% at a gain f 200 ^iv/div was fund. Figure 3.2.1: Calibratin f the SMES acquisitin and analysis system. Frequency generatr EMG machine Filters &DAQ card Preamplifiers scillscpe 51

100 Table 3.2.1: SMES acquisitin and analysis calibratin. Sensitivity Parameter Generated Signal System Result: Extensr System Result: Flexr channel channel SOO^V Frequency (Hz) 100 Hz 100 Hz 100 Hz RMS ( av) ^V lav Frequency (Hz) 100 Hz 100 Hz 100 Hz RMS (^V) ^iv The placement f electrdes n the frearm fr the recrding f the SMES. The specific sites fr lcatin f the extensr electrdes were n the belly f extensr digitrum cmmunis (EDC), ne third f the length f the frearm measured frm the lateral epicndyle f the humerus. The flexr electrdes were lcated by firstly identifying the belly f the flexr carpi radialis (PGR) accrding t surface anatmy guidelines (Lumley, 1996), and identifying a pint n the muscle, ne third f the length f the frearm distal t the lateral epicndyle. The length f the frearm was taken as the distance between the lateral epicndyle and the radial stylid. The skin f the right frearm was prepared at the landmark sites by rubbing with antiseptic 'Steret' wipes. The skin was allwed t dry, shaved with a dispsable razr and finally rubbed with fine sandpaper ('Cardipreps'). The skin impedance was then checked using an impedance meter t ensure a value less than 4 kq. Niclet Blue Sensr Dispsable Pre-gelled Fam Backed Electrdes (Side Snap), with a detectin surface area f 1 cm were applied t the frearm n the extensr surface (extensr channel) and the flexr surface (flexr channel). A biplar arrangement was used t allw differential amplificatin. Tw electrdes per channel were applied, with an interelectrde distance f 1cm fr each and the electrde psitins were recrded using hrizntal (a fixed scale n the arm rig) and vertical (inverted depth gauge) scales. The grund electrde was applied t the sternum. 52

101 Figure 3.2.2: Psitin f extensr electrdes and arm in rig fr frearm SMES analysis during grip. Grip bag electrdes Wrist in 30 extensin leads Frearm clasp and strapping Figure 3.2.3: Psitin f flexr electrdes and arm in rig fr frearm SMES analysis during grip. Wrist in 30 extensin Frearm clasp and strapping leads 53

102 33 The assessment f grip strength Subject psitining and grip testing. The subject was psitined accrding t the American Sciety f Hand Therapists recmmendatins fr the measurement f grip strength (Fess & Mran, 1981). Figure 3.3.1: Subject psitining fr grip testing. Subject seated Feetflatn flr Shulder adducted Elbw in flexin f 90 Frearm in neutral psitin Wrist in 30 extensin An arm rig with an adjustable elbw rest and wrist straps was munted n a stand f adjustable height. The rig had a hrizntal scale attached t allw recrding f surface landmarks. The rig and stand allwed the subject t be psitined as shwn in figure 3.3.1, which is the psitin recmmended fr grip strength testing (Fess & Mran, 1981). The peak grip strength was assessed using the grip bag. The subject was asked t perfrm her maximum grip n three sequential tests, at 20-secnd intervals, each lasting 3 secnds. The mean f the three tests was taken as the subject's maximum grip strength (MGS). Sftware was develped* fr testing and analysing grip, which allwed a target grip t be calculated accrding t the maximum grip. The subject had a visual feedback f their grip and the given target pressure was displayed n the cmputer screen. 54

103 3.4 The Assessment f Frearm Muscle Crss-sectinal Area (CSA) and Vlume. Three methds f assessment f frearm muscle mass were applied during the study and cmpared t determine the ptimal methd. Tw f these techniques invlved the assessment f CSA and the ther assessed muscle vlume The Assessment f the Crss-sectinal Area (CSA) f the Frearm. Tw methds f assessing the crss sectinal area f the frearm were used. These were the skinfld caliper technique and single slice magnetic resnance imaging (MRI) f the frearm. The skinfld caliper technique was used in the initial assessment f frearm CSA. Skinflds were measured at the site f maximum frearm circumference identified n the extensr aspect f the frearm and n the flexr aspect f the frearm level with the site n the extensr aspect, using calipers as described by Helliwell and Jacksn, _ 2 CSA = 7I(F ypc- tsti+stv) R-U cm^ where: FOC = frearm circumference (cm) R= area f the radius (cm2) U = area f the ulna (cm2) Star frearm skinfld thickness meaani n the extensr aspect f the frearm (mm) Stv! frearm skinfld thickness measured n the flexr aspect f the frearm (mm) R+U NB: a duble fld f skin was measured by the calipers. R and U taken frm tables f bne diameter (Vutama and Helela, 1969), assuming circular crss-sectin (Hrsman and Leach, 1974). * Dr Patrick Jnes, Reginal Medical Hiysics Department, Suth Cleveland Hspital. 55

104 This technique was nt fund t be repeatable ver same day testing f 8 cntrls and was therefre rejected as a methd f evaluatin f the CSA f the frearm. As a result f this, magnetic resnance imaging f the frearm was used fr bth crss-sectinal area and vlumetric measurements f the frearm muscle. The-subjects were scanned in the prne psitin, with the study arm flexed and internally rtated at the shulder, the elbw partially flexed and the frearm prnated. Crss sectinal area f the right frearm musculature at the site f maximum extensr muscle area (lcated by initial imaging in the crnal plane) was measured frm TWl MRI sequences btained n a 1.OT Siemens Impact Scanner. The uter edges f the frearm muscle cmpartments was identified visually n the cmputer screen and traced manually using a cmputer muse and tracer tl. The area within the muscle cmpartments was then calculated using an analysis package Vlumetric analysis f the musculature f the right frearm. Vlumetric analysis f the musculature f the right frearm was studied using a Siemens MRI Scanner*. A 15 cm sectin f the right frearm was scanned, initially using three separate scanning techniques (Tl weighted. Prtn and 3D), in rder t ascertain the ptimal scanning prtcl fr use in further assessments in the main study. The details f this initial study are further described in Chapter Five. The prximal scanning slice was lcated just distal t the superir radiulnar jint. The subjects were scarmed in the prne psitin, with the study arm flexed and internally rtated at the shulder, the elbw partially flexed and the frearm prnated. Eight, 1 cm slices with 1 cm intervals were imaged using the Tl-W technique and fifteen, 1 cm slices imaged using the prtn technique. The mean number f slices in the 3D studies was 22. * Scanning was perfrmed in the Department f Radilgy, Suth Cleveland Hspital and analysis f the scans fr frearm muscle CSA was perfrmed by Dr Rbert Campbell, Cnsultant Musculskeletal Radilgist, Suth Cleveland Hspital. * Scanning was perfrmed in the Department f Radilgy, Suth Cleveland Hspital, under the supervisin f Dr Rbert Campbell, Cnsultant Musculskeletal Radilgist. The develpment f the analysis technique and analysis f all scans were perfrmed within the Reginal Medical Physics Department, Suth Cleveland Hspital by Mr Darren Hgg & Mr Rbert Ryall. 56

105 Each slice was stred as an image file n the cmputer. The file frmat was a square matrix f 256*256 pixels, where each pixel had an intensity (grey level), representative f the tissue type at that pint n the image. Since each slice was f knwn thickness (1cm fr the Tl-W and prtn imaging and 0.6 cm fr the 3D scanning technique), each pixel represented a calculable vlume and is referred t as the vxel. The segmentatin prcess. The digital prcessing in the frm f segmentatin was used t analyse the images, using the HERMES medical image prcessing sftware package (Nuclear Diagnstics Ltd). Segmentatin used the technique f regin grwing, starting with the middle slice, where a pixel (the 'seed pixel') was chsen which reflected the muscle being assessed. A regin f similar pixels was then identified (muscle regin) and thse pixels with intensities utside the seed pixel range were rejected (backgrund). Similarity criteria (Hmgeneity Range and Edge Weight) were set manually, which cntrlled the sensitivity f the identificatin f pixels as muscle r backgrund. The Hmgeneity Range and Edge Weight settings were selected in rder t allw the mst cnsistent and sensitive identificatin f muscle tissue withut misclassificatin f nn muscle tissue, while being flexible enugh t classify mst muscle areas with a single seed pixel. These parameters then stayed fixed fr all ther images acquired using that specific scanning technique (e.g. Tl-W imaging). Segmentatin f the ther slices was then perfrmed. Placement f the seed pixel in a similar psitin t that in the middle slice was fund t be the mst apprpriate site fr accurate seeding in the remaining slices. Sme slices als cntained islated muscle regins; these needed t be segmented separately. Summatin f the muscle vxels prduced an estimate f the muscle vlume in the sectin f the frearm studied. In sme cases, the distal (1st) image lacked adequate cntrast t permit accurate definitin f muscle tissue using the segmentatin technique. In the assessment f the prximal (15th) image thrugh the inferir RUJ, segmentatin incrrectly classified the jint as muscle. Therefre the distal (1st) and prximal (15th) slices were discarded frm each Prtn series. Each series then cntained 11 slices cvering an 11cm regin f the frearm. 57

106 3.5 The Assessment f Rheumatid Disease. The evaluatin f rheumatid disease status in subjects with RA invlved the evaluatin f the severity and activity f the disease. Assessment f the disease activity was subdivided int evaluatin f the lcal disease activity in relatin t the right hand and wrist and systemic disease activity. The severity f disease was assessed by the grip strength f the right hand and a defrmity scre. In a subset f subjects, the hand bne density f the right hand was als used as an indicatr f disease severity (Peel et al, 1994). Hand bne densitmetry was perfrmed accrding t the technique described by Devlin et al (1996) using a Lunar DPX-L Scanner. The subject was psitined as shwn in figures and 3.5.2, with the right hand placed flat, palm dvrawards upn a perspex bard. The acquisitin and analysis sftware used in this measurement was based n the small animal sftware package (Lunar Crpratin, Madisn, New Yrk), in the methd described by Devlin et al (1996). A six-pint regin f interest was used t measure the bne density f the right hand and wrist, excluding the distal radius and ulna. 58

107 Figure Patient psitining fr bne densitmetry f the right hand using a Lunar DPX-L Scanner. Figure Clse-up view f the psitin f the right hand n perspex bard fr hand bne densitmetry. 5')