• I~cliahlc Isokinctic Evaluation of Strength and Neuromuscular .'atigue to Determine the Effects of Pyridostigminc in Subjects with l'ost-poliomyelitis Syndrome
Submitted by: Monica Roscmondc Kilfoil, BSc.PT. School of l'hysical & Occupational Therapy McGiII University, Montreal
• Datc Submittcd: August, 1992
A thcsis submittcd to the Faculty of Graduate Studies and Rcscarch in partial fliifillmcnt of the rcquirements for the dcgree of Masters in Rehabilitation Science. ©
Monica R. Kilfoil, 1992
• ACKNO'VLEJ)(;EMENTS • This thesl~ \\ork L'ould not havl' hl'cn c01l1pkted without thl' .l'SISt.\IlU' nt 111\' advisors. Drs. DMt.,,1 St-PICITC, NR Cashman. DA TIOpn and pwr 1':' D.IIIIIl'l1h.1l1ll1. tu
whol11 1 am grateful for t!lei! guidancc. utlllO:-.t patll'ncl', and ullsl'lli-.h 'Uppllll
To aIl the subJccts who 1).\1 tiCIpah.'d 111 ll1y ~Iud it':-'. 1 .llll l'Ilt \1 cl" gl.ltcf III .l1ld
wish to ex tend to you aIl a SlIlCCIC Ùlank.-yoll fOl yOlll tmlt' and l'Ill'I~!y
1 acknowledge ail fellow graduate ~tlldenh bUI. in paltllul.U. l'ailla Mattlll'\\'-'.
Kathleen Nomlan and Sandy Chambers for thelr assistance in data rollel'tloll, alld ail
ancillary activities related to surviving graduate school.
1 acknowledge the trell1endOllS sccretarial, Icchnical, and above ail hlll1lorolls
support provided by Colleen, Joyce, Sylvain and FI ank
• DEDICATION 1 dedicate this research thesis to rny family, in particulm ln Mattha, who plovl me with unimaginable support and love during me pcriod of Illy graduatc stll(!Ics. " Resiliency is an important factor in livlll~ 'l'hl' wlfuls of lift' mav /)('lId Il.\, huI ifwe have resilience of spirit, they canllat breaA. U,\ To cofiragl'(I/(.\[Y .1I1(/[glll('11 agalll after our heads have been bowed by defl'al or dl.\apfJolflll/'/('lIf, 1.\ 1IU' .\'II/)I·t'II/(' It'sl 01 character. "1 1. Author unknown, from PClty, J. Applcs of Gold 19X2 P 71 C.R Glh~()11 COlllpany ('OII1I1':CIJUII • 0TATEMENT (W AllTIIOHSIIIP • 1 hel ehy LCI tif y that 1 am the malll author of ail the manuscripts ll1 this thesls. aho c1alll1 full re~p()Il~JhJllty for the content and style of aIl text\ not specifically indicated a\ heing "1l1 preparation" . • • ii TABLE OF CONTENTS • ACKNO\VLEJ)<;EMENTS DEIHCATH)N STATEMENT OF Al JTIIORSIIIP Il TARLE OF CONTENTS III LIST OF TARLES " LIST OF FIGURES ,'1 AHSTRACT AHRÉGf~ 1.0 INTROI>UCTION 2.0 REVIEW OF THE LITERATUIU: S 2.1 Poliomyelitis (Polio) S • 2.1 a) Etiology 7 2.1 b) Pathogenesis 7 2.1 c) Pathology X 2.2 Post-poliomyelitis Syndroffi:! (PI)S) lU 2.2 a) Definition and Epidemiology lU 2.2 b) Signs and symptoms 12 1) Psychological: 12 2) Systemic: 12 3) Respiratory: B 4) Neurological: B • iii 5) M U-'llllo.,helcfal: J.3 • 2.2 c) Efilllllgy 14 ( 1) Chronic polioviru-. infection 14 (2) Imrmmological mcchani~111 ]4 (3) Early agin~ or o"cruse 15 2.2 d) Pat ho~cne~is of IJPS ]8 2.2 c) (:Jinkal Managcment of PPS 24 2.2 n ('Iinical Mc •• .,urclllcnt of Fatigue: 27 23 Met ho J.U i) Ar,jdl' 1 31 J.O ii) ArtÎclt' Il 44 4.0 ( '()nchrsion 62 • 5.0 Limitations and Rccmnmendations: 64 (dt Appendices 66 A) '''urld IIcalth Organizatiun (WHO) Polio Statistics Il) Consent Forms C) Medical Chart Review Form D) Visual Analog Scale of Pain 1 Clinical Status Questionnaire E) Borg Seille uf Perceived Exertion 7.0 References 67 • iv LIST OF TABLES • Article 1 Table 1. Il1tr.l-cla~ ... COli l'lai 1011 CncnlL'lt'llh lI( 'C) 101 the \1Ullllllll' \ ,lll,lllle ... pl peak. 100qul'. all~k ut IW,Ik. IOllllll', IUlque dl" t'lllPl'd ,II 1\\ Il 'P"I11Il .loi nt angle ... l() 7'), 1 0) 1.ldl,lIl"') hy tht' k.:Wl' C\Il'INlI' .lIld Ilnlll', aeras:-- fOUI te:-.I Vt'lIlClllt':-. Table 2. Intla-c1a:-.:-. ('ollt'laIIllIl (\lt'tlllICl1h (I( '( ') tOI Ihl' (luit (lI Il,' V,\ll,lhk\ 01 total work, aVL'ra~t' and 1l1.1'IIllUIll powel of the k.lll'" t':\ll'n"'lIl ... ,1IId flexor~, acro:-.\ four le\t Wllllllle<; Table 3. Intra-c1ass COllrlatlon ('oetfICH'I1I\ (1('(') tOI Ihl' llulllllllt' V:lIl,lhk 01 peak torque of the knl'l' e"lL'n~or:-- .lIld Ikxor" l'valll,llL'd al 10111 Il',1 velocitIes A L'Ompall'>llll nt 1dlahlllly aLl 0\\ Day ... 1 alld 2 \,,'1 \11\ 1la\'\ 2 and 3 Article 2 Table 1. Subject of Charactenstlls Table 2. Visual Analogue PaIll Score:-- • Table 3. Ratings of Perceiyrd Exertlon Table 4. Intra-Class Correlation (,()eflll'lent~. (1('(') lor the Olltl (li Ill' val J,lhll'~ of peak torque, and torque devcloped at Iwo :-,pt'rllil IOIllI .1Il}'It'~ (079, 1.05 radians) by the knee exten<;ors and llexor:-. A lOlllp.III\1l11 01 reliabilJty acro:--:-- Ddy\ 1 and 2 ver<;l!'> 1)ay\ l, 2 and ~ Table 5. Intra-Chlss Correlation Cocft IClent~ (1('(') 101 the OlltUlIl1I' Viii Jahlt-s of total contractile work and average power 01 Ihe km'(' l'xtl'n\()I~ and flexors. A comparison ot Ichahlltty aelO\~ U.ly:-' 1 and 2 V('I\II~ J )ay<, l, 2 and 3 . • y • A ,,'ic/t, 1 l'i~lIre 1. Torqlll'-ve!OLlty curvc,> 01 the knce cxtenllor and f1exor muscles II1 PPS "llhJl'Ch Fi~ure 2. A veragc power a!'> a 1unctfon of vclocity in PPS subject'\. Artide 2 Fi~lIre la. Total contractIle work of knee extensor muscles of PPS versus nonnal control !'>ub,CCh, rllc Fi~lIrl' 1 h. A Vl'I age power uf the knee ext'~nsor muscles of PPS ver!'>us nannal conll 01 "'lIblect~, I1lca ... urcd acro~'i three test day~. Figllre 2a. Ab,>olutc torque of the knce extellsor mu~c1es of PPS versus nonnal control ,>uhwct:-- dUfing the fatigue I1rotocol. Figllre 2b. NOImall/cd turque of the knee exten'ior muscles af PPS versus nonnal control :--uhWct 'i ch" II1g the fatIgue pmtocol • Figllre J:I. Total contI ,let rie work of the knee extensor muscles of PPS subJects whilc ()N pyr Idll,>tlgmIl1t' for four cI,tY'> versu ... OFF far one day. Figllre Jh. A ver age powl'r of knee extensor muscles of PPS subJects while ON pyndo!'>tlgrmnc for four days versus OFF for one day. Figure 4a. Angle-speCIfie torlJue of knee extensor musdes while PPS subjects were ON vcr :--us (>FF the pyl ICiOlltIgmIl1e. Representation of responders to the drug III term:-. of an effect on strength. Figure 4b. Angle-speci1ïe tOlque of knee extensor muscles while PPS subjects were ON versus OFf· the pyndostIgmine. Representation of single male rl'sponde) to the dllrg III tenm of fatlgability. Figure 5. Angle-specifie tOique of knee extensor muscles while PPS subjects were ON versu:-- OFF the pyndostigmine. Representation of non-responders to the • vi ABSTHACT • T",o .. ubJl"ct gwup", :-.t'Vl"l1 PPS (4 malc:-., -' Iem,lIe,,) and 1." Illlllll,tllllll!llll-; (1) females, 6 males) welt' matched on the ha\ls of age, IWlght and wl'l!!h! and pal!lllp.I!t'd in this stucty. Three repeatl'd meaSlIll'lllellls weIl' cOlldul ted tll t'vaIUal\' Ihl' ll'lrahllllV (lI isokinetic measurement of strength (at 4 veloc!tle:-.) and fatlgahrllly (~') Il'llplPlal contractions at 3.14 rad" S-I) Data from t",o suhsequent !t'sI day:-. \WIC u\l'd l(lev,tlualt' the fatIgue responses of the PPS suhJect:-. whlle ON 01 OFF pyrido"llgllllIH' Si/'nilil alli st! ength ctlfferences weI e ~een hetween the 1wo gInUp:-', hnwl'vl'I Ihelt' wa\ IlO Ilh\t'I vcd difference 111 the 1 ate of ckvel op Illl' III 01 LltlgUl' Rl'Ilahrllly 01 "'Ill'Ilglh \\',1\ d\'I\\()I\..,II:llcd for the knee exlensor:-. and flexOl:-' 01 Ihe PPS \uhll'L"I\ allci Ihll'l' l\1II\t', \l11Vl' Inl da v... Fatigabihty of thc knee extensors 111 J>J>S subll'CIS could hl' Il,,,led Il'II,l Illy allt'l 1hic\' le\1 days but more lime would be reqUlred for rchable performalLl' 01 the hUel' lIl'xOIS • Reliability of strength and fatigabihty wa:-. :-.ecn 10r hoth the knet.' extensO! and IkxOlS ni the nonnal controls after only twC! con~eclltlve tl'~( days. A hl'Iwltclal d'kcl 01 IIll' dlIIg on fatigability was not seen in the three fcmale PPS subfccts, huI wa:-. c!e\llon<,llaled III Ollt' male subject. The drug appeared to have a hencflclal clfec! on strcnglh in Ille relllallllli/' three male subjects. • • ('l'tll: {-(ude utdl..,e deux groupe~ dc su/eh, :-.cpt ~uJ('t:-. ayant le SPP (4 homme~, 3 kIlIIllC..,) l't J) LontrÔJe.., normaux (l) femmc.." 6 hOl11me<;) comparable.., en âge, grandeur et pOld.., 'l'roi'i lépétitIOm cIe.., mc~ures ont été faite\ pour évaluer la reprodlllsihilité des ll1e~un.:~ Isoklllé!1411eS de force (à 4 vitesses angulaires) et de fatIgabilité (25 contractions altl:rnatlves à 3.14 rad.s- '). Les donnés de deux JOUI~ de test suhséquents ont été utilisées pOlU évalucr les répon:-.e ..., de fatIgue de:-. ~uleh PPS alor~ qu'ils prenaient du PYIlc!O:-'IIJ!I11IIlt' ou Ilon. De'i (lJfft~rellle\ ~lgnitlcatlVC\ ont été oh\ervée~ au nIveau de la lo/Cl' l'IIIle k:-. deux gJOupe.., l'OUI ce qui e:-.t du taux de dévéloppement de la fatigue, !oUldOlS, aucune dIfférence n'a été obtenue. La reprodulslbilité de la force a été c!{-montlée pmll 1(':-. exten'ieur:-. et fléchlsseur:-. du genou chez les sujets PPS après trois ,ours consécutIfs. La fatIgabIlIté des exten~eurs du genou des sujets PPS a pu être testée • de fa~on fiable 101:-' de troi:-. IOLlr~, lllaIS plus cie temps serait requis pour une performance leprodulslhle dcs fléclllsseul.., du genou La reprodUl<;I!:iIlIté de la force et de la fatigabilité a l:té ohscl Vl-l' pour k:-. extrn:-.eur:-. et les fléchIsseurs du genou après seulement deux jours l'ons~cutlts l'hel. les contlôle:-. normaux. Un effet bénéfique du médicament sur la fallgabilIté Il'a pas été vu chez le:-. trotS sUjets fémmins PPS, mais a été démontré chez un ~ujl't masculIn. Le médicament a semblé avoir un effet bénéfique sur la force chez les tlois autres sUjets masculins . • I.n INTRODl1CTION • Attcl 20-40 yt',lrs or fUllcttnn,t1 suhlllly, ,IPPlll\lIll.llclv ~) ')(IC; (11 p.II,lh (Il 11111111 SlllviV()I~. are prest'Ilting \Vith the ~ympt()f11\ of pO\I-poIH1fll\'l'IlIl\ \\,1111 1l1111\' \l'I'S) Fatigue, new mLJ~c1e \Vcaknc~<; and palll ale Ihl' thft't' Pfffll,IIY :-.ymptol11:-' F.ltlg\1e 1\ reported by approxlInately X()(/r of patit nlS, Thl" t'Ilology and pathogl'lIl'\I'" 01 PI'S remains unknown Early aglflg and OVl'rusl' 01 enl;uged. J('lI1l1elvatt'd molor lIlllh Illay result in nelllomuscular synaptlC tl ofmllscle fatigahtllty a!ld gCIlt>lahlt'd fatlglle Los\ ni 1('llllm.1I :I\onal t'l1l1ln,l'''' 1\ p.llt 01 an ongoing dencrvatlon proccs\ WhlLh may lllldl'Ilw Ihl' dt'Vl'inpflll'III 01 IIC\\' IIl1l\l le weakne<.;s, Management fnu;<;es 011 tll'atml'nt (lI thl' 'iVIlIplolll\ 'l'hl' \1\l' 01 Il "dllloll.1I exercise trammg to II1Clease :.t1englh and cndmallLl' may IlO{ hl' applopllalt' Inl .111 patients with PPS, In the case of nelllol1lu'ilular Itltlgul', phal m.tcolo!!lcal lll.uwgl'IIH'1l1 • is an alternative. Clinical tnab of pyndo'IIt'IllIIll' 10 Il'duu' lll'lII()I1lIl<;CIII,1I latll'lIl' h.IVl' shawn positive results in the lll'lIromllsL'ular dl<;Oldl'i of mya ... thcllla glavl~ (Engt'l, Il)X7), and most recently, PPS (TroJan and Ca'ihman, IlJXl}) Ilowever, no qllantltatlve Illl'i1\1l1l"'" of nellromuscular fatigue in persons wlth PPS have yet becll ohtallll"d and thl':-.e ,Ill' essential in arder to evaluate the effectivcnc:-.~. of thl~ mediLatloll It is important to quantify rellably changeo.; III the ph Y"" IL a 1 heallh ot patH'lIt\ Will! PPS so that progression of the (hsca~e l'an be ll1ol1l1orcd and treatlllL:nt OlitLO/lH' .... LillI 1)(: measured. It has not been showl1 that PPS ~lIhleLI .... dd fer /rom normal subject~ in terms of longItudinal change ... III ~trellJ!th ovel tlllle (A)'w. Il)IJI. Dalakas, 19HX; Munsat et al. 19H4). Neliromu~clliar fatiglle ha .... hcen the ,>ublcLt (Jf 1lI11ch • J rl''''('arlh III nOImah but kw .,tudlc.., have IIlve~tlgatcd the rehabJllty of fatigue testing • PI(llocol.,. Morcover. there j., a nccd for a clearer undl.'r.,tandlllg of what fatigue in PPS r., and how tn relrahly te .... t and l1lea~urc it. 'l'Ill' rcliahtllty of .,trength tc.,trng ha., becn ~tudled extensively 111 normal subjects ancl III ~()Ille patient p()pulatlOn~, hut not in PPS Strength was measured first to provide infonnatlOll on the f()rcc-velocity curves of PPS ~ubJects (4 te~t velocities) which was IIccded III orcier to deterlllll1C If a fatigue protocol performed at 3.14 rads. sec·) would be ka:-'Ihlc and wC"lI tolcrated by PPS slIbjects. Once isokineti(.; strength testing was shown to hl' rdral,le and weil tnlewted by the subJects, an i'iokmetic fatigue protocol was th en tl'!'>tl.'d. RescaJchers have lI~ed lsometnc and isokmetic fatigue protocols to study fatigue 111 hUll1un quaollccps rnu~de (Bigland-RItchie et al. 1978; Gandevia and McKenzie, 1988; • Newham et al IlJlJ!). However, only a few studies have examined the question of Idrabihty of the fatigue protocols of ankle (Thomas et al. 1997) and shoulder (Gerd le et al Il)XlJ) muscles. Rehability of fatigue testing on patient populations remallls to be \I1vestr1;!atcd. An Isokllletic protocol was chosen to evaillate fatigue because it is dynamic and more tunctIOnal than an isometric test. ln addition, previous studies which have lI~l'd submax Jlllai isornetnc protocols have not been able to distinguish PPS subjects from nOll11al contlOb in terrns of the rate of development of neuromuscular fatigue (Rodriquez and A1;!lt" Il il) Thelefolt'. the objectives of these studies were as follows: Study #1 a) ta evaluate strength obJectively and reliably in PPS subjects compared ta nonnal contrais. Study #2 • 2 a) to develop an Isoklllctic fatigue plOtolol whiL-h wlluld l(ualltlfy IIl'IIlOlllll'l'ul,lI 1,lIlglll' • reliably III .... ublects with PPS. lontIa~tl'd to nnrm,Jl lllllllllls. h) tll a...... c ...... thl' -;l'II~III\'1I\' of sueh a protocol 10 differentJatc PPS flOlll nOlll1al cOlltlOl:-. and c) III l'\'aluah' tlte etlert of pyridostigmine on nellloll1uscular fatigue tn PPS slIbll'L't, into two main section~. The first part I~ the H.'VICW 01 the IItl'llltlll e l'hl' -;l'rnnd pail I~ the Methods, Results and Discus'llon containcd \\'11 h\l1 t wo ,\1 Ill' les. l'hl' 111:-.1 al tlde IS 011 the reliability of isokinetic evaluatIon of strcnglh III a sampk of "'lIhjt'( ts wlth pmi poliomye1itis syndrome (PPS) (KIlfoJl and St.PIl'IIt'. Il)t)2.111 plt.' ...... ) 'l'Ill" "'l'lond .Illllk involves a sample of sub.lects with PPS contra~tcd tn normal cllnunl ~lIbJt'LlS TIII:-' allit Il addresses the development of II rehable, dynaIl1lc Iso\-"IIletll. latl,!!lIl' plOtol'ol. whlt It III 111111 is used ta differentiate fatlgabllIty in ~lIbjects wlth PPS vel~US Ih))Jllal control" and tn detennine differen..:es in fatigability of PPS subJccts whde ON or OFF the lIlt'dicallon, • pyridostigmine. "The candidate has the option, subJecI to the apploval of the IkpaltllH'lIl, 01 incIuding as part of the thesis, the text, or duphcatcd published texl, 01 .III ()1I1'1Il.I1 pap(,l, or papers. In thlS case the thesis must still conform tn ail other Irqllllt"IlIt'lIh t'xplallH'd in Guidelines Concerning Thesis Preparation. AddItIOl1al materral (plOt (" data as weIl as descriptions of equipment) mmt hl' provlcled 111 ~ut'ICIt"/l1 (!clat! (e 1! III appendices) to allow a c1ear and precise 11Idgcmcnl 10 he made 01 Ihe IIl1portallle alld originality of the research reported. The the"i~ ~hould be more than a merl' colleclIOn of manuscnpts published or to be publlshecl. ft mu .... ' mclude a gennal ah .... tract, a 11It! introduction and literature revlew and a final overall conclu'IlO/l COll/lectlllg text:-. wlllch • 3 plovlde IO!!H;al bndges betwecn dlffcrent manuscript~ are usually de~irable in the interests • 01 cohe'>JOn. It I~ acceptahle for thc,>cs to indude as chapters authentlc copies of papers aIready published, provldcd thcsc arc duplicated c1early on regulation thesis stationery and bound as an Illtcgral part of the thesi~. Photographs or other materials which do not duplicate weil must be mell/deo in their original form. In such instances, connecting texts are mandalory and supplementary explanatory material is almost al ways necessary. The jndl/~101l of manuscripts co-authored by the candIdate and others is acceptable but the candIdate IS rcql/ired to make an explicit statement on who contributed to such WOJ k and ln what extent, and supervisor~ must attest to the accuracy of the daims, e.g. hefOfe the Oral Committee. Since the task of the Examiners is made more difficult in thesc cases, Il IS in the candidate's interest to rnake the responsibilities of au th ors • pcrfectly elcar. Candidates following this option J.lUst inform the Department before it submits the thesis for review." • 4 2.0 R.:Vn:W OF THE LlTERATllRE • 2.1 Poliollnelitis (polio) Paralytic polIomye1ill" (polIo) is an acutc fl.'hnk 111111."" \\'llIl'h Il'Slilts 111 neurol11uscular dysfullction Reports of polio fllst appe:ued lJ1 the Illl'dlcal Ittt'Iallllc III the 1g40's. It first appeared as an epidcmÏc IIlness in northcl Il Euwpc and NOl th I\IIU'I ICa at the end of the nineteenth century. In the lIlitlal polIo l'Pldcll\ll", up tll \lJ\O. dlll (0-4 years) were affected most, with males under the age of 15 hem).! atkctl.'d mOlt' thall twice as often as females (Weinstein, 1957). The latcl l'Pl between 1952-1955, also affected adults and the scveI ity of the dm'aM' 1IlL'Il'.I:-'t·d wlth increasing age of the patient (Halstead et al. Il)X5; VaIughe,c ct al l'nN) I\lllll(hIlg 10 the National Centre for Health Statistics in the United States (US), thell' Wl'IC IIH1IC than 640,000 people alive III 19X7 with a history of paralytlc polio (a<; uled hy Ilabtl'ad ct al • 1990 in Munsat, 1991). These figures indH.:ate hal polio is thl' St'lOIJt! 1Il0,t COlll11l0Il cause of disability after stroke (Halstead et al. 1<)l)() 111 Mun:-.at, IlJ(1) S II 111 1:11 comprehensive statistlcs have not been compiled f or Canada, hut il IS hel Il'ved to 1)(' approximately 10% of the absolute US figures, and hCIIcc the :-.allll' IIlclclt'I1Ll', The province of Manitoba registered 1540 hospital admissions for ca<;c,> of paralylic pollo between 1950-1959 (Alcock et al. 19X4; Kaufert et al. 19X5), LIttle 1:-' known abOlit the incidence in other provinces. In 1955, the Salk (inactivated) polio vaccine was mtroduced followlI1g tll(' hallci<; field trial. In late 1961, the Sabin (live atfenuated) oral vaccine wa:-. IIItlOclUL'('d 'J'lJ(~ vaccines were and are effective means of preventing paralytic polio mfeLlloIl (TIIllhury, • 5 1 of 11ll1l1l1l11/atlOll wlth a goal of Y()((' LOverage hy the year 2()()O, a~ weIl as disease CI adlcattoll IIl1tta\IvC~ throughout the 1YYO's (Melnick, 1992). In reecnt years, in dcvcloped coulltr le~, 'iporadlc cases of polio caused by reactions to vaccinations with 11l1ltated fOllm of the attenuated form of the live polIo vaccine (Sabin) have been reported (Varughc\t' ct al. 19X1J, Van Wezel, lYXl; Wlechers, lYXX; WHO Statistics). Secondary IIlfeCtIOJl~ Illay rc.\IJlt from contact of unprotected or immllne-compromised indivldllals wllh Ict:ently vaLcinated infallt~ or chtldren « 10 years of age). ln developing countries with tempcrate dimates, the live-attenuated vaccine, even when given as a full course of imlllllnizatilln, IS assoctated wllh lower rates of successful immunization th an the oral • vaccll1t'. ThIs IS due in part iO the lability of the vaccine if not properly refrigerated, but also becall~c of interferl?m:e by other enteroviruses prevalent among the populations of these countries (Salk et al. 1YX 1). Since the virus is mûst commonly spread by an fecal oral IOlIte, secondary infectIons are mfluenced by such factors as family crowding, hyglcnc and samtatlon conditions (Tnnbury, 1YX3). The WHO cautions that even in countlles whelc polio has been eradicated, imported cases of wild poliovirus From cndemic reglOlls in 01111 countries may oceur, and continued surveillance and complete illllllllIlizatlon \Vilh the oral polio vaccll1e is recommended . • 6 2.1 a) Etiolugv • Polio lS c:lllsed by distlllct RNA )11 COI 11<1\'11 li Sl'., , of \\'llIdl tht'Il' ;lIl' tllln' IllaJlll serotypes (I,I1 and III) (Kital1lllla ct al 19XI), The VlIlIses ail' lll'lIJ(ltllllltr and l'an pass across the blood- bralll ban 1t:'1 to attack the antcIIOI hOI Il l'l'II '> llf tht' .,pma 1 l'lH d, especially the lumbosacral and cervical enlargcll1cnts (TlInhllly. Il)~n) They Illay aftlyt the motor nerve nuc\ei of the bralllstem ::nd l'an m!dlIate the letllulal !!lIllIatllln 111 the medulla, pons and midbram, Cerebellar, thalamlC. hypothalamll. and pl eCl'1l11 al motol wrtex cells may be affected, whelcas the white mattcr IS lInaftl'l'ted (Bod l,Ill , II)·lX, Il> 11), Nathanson and Martin, 197lJ). EpIdemIes of the Type 1 VII li'> ait' tlll' Ill< l"t Clll1lllHlIl Both of the polio vaCCines contain each ')f the three scrotypes of the pOIIOVlIll" (J'llllhllly. 19~G), 2.1 b) Pathogenesis • Research on the pathogenesis of polio has been conducted on Illonkey". and tl~Slll'S from captive-bred monkeys were used for the devrlopment and l'onU olof the prodllctlOn of polio vaccines (Van Wezel, 19X 1), Humans arc the major natural h()~t fOI the enteroviruses, of which the poliovirus, wlth ItS threc ~erotype'), I~ the 1Il()')t UIIl1Jl101l 'l'hl' enterovirus enters the hast via the mouth and undergol'~ II~ fll~t IcpllLéltloll /11 tIlt" epithelium and lymphoid tissue of the upper resplIatory and ga~trollJtl'~tJllal tIlle!'>, 'l'hl' virus can reach, via the bloodstrealll, ">Ites other th an the bralll and ">plllill CO/cl \\lll! a\ the heart, liver, pancreas, lungs, vascular endothellum (TlInbury, I depend on the particular strain and trophism of the v/ru,,>, The Vln/'), III the proce~\ of replication, will cause cell necrosis in the affected tis\uc\. The carly élntiho • 7 1<., Illedlat~d by iml1lllnoglobulin M, whJ(..h is replaced within 0-12 weeks by • IllllllllIJO!!loblllin-(i antihmllc:-. Tcrmination of the viral infection dcpcnds on nntigen antibody JI1teractlon:-. and per:-.istcllcc of the polIovlrlls can be detected in immllne compronmed indlvldual" (Jokllk cl al. 1~XX). There ,IIC two typc~ of acule polIo, non-paralytic and paralytic. As mally as 90% of pcr~orls mfl'L1l'cI with the polJovlruS may ~how ollly mi Id slgns of an aClIte systemie IIlfection C.I;. lever, gl'neral malaise, diarrhea and loss of appetite. Progressive paralysis doc:-. Ilot d~velop, and r~Ulvcry wlthout residua occurs withlll days (Halstead et al. 1985). These cas~s ale com,ldclcd to be non-paralytic. Cases of transient weakness or mild paresls of Icss than scventy-two hours duration are also considered to be non-paralytie (Codd ct al. 1lJX5). The cases of paralytlc polio present with the febrile illness but, within days, • devclop signs of melllngeai irritation (headache, neck stiffness and vomiting) and rapid plogresslve motOl wcakncss associated with hypo- or areflexia. Sensory funetion is plcscrved (Tllllbury, !lJX3). The pattern of weakness may be symmetrieal or aSylllmctl ical ploducing a mono-, para-, hemi- or quadriparesis or paralysis. Patients who survive the acutc IIlfection will have a period of stable paralysis which may last for days or wel'ks. Aftel tl1ls ume. recovery from the paralysis will proceed slowly over a period of J months to 2 years post-infection (Dalakas et al. 19X6). 2.1 c) )Ja~ hology The extent of residual paralysis depends on the number of motor nerve nuc1ei affected dlrectly by the virus. If the virus has destroyed the motoneuron 's cell body, • 8 palaly~ls wIll be l'vIdent duc tn l'l'Il death and \Valkllan dl'!!l'nLl.lt\ll1l \lf the lll11tlll .1:\011 • and pres)'napllc 11'1l111nai :1\011'. Il I~ accl'pll'd th.1t the 1I1111al polrO\'IIIl' Illklllllll ilia\' affect fJOrn 2-lO()(;é of 1110tOl J1uclei III the blalll~tl'111 and ~plnall'llJtl (Jo"ll" l't al Il):-;~) Those l1lotonellJl)n~ wlllL h do not lI11del!!() degelwl ,lt IOn \\·11 h,I\'l' t hl..' l "pal 1t \' 10 ~t'Ild 0111 axonal ~prouh ln Il'll1lH.'rvate adJacent denl'rvall'd 111l1'ck 1I111e ... (Bodl.\I1, Il)·lt)), Sprout1l1g will be maxllllal \VIthlI1 2-1 X l110nlhs (\Vlt'l hel ... , Il)~X) In the early stages of pobo a declcasl' in the observed I1IlIllht'l of 111(10) IIlIlI adlon potentials confirms the existence of alplla l1lotnnrlll on,ll l'l'II de ,lth 'l'hl' subeq tIl'lll lIlcrease in theil amplitude and ctlll a110n \Il respons\" to ~tlll\lIlatron II1d\l:ah'~ lh.\1 reinnervation ha~ taken place through collalewl sprouling (BUl ht,d ,md II00ll "l', Il)4·t), Single fibcr electrornyography (SFEMG) stlld)c~ Il'vcal-; alllnllea,ed film' knslly, 11\1 thel suggesting an enlarged l11otor unit. This process ot collatclal SplOlIlillg Ily t('ll11l11al axonal • endings in polio ha~ been confilmed III laboratory l1lodels as weil (J>l'~II()l1k t't al 1()XO; Tomlinson and Irving, 1(77) M lIscle bIOpSIes ta"l'n from labol a tOI y lllodcJ, of polIO showed small anglliar fibres and hypcrtrophlc fIlm'-; which llIay he IndIcatIve thal :-'()JlIl' muscle fibres remained denervated, whilc othels hyperllOplllcd 111 rcspOIlSl' 10 ail IIlcleased workload, Electrophyslological slgns of denervatlon 111 acutl: pollo were Il'cord('e! as spontaneous activlty (po:-.Itive :-.harp waves) and fihrillatioll potenllab, A ... 'lIlll'\:-.flll reinnervation oCC'urred through sprouting, thc,e slgn\ dCUl:il ... ed (Bocllan, 1()4(J) Furthennore, the se abnormal electrophYSlOlogical fïJl(lIn1!~ charactcfI\tic 01 Ihl' .tellle pha~(: of polio have been verifled by reeent JOllow-up :-.tudlc:-, of pCf\On:-. who COlltl actcd polr!) • 9 (hrcctly or Indlfl~ctly through vact:ÎnatJon (Wiechers, 19XR) . • The /llOIOnellfOII populatIon ot the brainstem and spinal cord of paralytic polio :-'lIIVIVOI could thl'oretlcally he made up of 1) motoneurons which were unaffected, or partially alkckel hy the vI/al II1fectrrn, and now through collateral sprouting support t'nIaI peel lI1otor lInlt tl'rr/tolles wilh II1creased metabohc demands and 2) motoneurons whlch havc Ilot rl'LOvelt'i! L Ilhlcs (BO(fJall, IIMX, Dalaka" et al. 1tJX(1; Tomlinson and Irv1l1g. 1977). Although cast:s 01 pollo continue to occur, predominantly in developing countries, polio as a hcalth ulle problem 111 dcveloped countries was nearly forgotten until the !('cO!!llItioll of the :-.equelae tn the poliovlfus IIlfection, now known as post-pobo syndrome (PPS). AIl SlIIVIVO/S of f1aJalytic polio comprise a population of persans "at risk" ta dl'velop l'J>S (Ilalstead et al. IlJX5) . • 2.2 Post-pulimnvclitis Syndrome (PPS) 2.2 a) Uelïnition and Epidemiology PPS JI; a tl'Iln applJcd lo a complex of systemic, musculoskeletal and neurological symptom:-. ~el'Il 111 apploxIIllately 2Y}(, (range 20-50%) of persans with a history of pal alytle polIO (Codd et al IlJX5. Halstead et al. 1YX5). Researchers also use the term, post-pollo plOgll'''''lve Illuscuhu atrophy (PPMA), ta apply specifically to the phenomenon 01 Ilt'\\' muscle weaknes" 111 )llcvlou'Ily dffected or unaffected muscle groups (Halstead et al. IlJX5; \)alal--a:-., Il)X(l). Those pollo SlIlVivOIS who, to date, do not report new health plohlel1l~ dlll'ctly Ielated to thelr earher illness, are refeITed to as asymptomatic polio :-'111\'1\'01 ~ • • Hl PPS oerurs, on average, 35-40 years following the 11111 laI pol Il) Y\llI'i iIlk .... t WIl • (Codd et al. 19X5; Halstead et al. IIJX5: Jubelt and l ,1'" Il l11an. IlJX7: l\tllldl'I et al \ln 2). If there are over an estimated 640,(}()() IIHhndu,lI-. 111 tilt' li S \\'Ith a 11I-.to1Y ut p,II,lIytil polio (Halstead et al. 19l)() ln Mun:-.at. Jl)ln). and If Ollt' 111 fnlll t('udd ct ,II Il)X'); Halstead, IYX7) of slIch inciIviduals develops PPS. then thell' may hl' llHlIe th,1II 1hO.O()U cases of PPS. The incidence of PPS may altllalJy hl' Illgl1l'1 JI tllll' 1I1nwkl:-' tIHl"'C slIrvivors who are at plesent asymptomatil- and/ol h,lve Ilot sOllght IlWdll al attcntloll l'PS appears to be directly related to four malll chaI actenstics of the of illness necessitating hospitahzation, 2. onset at \0 yeals of age 01 older, ~ nt'ed lOI assisted ventIlation, and 4. qlladnparesls (Codd et al. 10X5; Ilablead et al. 19X5) There are three entefl'-l for establJshlllg the ex 1:-.tl'nl'l' 01 PPS. 1 pl IIlI pal al yi Il polio ronfirmed by history, physlcal and nCl\J'Olo).!ICdl cxammallon, lahlll alOI y alld • electromyographir evaluatlOns; 2. partial to maxllnal neurologllal InOVI"y lollOWl'd hy a period of neurological and functional stability for 15-20 years; 3. gIadu.t1 01 ahlllpl onset offatigue, non-disuse weakness i.l previously affected or \lllaffe<.:tcd Iml)lk groups, or musculoskeletal pain (Mulder et al. 1<)72). It is important to realize that fatIgue is the most common symptolll Il'ported hy over HO%, (range 75-X (Halstead, 19X7), and ncurol11u:-.culaI fatigue will he the pnmar y fOlll) of thl) -.;Iucly. Although fatigue 1" not ul1Ique to pollo 01 PPS, Ihert' are kw \tudll') whKh IHov1C1e li reliable defmItion of fatIgue or of its objective mea"urcmcnt III PPS . • Il 2.2 h) Signs and sl'mptoms • The course of PPS is a slowly progressive one which has the following t.:haraeten~tlc", 1) PsydlOlogical: PPS i~ a senolls J1lcdieal prob!cm because affected persons face an uncertain future. Ilavmg aehlcved vanolls Ievels of recovery from a significant disabling illness, they are feaJflll 01 anotlwr detenorallOl1 ln thelr funetional abilities and independence (Halstead et al. 1 ()X'i) ChrolIIe strcs~ and anxlety and an individual's perception of the level of effort rCljuircd 10 pClform daily aetivities may complicate the presence of depression (Bruno and Frick, 1()l) 1) Ali of thc~e factors may intluence fatigue and may affect the individual's ahlluy 10 cope wilh and manage their new symptoms (Berlly et al. 1991; Conrady et al. ItJXt)) . • 2) S)'stemic. Gcncralized systemic fatigue is a common complaint in 80% (75-89%) of patients with PPS (Cood et al. 19X5; Conrady et al. 1989; Halstead et al. 1985). It is often descrihed as an overwhclming exhaustion or "polio wall" (Munsat, 1991) which is brought on hy Illlllimal cxcrtlon and mtcrferes with function (Jubelt and Cashman, 1987). Owen and Joncs (19X5) attnbuted fatigue in PPS to a genelal state of deconditioning. Other autlHlI s point out that fatigue is a'\socÏated with symptoms of decreased ability to ClHlccnllatc, tn thlllk l'kat Iy or ta lcmember events. Drowsiness or a decreased level of akrtness has also been reportcd (Bruno et al. 1991). These authors make the point that Il'sidual post-enccphalittc lesions in the central nervùus system (reticular formation, • 12 hypothalamus and thalamus) should be considered as possible etlOlogics llf tatiglll' lf1 PPS • A precise definition of neuromllsclliar fatigue in PPS IS neces!\allly the sllbll'ct llf ongomg lI1vestigation. 3) Respiratorv: Restrictive respiratory functlon may dcwlop 111 the pn.'!\l'nll' ot Il'Spll aloly IllUSCIe weakness and associated postural defm mItlcs (kyphoscoltosls). SlIpelllllpll'\ed 1l'~pilaIOl y tract infections may fmther compromIse pulmot1hry tlll1clion and may ll';,d ln Il'sl'lIalOly insufficiency (A1cock et al. 19X4; Bach, 1(91). 4) Neurological: Impaired axonal or neuromuscular transmiSSIon may Irae! 10 Ihe onsel ot lIew muscle weakness and/or muscle fatigability (Jubelt, Il)X7l. ('o()lncs~ 01 dlo;lal eXlll'lllltll'~. discolouration and co Id intolerancc may be duc ln damage lu ... ympalhellL • intermediolateral columns by tbe original poliov IIU" intculon «'a:-.hlllan el .11. 1()X7;. Increased somnolence, dizziness, syncope and headachcs may occur III PPS (Ilaistcad cl al. 1985). There have been case reports of dysphagia (Cosgrove et al. 19X7; ('ot'Ilto and Rerranti, 19(1), obstructive sleep apnea or apnea of central ongin in pcr<.;ons with a history of bulbar involvement (Fischer, ] 9XS; Guilleminault and Motta, I97X). 5) Musculoskeletal: Muscle pam oœurs in approximately SO% of pcrsolls Wltlt PPS, and may re\ult from only light physical activity (Halstead ct al. 19X5) Pal\1 01 mu\clIlo\kcktal Oflglll associated with joint instabilities secondary to muscle weakne~~ or lIgament(JlI\ SplaJll~, may develop (Perry and Fleming, ]9X5). ft has been propoo;ed that the OII1!Hlal daillage • 13 (Hoc) ian, 1tJ4tJ) to enkcphal i n-producing cells in the substantia gelatinosa and • pcnaqucclul.,taJ 1:!rcy rcgions, may helghten a polio survlvor's sensitivlty to pain (Bruno, J ullaf fceled hy the 1I11tlal virai IIlfectlOI1 ThIs new weakness may stem from various lInciellyll1!! L :-'IlSccpllhlllty tn fallgue may he 1ll11ltlfactonal as weIl, with the most hkely sItes being plc:-.ynaptlc Âs WC will :-.cc under the etiology and pathogenesis section, eviden<.:C exists for the lradty of ncuromuscular Junctiol1s in PPS patients, which could contribute to the devclopmcnt ot new muscle weakness and fatigue. 2.2 c) El iulugy Several possible ctiologies of PPS have been proposed, and will be briefly sUl1unanlcd III the following section . • ( 1) Chrunic tJuliuvirus infection: It has been hypothesized that the poliovirus may persist and UlIl posslbly le ad to the development of the new symptoms of PPS. Evidence fOI this IS based on results of reactivation of the poliovirus in laboratory mice (Miller, 1tJX 1). In humans, SCI um analy'\es for poliovirus antibodies have not conclusively shown that symptol11atlc or asymptomatic polio survivors have higher viral titres (Dalakas et al. 1(jX6; Juhelt and Cashman, IlJX7). Furthermore, the trigger which presumably rcactivates the virus 1l'l11alllS unknown. (2) Imlllunnlugical mcchanism: Immullologlcal mechanisms are known to cause l1l'lIlOll1uscular (hsease C.g. myasthellla gravis (Engel 19HO, 19H7) and have been l'onsidl'rl.'d as a possible etiology of PPS, as weil. Evidence of a lymphocytic response • 14 was demonstrated in muscle biopsies (lf li small :-':bnple of pohp Sl1IVIVOI S (sl'ven patlellts • with PPS and six asymptomatir patients) lDalak.a:-. et al. !t)X(l). Illl\\'l'\'t'I. Ill'l'allse immunoglobulin G 111 ohgodonal band:-. of l't'lebw:-,plIlal nuit! \Va\ oh:-'l'I'ved III both groups, it remains unceltain as 10 the IOk 01 1I111111111olngll al 11~L'L'halll\llI" III Iht' l'tllllll).!V of PPS (Dalakas et al. II)H6). Furthcllnorl'. olher H.':-.e,lIL'hl'l\ have Illlt hel'Il .Ihlc III replicate this work and tnals of lInmUnOSllppH~s:-.ant Ihl'I.Ipy h.I\'l' 1101 hl't'II l'II l'lI IVl' (Halstead et al. 1990, III M lInsat, 11)1) 1) (3) Early aging or overuse: It is plausible that early aging or overuse of motor units could undcrhc the pllllcipal symptoms of fatigue and new muscle weakness in paralytlc polio SlIIVIVIll ~ EVJ(kllll' IIlI this hypothesls must consider what is known abOlit thl' IClIlllclvaled 1110101 \I1111~ III persons with PPS. As already discussed, it has been shown that altel the Il1Itlal pOllllVlIlIS • infection there are motoneurons tllat may be pmtwlly 01 Illlly ICLOVl'Il'd wlth 1l'I.IIIVt'ly normal or greater than normal innervation ratio (Bodwn, 1<)4 1); J)alak,,~ cl al Il)rI(), Pestronk et al. 19~O), The <..:CIl bodies may have to support more th an lIve to '-.I:WII tlllll'~ the normal number of motor end-plates, and thercforc mll~t opera le at maXImal lapallty in order to sustain the in<.:reased rnetabohc demands (ElIlar<;\OIl el al. Il.Jl)()) 'l'Ill' .lXllIlill sprouts that accur at an early stage III developllIent may not hc ... t.. hle indl'llIllll'ly ancllllJ', instability may lead ta delays or intermittent fadurc\ 01 Impul ... c propa)!all(lII ( 'a ... III1I.1I1 et al. 19~7; Maselli et al. ) <)Sl2, Wlccher ... , I defects in the Illotoneuron cell's DNA rcpalr mcchalli ... m ... , Icduct!olJ', III mH.NA, deuea ... cd protein synthesis, or loss of troptllC fa<.:tor:-., tht: cnd-plaw may lad LOlllpJetely and Il](" • 15 1l111'.c1e f iber bccome'. dcncrvatcd (Dalakas et al. 19H6). The loss of muscle fibers within • a lelllncrv:t!cd motor unit is ~ubstantiated by macro-EMG studies of polio survivors, which havc "hown a dCCrCd'.c in amplitude of the signal (Wlechers and Hubbell, ln 1; W ledH'I .... , 1()XX) 'l'lm re .... ultant dcncrvation of myoflbel ~ may lead to a dlsproportIOnate 10\\ (lf lllotOl fUl1ctlol1. Mlln~at (19lJ]) ha~ lI~ed the teml a "crash effectIf to describe what happl"n" whl'Il ('nlar!!cd motor IInJt~ reach or exeeed thelr Illetabolic reserves or ability to \Plollt and tel Icil1nnvate Ilclghbounng 1ll1l,>c1e flbers. 'l'hi" hulUll' of synaptlC connection has been hypothesized to be accelerated by overuse The degree of fllllctional recovery, the weight-bearing function of the lower l'Xl/l'IllIIIC\, or tl'c po~slhle harmful effects of exercise have been considered overuse factol\ whlLh coulci cOl1tllbute to the development of PPS (Perry et al. I<.JX7; Speier et al. 1()X)) It IS known that the new weakness of PPS occurs more commonly in muscles • af fl'lIed hy tht' OIlginal VII al infectIon (Codd et al. 19X5; Halstead et al. 1985; Jubelt and ('ashmall, 1tJX7) Furthermore, muscle groups which are active during weight-bearing actlvIlIt'S have hren ohserved 10 devdop new weakness more often and more severely than lllu"c1e\ wlm:h .. T not used for weight-bearing activities (Maynard and Roller, 1991; W IIldehanI.. t't al 1991) The effeet of exercise training in PPS remains controversial (Bcnllett. 1t))H: MItchelL 11.)53). 011 the one hand, muscles may already be functioning I1eal thelr lllaXlI1ll1111 pntrlltiaL and wOlild not be ahle to adapt to a further increase in \\'ntldoad EVHlt'nce f 1lI thi~ cOl1le~ from studies on partially denervated muscles in aIlIlllal" 1krbisoll et al. (llJ73) reported pathological evidence of muscle damage (e.g. t 1het "pllumg 01 necl mis) which was associated with the intensity and duration of • 16 exercise, He proposed that exen:ise may be dekterious tn the Il'l'O\'l'I y of fUJlL'lton III • partially denervated muscles The same hypllthesls ha~ been suggl'slcd lu apply in PPS as weIl. On the other hand, other authOls have argut'd fOI the bl'ndll'l.tll'ItCl'ts ut nlln fatiguing but progressive ~trengthen1l1g exelL'l~e ptngrams. ni .ll'IOhll and ll111hllt 1\' Il.llIllllg programs to lI11plOve muscle function (Dean and Ross, Il)XX: Ft'ldlll.ln .md S\lsj..olnl'. 19S5; Grimby et al. 19X9; Gross and SChliCh, 1YXlJ, Jonl'~ ct al. Il)Xl), "V1111l111 l'I .11. 1ql) 1. Twist, lYX7), Further ~tudies which use mOlI' OO,lCL'IIVl' and Il' Llhle llulL'Ollll' measurements are required before the effec!" of exerClse trall1mg L'an hl' detl'llllllll'll. Other researchers have consldcred whcther motor unit dysfllnL'tlOn III PPS l'ould be explained by early aging, It is known that the Il li 111 bt' 1 01 molOl IIIl1h dl'u\'aSl'S in normal aging humans by the ~ixth (McC'omas et al. IlJ73) 1lI sevcnth ('l'\llllltn~()11 ancl Irving, 1977) decades. It has been hypothesized that these IH 'Illal age-IL'lall'd Lllallgl'~ • could underlie the occurrence of PPS. Howevcl, the Impollanll' 01 agln!! III thl' pathogenesis of PPS remains controversial. Dalakas ct al. (19X6), ()b~l'I wei ,[ 1(~, pel annum dec1ine in strength in symptomatic polio ~urVlvor~, Icss than (10 yc;u:-. (lI age, which IS not significantly dlfferent from the normal rate of aglllg, Othel al1th()J~ haVI' confirmed these findings (Agre and Rodriquez, 1991, Munsat cl al. 19X4) PPS ha,> bœn diagnosed in pollo survivors III their 3{)' ~ and after the sevcnth and clghlh dCLadl''> (lI tlwlI lives (Halstead et al. 1990, in Munsat, IlJlJ 1) The~e latc OLClltrl'IlLC'i :-.upporl tltl' evidence from epidemiological studle~ which \uggc"ts that the Icnl:!th (JI the IIltcrval between the acute polioVITUS infectIOn and thc appearanLc of ncw :-.ymptoll1'>, allclnot age, is the more important factor (Halstead, IlJX7; WlIldehank et al. 19lJ 1), • 17 ------ 2.2 d) l'athogenesis of pl)S • Mcch;mism!o, undcrlying dccreascd muscle strength in PPS Â\ p/cvlOtI~ly d,.;clIssed, abnormal neuromu~cular transmission or denervation could underhc the ncw wcakncso.; and fatigue symptoms which are characteristic of pcr\()n~ wlth PPS (Wlcchcr~, 1YXX). Mu.\c1c .\tr~ngth l'an hc dcfmcd as the maximal force or torque that a muscle or mll~c1e !!fOUP clin gcncratc al a ~pcCifled veloelty (Knuttgen and Kraemer, 19H7). ft can he l1Jl'a\lIIt'd LInder voluntary or electrically elicited conditions. In normal subjects muscle stren!-!th IS known to decrease with increasing age due to loss of motar units and/or atlOphy 01 the Icmaming muscle fibers. It increases lhrough high resistance training (AllIano.;soll et al. )lJXO; Maughan et al. 1Y86; Sale et al. 19H2; Sale, 1988) and decreases wllh inact/vity (MacDougall et al. 1980; Robmson et al. 1991; St-Pierre et al. 19H7). The • fOJ('l' that a ll1u~c1c genelales is dcpendent on the slze of the muscle fiber and can be IIKleased cither by recruitment of additianal motar units or by increases in the firing rates of active motor units. Recruitment of motor units, according ta Henneman's size r'lllclpIe () 965), may predominate over rate coding as the mechanism responsible for inclcaslI1g the force output. However, this predominance may depend on the size of the muscle. on the speed and intensity of the contraction, and on how long the contraction IS o.;ustained (DeLuca et al. IlJ82: Bigland-Ritchie et al. 1(83). The performance of most aL'tlvJtle~ ot datly hVIl1!-! does not leqUlre the use of high-threshold, fast-twitch motor lin Jt~ Mllsde strength in a patient population, such as PPS, may be influenced by the • 18 above factors but over time the fewer nUl11ber of fUllctioning motol 111111" wllh 1I1lsIahk • neuromuscular connections may not be able to maintai Il the l'nIa 1 gl'd Illot nI IIml Il'lIItlH y produced through reinnervatlon. The denervation whlch ma)' lnllo\\' WIll j'lOdllll' I11I1M:k weakness and atrophy. Evidence of this process of ongoillg dcnClvatloP and 1;\Ill111' 01 II1capaL"lt)' fOI further reinnervation comes from abnormalitles such as 1I\1II11allol1 and ta~rtclllal\On potentials on conventional EMG stlldies. The oCClInencl' nf JlIIl'1 and hlOl "-lI1g wlth SFEMG studies, and reductions in the amplitude of macro-EMG IllcaSllles 01 Ihl' motol unit size and density ure also signs of denervation of muscle llbcl s Howewl, a significant degree of denervation can oœur before muscle Wl'aklll'S~ WIll hl' dt'tl'lIcd by manualmuscle testing (Brown, 1Y73; McComas et al. Jln3). Muscle biopsy results from polio survivors has also becn IIsed 10 illvc~tigale tht' 1 • pathogenesis of PPS (DI achman et al. 1<)()7; Poskanzel cl al. )1)6 )). Loss nt IIHl!vldllal muscle fi bers and evidence of group atrophy (Cashman et al. 1()X7; Dalaka:-. et al 1()X(I; Einarsson, 1990; Grimby et al. 1999) have been observcd. Oroup atrophy 1" usually characteristic of 10ss of the wilole motor unit. The group atmphy M'l'Il III :-'OIllt' pallcllb with PPS could be explained by axonal branch dcgeneratlol1 III an cxten~JV('ly hranchecl motor unit, and not necessarily be due to loss of the whole m()tol 11/111 ( ':l'.. lIl11an et al. 1987). These findings were seen In biopsle~ taken from l1lu"de,> of poho '>ll/VIVOI'> whlch were (1) weak secondary to the 1I1itJal mfectlon and SUh:-"l'qllently f ll/thel wt'akl"I)(~d (2) spared by the initial infection but later weakened or n) pre:-..umed 10 he normal. The presence of small, an,(~ulated fibers with immunohl<.,tochemll.al evidcllce of "hllorlllai • 19 acculllulation 01 neural ccII adheslOn molecule (N-CAM) beyond the motor end-plate • regHHl, and wlthin the cytopla.,m of the myofiber and mterstitial cells is indicative of actIve delll:rvatlOl1 ('a"llIl1al1 et al IlJX7), j\1eclmnislJI\ IIIldt'rlying increased nellrum'J~clliar fatigability:  UlIlllll",ve dd IIlIWln of fatIgue doc:-. not exist. However, muscle fatigue can 11l' op('rall()lIally (kflllcc! ;:~' "a lariUle to maintalll the required or expected force and power outpllt" (Edward ... , 1 jll'/lphcrall.Olllponcnt:-.. Â:-. rcscarch ,)n neuroll1uscular fatigue proceeds, it IS becoming 1ll00e appalt'nt that a systems approach to the ll1ultisegmental nature of motor control is mOll' appr opllalL' It has bren pointcd out that rC'iearch on muscle fatigue must foeus on thll'l' a ... peL!:-. of the neural LOntrol of the motor unit dh.charge, namely 1) assessment of tht' uq!ll'l' ot maxllnal nculal dnvc to thc musclc (muscle and artificial wisdom) 2) • a:-'''l''iSlllent of the leflex reduction 111 motoneuron discharge rate during sustained MVC (sem,or y kedhad, hypothc:-.is) and 3) examination of the plasticity of the relationship L)('tween the motoncuron discharge rate and the amount of force produced (force latlgahilrty lelatlOllshlp) (Gandcvla, \lJl)2; Stuart, 19(2). Fatlguc may ICSUIt l'rom a decreased central drive w~'icn could result in sllhm:tx IIna 1 Illusl'ular act ivation. Events at and distal to the neuromuscular Junction may rontllhutl' tn pl'Ilphclal fatIgue: l) instabihty of transmission in plesynaptic terminal ;t\O/l" 2) redul'tlon 111 the nUmbl'1 of ÂCh Vl'~lcles and 111 the amount of ACh released into s)'naptic l \elt 3) changes 111 depolar ization of the motor end-plate or in conduction of the actloll pntt'ntlal along the s.ucokl11l11a 4) alterations in calclllJ11 metabolism, re\ease und • 20 uptake 111 the tr ansver se tu bule :-. y:-.tem nI sarcnp las nllc \l'Ul ilium 1lI .5) l'ha ngc-; III 1hl' • enzymes of the le~pilatOly ch.lin. 111 the llmtlal'l1k pIOtl'11l\, or III the l'IU:-.\-hIIdgl'CyL'lIIl)! rate (Bigland-Ritchie et al. II)X3; Ed\\';ud:-., \lJX3, jl)X-l). Technl(.Jue~ are now available wlllch pl'IIllIt the dltTl'Il'nll,lllllll lit l'l'nllal IIIlIll peripheral mechanisms of fatigue: The twttch IIltClpolatlOll tcdullqul' ('1'I'i') (I\kllon, 1954) and the comparison between the fatIgllc-lIldllced dl'L1l'a:-'l' III VnltllllaI y Vl'I SlI:-' electrically evoked contractions (Newham et al. 19lJ 1) TheM' lechlJlqlll's h,IVl' kCII tlsl'd by various researchers to II1vestIgate llellromll:-,clIlaI fatlgul' Illl'Ch.lIll:-.m\ III :-'111.11 l, IIIIIIII:-'Il hand muscles (Bigland-Rttchie et al llJ7X, llJX(l, Ikllt'Illall' et ,,1 flnn, (i.\lHleVI:! and McKenzie, 19XX) and 111 large I"nb ll1u~c1es (BIgland-RltdlIt' cl.tl 1I)X n and III respiratory muscles (Bellemare and Grassino, IlJX2). SOllle l'Olltr acllctol y It'..,III .... h.IVC come from research employing dIfferent fatigue plOlocols (fklangl'I, Il)S \) 1IOWl'WI, • most of the available evidence suggests that, although lentl al fatIgUl' llIay Olllll, peripheral factors are predominant (Edwards, IlJX4; Bigland-RItchle l't al. \ IJ7X, Il)X3). It is of interest that earlier research has shown that a declillt' III ..,mlau· electromyographic (EMG) activlty can he seen 111 su:-.tamcd maXIIIlUIIl voluntalY contractions (MVe) in humans (Thorstensson and Karls~on, 11.J7(1) and wlth electllcal stimulation in animal models. A muscle under stlldy may be l'ully aLtIvatl'd vollllltalIly but signs of fatigue wOlild eventually ensue with the suhlcct no IOllger h,;ing aille tn maintain the force output despite evidence of maxImal central activatIOn Il ha~ al<.;o h(~en shown that a progressive decrease in firing frequency of motor Unit<, whlch paJallded tll(' decrease in contractile 1lpeed dUfIng the MVC's Illuy occur (Blgland-RuchH': ct al. 1IJX l, • 21 1(JIn) 'ilm change III motoncuron actIvatIon wa-; thought to be a compensatory • 1I1t'LhaI1l'>1ll to avold fallguc. lIowcYeI, the precI~c link bctween J1lotoncuron excitation alld kedhack 1rom the l11u,>dc I~ the -;ubJect of ongomg research (BIgland-Ritchie et al. 1<)<)2; hll-!cI ton ct al. IlJXO, Enoka ct al. !lJXX, 1')<)2). A'> thc~c tcchnJque~ have not been used in PPS, liule is known about the IlllpOI tance 01 œntl al 01 peripher al fatigue ;i~ thlS patient population. The perceived cf for t, mot Ivatlon, and the prc~ence of pain or depression are factors which influence cl'Illral latlgul' It 1\ ,II~() 1I1lpOnant to Icmember that it may be dlffH;ult for subjects in chlllLal :--tUcIll'\ tn dl,>tlllguI,>h bctween muscle pain and fatigue symptollls. In addition, villlahIllty 01 latlgue ~yll1ptoms wlthin a subJect over the course of a days aetivities and hetwccll ~UhlL'Ch Illu:--t hl' controlled for. Nevertheless, to date, investigations of the most IJke/y call~e 01 neuromuscular fatIgue in PPS is the presence of altered neuromuseular • II aIlSIl1I~SI()n plOpeltlcs. But the precise locatIOn of the defeet, either in the terminal axonal :--prout:-- OI 111 the synaptic deft or motor end-plate remains to be detennined. EVidence for the frailty of neuromuscular Junctions in PPS patients eomes from e/cctlOphYSlOlogical studies whlch include conventional EMG and SFEMG. Conventional EMG ohsel vatlons of reduced motor unit action potentials in response to repetitive stimulatIon IS suggestive of neuromuscular transmission defects. The SFEMG technique pernllt~ extracelluhu recordings of abnormal "jitter" and blocking in motor units (Cashman et al. 1YX7; Dalakas et al. 19X6; Stalberg et al. 1975; Wiechers and Hubbell, 19X 1: Wlechers, 19XX). Jmer IS a measure of the variability of the time interval between two lIluscle fiber action potenti:tls from the same motor unit and reflects variability in • 22 synaptic tran.,missIOn rates. Blocklllg is a complete failult' 01 IIltl'IIUptIlHI Ill' • neuromu~culal tran ... ml~~101l of the Ilt'r\'t' actIOn pntl'ntlal tn thl' 1I1l1"l Il' 1lI1'1IIhl.llIl' 'l'Ill' presence of the ... e abnnrmalitlt's I~ eVldl'lICl' that tht' l'II 1.11 !led ll\(ltllr IIl1lh .lit' Ilot ~t,lhk indefinitely (WleL'lH."ls, 19HX) The ~al11e authOl [l'poltet! that an 1I1l [l'a"l' III pltCI ,111<1 blocking was related ta a longer time int('[val SlIllT the OIlglnal pollovlIus IIIketloll These findings were seen in bath symptomatic and a"ympt:lI11atll p:lIalytll' po!to :-'IIIVIVO[S (Cashman et al. lYX7; Wiechers and HubheIl, 19X 1) Ilowl'Vl'l, pltCI ,lIld bl'll ~lIIg \\'CI C greater in symptomatic patient~, and gll~ate[ in tIH)"l' ~yl11pt(llll.tlll patH'lIt-; \\'Itll a significant time lapse sinœ the il1lllallilness. Macro-EMCi ~tlldll'\ (lI pollo ~\IIVI\'O['-. haVl' shawn that the decrease in amplitude of the signai IS dUl' tn 10-;,01 IlHI'-.lk ttlWI ... WIIIIIlI a motor unit (Stalberg, 19XO, 19lJO; Wlechers, IlJXX) Rl'l'l'Ilt WOII-. 011 '-.ylllptoln,ttll' patients has revealed a positive correlation between impain'd lJelJlOIIIU,t IIlal tl grouping on muscle biopsy. However, these fmdings do Ilot l'Ollllllll Ihe presel1u' 01 absence of new symptoms (Maselli et al. IlJl)2). Animal stlldies have shown that partial denervatlOn 18 a\~oclated wlth a ft'Iatlwly high proportion of type 1 or slow-twitch motor unrts (Miller, Il)XI) PPS 1\ a hUI1l:tn model of partial denervation with ongoing reinnervation through collateral :-.prollting which resuIts in fewer but enlarged motor Ul1Jh. COlltrovcrsy ex"t'i ahollt the predominance of one fiber type or another in subJect~ with prior polIO who llIay or may not have developed new symptoms of PPS (Dalaka'i et al 1<)XÔ, ElJ1ar ...... o/1 ct al 1<) Research has shawn that the enlarged motor unit terntorie\ may be more slI ... ceptible to • 23 fatigue and that the clllarged motor Ul1lt may be a le~~ efficIent mechanical unit (Mllner • BlOWIl et al. 1(J74) SO!11C pO\\lblc factor~ whlch may contnbutc to thl:-' IIlcfftclency and g/eatc/ \u~Lept/bdJly 10 fallgue Illay inclllde. 1) loss of neu/otrophrc rntluence on rnel/v/dual Illll\cle f1hrr~ w/lhl/1 thc enlarged motof unit terntOlY, or 2) the presence of wnnccllvl' ti~~lle ha"ier~ wh/ch IH1lIt rcrnnervation and may lead to unpaired metabolism or 1) fadu/e or nellromu~\:LJla/ tran~mlSSlOn and excitatIon of muscle fibers. In addition, Ihe fi hl 01 IL change:-. a~\()Lialed with atrophy may reduce the efficiency of the contraction, )1lcdISPO\llIg Ihe nllJ~Lk to fallgue 1/1 ~UJllln;lIy, cldl" flOI1l e1ectlophysiological studies and muscle bIOpsies suggest Ihal f adllll' (lf \ ynapllL' connections or fallout of terminal axons may underlie the occurrcnce of pPS. IIowever, il IS not possible, at present, to distinglllsh unequivocally helwct'n ~ylllpt()l1latlL' and a~ymptomatic polio survivors, and until this is possible, the • dinlogy and pathogenesls underlyrng PPS remarns elusive. 2.2 e) Clinical Management of I)PS: (,Imical management IS aimed ut the three most common neuromuscular sequelae 01 pollo. lllusLulnskeietal palll, weakncss and fatigue. Musculoskektal pain symptol11s are usually managed pharmacologically with non R R stcloidal antl-inflal1llllatory medicatlOns (e.g. Naprosyn or Voltaren ) (Jubelt and Cashman 1lJH7). In the context of fIbromyalgia symptoms, low doses of the anti R dcplessant anlltlyptilhlle (EbviI ) have also been shown to be useful (Cashman, personal COIl1I1lUnH:atlOn, IYY 1). M usculoskelt'tal pain due to abnormaJ biomechanics of joints and Illuscles can be rd ieved, in paIt, by the prescription of apprcpria1.e orthotics ~~,ld mobility • 24 aids (Agre and Rodllquez, )l)l)(); Pen y et al. IlJl'i7) Pain i __ h.1l11Wn (0 IIlhlhlt IlllIsde • contIal'trle force, '\0 ItS II1fluence mu __ ! he 1l1011l11llt'd (AIVld'llll. )l}X7) Muscle weaklH."~'\ may Ill' dut" to carly ,1t!11lt! alld 0\ l'11I"l' 01 mo(ol t1I1ItS. 01 dllt' to muscle disll~e. Bcl'ause the etlo!of.!YL _ of PPS 1" unkno"'ll. the Il'\e (lf ~11l·nf.!(IH'nilH'.. ~ .... exereises in the treatment of persons \Vith PPS IS conlrowisial. Farllel ll'sl':lIl'hcIS concluded that strengthening of partIall y denervated musl'le" III po ho ~1II \' 1VOl s 1 l'Sil 1tl'd in further weakness (Bennett and Knowlton. )l))X; MltdH'II. Il)')3). F:\Ily npl'lll11Cntal work with a rat mode! of partial denervatioll ~1I!!gc:-.tl'd that dall\.t)!l' lOllld Il''ult 110111 overuse of a Innited number of motor UIlIt" (I1l'I1)I"O!l cl al Il >73) ()n Ihl' olhl'I hand, clinical studles on persons wi th PPS and olhel fOI Ill" 01 p:1I t la 1 dellCI v,II l(l!l ((' g. amyotrophie lateral sclerosis, neuropathie~ and pellphelal nCIVt' Ie:-.mn,,) haVl' ~lIggl''iI('d that strengthening exercises (bnef Isometnl' ()( Isokllll'tlC l'Xl'llI"l'~) lIIay 1t'''lIlt III • improvement of strength (Einarsson, Il)l)); Feldmall and So:-.kolne, 1()X5; (;J()~s and Schuch, 1YX9; Owen and Jones, 1YX5). Other trallling progl ams 10 IInprow al'mille capacity or mobility of persans with PPS have bren examlll('d, hllt ()nly III l'aw ~tll("l''' (Dean and Ross, 1YXX; Twist and Ma, 1YXO). The 4ucstinn nt whethl'I ext'ru"l' lI11proVl'S or worsens muscle functlon in PPS remains unan'\wercd. Fmther stlldle~ wllh rellahle and objective measures of strength and fatigahility arc rcqllircd Fatigue symptoms l'an be managed l'onservatlvely hy 1l1()(lIfIClltIOn\ JIl a pal)(,IlI'~ daily aetivities (ADL). They can be advlscd to redul'c the inlemlly of thclr phY\Jcal activity (e.g. work or exercise) and to jnter~pe . .;e frequcllt rc~t PCfI()(t... 111 an effort 10 prevent the onset of this disabling symptom whllh Jnterrllpt~ thclr funLlJoll and ahlllty to • 25 \1I\lalll an acllvily J'Of lho:-.c patient" ln whom p~ncrahzed fatigue i,> of primary concern, • who (lJ\play localJ/cd mu\c1c faugabdity 011 LlllllLal CXamll1atlO11 and for whoIn con:-.crvatlvc mca,>urc:-. arc lI1adeqllate, phannacological management may be considered ('l'J oran and Ca:-.hman, 19X9). AntJlhollllc:-.tcra~c age nt:-. , ~uch a:-. pyridostigmine bromide, block the hydrolysis of acctylchollnc (A( 'h) by acetylchohnesterase (AChE) at the neuromuscular junction and Ihus rnamtalno., Ihe amollnt of ACh 111 the :-.ynaptic deft for a longer effective tnne period « ;O()(!JII.1Il el al IlJX5). Th,,> cil ug has abo been :-.hown, in alllmal studies, to IIlcrease the al j JJllly 0/ end-plate 1cceptDr\ for ACh Pyrido:-.tJgl11lne blOl11lde ha~ been shown to alter 11ll' UlntlaLlJle plOpCltJCS of rat :-.keletal mu~cle wlllch return to ba~ehne within 1 dayof wllhdl awal of the drug. In addition, the drug, as administered III this study, did not appeal to have a cUlllulatIve, desensitizing effect on ACh receptors (Adler et al. 1992). • Ilowever, III hlllllan:-. Il ha~ been :-.hown that the factors of decreased sensitivity of ACh Il'ccplor to ACh, slIllctural changes 111 motor end-plates, or variation in drug absorption and Il'nal exclellon may affect the drug's therapeutic level and function (White et al. Il)X 1) Pyndostlgmmc has been used effectively in the treatment of post-synaptic clysfullction ot acetylcholine receptors In myasthenia gravis (Engel, 19X7). Clinical trials on largel :-.amples of PPS has been proposed to verify the drug' s efficacy in individuals with PPS. Side effects 'lIe Illost acute ui-nn initiation of the drug, and include diarrhea, gastlolllte:-.tlllai cramp:-., Illcreased unnary frequency and blurred vision. These side effects l'an hl' well-nllltr olled with muscarinic anticholinergic agents such as oxybutynin chloride 01 plOpantheline hlomide (Trojan and Cashman, 1989; Goodman et al. 1985). To • 26 ----_._---_ .. _._------ millÏIllIZe the lI1cidencl' of slde ('fft'L'IS. tht' symptom:ltiL' pollo SUblt'L'to.; :\ll' 1Il111all" • prescribed 30 mg once datly Thlo.; dosage i... Ihl'l1 IIlClt'a't'd hy .'0 Ill]! l'\ CI \' l"'ll da,,'i until an appmpllate 1l1.1\.1I11l1111 daily do:-.agl' te !!. 1Xtl mg) l' all.lIlll'd D.lllv pyridostigmlllc doses art' adJustcd accOIc!Ing to l'lll1lc.1I t'valuaIIOI1' nt .\ p.lllt'III'S :-.Ialll:-', but techl11ques to detcrmine plasma COllccntlallOlb of thl' (ilug III Ihl' all10llnl 01 erythrocyte-bound acetylcholinesterase enzyme (llenze et al \(1) \) aIt' aV:lllahk hUI expensive to use loutinely. 2.2 f) Clinical Mcasurement of Fatigue: Much of the reseafch 011 neulomllscular fatigue has ht't'Il lOll and has exam1l1cd changl:s in 1ll11'icle fUl1ction whlch L'ould allOllll1 lOI 1.lIlgUI' Researchers have devised fatigue II1dices. in an effort to quantlly fallgue, :-Udl :t'i 11It' percent dedine in torque over time, or the ratIO of the tOlque 01 Ihe la,1 3-'i t'lllltl:llllOIlS • to the first 3-5 contractions 1I1 a fatigue prolocol (Thor :-tt'IlS:-OIl and K arl'i,on, JlO(,) However, the reliabihty of these IIldlCCS remains to hl' ,11Own III l'PS fil addlltOIl, litt' application of these mdices, developed on normal control ~ubJt'ct,> ha,> 1101 111'1'11 111'0r ()ll~ly tested on subJects wlth motoneuron disorders, speciflcally PPS hlltht'II1111It', III'> drtlrulll to distmguish whether peripheral or central fatlguc llleChallr~lll:-' are IlIl"dolJllllant Wlll'JI examining the whole, human orgal11sm with a complex p~yclll' Partit IIlar 10 Ih(' sllIdy of hum an subJects wIth r?S, is the raie played hy su ch lactor '> a,> depre""lorl :t,>"ouall'd with a chronic, dl~ablin!! di..;order. In adchtlOll, thc pcr,>ollallly ';,111'> 01 Illdlvldllab wh() have survlved and maximally recovered from a drsabling rllne", Will IIlthll'rlu: bow tbey will deal with the prospect of a second di~abling IlInc", (Maynard and ({(Jlln, 1()I) 1) . • 27 Tht.:"l: lactol'> ~h()uld be con"Hfelcd 1/1 the clin/cal a~"e<;"lllent of PPS The use of • ancdlaly quC,>lloIHlalrc,> and ,>cale,> whlch can monitor c1inicalchangc in p"ychologlCal or paJ/1 parametel'> , ... advJ\ed. PPS patJent~ may be at the lower end of the "pectrum of t.:xt.:rcI~e lolerancl'. Fallgue Illay be as ... ouated wlth law leveb of exercIse 01 with the complet Ion 01 lOutllle dally f unctlons, exclusive of exerci<;e training. For this reason the c1evdopmclIl and u~c 01 fllllctlonai ~cales appropnatc ta PPS IS of importance. 1'0 date, report.'> 01 1allguc 111 PPS have been IJlmted la subjectIve data abtalrled From qlH'<;llOlIlIallt':-. 01 clllllcal :-.cale~. The vah(hty (mtclllai can:-'l~te/1cy) Jnd relIabIlity (inter and 11111:1-) (lf li h111!!lIl' SewrIty Scale (FSS) wa~ del1lon~tr,lted 111 a samrle of per~ons wilh lIlulllpk :-.rlelO\!" alld :-.ystcmlc lupus erythcmato-;u<; (SLE) where fatigue is a dl~ahllllg :-.ymptol1l (Klllpp et al. IlJXX; ISlXY). This scale was able to detect the presence 01 ah~l'nLe of cl 111 Ica 1 change over time. The values on the seale correlated weil with the • IlIlcar vl ... lIal analogue ~('alc (VAS), which has alsa been used ta evaluate fatigue (Scott and Ilu:-.kI:-. ... UIl, Iln(), l 'J7l). Another linear scale sim:lar ta the VAS has been used ta l'vaillate fatigue 111 pel ~O/1:-' WIth PPS (Hare et al. )<)X5). This partlcular scale was used 10 l'valuate Ihe l'IIl'Lb of pyridoslIgmine, an anticholinesterase agent used to treat fatigue syll1ploll1:-' III PPS (TroJan et al. J lJXt). A decrease lJ1 fatigue symptoms (Hare et al. 1985) alld an IIlClea:-.e 111 fllnctlOn (Katz, 1<)63) were reported in 16 of 27 (or 04%) PPS subjeets III a Olll' llIollth Hlal of rylldo~tlgmllle (Trojan and Cashman, 19X9). The Borg Seale (Bnrg. Il)X2) was dl'vcloped wlth tl'stmg of subjects on cycle ergometry and recording physlOloglral ml'a~llreS which eould be correlated with subjective ratings of effort. It may hl' a llSl'flll tool to assl'SS fatigue 111 PPS subjects, if used in conjunction with objective, • 28 quantItative outcomc mea:-.uIL'\11l'l1t.... nt fatl!lut'. a, ha.; lwcll dl1l1c 111 1.\(\!-!1Il' ,tlldll" llll • nOll11al conllOl, (Gl'Idk et al. \l)XX). l'Ylldo:-'(lgIl1II1C ilia)' :tlln 1.1Il' Ill'1I1111111l'l'lII.\l 1.\(I)!lll' III ~ol11e patIellt:-. \VIth PPS hut Il IS not h.nl1\\'l1 ln altl'I the lll\Il"'C III (ht' dl'llldl'I However, no quantilatlve mCa\UICment (If fatiguc W:I:-' uSl'd .• lIld thc c\'aIU,\(lllll IHOl'('dult' ... may not have been sensItIve el10ugh 10 detecl ~l11aJI chall!!c:-, III Ihl' \uhll'L t!'>' t Ullcllllll Long-term, prospective stlldil'~ are reqlllred 10 bl'ltl'I dOCUIlll'llt tlll' l hangl''i 111 I]('alth status, dally functÎon, nerve and muscle propcrtil's III pollo ... UIVIVIlI:-. (1 .Illgl' l·t al. II)~N) Clini<.:ians are encoulaged 10 lise obJectIve outCOI11L' IllL.. \\lIIl· ... III tll':ttlllg PPS p.I(Il·llh • • 29 ------ • .tU Mctl)(Jd~, RC~lJlI.." J)iscu~~i()n • • 30 3.0 i) Article 1 • Rcliabilit~, of Cybc\. Il Isoh.inl'tÎl' Evaluations of Torquc in p()st-Poli()m~'l'Iitis S~'I1Clrtlm(' Monica R. Kilfoil, USc.PT, Diane M.M. St. l'il'lTl', Ph.n, School of l'hysical & Occupational Thl'rapy McWII lJniversity, Montreal, (jucb('c, Canada Address Correspondence & Reprint Requests to: Diane M.M. St.Pierre, Ph.l) • School of Physical & OccupationalTherapy, McGiII University, 3645 Drummond St., Montreal, Quebec, Canada "3(; 1 YS Research supported by Medical Research Council of Canada Grant #MAI0328 Strength testing in post-poliomyelitis . • 31 AC 'KNOWLEUC;EMENTS • The élullJol\ w()ulcl Ilkc to thank Dr~. N R. Cashman, DA. Trojan and PlOf. R. Ua Il lien bau III j 01 thel! a\~i\tancc /Il rcferring ~lIbJect'. and fOI rcyiewing the rnanllsnipt. Wc IlJank P Matthew\ and K. Norman for thelr asslMance in data collection. Sincere thanb arc cxtended 10 alllhe \ubjccts who ~o wi1Jingly donated their time and energy for thl' sllldy . • • AIJSTRACT • The all11 ot llw, \wd)' wa\ 10 a'\L"l'ltdin tlll' Il'II,lhIllly (II I\U"llIl'tIl :--tll'ngth measurements 111 a population nt po'\t-POIll1111yl'litl\ '\uhlnh (pI'S), FIght '\Uhll'l't:-- H males and femak:--, 111ean age of 47 :)± j() and S(I,X± I() y, Il':--pcl'tlvdy) \\l'Il' l'valuatl'd, on a weekly basl" for tllIce weeh at approJo..llllately the \;\llW tlllll' 01 d,IY DUllng l':trh test sessIon the knce f1cxOls and exten",or:-- (htlatl'Ially, Whl'Il' pm\lhlc) \\l'Il' l'Valu,ltl'd, SubJects became fatmhar wlth the el{lIlpmellt pllOl tn Il'lllldlllg t!tll'C Ill:t\lIll,t1 contractlon:-. al the f01l1 te\t vdoutIc:-. (1 ():), 2,(1), 3,14, -1 IXI,Hh" 1) :\ I\\'l)-Illllllltl' Il':-.t period wa" allowed bdwl'cl1 sets of contI act IOn:-., l'hl' vallahlc\ 01 1'(' ,\" tlll li Ul', .1IIgll' 01 peak tOlljue, tOll/ue at :-'pCCltiC .I0111t ,lngk:-- (0 7l) and I,():) 1,1<1,,), tlll,1I l Olltl,Il tdl' WOI", maximum power and avelage power were Il1ca:-'lJIt'd on-llIlt' \VIth thl' ('ybl'x Il :-.ystl'1Il using a cOlllmelclUlly available softwaJe package, ln both Illu:-.ck glulIl", ,rli tlll' v,lIlahks • were sigmfIcantly weaker on the must affectcd, but tl'"tahle IIll1h (p' 0.(1) III :-'lIhWC1S where both limbs could be tl'sted (n=5), Peak tOI que and total \VOl k !lI thl' li uadllu'p:-, were observed to decrea:-.e WIth IIlcreasing vdoCIty of 1l10Vl'1llt'llt 'l'Ill' l'fiel'" 01 \'t'Iollty were less apparent 111 the hamstlIng:-.. Avelagc and maXlIllll1ll pOWt'1 devl'l0pl.'d hy thl' knee extensOls and f1exors IIH;reased WIth increa"ing ve!outy of IIlOVl'llll'lIt Rl'lIahlllty of performance ovcr thrce te:-.t SC\\101l:-. wa:-. conflll11ed hy the IlItl,ILla..,,, LOllelallOIl coefficient (ICC) values clenved from the ul1Ivariate ANOVA'.., calullalt'd 101 C;Jt Il of Ihe above variables (>O.XO), Angle of peak torque, howevcr, wa\ nol IOlllld to Ill" a lellal>1l' measurement across the tluce tl':-.t :-.e:-'~lOn:-. AIthough ",uhJt'cI\ III tht' pn'\l'1l1 \Illcly Wl'f(' tested on three separate occa~ions, rclIability of peak torque OVl'1 Iwo Il'"t "l'\o.,IOIl:-' wa", • also observed, However, peak torque of fleXIOn wa:-. more rdlable on Day", 2 alld r~, TI"", Wd ... l· ... J1l'uaJly Iluc lor kncc flexIOn at 2.()l) and 3.14 rads SCl:'. In conclusion, this study • dl'1ll01l\tl,lted Ilia! a C'yhcx Il l~okll1etlc device i~ a rcliable meam. ta evaluate strength in JWI ... OIl" wlth PPS Key Wor • • INTRonUCTH )N • Poliomyehtl:-- (polio) 1:-- (:lll,ed h)' thl.' mkrtlOll nI hum.1l1 hll"h \\ 1111 thl' neurotropic polioVlIU:--, wlllch 1:-- known to inter! a "lige 1)Çln'lltag~' (2-lU(}C;) ul tlll' 1\1111111 neuron pool at vaIlou:-- Icvel:-- of the fll'lllaXI:-- (.\I1tt'IIlH hOln ldb, III 0 Il 11 IlUdl'1 nI' Iht' brainstem, hypothalamus and thalamlc nllclel and cell ... III tht' pICl.l'nll.tI gYllI') (Blldlan. 1949). ApproxIInately 90% of the pohomyclltl'\ VIIII:-- IIlll'dlOIl'\ aIl' nlln-pal.t1ytll.· Poliomyelitis is now a preventable dlsease, howl'vel. I.llge 11lI1Ilhl'l:-- (lI pollo "'lIIVIVIIIS remain. In 19X5, and more recently in 1t)l)(), the Nallnllal ('l'nll'I fOI 1Ie.dth Slall,>tll' registered ovel 640,()()() paHtlytic pollo :--urVIVOI:--. 111,d-..lIl~! poliO Iltl' 'l'WIIlI IC.ldlllg 1 alhl' of phy~lcal chsahllity in the United States (Mull,at, I l )1)1). l'lm 1',lInl.l!I' 1" 11I1'IH'1 th.lll the 250,O()() Jeported by the U.S. Depallllll'nt 01 Ikallh .I11t1 l "Jlllall SI'l VIll'\ III Iim 1 (Bruno et al. 1991), Furthermore, epldellllologll,tI :--tllCllI''\ haVI' dl'!l'llIllIll'd thal • approximately 25%-50% of cases of paralytlc poll() will dcwlop wh"l 1... III)W Il'l())!lllll'c! as post-pollo syndrome (PPS) (C'odd et al. 19X5: Jlal ... tead l'l al 1')X')) PPS is a complex of systemlc, l11u~LlIloskt' letal and Ill'lIl0logll,d plohlelll\ 'l'hl' three primary symptoms of PPS are fatigue, palll and new wt'akm"\\ III IlIlt\l IL- J!IOltp:- which were affected or unaffected by the onglOal polioVllu\ mlntH)1I UulJt'11 and Cashman, ] 9H7). The etwlogy of PPS remain:-- 1I1lknOWIl Tltt' enlal J!ed, n"UIIH', vated motor units may be vulnerable to carly aging and OVCllISt: wlllch llIay kad 10 the 10"" of tenmnal axonal endings and thus, new 11111\c1e wt:akne:-., (Wlccher", I Neuromuscular synaptic transmission defect~ may lead to the devclopment of IlHI"c1e fatigability and generalIzed fatIgue (Bruno et al. 19<)1). The po:-,t-encephalllil Inloll" of • 34 poliO have al,>o heen con:-'Idcred a,> pO"'>lblc factor:-. in the devclopment of fatIgue III PPS • (HI 1III 1) ct al. 11)1) 1) CUI lent cl 1/11 cal II1tervelltron III PPS hy ,"'pecia!J:-.t:-. 1I1 neurology and IchahrJJlatlu/l medlclllc 1:-' al/llcd at lllanagll1g the~e tlnee mo:-.t C0l111110n and disabling '>ymptolm. Ilowcvel, 1/1 ordcl to be ahle to evaluate the efficacy of a treatment IIltcrvcnllOIl, rchable mea:-.urcl11cnts of l11uscle strength, endurance and pain must be a,>sllrcd. Althollgh isoklllctic dynal110llletry has been used as a Illeasurelllent tool in persans wllh nCUlOlllllsculal d,,>ordcl s, slIch as l11uscular dystrophy (Filusch and Burnett, 1989; Md 'al tncy ct al. II)XX), amyotrophic lateral ~cIerosis (deBoer et al. 1982; Sajak et al. 19X7) and III l'PS (GlOS'> and Schuch, 1YX9), ttst-rete-;t reliabilIty of the Illeasurelllent was Ilot addles~ed specllïcally. Therefore, the purpose of this study was to ascertain the Idlabiilty (lt Isokll1l't1c Illt'asuremenl~ of strength in subjects with PPS, who were • cvaluuted on lillee separate occasIOns . • 35 METHODS • A total of e1ght amblilatl1ry sllb]l'L'''' ("~ Ill,dl''' and Il' l11,dl'~. IllCall ,Il!l' of 17. 'i 1 1Il and 56.X± ln y, re~peL'tlvely) \Vere t'vaillatcd. Ali ~t1bJt'l·t~ \\'l'Il' dl,I1-!.llll\l'd \\ Ith PI'S Il\' hi~tory and physical exalll and plovHkd thell 1I11011llt'd. \\'IIIICIl L\lIl\l'llt tn p:lltlllp,ltl' The study received the applOval 01 the 1I1livelsity Ethlc.., COIl1IllIttt'C Ail ~lIhJl'\ ts \Vell' required to have a minimalmanual 1l111-;de !!lade (lI' ~ III the qlladllL'eps and of 2+ III thl' hamstrings (Medical Research Councll. IlnX) III OIdel tn Iw tl'~tl'd 011 thl' ('yl't'" Il Isokinetic device. SubJcct-; with knee 101l1t pathology. 01 wlth any othl'I nl'lIllllogllal (1( neuropsychiatrie disorder weil' t':\cluded t!OI1l the study Test-retest rehabihty 'va~ as~essed hy cvaluatlllg the "llhll'Ch on a wl'd.. ly ha 'w. for three weeks at apploxlmately Ihe ~amt' tlllll' ni day. DUflll!, l'al h le..,t ~l""I()1l the torque of the knee flexors and extensors (hrlatl'rally. whl'Il' p(l'.,~lhk) wa\ dt'ft'llllllll'd • Subjects became familiar with the Cybcx pflOl to Il'wldIng thll'(' 1ll,lxlIlIal l 01111 dltllln:-.. at the four test velocitie~ (1.05, 2,()l),:) 14, 4.IX rad:-...s 1), A tWO-IllIl1Utl' I('\t pt'lJod W,I" allowed between sets of contractions. The order of tcsting by ~pl'l'd 01 IlInh was Ilot randomized. The torque of the knee flexors and ex tensors was mea~urcd O/l -1 Ille wJ1 h t Il<' ( 'y 1)(' x II system (Lumex, New York, N.Y.) uSlllg a CO III 111 crt'l a Il Y avaJlahlc ~oftwall' paüa1!(' (Flex-o-Ca1c System Versloll 2J)2-CY from Elcctrosport Ine., Toronto) 'l'hl' '>peed of movement and the angle of excurSIOIl were recorded ~imultane()lI~ly with the torque signal. The dynamometer was calibratecl accordmg to the Illallufacturer'~ recommendations and an undamped torque signal, corrected for the cHeu of WavIty, wa<; • 36 Il'l'I\Il'wd • I:ach :-.ubJcLI wa:-. ,>cateel on the Cybcx Il chaIr with the 11Ip" flexed to 1.75 rad~. Slal1J11/at)()1I :-.trap~ were plaœd acrol,~ the II unk, around the wal:-.t and mid-thlgh of the 1111111 tu hl:' te:-.tecl. The analor1llcal axr:-. of the knee JOlJ1t was visually aligned with the aXI:-' ot rotation of the dynamomcter. The lever mm of the clynamometer was adjusted to rc:-.t 2 Clll. proxllnal tu the lateral malleolus. This length of the lever arm was recorded and IItIlJ/:ed III ~lIh~cqlll'rlt evaillation-; for each subJcct. Ver hal elH Olll al!ellll. ..llt wa-; provHkd to each sub.lect throughout the test sessions. The VI~lIal Ânaloj!lll' Scak (V AS) wa~ lll\ed to monitOl pain, immediately before and !OlloWlllg the 1,1IbJect'~ performanle al each test velo<.:Ity (Scott and l-Iusklsson, 197(,). 1>1101 to cach tesi Sl'Sl,lOIl the :-'lIhJl"ct lompleted Cl clinical 5tatus questionnaire detailing any chang" \II ralll. fatigue (lI Inwer exucrmty strength dUling the precedmg week. • Standiud statl\tlcal method~ Wl'Ie u:--ed to calculate means. I\tandard devlations and l"llt'ffIlll'l1h of vanatInn auo:-." the tlHee test sessions and the four veloC/tles, for the followlllg vanahle-;. peak torque. angle of peak torque, torque at specifie .loint angles (0.79 and 1 m lads). total L'ontlactde work, maximum power and average power of the "-m'l' ! kX(l1 and extl'llSO! muscle:-- The intraelass correlation coefficient (lCC) was applled to the lllllVaI laIe A NOV A calculated fOI each of the above variables. A reliability coeffiCIent glt'alcr than O,XO was accepted as the standard for comparison in thlS study (ShlOllt and HCIss. 1971)) . • 37 RESULTS • Subjects The chalacteristics of the !'>UbJl'lh III nlll study aIl' SlIllll.lI tll uthcl Il'I'PII\ III thl' literature. The mean age of acute palalylll pnltol11ydlll\ \\'.\'; 31 \'l'.I1\ \\Ilh a IIH',," interval of 40.4 years ta the omet of new :-.ymploll1\ of PPS FIVl' \uhll't 1\ \\'l'Il' t\llll'Iltiv on a thrice daily, oral dose (fiO mg ) of pyndostlgnllllt' (Ml'\1I1l0!lK), ,Ill alHlI. I!olllll'Slt'i ,ISI' agent, which is used to treat fatigue symploms Seven of the elghl sublCCh Wl'Il' galllfully l'mploycd alld alllll.lIl1tallll'd \'l'IV.ll 1IV\' lifestyles. It IS noteworthy Ihat Iwo ~llble<.ts Wt'It' III thl'It :-.L',II! and Ollc III IIt'l ~l'wnth decade of IIfe at the tlme ot the ~tlldy Ail Wl'Il' amhulatOlY, fOll! \VIth IlO lllohIllty ;wb, one used an ankle-foot orthosis, one usee! a knl'c hlall' and Iwo \I\l'II a l a lit' 101 wal" Ill)' distances, Of the eight subJects who palliclpall'd III the study, only flVt' \uhWl'I\ hall • sufficient lower hmb strength to permIt htlatcral l'valuatIons. Torque-Velocity Cllfves Peak torque as a function of vclocity is illustrated in Figure 1 SICle A wa" dl'llIIl'cI as the weaker limb in subJects where both hmbs coulet be testcd and/of the Il'~o.; éd lel tl'd limb in subjects where one si de was too weak to he tested. Sicle B was dd iJled :10.; thl' stronger limb in subJects where both hmbs were tc~ted. In those subJect!'> (n=5) where both "mh~ could he tc!'>ted, peak torque of the quadriceps and hamstnng muscles, wa'i slgnificantly (p B Chy 42-46% and 31-45%, respectively, depenchng on the vcJouty). Peak torque of the quadriceps was observed to decrea<.,e wlth JI1crea<.,JI1g velocity of Illovenwnt and tll!' • 3X • leJ.IIIVl: raIe of decrea:-.e wa\ \lInilar on both sicles. The effect:-. of velocity were less appalL:1I1 ln the halll'>tflnlt' (Ftg 1). Similar re:-.ult\ were oh:-.erved for torques developed al a knœ IClrnl ant!k of (J 7lJ and 1 0:') ru(l'> (dala not ~hown). A verage power devdopcd hy the kncc extemors and f1exors increased with rncrea'irng veJoclty of movClllcnt (hg. 2) and was srgnificantly (p Ihan srde B (by 54-(11 1/'c, and 54-(13(Y", respectively). SlInil&:r results were observed for maximulll power (5(1-61% fOi exten:-.ors and 54-6<)% for f1exors). To(,t1 cOlltl actlk work, Ilkc tOlql'e, decreased with increasing velocity of 1Il0Vl'1lll'1It. Total work 01 the quadriceps and ham~trings was significantly (p< 0.(1) lowl'r on Sldc 1\ than B (by 52-7Ylo and 4lJ-57%, respectively). I{cliahilify No slgnifrcant difference 111 the outcome measures of peak torque, angle-specifie • tOI qucs, aver age power, maXIll1U1ll power and total contractile ",'Ofk over the three test SC!'>SIOI1:-' was ob:-.erved wlth one-way ANOVA analyses. Furthermore, the ICC values were peatel than O.XO (Tablc:-. 1 and 2) Angle of peak torque, on the other hand, was not round to be a reliahle Il1casuremcnt across the three test sessions. Reliabihty of peak torque over two test ses "ions (Day 1 and Day 2) or (Day 2 and Day 3) \Vas also assesscd. However, peak torque of flexion was more reliable on Days 2 and J tTahle 3). The coefficIents of vanation for peak torque of side A ranged from 10-12';(, and 15-20% for the knee extensors and f1exors, respectively. The procedure of isoklllt'Ilc t'valuation was well-tolerated by subjects, as indicated by low ratings (0-2) of palll 01 dlscnmfOlt on the V AS, for WhlCh acceptable reliability h?s been shown (Dixon • 3lJ and BiId, IYXI; RevIlI et al. IlJ76) • J>ISClISSION Isokinetil' dynamometJy has been ~hllwn ln Ill' a Idlahk Illcth(ld III 1I1l'.1'>1I111l)! strength in healthy, trailled indlvldual.., (Pellll1 ct al )lJX7); 111 1I1l11.tIllCd IIldl\ 1<111.11'> III both sexes (Harries, 19l)(); Johnson and SIl'gal, !97X; Kr.llnel et al IlnN, 1\1.1\\lbkv .lIld Knapik, IYX2; Mayhew and RolhstCIIl, IlJX5; Montgoll1l'IY et al )l)Xl), \{oth'\\'1I1, l')X'\ Thigpen et al. 19lJO; Thorstensson and Karlswn, Il)7Cl, TI ed III 1lIl' k. )l XX) and III l'Ide JI y subjects (Laforest et al. )lJlJ()). Mul'h ft·..,.., is known abolll how Idlahly \tll'Ilglh l.1Il 1)(' measured in vanous patient populations The pll'~l'IlL'l' of 1l1010l 111111 Il.11l\llIllll.ltlllll (enlargement, changes III contractIle charactenstll's), mllscle wl'aknt'~s, allt! IIIl' plllt'lIllal for a wide variation 1Il performance in sub,ect~ wlth 1ll'1II01l11ISCular dISOIdl'l-;, creatt' a particular challenge to c1inicians and lescarchers. As wLlI, knowll'dgt' 01 thl' Iltlllll.l'i 01 • test sessions required before reliablc mfOlll1atlon l'an hl' ohtallll'd IS an IlIllHHtant consideration in measunng performance. Kozlowskl (1 YH4) reported reliability coefficients of () X2-() lJX, fOI l-;okllJ('tIC strength of the paretic lower hmb of Il hCllllparctlc slIbjcct<;, mea~url'd 011 Iwo dllft'n'lIl days, The reliability coefficients were somewhat hlghcr «() t)()-(). (]3) lor the 1l01l-p,lreIIL Iimb in these subjeCl'i. Tripp and Harris (l9Y J) used the Lido isokinctlc dcvicc to ~tlldy te\t-retcst reliability of peak torque at two velociues in 20 subJect~ with hcmlpare~ls. The ~lIh,ect\ were evaluated on two different days, separatcd by a two tn four clay mlcrva!. They reported lCC values of 0.92 at 1,05 rad/sec, and (J.1)5 at 2.14 rad/~(~L. HorcnCl' and • 40 SLhwll)('ckcr (J!)Hl)) /cpOlted ICC value,> of (l,lJ4-0.lJ7 for peak torque value~ of the knee • extell\o/\ and Ilex{J/\ 111 young \Uhlcct\ (5-1 () yca/ \) w/th Il1U\LlIlar dy~t/Ophy tc\ted twice wlIllIll two day\, hy the \ Anotlw/ \!tHly LOlllp:lled 10 ambulatOlY ~ublccts with multIple sclerosis (MS) ta 20 healthy LOllt/01 \UbjClt'i (Armstrong et al. 1l)~3). Data on peak torque, angle of eXlUr\IClJl and total work at 1.22, 3.32 and 4.02 rad~ SI were compared between the two 1!IOUpS, fOI hoth the strength and fatIgue te~ts. Hlgh reliability (Pear~on's r=O.99) was dClllol1\tratl'd lll'twl'l'/1 two trial\ within one test ~e'ision for both the MS and control Sl/hWl t'i lIowcve/, le ...... l'elrahle /C'iult~ wele ~hown for three additional MS subJects who llnclerwl'nt tlllCl' /cpeatcd tesh (at 0, 6 and II wecks). Althou1!h the rehabIllly of sttcngth testll1g has been demonstrated 111 various populatIOns, gl'llcralwlbIlity of thesc results ta PPS is lllllited, because assessments were • perfo),llled on Ill:althy control individuals or on other patient populations. Differences in testing p/Otocols also 11I11I! the compaI isons which can be made between stl/dies. Our study demonst/ated that muscular performance of subjects with PPS, measured isokll1ctically, is rdiable. Although subjects in the present study were tested on three separa te occasions. /ehabihty of peak torque over two test sessions was also observed. The rehabIlity 01 peak torque on Day 2 and 3 was slightly better than on Days 1 and 2. This \Vas l'spcCIally trul" for knee flexion at 2.()l) and 3.14 rads sec-l, as indicated by ICC valut's Imwr than (l XO. The percentage of variation observ~d in our PPS subject'i, was 11Ighl"I' than those reportl"d in normals (Johnson and Siegal, 197X), but were similar to thosl' repolled fOI other patIent populations (Giles et al. 1990; Tripp and Harris, 1991) . • 41 InterestlI1gly, the valut'" \\'t'IC 11Igher 111 f1l'XIllIl than 1Ill'\tl'n~lon. abo ~ll~~l'"llI1g a ~1l"III'1 • vanabdity. Why "Ub'l'L'h rl'ljulIl' 11100e WHe tll dCIlHlIl"tIalC lcllahll- )1l'l Illllllanu' III ~Ill'l" flexion 1:-' uncle:u Tht' d I~l'Il>pancy ma)' Iw dUt' 10 1hl' f.lcl 1hat a ll'llJH ill ,JI )" otlllili III extension-flexion wa" cmployed Although reCipllll',tJ pJ(IIOl'o!-. ha\'t' hl'l'Il llïHlI Il'd III hl' reliable IP normal healthy COlltlOls, and ail' clll11l11only u"cd dlllll'all\', \\'1' h,I\'I' nh't'lVl'd that subjects need to be rt>ll1l11ded to pcrtorm a l11a\ll11,11 IkxulIl l'iimt It has been suggested that te:-.Hete"t Il'Ilablllly III 1l1l1\lle Pl'lloIlll:llltt' 1\ influenced hy I1lU~cle stIength. The WOI k 01 wlth rheumatOld arthnti" versus healthy LOlltlnl" "h(lWl'd Ih.lt Ihl' II'"t Il,,,1 \l''''IOIl \\',1" reliarle for contrais and !\ubJccts who LOIlld gl'Ill'Iatc .t pt',l~ 101qul' 01 )" NI11 (lI Illolt' However, a second test wa~ found to be I1t'Ll"!\al)' lor ,l'Ilahll' Il'sldt-. 011 \W.\~l'I 'lIhWlI'" The results of our study on sublect~ wlth PPS do nut l'OntHIll thl'''l' tllldlllg ... 111~'h 1('(' • values were obtamed at the ~al11e te"t vcloL'l tll'" (1 (JI), 2 (J(). 3 )4 l ,Id ... ~ 1) dl"PIfI' Ihl' inclusion of 0 of X subJects who produced tO/qlll' of le~:-. than ')4 NIll hHlhl'llllOf(', previous work in our laboratory ha!\ shown that rdlahllity of strel1)!th 11'''llIIg 1:-' 1101 influenced by the age of the subJect, although strength dcclllles wllh advalll'lllg a!!(', particularly at faster veJodties (Laforest et al. 1()l)O) PPS ~lIhJt'CI" 111 Iht' llll/l'Ilt :-'Illdy were found to be weaker than age, helght and welj!ht-méllched LOl1tJO].., by 4X and ~ ~(Y," respectively, m the knee extrnsors and f1exor~ The question of whether aglflg of the If1cllvf(llial IllflllCncc.., Illotor llllit d Y'" fllf Il 11011 in PPS remains controversial (Wmdebank et al. 1t)l) 1). It i\ klJown that the 1lI1111hl'f of motof units decreases In normal human aglflg hy the :-'Ixth (Mc('ofl1a ... el al 1()T~) or • 42 ....\·v(·1I11I (l(lIllllIl .... OII dllCf Irvl/l}.!, l'n7) ckcade,>. If Illotor nClIJon los:-, with advancing age • V.d\" 111"1"1 laLlor III PPS tllen one would L-XpCLt to fme! a ,tead)' declllle lJ1 fUl1ctlon of p.J1.tfylll Plllro ,>urVlVOI" wlth InUCa'lIlp age A" a matter of faL!, Dalaka, et al () 9X6), oh\I'IVl'cf a )Ik per ail III 1III deLline In ,trength in ~ymptolllatIL pollo 'iurvivor'l, le'ls th an (,I) yeill'> of a)!c, w/m,1l \.,ta" not ~lgnIfJcantly different l'rom data on normab. Other ,llIthol \ have L have al\o oh"erved tha! our ('Ide ..,t :-'lInlcct'> were no! Ilece:-,~arily the weakest, fllrther \lI~!I!l·"II/I.!-' thal tht' IIldlvldual'" ag~ 1., not the mo.,t imp0!lant factor contnbllting ta IllU\l Il- wl'aknC\\ III PPS, 01 IUlther Intere,>t, PPS ha'i been diagnosed both in polio \IIlVIVOI \ III thel! .1(1':-, ,Ille! altel the :-.eventh and l'lghth decade:-. of the Ir lIves (Ciocon and Pottel, )l)X l); lia l "tcad, 19X7) ThiS infOl matI on supports the evidence from epH!ell1loloj.!ILal :-.1lJ(lrc:-, whlch ~lIgge:-.t:-, that the length of the Interval between the acute • pollovilu\ IIlfl'LlIO/l and the appearance of new symptoms, and Ilot aging per se, is the IlHlIl' 1!1lpOltani factor (lIal,>tedd, )9X7; WlI1debank et al. l'NI). ln L(1I1clll:-'lOn, our 'Itllcly demomtrate~ that :-,C'nal isokllletic strength assessment IS a ll'ha hie ml'thod 101 mea:-'lIrement of nm~cular performance in subJects with PPS. HOWt'Vl'I, It IS !l'COI1lI11l'IHled that a :-.ufflcient Illlmber of te~t sessions be conducted to c\tabhsh a :-.table ba:-.eJlIH' of peJ/ormance 011 thIS particlllar patient sample in order to c>..amllll' thl' l'!led 01 a thl'Iapelltlc IIltervention. It I~ proposed th nt a Cybex II isokinetic devll't', If u\cd applOpllatt'ly, Lan measllIe chnicnl change and may be lIsed to examine the l'trect of vallOllS treatment mterventions to ameliorate strength in persons with PPS . • 43 Table 1 Intra-chlss Correlation Coeffidcnts (ICC) Umb l\lovcltlcnt "clodty PT AI1~lt· P r TOI 'lm' (,U Til ni m' ,1., rad.s-I dt'g dl'g • Affected 1.05 0.82 0.90 0.9 1) Extension O.·'N 1 N=8 2.09 0.99 0.88 0.9 ' 0.99 3.14 0.98 0.84 0.98 O.tJN 4.18 0.99 0.34 0.97 0.98 Flexion 1.05 0.95 0.39 0.98 0.97 2.09 0.81 O.fU 0.96 0.9(, 3.14 0.92 0.70 ().94 0.96 4.18 0.94 0.46 0.88 O. ·'4 Unaffected Extension 1.05 0.95 0.88 ().94 0.87 N=5 2.09 0.95 0.5(, 0.97 ().9(, 3.14 0.87 0.54 0.96 0.97 4.18 0.98 0.72 0.9(, 0.96 Flexion 1.05 0.96 0.91 0.97 0.96 2.09 0.83 0.26 0.89 ().90 3.14 0.91 0.20 0.95 O. tJ (, 4.18 0.98 0.57 0.97 0.97 • PT Peak Torque • Tahle 2 Intra-c1a'is Correlation Coefficients (ICC) • Lirnh Movement VeJocity Total Work Average Maximum rad.s-1 Power Power Side A Extension 1.05 0.91 0.98 0.89 N=8 2.09 0.93 0.98 0.94 3.14 0.86 0.98 0.98 4.18 0.90 0.98 0.98 Flexion 1.05 0.97 0.91 0.95 2.09 0.96 0.95 0.95 3.14 0.95 0.88 0.84 4.18 0.97 0.91 0.93 Side B Extension 1.05 0.80 0.93 0.93 N=5 2.09 0.84 0.94 0.92 3.14 0.89 0.98 0.90 4.18 0.99 0.97 0.94 Flexion 1.05 0.93 0.97 0.97 2.09 0.99 0.97 0.94 3.14 0.92 0.96 0.90 • 4.18 0.98 0.98 0.98 • Table 3 Intra-c1ass Correlation Co('fficiellts (Ie(') • Limb Movcrncnt Vclocity PT 1'1' rad.s-l 01/112 D2ID3 Side A 1.05 0.91 0.93 Extension N=8 2.09 0.92 0.97 3.14 0.86 0.82 4.18 0.98 0.96 Flexion 1.05 0.98 0.93 2.09 O. (,5 0.9(, 3.14 0.77 O.SI 4.18 0.94 0.98 Side B Extension 1.05 0.98 0.98 N=S 2.09 0.98 0.97 3.14 0.98 0.97 4.18 0.98 0.9S Flexion 1.05 0.97 0.94 2.09 0.72 0.92 3.14 0.85 0.87 4.18 0.89 0.91 • PT Peak Torque • J'i!;lIfl' / TO/que- Velocity curves of the knce cxtcnsor and flexor muscles. Peak torque • valucs arc di~playcd for: Sldc A: 'IllC wcakc.<,t IImh in ~uhjCClc; whcrc both limbs could be tcstcd and/or the least affccted 11mb in suhjccl<; where one side was too weak to be tested. Sidc B: Ine strongcst lirnh in subjccts where both Iimbs were tested . • • Figure 1 • Day 1 240 240 -E z 220 -E 220 z - - 200 200 c 180 o 180 • CIO 160 160 c .!m 140 140 )( ., W." 120 120 .,0 100 :s 100 ...C- 80 80 o ... 60 60 .à: 40 40 .,• 20 a. 20 o o 1.05 2.09 3.14 4.18 1. 05 2.09 3.14 4.18 Veloclty (rad.s-1) Velocity (rnd.s-1) • 240 240 220 220 -E -E z 200 z 200 - 180 c 180 c 0 0 160 160 -;c )( .!ct 140 .!m 140 u. u..., al 120 120 .,~ G)~ :su) :su) 100 c- 100 ...C- L- 0 80 ....0 80 .... 60 60 .:tt ~ cu ID 40 al 40 ., Q. Q. 20 20 0 0 1.05 2.09 3.14 4.18 1.05 2 09 3 14 4 18 • Velocity (rad.s-1 ) Velocity (rad.s-1) • f<ïxu rf1 2 Average power vcr!>us VcJOClty curve!> of the knec extensor and nexor mu!>c1es. Average power values arc displayed for: Side A and Side n, for dcfÏnition sec Figure J . • • Figure 2 Day 1 ...... •[2] Day 2 110 -ca 600 .. 600 ~ m Day 3 ca • -- ~ c SOO --- 500 0 c • 0 cm 400 ~< 400 ~ II) II) Gl M" w- )C- t/) w(/)-" 300 300 "- II) ~ :c GI 0 200 :c 200 a. a.0 •01 GI 100 100 DI "- " ~ •> "GI > 0 < 0 < 1.05 2.09 3.14 4.18 1.05 2.0 9 3.14 4.16 Veloclty (rad .•-1 ) Voloclly (rad.s o l ) • -...... 110 .. 600 :::CIl 600 .. ca ~" ~ -- 500 -- 500 c c 0 )CID ~< 400 )C 400 CD CD CD Gl LL_ LL- -"t/) - "en 300 300 .. ~ CD CD ~ ~ 0 0 a. 200 a. 200 CD Gl DI 100 DI ca 100 .. Jo. "CD QI > > < 0 < 0 1.05 2.09 3.14 4.18 1. 05 2.09 3 1 4 4.18 • Veloclty (rad.s-l ) Vcloclty (rad s-l) .tU ii) Artide Il • I{eliahility of' bokinctic Evaluation of Neuromlisclilar Fatigue and the Effecls of Pyridustigrnine un Suhjects with Post-poliumyelitis Syndrome: A Pilot Study J M. Kilfoil, HSc.lyr , n.M.M. St-Pierre, PhD!, 2 2 D.A.Trojan, M.D. , N.R. Cash man, M.D. J School uf Physical & ()ccupatiuual Therapy, McC;iII lJniversity, Montreal, Quebec, Canada 2 Dcpartment of Neurulugy, Montreal Neurological Institute, • Mun. real, QlIebec, Canada Addrcss Reprint ReCluests tu: Diane M.M. StPierre, Ph.n 8chool uf Physical & Occupational Therapy, McGiII University, 36S4 Drummond St., Montreal, QlIebec, Canada H3G lYS Rl'scal'ch SllPl101·ted by Medical Research Cuuncil of Canada (;ran' #MAI032N Fatigul' in pust-puliulIl)'elitis • 44 Acknowledgements • The authol'> would IIke tn thank PlOf R. Dalll1l'lIb.1ll11l .\IId P i\ 1.lttlle" ... hll thell assistance 111 data collection and K. Norman fOi a\:-'I:-.tin!! wlth d.ILI lolll'ltlllil .I1l1! Illi revlewlIlg the manuscnpt Sincelt' thanks ale extended III ail the ","hll'l t:-. \\ 110 :-'0 willingly donated their time and energy for the stndy • • ABSTI(ACT • ()uanlllatlve Illean:-. of rehably evaluating fatigue JJ1 PPS remain to be clclJ1oll,>lIaled ln the clIIrent study, a fatIgue protocol wa:-. dcveloped and tcsted for ICllélhllity on 7 PPS '>lIb/ect<. comparecl ta 15 normal controls. The sensitivity of the protowl to dctcct an effect of pyndo:-.tigmme, an anticholinesterase agent used In the lIeatlllcnt of PPS, wa:-. abo a:-.sesscd. The protocol conslsted of 25 reclprocal contractions of knl'e fleXIon and extension perfonned 011 an isokinetic devlce (Cybex II) at 3.14 lad:-. "Cl. 1 RcllabdJty wa:-. a,>:-.e,>"ec\ by three baselme mca:-.urements made at weekly IlItl'lvab, al applo.\llIlately the saille lime of clay. SeIl,>Jtivlty was evaluated on two :-'Ub:-'l'qlll'IJI Wl'l'k'> wlllle the PPS slIbJects wele either ON (00 mg tid) or OFF the IJ1CdlLalloll The slllgle evaillator wa:-, blinded to the date of withdrawal or re-initiation nf the (h lIg, however, 110 placebo drug was used to bhnd the PPS '>Gbjects. Each subject's • lating 01 )lclu'lved exeIlJOJl (Borg scale) and pain (Visual Analog scale) were monitored. Intra-cla:-.s lOlJelatlOI1 coeffICIents (lCC) were calculatec\ on the uruvariate ANOVA's of tht.' abslIlute and Idatlve fatigue mdlces. SlIllple linear regression analyses were applied tn the angle-speclflc tOlljUt' of the knce extensors. The resultant slope values were th en subjl'ctl'd to multiple hnel" IcgIrssion analysis. Paired t-tests were used to compare the PPS slIb)l'cts' petfm mancc while ON or OFF the drug. The ICC values for total work and avelage powel of the knee extensor:-, showed reliability (>OJW), but reliability of knee tlexOls W:l:-. :-.hown only for control subjects. The relative fatigue index was not shown to be Il'hahle The plOtocol dld not diffel entiate between PPS and con troIs in terms of the laIe nI' dewlopmcnt 01 fatIgue. The protocol was not sensItIve enough to detect an • el kll 01 the dlllg on LiIIgul' acro:-.s the group of PPS sub.lects. However, 3 males were weaker and 1 male dell10nsIJated lncrea:--t'd fatlgahlltty whIle 01+' the llIl'dIL.IIIIJll Thu,>. • fatlgabllity ran be tc:--ted It'hab\y \VIth an Isokll1t'tlL' plotllL'll\ Whllh 1" a\"ll \\l'll Illkt.lled by subject:--. Howevel, modIfIcatIon!'> of thl' plOtocol aIl' 11'qulIl'd 111 Olllel ton.tllI.1Il' tltl' effect of a drug 11lterventlOn fOI PPS Key Words: Poliomyelitis, Post-poliomyelitis syndrome, Fatigue, Pyridostlgmine, Isokinetic, Reltahlhty • • 1N' J'1{ ( ) 1) , J( ~'J' J( ) N • J-;1l1J!1I~ 1<., lh~ IllO',! UJIlllllUn 01 th~ thllT pnmary ~ymptom,> of po,>t-poliomyelitls "YlldJ(lIllc (PPS), OCCUfflll)! ln XWk, (Ian)!e 75-X et al. IIJHS, l'abtead et al. 19X5) Neuromllscular fatIgue oœurs folIowIIlg ev en low kveb of physilal actlvlty (Mun\at, 1()l) 1) and Illay be associated wlth translent weakness on CXCltlOll, Whllh J1nplove~ wlth rest. Recovery takes minutes or hours and varies from Olll' IIldlvldllal to anothcl. Currently, fatIgue symptoms in PPS are managed UlllSl'lvatlwly hy modificatIon,> of a per~on's daily actlvltIes. l'Ill IIJO\I' pallcllt~ 'vho aIe (iisabled by fatigue whlch does not respond to COIlSI'IVaIIVl' mall.tgl'Illl'nt, pharmacolaglcal management may be considered. The nCliwlllllsculal li al1~ml~\IOn dcfcct III PPS IS believed ta be pre-synaptic. Defective telllllllai axonal conduction, the los!> of termmal axonal sprouts, or the impaired release • of the Ill'ulOtlall!>Jlllttcl, acetylchollllc, may underlie the defect (Bradley, 1n7; lubelt and Cashmall, 19:-17, Stalhcrg et al. 1974; Wiechers, 19RX). Anticholinesterase agents block the hydl()lysl~ (Jj acetylchohnc (ACh) at the neuromuseular jllnctlOn and thus enhance the actIon of ACh III IlCllromusutiar disOIders (Adler et al. 1992; Goodman et al. 1985). PyIidoslIglllllle, WhlCh i:-. an oral anticholinesterase agent, has been used effeclively in the lIeatmt'llt of the post-synaptic dysfllnction of acetylcholine receptors in myasthenia gravis (Engel, 19X7) P,ellIl1InaI y work suggests that it may be efficacious in PPS (Trojan and ('ashman, )lJXlJ). Indeed. a one-Illonth tllal of pyridostigmine revealed a decrease in fatIgue symptl'Ills as determined by a hnear seale (Hare et al. 19X5) and an increase in the Rn t!ld funL'tlOn.ll mdex (Katz et al. 19(3) lI1 16 out of 27 subjects (64%) with PPS • 48 (TIOjan and Cas/umll1, IlJXlJ), Basl'd nn thesL' l'llrOlll.lglIIg 1l'';UIt.;. ! ut 11Il' 'Ill" le' \\ lulll • employ quantitative methods to l'valllate fatlgllL' 111 PPS !'thoulll hl' llllldlll'll'd To date. fl'\\' plOlncol\ havI.' been dt'vdnpt'd 10 It'hahly qll,lllltly IH'III1111IlI\llll,\I fatigue in PPS, One rese,lflh group (AgIl' and I{ndllqllt'/. Il)l)(); RO 19(1) has used an isometric fal1gut' Plotocol III evalllatt' PPS SlIbfl'lIs, hll\\'l'Vt' 1 , the question ofreliability of rneasuremcnt wa!'> not evalllall'd PielII1lIIlaly \\'01" (Klllmi ,lIIlI St-Pierre, 1992, in press) 111 our lab has estabhshed that l';O"II1t'tlc SIIl'llglh Lall hl' Il'hahlv measured in PPS !'>ubjecb, and that the Isok JI1l't Il plOu'dUll''; aIl' \\'l'II 1okl ated Il,, tlll' subjects. The present !'>tudy will extcnd thls \VOl" 011 IMlf...lJIl'tll tl',tlllg 10 ,l''\'\\ IIIl' reliability of adynamie, isokllletIc fatigue plOtowl Oll ';lIhll'l't:-. \\'1111 PPS '1'11(' plolmol will be used to detefl11lne the effects of pyfldostlgmrne Oll Ill'UIOll1ll'llll,1I t,ltlglll' 111 a group of subJects with PPS who showed a subJective IllIp/OVCIIH.'llt III tatlglll' '>ylllptolll'> • in the preliminary study by Trojan and Ca!'>hmall (llJXlJ) . • 49 ~\1I·:III()I>S • 1\ 1(j1,1l 01 \\:\'l'/1 dlllhlllaiory PPS \UbJCCh (4 male<;, 3 fcmales) and 15 normal LOnl! (II .... lIIJJl·LI\ «() Illak .... , <) lemalc\) gave infOlmcd, wrrtten con\ent ta paItICIpate in the \llIcJy TheIl' wa\ no \'gnrflLant (hffcrcllcc bctween the two group" of ~ubJects in terms 01 a~c, :-.ex, hCI!!ht and wCIght (Tabk 1) The mean age of acute paralytIc poliomyelitis wa~ 4.5 ± 3 9 yr wIlh a ll1\:an IIltcrval 10 on~et of PPS of 42.1 ± 11.2 yr. AlI of the PPS \lIhJCLl~ hac! nCUIOl1lll\lUlaI fallplc a\ a pnmary symptom and were known subjective Il'\/)(lIH!l'!\ 10 PYlIdo<;I!,l'lllll1l' (/'!O"1Il and ül\hman, IYX9). Ali ~ubJects were required 10 have d Illlllll1111111 Illdllual 1l11l\lk gracie of 3 III the knee extensors and 2+ 111 the knee f Il'\o! ~ III OIdcl to pel l'DrIn Ihl' l'.. oklllttic testing (MedIcal Re~eaJch CounClI, 197~), SllhJeLl~ wIth k.nee Jotnl pathology, Ol with any other neurological or neuropsychiatrie dl'wrdcl Wl'Il' excluded 11 om Ihe study Prescribed medlcations were recorded, but not • wrthlH'ld tWIll the .... lIhWlh ~xp('rilJwntal l'rotul'ol 'l'hl' d) naIl1ll 1allgul' Plotocol consisted of 25 reciprocal, maximal isokinetic l L'OIlII adlon\ (lf k. flCt' t'x Icn~i()fI and fleXIOn, (unilaterall y), at a speed of 3.14 rads.sec· , Vl'I ha 1 l'IlUlllI ap.l' Illl' Il 1 \\ a \ provlded to each subJect throughout the te~t sessions. A Il'peall'd Illl'.I\UI t'\ de\l)!n wa~ uscd to evaluate the subjects at weekly intervals. Three ha'clmt' Illt\I\UIC\ \\t'It' u.... t'd to t'Àamine rehability in both groups. At baselme, the PPS ~lIhJl'Ch \\'Cll' tak.lIlg Ihe mall1tenance dose of pyridostigmine (ON 60 mg orally, three tunes t'valuatwl1 'l'hl' halt-lIk of pyndostignune is three hours (Goodman et al. 1985), so a • 50 minimum time of -l-X hOlIl~ elapsed artel the (hllg \Va!'> \\ IIhdl,I\\ Il (OFI) l'Ill' LIII~!Ill' • protocol wa .. then repcated onl y onL L' to a\!'>l'SS the subJl'ct'!'> IC"IHlllSl' OH: t Ill' 1II IIg The date for the withdrawal of the (h ug wa!'> sckctcd 1'01 cach sllhwrt alld the slIIgk cv,tllI,HllI in the study wa!'> kept blind to the date 01 witlHiIawal 01 le-mlllatlon 01 lhl' d11l1' :\ placebo drug was not w,ed ta hlllld the subJl."rt!'> in this prc\imillary !'>llIdy Instrumentatiun for Data ('ullcction: The Cybex Il sy'item (LlIIllCX, New York, N.Y) litled wlth a l'Illllllll'illally available software package (F1ex-o-Cak System Ver SIOIl 2,02-CY ft (lm Fiel 11O"lhll 1 Illl , Toronto) \Vas used ta l11l"a'illIC an lIndal1lpl'd tmquc !'>l!:!l1al. LOlll'lll'd Ill! Ihe l'lied ul gravity, Each subJect was !'>cated on the Cybex Il Lhall Wllh Ihl' IlIp" Ik,\cd \Il 1 75 1:1<1'>. Stabilization straps were placed acros!'> the Irunk, and around Ihl' w;ll:-.I and 1ll1l1-lIlIgh (lI the limb to be tested. The anatornÏçal axis of the km:e Joinl was vl!'>lIally aI11!Ill'd Wllh Iht' • axis of rotation of the dynamometer The lever arm (lI the dynalll0l11l'lt'1 \Va\ ,«1,11\1('<1 10 rest 2 cm. proximal ta Ihe lateral malleolll!'> The lever aIm knglh W,l', Il'lI)/(!t' utilized in subsequent l'ValuatIOns for each suhJcct Prior to each test session the ~uhJect complcted a dlllleai 'italu\ qlll'~tl{)ll\laJH' detailing any change III palll, fatigue or lower ex trCIllIty !'>trength cl IHIIl).! 1hl' pn'u'dlll)! week (Appendlx B). The Vlsllal Analogue Sude (VAS) wa\ u:-.cd 10 1ll01111()( palll (Appendix B), 1I11medIately befon; and folluwrog Ihe "ub,cct'!'> [1eIfo/lllilm (' ()I IIIl' lalll'lI(, protocol (Scott and Hu~kl"'iun, )lJ76). 'n addition, the I (Borg, 19X2) (Appcndlx C) wa<., completed by eélch ~uh,Cd 11ll1l1l'dlah'ly f()ll()wllll' completion of the fatigue protocol. • 51 Stati.,tÏ<'al Analv.,c ... : • Me<1ll'. and ..,tallda/d d~vlatron., were ealculatecl and unpailed t-tests were Jll'II CJIIlll'd t() dl't~r JllIJH~ ~rgnif ieallt diffcrcnce~ between the characteristics of the two l'IIlUP\ (lf 'lllh,ClI\ The torqll~ or the kncc extensor~ and llcxors, developed at two speciflc joint angle\ (().7lJ alld 1 ()') 1 a(h) for l'ach of the 25 contractions, total contractile work and (lvel al!~ pOWCI WCll' thc dl'pcndcnt varIables A relatIve fatIgue mdex (ratIO of the last :) ovel Ihe 111..,1 5 lonll al IIOIl\) wa~ abo caJculated (Thorstem'lon and Karb~on, 1976). l{l'IlahrIlty Via\ (ktCIIllIIlCc! hy lJ~C of the inlracla~s correlation coeffIcient (lCC) applied 10 Icpcated Illea'lllll'~ ANOVA analy~e~, 011 the aforementioned variables acIOS~ Days 1,2,3 vel MIS J).ty~ 1,2 in hoth gr oup~ of ~ubJeets (Shrout and Fleiss, 1979; Equation 1.1). Ba~ed on the n~~lIlb or the Idlabrhty analyses, data on torque, work and average power • 01 the kncc extensO!" Il o III tl'\t~ on Days 1,2,3 were u~ed for comparison between the two !!I ou p~ of ~lIhJl'cl\ Simple 1III l'al regll'~\ion analyses were applied to the angle-specifie torque of the klll'c l'xtl'Il~()(~ 101 ail 25 contractIons of the fatigue protocol. The slope values were ~lIhfl'cted tu Illultlpk Irncal /eglt.·~~ion analysls. The ~l'Il-;ltIVlty ot the fatigue Plotocol was determined using paired and unpaired t-tc~t~. 1) hel\\'l'{'n PPS ~lIhfl'el'; versus normal controls and ii) while the PPS subjects Wl'Il' ON 1lI OFF Ihl' dlug Non-par pel tnrllll'd 10 detell11l1ll' if pall1 1Il1luenced perfonnanœ of the fatigue protocol within and • 52 between the two groups of subJects. In add itlon. pa 111 and fat Igut' seilH'" Wl'Il' l Illllpall'd • \\'CIl' Of while the PPS ~ubJel't" ON OFF the drug, RESULTS Nunparametl'Îc Data: Before reliability of a fatigue protocol ean bt' establishcd. tal lm S SUL h .IS thl' kwl of perceiv~d exertion and the mtluencc ot palll ~hnuld IK' .Iddlt'ssed Thl'll' \Va~ 110 significant difference in the VAS scorc'i betwcen the PPS and 1l01lllai "UhJt'll" (Tahll' 2) Furthermore, there was no ~igniflcant dlfklcnlc whllc the PPS :--uhWLI:-- Wl'Il' ON 01 OFI the drug. The PPS subJects leported Ievl'l~ 01 pClcl'lVl'd CM'IIHIII 011 tlll' BOl)! \l ah' following performance of the fatIgue protocol wlllch were Ilot :--tatl ... tlcally (1111l'1(,111 110111 the nomlal subjects (Table 3). Howcver, they rf~p()[ tcd 11IghcI lever:.. of l'f t 011 wIll k 01 + the drug versus ON (p • both groups of subJects and pall1 dld not appc,1I tn IIlfhll'llll' thclI perl Ollllalll l' Reliability uf Fatigue Protucol: PPS versus Normal Controls: The angle-speclflc torque of the knee exten!'>or~ (at () 7lJ and 1.05 r after two test days in PPS and normal controls (Tahk 4) Ifowevl'I, the klH~l' fkxor~ weil' more reliable after three ruther than the fïf'a two n:pl'atl'd ll1ea\lIlCllIl"nl\ III l'I'S and normals. The ICC values for total wO/k and avera~e power Wl're 11Igh fOI the kn('(' extensors and flexorl\ in normals after only two days 01 test 111 1:' (Tahll' 5). Ilowever, tlllcl' test days were required to show reliabil'ty of total wc" k and average power of the knœ extensors in PPS subjects. Total work of the knec f1CXOf\ III PPS ,>ublcct\ wa ... not reliable evell after t'lfee test day~, and the ICC value for average powel wa" hlghcr alter • 53 ------_.... _-- ttH" III.,t two clay., rathel than after three test days. • 'l'Ile relative latI1-'ue I/Hkx (PPS (J.05, COlltrob () 0(4) dld not show reliability. B :l'.. ed O/l t he re~u Il,, 01 1 d 1ahll 1ty tC .... tl/lt! of the rCl iprocal fatigue protocoI, the outcome vanabk .... 101 total WO/ k and avcl a1-'c power of the knee extensors, and the sIopes of the rcgre~<;I()/l analy~l""" weIl" u.... ed fOI companson of fatIgue responses of PPS subjects versus nOllllal LOl1trol'i, and whlle thc PPS ~uhJects were either ON or OFF the medication. Scnsilivily (,,. l'm'oeul lu Evaluate Fatigability of PPS versus Normal Subjects: Tht: PPS ~lIh,Cl h w (F1glllc la). Olle wou Id expect that the value:-- for average power to be Iess in PPS ~lIh,Cl't:--, but llm wa .... not ob-;erved (FIgure 1b). Further analysis revealed that the time penoe! through wlllch the PPS subJects were generating torque sufficient to be registered by the softWaJC plOgram was less th an that of the normal controls. Therefore the finding • of no e!ilfell'Ill'l' III average power was considered to be an artlfact of the analysis pIllCl'e!lII e. Although the PPS subjects were weaker lhan normaIs, there was no significant (lIf tel l'net' 111 the rate of development of fatigue, as shown by the plot of sI opes of the Il'gresslOll analyse:-- of torque output (absolute and nonnalized to the first contraction) as li fUl1etlO11 of lime 10 complete the 25 contractions (Figure 2a,b). The pt'Ict'ntage decline III normalized torque was not statistically different between the 110llnal contIols (36 ± 12(l(') and the PPS subJects ON (38.4 ± 26%) or OFF (41.8 ± 14.9();,) tht' (h lIg. The normal subjects took approximately 30-31 seconds to complete the fatIgue protocol but tlll' PPS subJt'ct:-- requlred, on average, 33 seconds f( r completion . • 54 • ln addition, multiple reglession analysls shO\wd that the twn !-!1l11IP\ hl'h:t\'cd \1Il1il.lIl\' with repeated te~tll1g. ûvc[all. tht' lit 01 the rq'![l's\1l)11 11I1t'~ fo[ the PPS \\1"1('(1\ « lN 2 2 drug R =(U\4; OFF drug R =O.76) \Va\ 11101l' \':tllable th,tn the IHlII11,II lOIlIIO\ ~lIhll'l" 2 (R =O.lJ4), as reflected by the hettel fit nf the Iq!Il'\~lon \lI\l'\ tn tlw 10HI\l1..' da!., Sensitivity of Protocol to Evaluate Fatigabilitv uf PPS Suhjt-ds ON ur OFI· n!.~: Although reliability of perfonnance was ~h()wn fOl IOlal \VI li!.. and :tVCl.lgl' IHlWl'1 of the knee extensors, the protocol was not semilive el1o\l!-!h ln dell'll an l'Ilell 01 Ihl' drug. Values for total work (Figure 3a) or average power (Flgllle 3h) (hd 1101 the PPS subjects were ON or OFF the drug Ilowew[. Jt was appalt'l1l hum the v,!lw'\ obtained from the regression analyses, fhat the PPS suhjl'cls cou Id hl' divided JIllo responders (n=4, males) (FIgure 4a,b) and non-responder-; (n=3, fcm.dl's) (Ftgllll' .5) l'hl' performance of four subJects OFF the drug was lower Ihan Ihe :lVt'[ a/'I' t Iwo ,Iancla[d • deviations whlle they were ON the drug. Of th('~e four ~Uhjl'l h, h()wl'vcr, ol1ly olle demonstrated true fatigabllity while OFF the drug, a~ ~h()wlI hy Ihe greall'[ r:egallVl' slopI' of the regression ltrle (Figure 4b). The other threc slIbJects were unahk 10 ~'('neral(' a~ much torque at the beginning while OFF the drug. • 55 1)i"(,II~"iion: • I{clia hilil Y '1'111:-- :--tudy .,h{)w~d that total wwk and average power were reliable only for the k/wc extcnlio/:-- III PPS :--uhjCCh, after three telit ~e.,s/On~ The mdices were reliable for kllcc extensor., and Ikxor~ of normal controls, after only two trials. This finding is c()n~/stellt with other reports in the IIterature for normal :--ubJects (Burdett and Van Sweanngcn, 1tJX7; Montgomery et al. 19XtJ; Wessel and Galbraith, 1tJX9), No data on /l'lIahlllly of lat/gue te:--tlllp 1/1 PPS I~ avat/able for comparison wIth the result~ of this sludy. IlowCVCI, OUI f I/1c!Ing IIlrlicalc~ that at Iea~t three repealed measures are necessary WJlh a leLiprocal 1allgue plolocol 1/1 PPS ~ub.lect~, III order to obtain rehable baseline IIwaSUlementli for the knce exten~OI~ Fewer te')t days may be required if the knee extcnsOl:-- welc tc.,ted in 1~()lallon. Rehable results on the knee flexors can be obtained • only al tel III 0 Il' than tluce lepeated measure"i. Day 1 should really be considered as a fllacticl' sc%ion fOI PPS ~lIbJl'<:h However, the relative fatigue IIldex was not reliable on l'Hhel PPS or normal sub.1ects and therefore ItS use is not recommended. It is Iloteworthy that IcJiabIllty of thIS IIldex wa~ onginally determined by a low (3.2%) coeffICient of val Iatllll1 (Thorstens"ion and Karlsson, 1no). In our study reliability was evaillated t1SlIlg the ICC taking mto account the high variability within the two groups. This rehablhty coeffiCIent is more stIingent and may account for the dIscrepancy in the rl'sulfs. Although lehability of isokinetic strength measurement protocoIs has been studied l'xtensively in normab and in !'Iome patient populations, reliability of fatigue protocols has • 56 not been investigated fully. Eailier WOIl-. [Will our I.lbolalory 011 Ihl' S,lIlll' ~lIhll'l.'l glllllp'" • showed that strellgth could be te:--ted lehably l'Vl'II in Vl'Iy wea" sllhjl'l'ts (1\1I111Il ,lIld St Pierre, 1()()2, in ple~,,) A Il'I.'lprocal pmtocol \\',1:-- chosen III IIII~ :--tudy 10 allll\\' lm comparison wlth plevlOu:-- ~llIdle:--. A reClprocal plOlOL'ol lt'q\JIlt'~ gll'all'I attelltlOI1 and practise in order ta perfolln flexion reliably. The IIlStlllL'tf()llS glVl'1I tll a !l,live SUhll'l'l must be very consistent to facihtate plOper eXCL'utlOIl ot the mOVl'lIIl'l1t III tWIl dll t'lIIons. The PPS subJects reqUlred one practice sessIOn and mOle than two d,l)''' of tl'stmg tn perform rehably. More lime woulct he reqlllled III OIdel 101 tht' PPS suhwl.'ts ln demonstrate reliable performalH.:e of the knee 1kxol:-- Sensitivity In this study there was no distinctIon between PPS subJects and 1l00lllai i.. Olltl ob in tenns of the rate of development of fatIgue The:--e results ale !>lIll1lal to the IlI1dlllg!> • of Agre and Rodnquez (ENO) and Rodllquez and Agi C (Il)l) 1), who w..cd ail 1\lll1ll'tl ie fatigue protocol. Reasonable altempts were made 111 ttm study tu cOlltflll lOI !>Ollll' of Ihl' possible central or mhibitory factors in fatIgue by a\kmg suhJeu:-- to report palll \ymptOlIl'-, and pereeived levels of effort. Pain dld not appear tn be a lal tor IIll1ltrllg !OIU: production, even though three male PPS subJects were weaker wlllie 0/'/- the drll~~ PI'\) subjects' reports of fatigue 1I1creased whde OFF the drllg as 1 ecor ded hy '>lor e!> 011 the Borg seale. However, these subjectIve repurt:-- WlTe rdatee! ln objective IJIldlllg~ of decreased strength in 3 males, and of greater fatigablilty rn one male :-,uhrect The subjective reports of II1creased fatigue by the fernale \ubJcct!> were not rdatl'd tn ohrectlve changes in the dependent variables. Even though the ~ubJccl\ werc kn()wlI rL,~jJ(Jllder:-, to • 57 pyfld()~tlgI1lIl1C upon cntry to thls study (TroJan and Ca'ihman, 19XY), there was a • dl\ucpancy bctwecn ~lIbJeLlivc outcOIllC mea~ure~ and objective mea\uremenl\ of fatigue. 'l'lm fJlldmg rClI1forcc'i the impOltance cf a better deflllition ana unc!clstanci!n!! of fatigue. It may he nccc~\ary 10 tc~t PPS sublCCb with more than 25 lsokinetll contractIOns, or more thun once wllhin a te'it scs<;lon (DlIrana et al. 1~~ 1) in order to reveal differences III faligahIlity belwcen PPS and control ~ubJects (normals or asymptomatlc PPS). The 1101 mal fatIgue curve J~ known to he comprised of both an IIlltIal fatigue phase and an clldLllanlc ()J stl"ady-\Iatl' pha\c.  ~hort fatigue protocol (e g. 30 'iCCS or less) may only 1 elleLl the 1 atl' of dl'vclopment of fatigue III the carly fatigue pha~e and would not evaluatl' the cnellll anll' phasc InlOi mallon on the rate of rl'covery from fatigue of PPS subJecl'> versus controls alsn couic! bc collectee! and tlm may be more sensitIve ta evaluate the effects of the drug. • It has been shown that the r.!lr of rccm ery from fatIgue may be a dlstmglllshmg feature of PPS subJccts l'rom asymptomatll pollo 01 nOlmal control subJects (Rodnquez and Agre, 1t)l) 1). PPS i~ assocJatcd wilh a slgl1lfH.:ant loss of motor units (Borg et al. 19X9; Borg and lIenllbson, 19lJI; Elllarsson et al. 19Y()) and Rodnquez and Agre, (1991) reported hoth li IcductlOI1 111 numbel and III lecruitment of motor units in symptomatic PPS slIbjects l'ompalt'd tn asymptomatic slIb.Jects. However, these factors alone wOlild not explain the plolonged prlIod for Iecovery of strength followll1g performance of their 1 ~omelllc fatIgul' pIOWCO!. The PPS slib/Ccts differed 111 thdr level of involvement and disability following pollo ong1l1ally, a\ dett'lllllnl'd by retro"pective chart reviews prior ta entry to the study • 58 (Appendlx D). No fOI mal scalr \Vas used to dasslfy the SlIbll'l't' bl'l alise nOlll' han' IWl'1l • validated on PPS ~ub,l'l'h The observatlon~ or tht' appalt'1l1 1I11Il1t'llct' nI Ihe dl III! Oll muscle strength lllU'it be furthcl lIlVl',tlg.lIl'd Il l' \..nO\\'n III dl,(lldt'I~ \\ l11ch alfl'l'I the mataI' unit that muscle strcngth assessed manually l'an he m.llntalllt'd ln tht' llol111al 1 angl' up until there is a greater th an 5()-7()Ck) loss of f'lllL tHlnal l110tlll 1I1l1t'i (Mc('ol11:1s and Upton, 1973: McComas, 1YY 1). lt i~ possihle that 1111er suh!t'l'I d LI klt'lll'l''i III thl' lllll11hl'1 offunctional motor units could account for observcd dlltclenlTs in ~tll'l1~!th alld appall'Ilt fatigability or resistanœ to fatigue The fatigue protol'ol usee! in this stlldy was not ~ell'>ltlvl' tn dl'It'l't an dll'l t 01 pyridostigmine on fatIgue across the group of PPS ~uh,ells l'hl' plOtowl ilia)' 1\(11 h.1Vl' been strenuous enough to demonstrate changes III faligahlllty III .dl 01 tht' l'PS 'i\lh,l'lt~ However, the reslllts of the torque regresslon anal y~l'S ,howed nt' 1!.lt 1Vt' ,Iupl' v:d I/('S ! 01 • aIl of the PPS subJects bllt wlth lIlter-lIlcilvldual dlllen.'nu', Tht' 1.l1I)'l' 01 pClu'lItage decrease in torque over tllne also varied hctweell PPS :-'Uhlt'lt~ hoth (>N alld (>FF Ihe drug. Indivldual differences in functlOnal ahllitle.." habituai alllvlly Il'vcb, ()J ..,tage 01 disease might influence a subject's fatlgabiiIty. Il IS po..,sihle that the ..,m.dl ,.Ilnrle sile with high inter-subject vanability would preclude the detec!lof1 01 a drill! el tect ln addition, individual sllbJects may have shown a proglc:-'..,Ive IInpIOv{'1llt'1I1 III thCH perfonnance of the protocol over the course of flve te~t ~C'i"I()n,>, alti olll'h " tratlllll!! effect in this patient populatIOn was not ohserved A '>Ulgll' l'valuatIOn wllrle O"F the drug, although nccessary in thi:-. pilot stlldy for ethlcaJ rea..,Uf\.." dlcl not pe/lnrt relmbdlly testing of performance OFF the drug. The av,ulabd ity of data from more rcpealt-cl • 5<) III~a\llI~\ 0/+ th~ drllg C()lIIpUl~d to ON, or the u,>e of a placebo, may have increased the • chancl' of (kt~Ull1g a change. Il 1\ cliff iClllt ln expJam the gcnder dlfferencc\ \een in the effecI~ of the drug In Ihl'> <;llIdy. Thi\ ob\clvatJOn could have occurred due to chance on ,>uch a small group of ,>uhJcct<;. Alternativcly, thc dlfference may have been due to dlfferent metabohsm of the (IJ IIg hetwccll the sexes or It cou Id simply be explained by dlfference~ III actlvity levcls. It IS not known If the male subJects had a greater proportIOn of fa"t twItch fibers cilie to past 01 LUI/l'Ill aCllvity kwh Thi~ cannot be IIlferred from the results of this study, howeVl'l, J'lven thdt thrl'l' out ot the four male responders dJsplayed a greater loss ot strenglh wlllk Of+ tht: drllg Jather than an 1I1clea:-.ed rate of fatlgablllty. There may also hl' dlf'fcrl'Ilccs III the t'fleet of the chug which could be explamed by the stage of the (bea:-.e plogrl's:-'lOn 01 thl' balancc of reinnervatlOll/denervatlOl1 processes. • ln UlIH. hl'>lOll, the /Il'UIOlllllscular fatIgue 111 person" wlth PPS can be dlsabling and dcservl's plOpel l'valuatIOn and treatment. Antichohne<;terase agents, such as pyndostlgl11l1lC, have hl'en used effectlvely to lInprove neur omuscular transmiSSIOn in myasthellla gl aVIS, and show promise in decreasmg fatIgue Il1 some patients with PPS (TIOJan and ('a"hman, 19W)). The lesults of this study showed that a dynamlc fatigue plOtocol, tl'sted wlth the Cybex Il isok1l1etlC devlce, IS a reliable means of evaluating fatigut' of the kncl' extensllI:-' III sublects wIlh PPS, compared to normal controls. The plOtocol wa:-. not :-.hoWIl to be sensItive enough to distingursh fatigue responses of PPS subJect:-. ft om 1l00lllUI controls. Nor did the protocol drteet a positive effect of pylidostlgllllI1c on nt'llI ol11u:-,clllm fatigue m ail PPS slIbJects who had originally • fiO subJectively responded 10 the dlUg (TroJ.m and Cashman, 1QX9). P)'lIdnstll~t1lIlll' IS • beheved to mfluencc nCUlolllusculm t~ltiglle, but III thls study thls It''\UIt \\'a~ tlUt' hl! nnly one male sub.lect. HOWCVCI, the dl ug was shown 10 have a bl'nct Icial t'lIt'Lt on :-.11 l'ngt h 111 three male subjects. Thcse sub.lects may expericnce less fatIguc hl'cau'\l' 11ll')' :1I1' stronger as a result of the drug A larger number of sllblt'cts stll(lIcd, and mo(lIllcatHlm ta the fatigue protocoi would be ne<.:Cssary in arder to attcmpt 10 dllferl'ntlatl' the l'fred of the drug on strength or fatigabiltty. However, dcspite the study':-, llll11tatioIls, Il IS a first attempt to evaluate fatigue obJectlvely and also to detellllllH' the l'ffel t'\ of ll1l'dll,lliuII used to oeat the symptom 111 PPS. • • Tahle 1 Subjcct Characteristicr; Suhject~ Age lIeight Weight • (yr) (cm) (kg) l'PS 50.8 169.1 74.1 11=7 10.2 8.5 12.4 Normals 44.6 170.5 68.8 11=15 9.8 9.1 12.8 VlIluc., "re Means i. sv • • • Table 2 Visu al Analogue (VAS) Pain Scores PPS ON PPS OFF p-Value 0.85 1.62 0.69 0.9 3.2 PPS ON Normals p-Value 0.85 0.46 0.65 0.9 1.9 Values are Means ± SD • • • Table 3 Hating,li of Pcrccived Excrtion (Borg) Scores PPS ON PPS OFF p-Value 15. J 17.4 0.03 1.1 1.1 PPS ON NormaJs p-VaJue 15. J 15.2 0.18 LI 2.3 Values are Mean~ ± sn • • Table 4 Intra-class Correlation Coefficients (1 CC) Days 1, 2 • Subject Movemcnt Peak Torque Torque Torque Grou~ 1.05 rads 0.79 rads PPS* Extension 0.95 0.97 0.97 Flexion 0.81 0.74 ().57 Normals Extension 0.95 0.94 0.95 Flexion 0.78 0.85 ().85 Days 1, 2, 3 Subject Movement Peak Torque Tonlue Tonlue Group 1.05 rads 0.79 rads PPs* Extension 0.99 0.95 0.94 Flexion 0.92 0.78 0.85 Normals Extension 0.97 0.96 0.97 Flexion 0.85 0.91 0.92 • * PPS subjects at baseline on pyridostigmine (60 mg po tid) • Table 5 Intra-class Correlation Coefficients (ICC) Da ys l, 2 • Subjcct Group Moverncnt Total Average Work Power PPS* Extension 0.16 0.46 Flexion -0.48 0.89 Norrnals Extension 0.91 0.90 Fle:don 0.93 0.90 Days 1, 2, 3 Subject Group Movernent Total Average Work Power PPs* Extension 0.99 0.99 Flexion 0.73 0.71 Norrnals Extension 0.94 0.93 Flexion 0.93 0.91 • * PI'S subjccts at hasclinc on pyridostigmine (60 mg po tid) • Figure la. Total contractile work (group meall ± stalldard dr,'jatio1l) o} knee extensor muscles of PPS l'crsus 1lormal cOlltrol subjects, 11l('tlSlIrt'd '. across three test days. Figure lb. Average power (group mea" ± stalldanl del'iati01I) of kllt'C extensor muscles of PPS versus normal control subjccts, measlired across three test days . • • Figure 1a 3000 • UJ -Q) ::::J ..,0 - 2000 ~... 0 Day 1 ;: •fA Day 2 ... BI Day 3 0 UJ c: 1000 Q) >< W- o+-- PPS Normals • Figure 1b 350 -UJ ca ;:- 300 -... Q) 250 :: 0 Q. 200 Q) Cl ...ca 150 Q) > ct ... 100 0 UJ c: 50 Cl) >< w- 0 • PPS Normals Figure 2a. Absolute torque (group mcall of t'l't'rJ' fiftlr ('on/m,lioll _--{ standard deviation) of the kllec extensor muscles of rps l't'rSus normal • control subjects during the fatiguc protocol. Figure 2b. Normalized (to first contraction) torque (group meaTl :t standard deviation) of the kllcc extellsor museLes of l'l'51 l't'rSlIS 1lormal control subjects du ring the fatigue protocol. • • ------ Figure 2a 70 • 60 -E ...... -z 50 Cl) UI ::l"O 40 o~ca .... 1-11) -0- PPS 0 .... 30 Normals 0 ,... • UI c: ca Cl) - 20 w->< 10 0 0 1 0 20 30 Number of C· >ntractions • Figure 2b 3.0 2.5 Cl) ::l ....C" 2.0 0 1- 1.5 .... UI 0"0 Ul ca c: .... r;~ Cl) 1.0 .. I~ ">(:g r .1--- .r W ,...• -- ,. "0- 0.5 Cl) ca N ca 0.0 ....E 0 Z -0.5 -1.0 0 1 0 20 30 • Number of Contractions Figure 3a. Total contractile work (group meall ± standard de~'iatj(lll) of knee extensor muscles of PPS subjects while ON pyridostigmill(' ./ dtlys • versus OFF 1 day. Figure 3b. Average power (group meall ± standard dt'~'ùlli(}ll) of /..n('(' extensor muscles of PPS subjects while ON pyrillostigmille .J days versus OFF 1 day. • • Figure 3a • 3000 en -cv :::J ...,0 - 2000 ~ fBJ Day 1 ON 1... 0 0 Day 2 ON 3: Day 3 ON 1... .. 0 IL] Day4 ON en c ŒF cv 1000 • )( w- o-+-----...Jt:r.I. Days o'N OFF • Figure 3b 400 350 -en -ca 3:- 300 -1... cv ~ 250 0 a. cv 0) 200 ....ca cv > c:( 150 .... 0 en c 100 cv >< w- 50 • 0 Days ON OFF Figure 4a. Angle-specifie torque (at 1.05 rads) of km't' l'.\te1l.'Wr muscles (mean of every fifth contraction ± standard dl'~'iat;()ll) Wlli/l' ON • drug versus OFF drug. The illustrated reslllts are from olle l'/'S slIbjl'ct who is representative of 3 male subjccts who displaycd a POSitil'l' l'llat of pyridostigmine on strengt". Figure 4b. Angle-specifie torque (at 1.05 rads) of k11ec extl'IH'O" muscles (mean of every fifth contractio11 ± standard dCl'iatioll) w!zi/t' ON drug versus OFF drug. The illustratcd reslI/ts are from olle 1'1'.\' .mbject who displayed a positive effect of pyridostigmille on fa tigabilily. • • Figure 4a 100 o ON -E 90 • OFF Z • 80 -c: a UI .- "0 70 c:UI ...co (1) -li) 60 )(0 W • T'" 50 (1)- ::l co ...0" 40 a • t- 30 • 20 10 0 10 20 30 Number of Contractions Figure 4b • 100 90 -E 80 Z - 70 (1) ::l 0"0) ... (1) 60 0"0 t-o ... <0 50 o_ UI co c: 40 (1) ).: W- 30 20 10 0 10 20 30 • Number of Contractions Figure 5. Angle-specifie torque (al 1.05 rads) of kllt'C eXlt'llSOr musc/t'.\ (mean of every fiftlr eOlltract;OIl :t stalldard de~'iatioll) whi/,' ON drug versus OFF drug. The illustrated reslilts are from olle PPS subjt'C( who • is representative of 3 female subjects w/w displayed 110 cffeet of pyridostigmine. • • • Figure 5 40 0 ON • OFF ---E ...... z 30 C fil .~ 'C fil ca C '- cv Il) -0 w..->< • cv ca 20 ::J - cr '- 0 • f- 10+-----~----~------r-----~----~----~ o 1 0 2 0 30 Number of Contractions • 4.0 Conclusion • The symptoms ot fatigue and musclt' wl'aklll'ss ill110ng pl'r~lll1~ dl,I!!llll\l'd \\ 1111 PP\I polIO syndlome can hl' dl'\abling and drservl' plllpl'I c\'alu,lltnll ,Ifld 11l',IIIlWIlI Antichohnesterase agenls have beell lIsed l'flcclivdy 10 IlllplOVC lll'lIWlllll\llll.ll transmission ln persons with rnyasthenia gtaVIS, and show prollllM' for "OIllC palll'Ilt'> \\'1111 PPS, This study IS a tllSt attempt ta obJt'ctlvely l'vaillall' lhl' t'lin 1<; 01 lhe lI1l'dlratlllll Ill1 neuroll1l1scular fatIgue and isokll1l'llr "ul'lIglh III II1IS populalloll 01 1)('1 '>1l11'> \\'Ilh !l11\1 Jlollo syndrome The ft' ~e~lI ch 1 e la tcd 10 the Iwo pha"l''' 01 1111" t hl' ... 1\ 11l,IIIlI"l Il pt h,I" demonstrated that sellai l"Ok.IIWIll as~eS"'Il1l'l1t 01 ~\tll'Ill!th alld lall)'ahllitv (lI th\' k.lll'C extenSOI'" 1'1 li lchable method 01 l11t'asUrCI11l'llt DI 1ll1l"l'uLII pt'Jtllllll.lIlU' III \lIhll'l'" \Vllh PPS, lontlasted ta normal control..., HowcveI, t'ven thouglt Iellahllity 01 11ll'.I"'llll'\IWlll wa" shown, this plOtocol was Ilot sensItive ellough tn dI ... t i nguI\h Ilt'Ul Olllli "l UI,ll t .It l)'Ul' • responses of PPS subJect ... [rom nOlmal controls Even Ihollgh aIl 01 th\' l'I'S "lIhJl"rt~ were repoI tcd ta have had a pO~lIivc effect of the dlu!! on Ill'UlOllw"'lulal 1al IgUt' t 10111 il prehminary study, the objectIve lt'sult:-. of thls Slllc!y dic! not lOllfllll1 ail of thelll a~ responders, Jn lact, the thug hac! an appaIt'nt benefll'lal eflect 011 :-,ul'Ilgth III tllltT Illak subjects and on fatlgablhly in only one male <.;ubject. The telllale suhlt;ct,> d('IlI()Il~tl alt'Ii no beneficial effects of the drug on fatigahlltty, whlch wa~ Ullcxpl'Lted Tht' Illllltatlllm in the stlldy (hd Ilot allow for an explanatJoll of dl\CrCI,ancy III the t'lieu of the drug 1111 strength ver~us fatlgabillty HoweveI, this prelimlnary work cmpha\J7C\ the lll1!Hll tallce 01 relwhllny IIf • measurement of fatigue, Thl'> IIlfOrmatIOIl cali now be Lombll1cd wlth tlte ('Xpcltl"'(· of othel ll''''l'.lllht'l'l 10 ll:-'t' .\ 'I1.lIld;ud l"0I111'!lIC p\l1tllllll III L'lllllblll,t!lllll \\ Ill! Illl' t\\ Illlt • I\1terpolatlOl1 tl.'Chl1\qlll' .lIld :-'lllt.ll'C III IIld\\l'lIlll~ Cll'l'lI11dl'" III l'\ ,dll,lIl' I)(llll I1t"UlOl11l1SClllal f.ltIgue and 1l'un t'I\'. Onct' It h.\" hl'l'n dctt'lIllllll'd th,l! Ihe"l' \I1C!lHhh ,lIC reliable. vahd and fea"lbJc in PPS sub,ect:-.. Ihen a dll"l'I l':\'lIlllnatlllll (lI tltl' cf kl '" (lI pyridostlgmlI1t" l'an pJOceed. • • 03 s.n Lilllifafiow, and J{ccommcndatiom: • TIll' 1(''>tJlI" (Jf Ihl" ,>turl)' \llOUld he of IIHelc\t to both clJIlILlam and Ie\carchel:-' I('gardlll)! tlw eValiJatloll of \tlcll!!th and neuloJ1lu\uJlar fatlguc III PPS :-.ubJcct.., compaIed 10 nOlmal cOlltrob Jc.,oklllctic tc\tJng of :-.trcJlt!th wa\ shawn ta be lelrable. Hawevel, l..,oklIIelic tC\III1I! of fallJ!uc emploYIIl).! thi:-. -;Iudy'.., partlcular protocal was reIrable but Ilot valHI ln ICll1h 01 hl'JIlI! "Ilk III dl<,tlllgtll..,h hclwccn PPS ..,ubJect:-. and nOlmal controb, ar wll/k PPS "'Uhjl'LI\ WCll' ON 01 0/+ PYlIClo:-'llgll1lnc. The concluslon:-. Ihat Cdn be druwn IIOIlI Ilm 1l'''l',t1th ale 1IIIlllcd 1))' :-'ULII Ihlnt!" a.., the :-'l11all ..,ample ..,ize:-. and hetelogeneity 01 the PPS ..,uhJcLI'" LlIl1llalll)ll" parllclllal tn the te..,tmg plOcedlllc IIlclude, /) no l'Valuatlllll of I..,olllcll Il :-'lIcngth 01 fatlgab!llty 2) no detenmllatlOll of level ot motOl output as a J1l"ILentagl' of maximal voluntary activatIon (Mye) 3) lI1adequate control for the hulld up of lontl allile tl'!l\lon priOi to l110vement thIOugh a pre-~elected range of • motloll 4) pn..,.."hle lalllllc to Il'lOld Icsponses beyoncl the mitral phase of the fatigue curve and 5) no rl'L()J(I of pattcIIl of Icuwèry followlI1g fatigue. An ''\OkIllClll plO(olol ,.., ka:-'I ble to test ~trength and fatigability. It does not appeal to cau..,e 1I1ldUl' (1,lIn or dclayed l1lu..,c1e wreness which woulcl influence il subject's tOlquc output. A plO(tKol wlllch evaluate" only one muscle group at a time may provide 1II0I1." Il'habll." rl."~ulls tb,lIl a Il'l'lplOCal protocol. The use of an l\okinetic de vi ce equipped wlth d plc-Illad (!llctte rt al 1l )X6) \\'hich allows cantldctile tension to build before IIIOVl'IllCnt 1" pCllllitted 1t'duce" the Impact arufact ancl allows torque to b registered thlough a pIC-SCt standald lange of mnvement 's recnmmended. An isoll1etllC pIOtoLOI which penmts measurements at optimal muscle length, and • at a plc-de!èlmlllt'd pl'IL't'llt,lgC of m,I\IIlMl \nllllll,lI)' Ul!ltl,I~!I\l!\ \~t\'( ') \\\luld b\' .111 • option. This pIOtoL'olromhllll'd wlth tht' t\\I!L'l1 1Il!t'lpulatllln tl'llllllqlll' \\\111111 1'1\1\ Ilk greater contlOl ovel lTlltt,t1 .Il'tlvatlon and \\,(lldd Il11plO\'l' tlll' ('valll.lIlIll1'" ut \tlcll!~th ,\llli fatigability, The slze of the muscle \tudit'd woul<1 Ilot hl' a 1.IChH II Ullt' 1\ lUlll'CIIH'd \\ 11ft evaluating the effect of a dllIg on 1It'1lI0Il1U"1'1I1:11 fUllL'lIOII. ~111"r1l'\ slIIallrl IIt,1l1 tltt' quadriceps femorb could be studled, Thl~ comhlllcd with I\OIlll'!lll' tt'SllIlg woult! allo\\ for a larger sample of ~llbjt'ets with PPS tu hl' lt'l'llIlted The cunent ll1l'thodolngy could h,lve hl'l'II ~tll'ngthl'Ill'd hy litt' U\l' 01 Il Il li l' detailed questlonnalle\ W/lIl'h wou/d dOlumcllt dllklCI1l'l'~ IIlcalh SUhll'l t\ p,l'.! kvl'l (lI physica/ fItne~~ and been important to document any changl' 111 a :-'UbJl'l't':-, aLtlvity kwl whde ()l'I- litt' dlllg compared to the days ON the (hug, The apparent clteet nI tht' dl Il!! 011 \IIt'II!'lh III SIlIlll' • subjects and the ll1complete undel :-.tancl!ng 01 the phcnonll'l1on 01 ()Vl'lll~l' wl',lklll':-'\ III PPS subjects underhe the lI11pO/tance ofrecordlIIg actlvtly Icvcls ThIS 1lI101lllatHlllllIIghl help to distl11guish betwecn apparent weaknes<; and presumee! latlgahJllty • oS (, 1) .!.hU~IHli~'t'., • Al \"'odd 'kal1h Organil.atioll ("'110) Polio Stll1i.,1Ït't-. B) Vi.,,,al Analog Sralc of Pain 1 Clinical S1at"" (llJ('~.ionnaire (') BOf g S('all' of Per(,l'i\'cd ".xl'rtion 1)) MNlical ('har. Hcview Form E) ('on<"('nt FOI'm ... • • 66 7.(1 Refl'/"l'IH'l'''' Adkl \1. I\.'\hp,llllk SS, hhl,'1 RI \LI\\\clll)\1. \Ihllljlll'Iqlll' 1 \ I:fkl h Ilf \ldl,ll U(l' • P) Ildl)\(1i211l111l' ,ldll1l11l\II.l(1l11l 1l1lIll,111l1ll,tll,11l '~l'k(.tllllll'l Il' tllill (11111 I!lUIII,1i lit '\l'l'ltl'd TO\llol0t:: ll)l)~, 1.2 .2:1-31 AgIL' 1(', RndllljUl'/ A,\ :\l'llf(1lllll\L [IIJI tlllll (11111 l \llll(',III\llfl lIt \\ IIlJlhlfll,I(ll ,llld J~ymp\(1Il1,ltll polIn \Ubll'Lh 11) llllltllli ,Ub)t'Lh :\ll'\t Ph\'\ ~1cd Rclt,lhd IlIl\' 11)1)1l 7\ 545-551 AgIe .le. Ro(h lqUt'l AA Nl'U/llIllU'lUI,ll IUllltlOIl III poliO \lIl\'IVlll\ ,It (HW \'1',11 fllllll\\ "l' Arch Phy~ f\'1ed Rt'h,lhtl Il)lli. 7~ 7-](l Al1Ians..,ol1 A, Grimby (i, RUl1dglt'11 A (..,ometlll' allli l,nh.II11'tll. ljll,1!1r Il.l'JI\ 11111\1 Il' stIcngth III 70-yeal-old ml'n .Incl \\(1l1l1.'11 Sl..tIHI 1 RL'lldhtl ~kd Il))';Il. LI 1111 Ill).; Akol'J... AI\V, IIlldc" lA K,llIfl'lt PA, ,,",Iuklt .lM. I{ll~tllid 1 Rnpll.ttlll\' plllllllll\'l'lltl\ A tolhm -liP ~tl1dy ('an Ml'd A \~(ll 1 Il)X-L 1 Il) 1 li li) 1 ~ !Il Armstrong LE, Winant DM, Swa\cy PR, SCHik ME. ("1111.'1 AI., (il Ithl'Il (i \ )\111)' i~okmetlc dynamomdly to Il',,1 amhulatOlY l',llll'llh wlth 1Illlltlpk "1 klll\l" l'h)'\ TIIl'I !()X3: 63(X) 127.t-\27() . Arvld~on 1. RehabIlItatIOn of the athletc'~ J...nt't' Ml'dllllll' SpOI t Su 1()X7, 2X 2 ~X l·lfl • Bach .IR, Alba AS. PlIlmolJary dysfU/H.tIon and ... JeeJl dl~()Jd('Il'd hll'.Itltlll)' .1'. po..,t poliO sequelac Evaluation and manageml'nt OltlHlpl'dll\ 11)\)1. I·l( 1.)) 1 ~2() 1 ~ n Belangc! AY, McComa'\ AJ, L \1(,llt nI llIolm 111111 al tlvallOIl dllllll)! dlOlt J Appl Plty',)ol Respirat Envilon Excrcl...,e Phy ...,lOJ J l)X l, .') J (.')) 1 131-1 1 ~5 Bellemare F, Grassl110 A. EvaluatIOn ot hUJll:ln dlapill agm lalW!I{' J "ppl Phy\101 Re:-,pllat Envlfl)J1 Exercl"e Physiol !()X2: 5~ (5) 11% 120(l, Bellemale F, Wood'. JJ, Johan~~(ln R., Bigland-Rltl.hll' B. Motor'lIll1l dt:-'l.hal)'l' lalt':-- III maxImal volllntary contraction..., 01 three human mll\dl~"", .fOUIllai 01 N('lIlOphY<'lol()/'y ILJX3; SO((»: 13X()-1302. Bennett, R..L. and KnowltoJ1, (i.e. Ovel WOI k wl'aknc..,\ III parlJaJly delll'rvatt'd <,kt'll't:t1 muscle. Cllll Orthop 12:22-2lJ, ILJ5X Berlly MH, Strau.,er WW, Hall Krv' Fatigue ln po.,t-pollO "ynclrolllc Arch Phy:-. Mec! ll)l)l; 72'115-1 IX . • 07 BI)'LlIld I Blr"lll" J B Il! l.tllt! J< Ile Il Jl' B. ()OIl()V,lIl H', ROll \\0\ CS ('onductlOn ve!oclty and EMG powel "I)('lllllili dl BI.!!ldlltl-l Bigialld RIIlll1l' B, JO!Jdll\\()Jl R, LlppoJd OCJ, Wooch JJ. ContractIle speed and EMG lhangl'" dllJlllp latl.!.!ue 01 \ll\tall1ccI maxlIllal volunatary contractions. Journal of NCIIIOJlhY'>IOIt11!Y July. Il)X3. 50( 1) :1 J 3-324. Blgland RIlLhll' B, JOIH'\ DA, J lo'>kll1g GP, Edward\ RHT. Centrai and peripheral fatigue III '>lI\l.tlllcd lIlaXlll1Um voluntary C(lntJactlon~ of human quadriceps muscle. Clinical • SUCIlU' and Mokutlar McdlLïl1e J 07X; 54.009-014. Bndlan, () 'l'hl' VlIU'>. thl' 111.'1 ve cell and pal alysis. Bull Johns Hopkins Hospital 1949; X~ 1-107 Bodlan, J) 111~t()pathologll ba\i,> of cJlIllcal findings in pohomyeliti~ Am J Med 1949; (l'5(d-57X, BOlg. (,AV P\ydlOphysical basls of perceived exenion. Med SCI. Sports. Exerc. 19~2; l·l:Y77-JXI BOl g 1\.. BOl g .1, EdSl1 om L, GIIl11by L. Effects of excessive use of remaining muscle fJlll'r,> III 1111111 pollo and LV lesion. Muscle & Nerve 19RX; Il: 1219-1230. BOl g ". Bor g J. Dhoot G 1\.. Ed!'>tIOIll L. Gnmby L, Thornell L. Motoneuron fifing and l"l)[nYll,>1I1 type o! lIlu!'>c!e rlblC,> 111 pli or polio. Journal of Neurology, Neurosurgery and P'>ydll.ltl)' Il)~.;q . .12 1 J'+I-ll'+X. Borg 1\.. 1kllllbM1I1 .1. PIIOI pollOmyelitl!'>-redm:ed capillary supply and metabolic enzyme LOlltcnt III hypcrtlOplllL \Iow-twitch (type 1) muscle fibres. Journal of Neurology, • NClllO"IIlgl'l)' alld P,>yclllatly !l)0); 54:236-240 . Bradley WCi. Rel't'Ilt Vle\\" ()ll :tmyotlUphll 1,lIl'I.1I "l kl 1\"1" \\ Ilh (,1ll!,".I"!" 1111 • t'kctlUphy\IOlogll' \tlllhl'~. ~hl"l le 8: !'\CI \ l' IlJ:-\7. III (I){ 1- ,,(l~ BIO\Vn \VI' hll1ctIOll,t1 CllIl1I1l'Il"allllll (lf hUIl1;l\1Il11l!\ll lIlll\'. III hl'allh .llld dl\C,I"C IIHIII1,I1 of the !'\l'lllOlogll.d Slll'llle\ 1l)7~. 2(1 1(11) ~(ll) Bruno RL I-/lLh. NI\1 The p..,Vllllll0,t!) \11 Ihll\ll ", J1Il'llIdl' III pmi poil\! "l'qllll.ll· BehaVlOlIfl11odlltl\llillll.lIldp')lhOllll'l.tpy (lllhopl'dll' IINI,I,I(lll Il:-\') IIIH Bruno RL hIC\... NM. ('nhl'Il J PolIul'llll.'ph.t1II1\, "III',,, .llltl Ihe l'Itob l )!\' 01 1'0,1 pollo ~t'qlleIae OIthopcdlc~ 1t)1)J; 14(11) 12(J1) 127(1 Buchtdl F, lIonLl\l' P. EkltromyogIapmLdI ('\.lIl1\11,II\llll 01 palll.'llh ~lIlh'1I1l1! 1101\1 pohomyehll~ ur 10 () ll1onth~ atter the acute sla!!\' ot Ille d"'C:lSI' Al 1.1 ~kdll,1 ScanctII1aVlc.1 1(J4..J, (,XVI() 1).14X-I(J3 BUldett Re;, Van Swe.\Il11gl'lI J RelIabdlly of I\oklllt'Ill Illll\l le t'lldUI.tIlU' Il''''\'. !tH Il 1 .11 of OIthopaedlc and Spnrh Phy\lcti Thclapy )1):-\7. S( Il)) ·IX4-·1X:-\ Cash man NR, Maselh R, Wollmann RL, Ro()\ R, Sllllllll R, Aillei IJI L.III' dClll'lvallllll 111 patients WIth anteccoellt paIalylIl polinl1lyelIlI" Nt'w Ellglalld Joulllal 01 M('dlt Illl' 19X7; 317:7-12 • Ciocon JO, Potter JF, Po:--t-pohomyellti~ sequclac III tht' e1dl'r1y .Ii\( iS Il)X!), 37 2')(1-2')X. Codd MB, Kurlalld LT. Pollo'~ latc dleLl,>. Il)X5 Medllal .111<1 IIl'allh /\llIlual, Encyclopecha Bnttalllca }\)X5, 24\). Codd MB, Mulot'I DW, Kllrland LT el al Pol!oll1yeltll'. III I Coelho CA, Rerrantl R. Incidellce and nature of dy'.pha)!la III poliO '.II/VIVIll\ Ardl Phy'. Med Rehabtl IlJlJl, 72'1071-1075. Conrady LJ, W!\h JR, Agre Je, Rodllqucl. A/\, Sperllllg KB P\ycholo).!ll dwal t(,JI~tll '. of pollo !'>urvlvor<;: A prellminary repOit Arch Phy:-- Ml'd Rehabll 1l)X9, 7() tl')X-tl(d, Cosgrove JL, Alexander MA, KItt~ EL, Swan BE, Klelll ]j, Bayer I 1).11.1"'.1\ M(', 1Ldlell M 'l'hl' P()\(-po!Jo \yndroml' ln: Plllm F. AdvanLe" III ('OIJ1(·lllptIJ.tly 0:t"lIItdo,l'Y Phrl.trlelphlit,I',A Davl", IlJXX:51-lJ4. I)l'all L, Ho\\ J 1\.1odrlll'd dcHOl"/ i\, BOl/kn 1< J, SIl'lk /(' RelJahrllty 01 dynamomet/)' tn patients with a /lt'lIJOIJIIl\lllLII d/\"Idl'/ 1',IIi! f\kd ]t)X2: JJ(4) J()l}-}75, IkLIIla ('1. LdTVl'f RS. Ml('Ul' MP, Xl'nakl\ AP BeltavlOUf of human motor units in dtfktt'II1 Illlf\lk ... d\lffll~ 11Ill'.ulv V,IIYIl1f! LOntraLlIO!1<" J Physiol Il)X2; 329'113-12R. 1)JXO/l IS, Blld ] lA l\rplOdllllhIllty along a J(JlIl1 Vt"rtlcal vi"ual analogue ~cale. AnnaIs oj Ihl' 1< lH'lIJlIatfl DI\l'tI\C\ 1(JS], .1() X7-Xt) Dratllfll.lll 1)B. MlIlphy SR, Nf}2é1m MI>, Hill:-. JR. MyopathIe changes lJl chronically dl'/H'/Vdtl'd f1llf\llc A/cil Nl'lIJO] IW17, }(1:14-24 1)lfr.md 1\. M.doulfl 1', I{ICh,lI(J.<, (', Bravo (J Inlertnal relrab!lity of work measurements lt't(lIdl'd dllr Illg u Iflll'fllllL" rSO"'Jlletll knee cxtell~lOn and f1é'xlOn 111 ~ubjects with and • Wlthoul flH'llf\lal Il''lf\ Phy\ rhel 1\)l}I; 71 (11) X04-X 12 Edgl'IIOI\ VI{, (;()~I()w (iE, RtI"mll~"el1 SA, Spector SA, Is resistance to muscle fatigue Cllll(101 kd hy Ih IllctlllWlIr one\? N atlllt' 11)~.;o. 2X5:5Xt)-')9(), Edw,\ld~ RI IT BrOlhcfl1fcal ha"is of tatl~lIe III cxerCl:-.e performance: Catastrophe theory 01 IllU\llfldl Lltlgue, III' Knllltgen HG, Vogel JA; l'oOItman-; J (Eds): Biochcmistry of E\l'rL'i"l', [>/Ill(,l'dlllg>; (lj Firth Intcl natIOnal SymposIUm on the Blochl'llll\try 01 1:'\I'It.lse. ('hamp:llgn, IIlIno/" HlIlllan K1I1etic~ Publishels 19X3; 3-2S, Edw.lld\ RIIT New tcl/mlqUl''' for :-tlldyll1g hllll1an muscle function, metabolism and LUlgul' MlI"lk & Nelw Il)~4: 7'it}1)-609 ElIl:llSSOI1 (i. Mu\ck condltlol1lng III late polromyehtls. Arch Phys Med Rehabil January, ]l)l) 1; n, 1 1- 14 Elltal SSOI\ (l, (1llInby G, S talberg E. Electromyographlc and morphological functional L'llmpCn\.ltIOIl 1I1 Iate pohomyelitls. Muscle & Nerve 1<.J90; 13: 165-171. • 70 Engel A MOlphnlogll' and 1I11muI1opatl1l11ngiL 111I(hll~\ III lil}a\thl'llI,1 !~I,I\ 1\ ,lllti III • rongL'IlII.lI my"\theIlIL ,) l'dllllllL" J Nl'lIJ(ll i\:t'lIJ(l\lIl~~ "\'llll,lll\ Il);-';(l, 1; '177 .,St) Engel A. :\1"h"l.I K '1 hl' IlWlllbl.lfll' ,111,11 J... lOll1plc'\ III lllll1pkllll'llt al the l'Ildplall' III lllya~tht'llI,l,l'r",: ... :\1111 i\Y Al,ld Sll 1\):-17. ')()') ~2() "2 Enoka lH.,). R,IIlJ...lll LI. 11l)'llt'r i\lJ. Stll,IIIIHi l ,\tl~'llt' lCl.ltl'd dl,lIlgl'\ 11l11l'1I1(\lllll'I'UI.1I excllahtllty 01 laI hrlldlJml, IllU,L'll" MU"'l il' .\: :'\1'1 \t' N\l\l'lll\1l'I, It)SS. Il 112:; lU.' Enoka R1V1, ï'ray.l110\ ,1 N. L.lnllll\ Y. Hl".lIl 1 . 1~l'IIIJ...lll" I\Î\1. 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