Reduced Neck Muscle Strength and Altered Muscle Mechanical Properties in Cervical Dystonia Following Botulinum Neurotoxin Injections : A Prospective Study

This is an elec onic ep in o he o iginal a icle. This ep in may di e om he o iginal in pagina ion and ypog aphic de ail. Au ho (s): Ti le: Yea : Ve sion: Please ci e he o iginal e sion: All ma e ial supplied ia JYX is p o ec ed by copy igh and o he in ellec ual p ope y igh s, and duplica ion o sale o all o pa o any o he eposi o y collec ions is no pe mi ed, excep ha ma e ial may be duplica ed by you o you esea ch use o educa ional pu poses in elec onic o p in o m. You mus ob ain pe mission o any o he use. Elec onic o p in copies may no be o e ed, whe he o sale o o he wise o anyone who is no an au ho ised use . Reduced Neck Muscle S eng h and Al e ed Muscle Mechanical P ope ies in Ce ical Dys onia Following Bo ulinum Neu o oxin Injec ions : A P ospec i e S udy Mus alampi, Si pa; Ylinen, Ja i; Ko nilo , Ka a iina; Wei , Adam; Häkkinen, A ja Mus alampi, S., Ylinen, J., Ko nilo , K., Wei , A., & Häkkinen, A. (2016). Reduced Neck Muscle S eng h and Al e ed Muscle Mechanical P ope ies in Ce ical Dys onia Following Bo ulinum Neu o oxin Injec ions : A P ospec i e S udy. Jou nal o Mo emen Diso de s, 9(1), 44-49. h ps://doi.o g/10.14802/jmd.15035 2016 44 Copy igh © 2016 The Ko ean Mo emen Diso de Socie y Reduced Neck Muscle S eng h and Al e ed Muscle Mechanical P ope ies in Ce ical Dys onia Following Bo ulinum Neu o oxin Injec ions: A P ospec i e S udy Si pa Mus alampi,1 Ja i Ylinen,1 Ka a iina Ko nilo ,2 Adam Wei ,3 A ja Häkkinen1,2 1Depa men o Physical Medicine and Rehabili a ion, Cen al Finland Cen al Hospi al, Jy äskylä, Finland 2Depa men o Heal h Sciences, Uni e si y o Jy äskylä, Jy äskylä, Finland 3Depa men o Spo s Medicine, Aspe a O hopaedic and Spo s Medicine Hospi al, Doha, Qa a ABSTRACT Objec i eaaTo e alua e changes in he s eng h and mechanical p ope ies o neck muscles and disabili y in pa ien s wi h ce i- cal dys onia (CD) du ing a 12-week pe iod ollowing bo ulinum neu o oxin (BoNT) injec ions. Me hodsaaEigh pa ien s wi h CD olun ee ed o his p ospec i e clinical coho s udy. Pa ien s had ecei ed BoNT injec ions egula ly in neck muscles a h ee-mon h in e als o se e al yea s. Maximal isome ic neck s eng h was measu ed by a dyna- mome e , and he mechanical p ope ies o he splenius capi is we e e alua ed using wo myo onome e s. Clinical assessmen was pe o med using he To on o Wes e n Spasmodic To icollis Ra ing Scale (TWSTRS) be o e and a 2, 4, 8, and 12 weeks a - e he BoNT injec ions. Resul saaMean maximal isome ic neck s eng h a wo weeks a e he BoNT injec ions dec eased by 28% in ex ension, 25% in o a ion o he a ec ed side and 17% in lexion. A ou weeks, muscle s i ness o he a ec ed side dec eased by 17% and en- sion dec eased by 6%. A eigh weeks, he muscle elas ici y on he a ec ed side inc eased by 12%. A wo weeks a e he BoNT injec ions, he TWSTRS-se e i y and TWSTRS- o al sco es dec eased by 4.3 and 6.4, espec i ely. The s eng h, muscle me- chanical p ope ies and TWSTRS sco es e u ned o baseline alues a 12 weeks. ConclusionsaaAl hough maximal neck s eng h and muscle one dec eased a e BoNT injec ions, he disabili y imp o ed. The changes obse ed a e BoNT injec ions we e empo a y and e u ned o p e-injec ion le els wi hin wel e weeks. Despi e ha ing a possible nega i e e ec on unc ion and dec easing neck s eng h, he BoNT injec ions imp o ed he pa ien s epo ed disabili y. Key Wo dsaaMuscle s eng h; Muscle cha ac e is ics; Disabili y; Neck. ORIGINAL ARTICLE h p://dx.doi.o g/10.14802/jmd.15035 / J Mo Diso d 2016;9(1):44-49 pISSN 2005-940X / eISSN 2093-4939 Recei ed: Augus 19, 2015 Re ised: Oc obe 23, 2015 Accep ed: No embe 10, 2015 Co esponding au ho : Si pa Mus alampi, MSc, Depa men o Physical Medicine and Rehabili a ion, Cen al Finland Cen al Hospi al, Keskussai aalan- ie 19, Jy äskylä 40620, Finland / Tel: +358 45 1205 700 / Fax: +358 14 2692 931 / E-mail: [email p o ec ed] cc This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Non-Comme cial License (h p://c ea i ecommons.o g/ licenses/by-nc/3.0) which pe mi s un es ic ed non-comme cial use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. JMD Ce ical dys onia (CD) is a ocal dys onia causing in olun- a y ac i a ion o neck and shoulde muscles esul ing in ab- no mal, sus ained and pain ul pos u ing ha may lead o physi- cal disabili y and social wi hd awal.1 In ecen yea s, bo ulinum neu o oxin (BoNT) has become he i s line he apy o CD.2 A subjec i e eeling o neck weakness has been epo ed as one o he mos common localized ad e se e en s o BoNT.2-7 In clini- cal p ac ice, his may some imes be epo ed as ha ing di icul y keeping he head up igh . Al hough he e ec s o BoNT ha e been widely s udied,2,5 he e ha e been no p ospec i e s udies quan i ying changes in maximal isome ic neck muscle s eng h. Objec i e s eng h measu emen s may help iden i y pa ien s S eng h & Muscle P ope ies in CD Following BoNT Mus alampi S, e al. www.e-jmd.o g 45 wi h neck weakness a e BoNT injec ions ha causes di icul ies in daily li ing and he e o e need addi- ional s eng h aining. Addi ionally, e en hough CD pa ien s ha e equen complain s o neck en- sion, only one s udy8 has p o ided quan i a i e da a abou he e ec s o ini ial BoNT injec ions on he passi e mechanical p ope ies o skele al muscle in a clinical se ing, despi e ha measu emen de ices ha e been de eloped o his pu pose. Myo onom- e e s may p o ide an objec i e, non-in asi e ool o quan i y changes in muscle p ope ies a e BoNT injec ions ha we e p e iously ob ained using sub- jec i e me hods. The aim o his s udy was o e alu- a e he changes in neck s eng h, he mechanical p ope ies o neck muscles, and disabili y o e a wel e-week pe iod ollowing BoNT injec ions in pa ien s wi h CD who had a wo-yea his o y o BoNT ea men . We hypo hesized ha he mechanical p ope ies o muscle luc ua e a e BoNT injec ion, and his luc ua ion is e lec ed in dec eased muscle powe and ension, as well as disabili y. MATERIALS & METHODS Pa ien s Twen y- wo pa ien s who we e ecei ing BoNT injec ions in hei neck muscles in an ou pa ien e- habili a ion clinic we e in i ed by mail o olun ee o his p ospec i e clinical coho s udy. Eigh pa- ien s (3 women, 5 men) olun ee ed. Ten pa ien s denied because o he long-dis ance a el equi ed o egula isi s, and ou pa ien s denied o pe - sonal easons. The mean age (s anda d de ia ion, SD) o he pa icipan s was 57 (10) yea s; he mean body mass index (SD) was 24.7 (5.4) kg/m2. The mean du a ion (SD) om he onse o CD was 14 (12) yea s, and he mean du a ion om he s a o egula BoNT injec ions was 2.3 (1.6) yea s. The p e- dominan componen o he CD was o a ion o la - e ocollis o he neck, which was owa d he le side in ou pa ien s and owa d he igh side in he e- maining ou pa ien s. The local e hics commi ee app o ed he s udy. All subjec s ga e hei w i en consen be o e pa icipa ing in he s udy. In e en ion Two o ms o BoNT ype A, onabo ulinum oxinA (ona-BoNTA, Bo ox®, Alle gan, I ine, CA, USA) (n = 4) and abobo ulinum oxinA (abo-BoNTA, Dyspo ®, Ipsen, Pa is, F ance) (n = 4), we e used acco ding o he mos ecen ecommenda ions.2 The o al dose injec ed in o ce ical muscles was 100 U o ona- BoNTA and 500 U o abo-BoNTA. All pa ien s e- cei ed injec ions in he splenius capi is on he a - ec ed side, and he o he muscles injec ed a ied acco ding o he dis ibu ion and deg ee o dys onic muscles. The mean numbe (SD) o injec ed mus- cles was 5.4 (1.3). Injec ions we e pe o med by wo physia is s wi h se e al yea s o expe ience o BoNT ea men in hese pa ien s. Ou come measu es Neck s eng h o isome ic lexion, ex ension and o a ion was measu ed while he pa icipan was in he si ing posi ion and using a special neck dyna- mome e acco ding o he echnique epo ed in p e ious s udies.4,9 The bes esul o h ee maximal e o s was used in he inal analysis. The mechanical p ope ies o splenius capi is we e measu ed on he a ec ed and non-a ec ed sides wi h wo myo onome e s and wi h he pa icipan in he s anda d supine posi ion: he head was in a s - aigh neu al posi ion ( ace down owa d he hole o he examina ion able) and he hands we e beside he body. The Myo on-3 (Myo on AS, Tallinn, Es o- nia) enables measu emen o muscle cha ac e is ics by eco ding damped oscilla ions o he issue when a mechanical pe u ba ion is applied o he mus- cle.10,11 The Myo on-3, which is placed pe pendicu- la o he muscle, p oduces a sho impulse on he muscle. An accele a ion ansduce eco ds he da- mped oscilla ions o he muscle, and he oscilla ion equency (Hz) cha ac e izes he ension in he muscle. A loga i hmic dec emen o he oscilla ion cha ac e izes he muscle elas ici y, whe eas he os- cilla ion s i ness pa ame e (N/m) cha ac e izes he muscle’s abili y o esis he o ce ha is shaping i . Measu emen o he mechanical p ope ies o sple- nius capi is using he Myo on is shown in Figu e 1. Muscle compliance was measu ed wi h a compu - e ized muscle onome e (CMT) (Medi ehabook L d., Muu ame, Finland).12 The CMT quan i ies he amoun o issue displacemen as he p obe is pu- shed down and pe pendicula o he muscle.12 The esul o a CMT is exp essed as he wo k pe o med while he p obe comp esses he issue and is calcu- la ed as he a ea unde he cu e in he o ce-de o - ma ion-g aph (mJ). A highe alue indica es a highe 46 J Mo Diso d 2016;9(1):44-49 JMD compliance o he issue. Uppe apezius ac i i y was measu ed simul aneously wi h myo onome ic measu emen s by su ace elec omyog aphy (sEMG) using an ME1000 Analyze (Mega Elec onics L d., Kuopio, Finland) o assu e ha only minimal mus- cula ac i i y was p esen a es . Clinical assessmen was pe o med using he o al To on o Wes e n Spasmodic To icollis Ra ing Scale (TWSTRS) (0 o 85 poin s) and i s h ee subscales.1 The se e i y scale has 10 i ems (0 o 35 poin s), he disabili y scale has 7 i ems o ac i i ies o daily li ing (0 o 30 poin s), and he pain scale has 3 i ems (0 o 20 poin s). Highe sco es indica e g ea e impai - men . Assessmen s we e pe o med p io o BoNT injec ions ollowed by measu emen s a 2, 4, 8, and 12 weeks a e he injec ions. All measu emen s we e pe o med in a s anda dized manne by he same expe ienced physio he apis . S a is ical analysis The da a a e epo ed as he means wi h SDs. The mean changes wi h 95% con idence in e als (CI) om baseline o he measu emen s a ollow-ups we e calcula ed. S a is ical compa isons o he ou - come measu emen s we e pe o med using pai ed - es s. No adjus men was made o mul iple es - ing, bu his in o ma ion can be ob ained by mul i- plying he ac ual p alue by he numbe o compa - ison made. The le el o p < 0.05 was selec ed o in- dica e s a is ical signi icance. S a is ical analyses we e pe o med wi h SPSS ( e sion 22.0; SPSS Inc., Chi- cago, IL, USA). RESULTS The mean alues o neck s eng h, he mechani- cal p ope ies o splenius capi is on he a ec ed side, and he TWSTRS sco es a e shown in Table 1. The e we e no signi ican di e ences a baseline in o a ion s eng h o he mechanical p ope ies o splenius ca- pi is be ween he a ec ed and non-a ec ed sides. The mean dec ease in neck s eng h a wo weeks a e he BoNT injec ions was -28% (95% CI: -40 o Figu e 1. Measu emen o he mechanical p ope ies o splenius capi is using he Myo on. Table 1. Mean alues o maximal isome ic neck s eng h, mechanical p ope ies o splenius capi is on he a ec ed side, and TWSTRS sco es a base- line and egula in e als ollowing bo ulinum oxin injec ions in pa ien s wi h ce ical dys onia Baseline, mean (SD) A 2 wk, mean (SD) A 4 wk, mean (SD) A 8 wk, mean (SD) A 12 wk, mean (SD) Neck muscle s eng h Flexion (N) 92.8 (45.2) 76.7 (37.0)*83.2 (37.4) 90.3 (48.0) 90.1 (41.0) Ex ension (N) 179.4 (73.5) 128.7 (74.8)*127.7 (68.9)*148.8 (79.3)*172.2 (79.0) Ro a ion (Nm) 10.6 (6.6) 8.0 (5.4)*8.6 (5.5)*10.2 (7.3) 10.1 (5.8) Mechanical p ope ies Tension (Hz) 15.6 (3.1) 14.5 (2.1) 14.6 (2.5)* 15.2 (1.2) 15.4 (2.1) Elas ici y 1.26 (0.18) 1.34 (0.26) 1.35 (0.19) 1.41 (0.13)*1.39 (0.12) S i ness (N/m) 319 (109) 274 (93) 265 (82)*278 (53) 244 (32) Compliance (mJ) 22.1 (4.7) 23.8 (4.8) 24.3 (6.6) 22.4 (3.1) 21.7 (5.9) TWSTRS Se e i y (0 o 35) 12.4 (3.8) 8.1 (4.3)*9.1 (4.0)*10.8 (3.0)*13.6 (3.0) Disabili y (0 o 30) 7.1 (3.9) 6.0 (2.9) 6.4 (2.4) 7.1 (3.9) 8.1 (2.9) Pain (0 o 20) 6.3 (4.1) 5.3 (4.9) 4.2 (3.4) 5.3 (4.9) 5.3 (4.8) To al (0 o 85) 25.8 (10.3) 19.4 (9.1)*21.0 (5.7) 23.1 (10.0) 27.0 (8.4) *signi ican ly di e en om baseline (p < 0.05). Hz: he z, N: new on, m: me e , mJ: millijoule, TWSTRS: To on o Wes e n Spasmodic To icollis Ra ing Scale, SD: s anda d de ia ion. S eng h & Muscle P ope ies in CD Following BoNT Mus alampi S, e al. www.e-jmd.o g 47 -17) in ex ension (p = 0.001), and -17% (95% CI: -33 o -2) in lexion (p = 0.032). No signi ican change was obse ed on he non-a ec ed side o o a ion s eng h among consecu i e measu emen s. The o- a ion s eng h o he a ec ed side dec eased by -25% (95% CI: -41 o -9) a wo weeks (p = 0.008). A e wo weeks, howe e , o a ion s eng h g adually im- p o ed. A signi ican dec ease in ex ension s eng h was s ill e iden a eigh weeks, and a dec ease in o- a ion s eng h was p esen on he a ec ed side a ou weeks a e he BoNT injec ions. All s eng h measu es e u ned o he baseline alues wi hin 12 weeks. Muscle s i ness and ension on he a ec ed side we e dec eased by 17% (95% CI: -32 o -2) (p = 0.031) and 6% (95% CI: -12 o -1) (p = 0.030), e- spec i ely, a ou weeks a e he BoNT injec ions. Muscle elas ici y on he a ec ed side was inc eased by 12% (95% CI: 6 o 18) (p = 0.003) a eigh weeks, showing a educed elas ic capaci y. No o he signi - ican changes in he muscle mechanical p ope ies we e obse ed a e BoNT injec ions. The sEMG alues eco ded du ing hese measu emen s we e low a all ime-poin s ( ange om 0 o 14 mV). The TWSTRS-se e i y and TWSTRS- o al sco es we e dec eased by 4.3% (95% CI: -6.3 o -2.2) (p = 0.002) and 6.4% (95% CI: -9.1 o -3.6) (p = 0.001), espec i ely, a wo weeks a e he BoNT injec- ions. The TWSTRS-se e i y sco e emained signi - ican ly imp o ed compa ed o baseline un il eigh weeks a e he ea men . The e we e no signi ican changes in he TWSTRS-disabili y o pain sco es a any ime du ing ollow-up. No ad e se e en s we e e- po ed wi h BoNT injec ions, excep neck weakness. DISCUSSION This is he i s ollow-up s udy o quan i y he e - ec o BoNT injec ions on neck s eng h in pa ien s wi h CD. A he doses used in he p esen s udy, BoNT injec ions caused pa ial pa alysis o he mus- cles injec ed,2,5 and hus he educ ion in s eng h was expec ed. We ound no p e ious epo s ha quan- i y changes in neck muscles ha could be compa ed wi h ou esul s. The p esen s udy showed ha he luc ua ion in neck s eng h be ween consecu i e BoNT injec ions is subs an ial. A wo weeks a e ea men , he dec ease in neck s eng h was he la ges in ex ension, almos as la ge as ha in o a- ion, and was less p onounced in lexion. The ime equi ed o neck s eng h o eco e in he di e - en mo emen s a ied, and his was p obably due o he muscles ha we e injec ed. S eng h in all mo- emen s was no malized o p e-injec ion le els a wel e weeks. Häkkinen e al.4 showed ha CD pa- ien s wi h BoNT- ea ed neck muscles show sig- ni ican ly lowe peak neck s eng h compa ed o heal hy ma ched con ols. In hei s udy, he s eng h measu emen s we e pe o med jus p io o he nex injec ion. Howe e , acco ding o he indings o he p esen s udy, his was when neck s eng h was high- es in he CD pa ien s. Thus, he esul s sugges ed ha BoNT injec ion may ha e long- e m e ec s on maximal neck s eng h. The p esen s udy shows ha maximal neck s eng h is conside ably lowe wo weeks a e injec ion. The cu en neck s eng h alues a wo weeks a e BoNT injec ions we e ap- p oxima ely 50 o 60% o he maximal isome ic s - eng h ha was p e iously epo ed in heal hy sub- jec s wi h compa able age g oups.13,14 S eng h mea- su emen s in he p esen s udy we e pe o med wi h he same equipmen and es p o ocol ha we e used o he heal hy subjec s in p e ious s udies, and hus he esul s a e compa able. Fo una e al.15 ha e sh- own ha BoNT injec ions cause se e e muscle a - ophy and loss o con ac ile issue in no only he injec ed muscles bu also he non-injec ed muscles. Muscle weakness may be pa ly due o ch onic neck pain, which as was p e iously shown in pa ien s wi h ch onic mechanical neck pain.9 I is impo an o no e ha he pa ien s in he p esen s udy had e- cei ed BoNT injec ions a h ee mon hs in e als o app oxima ely wo yea s. The muscle mechanical p ope ies measu ed in his s udy we e al e ed a e BoNT injec ions. Muscle ension and s i ness alues dec eased a ou weeks a e BoNT injec ions, and elas ici y alues inc eased a eigh weeks a e BoNT injec ions. The esul s o he p esen s udy a e somewha simila o he e- sul s epo ed by Ma ulli e al.,8 who combined BoNT injec ions and physio he apy o he ea - men o CD in 15 pa ien s. They pe o med clinical e alua ion and myo onome ic measu emen s us- ing he Myo on-3 be o e and a one, wo, and h ee mon hs ollowing BoNT injec ions. Thei s udy ound ha muscle ension, s i ness, and elas ici y alues measu ed wi h he Myo on we e dec eased a e BoNT injec ions a one, wo, and h ee mon hs 48 J Mo Diso d 2016;9(1):44-49 JMD a e injec ions. Howe e , he di e ences in s udy designs be ween ha s udy and he p esen s udy may pa ly explain he di e ences in esul s. Pa- ien s in he p esen s udy had been ecei ing BoNT injec ions o yea s, whe eas pa ien s in he s udy o Ma ulli e al.8 ecei ed hei i s BoNT injec ions. I has been epo ed ha long- e m use o BoNT e- sul s in a dec ease in con ac ile issue and an inc - ease in connec i e issue,15 hus making he muscle mo e igid. Consequen ly, acu e changes in muscle p ope ies would become less ob ious. No changes we e obse ed in he muscle compliance alues. This esul may be me hodological: i was di icul o posi ion he measu emen de ice on a small, ound muscle. The CMT echnique is p obably mo e sui - able o la ge muscles.11 The indings in ou s udy on disabili y a e consis- en wi h hose o p e ious s udies epo ing sho - e m unc ional imp o emen in CD a e BoNT injec ions.2,3,5-7 In he p esen s udy, he TWSTRS- o al and TWSTRS-se e i y sco es we e signi ican - ly lowe a wo weeks compa ed wi h he p e-injec- ion sco es. These indings also showed ha he sco es e u ns o p e-injec ion s a e o e he cou se o he h ee-mon h ollow-up, as was epo ed in ea lie s udies.2,3,5-7 The p esen s udy shows ha he changes in clinical sco es a e associa ed wi h objec- i ely measu ed changes in muscle p ope ies. Fu - he mo e, he esul s show ha , despi e a possible nega i e e ec on unc ion ha included dec eased neck s eng h, he BoNT injec ions imp o ed he pa ien s epo ed disabili y. The ac ha he g oup o pa ien s who we e ea - ed in he p esen s udy had been unde going egu- la he apy wi h BoNT injec ions o se e al yea s indica es hei baseline disabili y sco es we e p ob- ably less se e e han hose wi hou ea men . The e- o e, he changes in he ea men g oup we e small- e han hose in he un ea ed g oups.3,7 Howe e , in his s udy, he aim was o e alua e changes in he pa- ien g oup wi h he long- e m use o BoNT. The small and he e ogeneous s udy g oup used in he p esen s udy may no ha e p o ided su icien powe o de ec small changes in ou come measu es. Fu - he esea ch wi h a la ge s udy g oup and a longe ollow-up pe iod is needed o s udy he e ec s o BoNT injec ions on muscle s eng h and he mech- anical p ope ies o muscles. This s udy showed ha al hough maximal s eng h, ension, s i ness, and elas ic capaci y we e educed in neck muscles a e BoNT injec ions, he se e i y o neck complain s dec eased in pa ien s wi h CD. 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