R e v i e w a r t i c l e A n E v i d e n c e - B a s e d R e v i e w o f H y p e r b a r i c O x y g e n f o r C h i l d r e n w it h C e r e b r a l P a l s y A B S T R A C T : This paper reviews the evidence in the literature fo r the use o f hypebaric oxygen (HBO) in the treatment o f cerebral palsy ( CP). To date there are only two published studies on the outcome o f HBO administration in CP. A pilot study showed significant improvement in gross m otor function, but provided a low level o f evidence. A recent multicentre, double blind, placebo controlled trial reported sim ilar improvements in both HBO and placebo groups, but no difference between the groups. This study had a high level o f evidence. The results suggest that participation in the trial produced clinically important gains in function. The outcome o f the study implies that HBO may have a placebo effect in CP KEY WORDS: LITERATURE REVIEW / EVIDENCE, HYPERBARIC OXYGEN / CEREBRAL PALSY BISCHOF FM, M.Sc Physiotherapy PhD' 1 Lecturer, Departm ent o f Physiotherapy, U niversity of the W itw atersran d. INTRODUCTION C ereb ral palsy (C P ) is “an u m b rella term co v erin g a g ro u p o f non-progressive, b u t often ch an g in g , m o to r im p airm en t s y n d ro m e s s e c o n d a ry to le sio n s o r anom alies o f the brain arising in the early stag es o f its d e v e lo p m e n t” (M utch et al, 1992). T h e m ain p rin cip le u n d erlying the m a n ag e m en t o f C P is to m ax im ize th e re m a in in g “ in ta c t” n e u ro lo g ic a l fu n ctio n , and to in co rp o rate treatm en t g ain s into activ ities o f d aily living. T ra d itio n a l in te rv e n tio n s fo r C P in c lu d e o r th o p a e d ic su rg ery , n e u ro ­ surgery, pharm acological agents, p h y sio ­ th e ra p y , o c c u p a tio n a l th e ra p y an d speech therapy. T h ese m o d alities have been in use fo r m any years. M ore recently, h y p erb aric o x y g en (H B O ) has beco m e a w id ely used in terv en tio n , and has rap id ly b ec o m e p erceiv ed as an effectiv e fo rm o f th erap y by p aren ts o f c h ild ren w ith CP. T h ere are at p resen t seven c e n tre s in S o u th A fric a alo n e o fferin g this treatm en t. H B O has also been p o p u la rised in th e S o u th A frican m edia, by w ay o f telev isio n p ro g ram s, m a g a z in e a rtic le s an d p re ss rep o rts. T h e re is a n e c d o ta l e v id e n c e o f its p o sitiv e e ffe c ts o n m o to r fu n c tio n , co g n itio n an d speech. H B O is a m e d ica l tre a tm e n t th at uses p ure o xygen to allev iate hyp o x ia at the cellu lar level. P u re o x y g en is p re s s u ris e d an d a d m in is te re d to th e p atien t in a h y p erb aric cham ber. H B O is a rec o g n ised m edical in terv en tio n for s e v eral c o n d itio n s , in c lu d in g ca rb o n m o n o x id e p o is o n in g , w o u n d s , an d d ec o m p ressio n sick n ess. It is a co n tro ­ v e rsia l in te rv e n tio n in n e u ro lo g ic a l d y s fu n c tio n , d u e to th e p a u c ity o f scien tific ev id en ce o f its effects on brain fu n ctio n in g . LITERATURE REVIEW H B O has been used sin ce the 1 950’s to trea t a w id e v ariety o f n e u ro lo g ical co n d itio n s, including spinal cord lesions, m u ltip le sclero sis, A lz h e im e r’s disease, h e a d in ju rie s an d c e re b ra l v a s c u la r accid en ts (Sukoff, 1984). H B O w as reco m m en d ed by N eu b au er an d E n d (1980) as an ad ju n ct therapy in the trea tm e n t o f strokes. T h ey stated that it c o u ld co n tro l cereb ral o ed em a, an d p ro v id e o x y g en to the in farcted and m arg in ally isch aem ic areas o f the brain. T hey rep o rted fu n ctio n al g ain s in their p atien ts afte r H B O ad m in istratio n . T his w as a retro sp e ctiv e b e fo re an d afte r study, w h ich p ro v id es a low level o f ev id en ce (Sackett, 1997). A stru p e t al (1 9 8 1 ) w ro te an e d ito rial in S troke, po stu latin g the th eo ry th a t th ere is a v iab le area aro u n d the cerebral infarct, “th e isch aem ic p en u m b ra” w hich co u ld b e im p ro v ed b y th e ad m in istratio n o f H B O . N eu b a u e r w ro te to the L an cet in 1990, referrin g ag ain to a p eri-in farc- tio n al zo n e o f v iab le, but n o n -functional “id lin g n eu ro n s” , w hich co u ld p o ssib ly b eco m e fu n ctio n al again by in creasin g o xygenation o f the cerebral blood supply, u sing H BO . E n h a n c e m e n t o f “ id lin g ” n eu ro n s, an d d ecrease o f cereb ral o ed em a are tw o o f the th eo ries u sed to ex p lain the e ffe c ts o f H B O in CP. T h e re is no p u b lish ed scien tific ev id en ce to su p p o rt the su p p o sed im p ro v em en t o f neuronal functioning in C P by adm inistering HBO. T h e first study o f H B O in C P cam e from B razil. It was presented at a m eeting o f th e U n d ersea an d H y p erb aric M ed ical S ociety in 1989, but w as never p u b lish ed an d can th e re fo re not b e evaluated. T h e firs t r e s e a rc h a r tic le to b e p u b lish ed in this field w as a p ilo t study from M ontreal (M ontgom ery e t al, 1999). T w enty-five ch ild ren w ith spastic d ip le ­ gia, ag ed 3-8 y ears receiv ed H B O at tw o trea tm e n t cen tres, 1.5 ATA (atm o sp h eres ab so lu te) fo r 6 0 m in u tes, w ith a total o f 20 treatm en ts. T h ey w ere assessed befo re an d a fte r the trea tm e n t regim en, u sing a n u m b er o f tests w h ich in c lu d ed th e G ro s s M o to r F u n c tio n M e a su re (G M F M ), the m o d ified A sh w o rth scale C O R R E S P O N D E N C E TO: F M B isch o f P O B o x 4105 G erm isto n South 1411 G au ten g Tel: (011) 827-6465 (H) (0 1 1 )4 8 8 - 3 4 5 0 (W ) SA J o u r n a l o f Physiotherapy 2001 V o l 57 No 4 21 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 3. ) for the m e asu rem en t o f spasticity, and v id e o a n a ly s is . T h e im p ro v e m e n ts in th re e d im e n s io n s o f th e G M F M w ere statistically significant. T he G M FM is a v a lid a te d a s s e s s m e n t to o l w ith p roven reliability (N o rd m ark et al, 1997). It m easu res fu n ctio n al lim itatio n s, and r e d u c tio n o f th e se lim ita tio n s is an im p o rta n t o u tco m e. H ow ever, this study in v o lv ed sm all n u m b ers, and th ere w ere no co n tro ls, th e re fo re it w o u ld receiv e the lo w est ratin g o n the ev id en c e scales (B u tle r e t al, 1999). A t the tim e this study w as u n d ertak en the Q u eb e c C o lleg e o f M e d icin e did not a p p ro v e the p rescrip tio n o f H B O for ch ild ren w ith CP. T h e resu lts o f the p ilo t study, an d p re ssu re fro m p are n ts o f C P ch ild ren w h o w an ted this fo rm o f tre a tm e n t re c o g n is e d by th e m ed ical au th o rities, lead to the d esig n an d im p le ­ m en tatio n o f a ran d o m ised , co n tro lled d o u b le b lin d m u ltice n tre trial, w h ich rec eiv e d eth ica l ap p ro v al. F iv e H B O ce n tres p articip a ted in the trial, w h ich w a s c o n d u c te d by C o lle t e t al an d p u b lish ed in the L an c et (2001). O n e h u n d red an d elev e n c h ild ren w ith CP, aged 3-12 years, w ere random ly assig n ed to rec eiv e e ith er H B O (n = 57) o r slig h tly p ressu rise d air (n = 54). T he H B O p ressu re w as 1.75 ATA and the air p ressu re 1.3 ATA. T h is w as the lo w est p ressu re at w h ich air co u ld be felt, thus en su rin g m asking. F orty trea t­ m ents, each lastin g one hour, w ere given o v e r a p erio d o f eig h t w eeks. C h ild ren w ere assessed at baseline, after 20 and 40 treatm en ts, an d 12 w eek s afte r cessatio n o f the in terv en tio n . T h e m ain o u tco m e m easu res used w ere: 1. T h e G M F M , for m o to r fu n ctio n . 2. T h e P E D I (P aed iatric E v alu atio n o f D isab ility In v en to ry ), fo r activ ities o f daily living. 3. S p eech an d la n g u ag e assessm en ts. 4. T ests fo r m em o ry an d attention. T h erap ists w ere th o ro u g h ly train ed in th e a d m in is tra tio n o f th e te s ts , an d b lin d ed to the c h ild ’s g ro u p allo catio n . S ig n ifica n t im p ro v e m en ts fo r all m e a­ sures w ere rec o rd e d w h en co m p arin g p re an d p o st in terv en tio n scores. T h ere w as h o w e v e r no sig n ific an t d ifferen ce b etw een the H B O an d p la ce b o g ro u p s in the a m o u n t o f im p ro v em en t. T his show ed that H B O and slightly pressurised a ir had the sam e effect. T h e au th o rs state th at it c o u ld be p o stu lated that air at 1.3 ATA is sufficient to p ro d u ce the sam e effect as o x y g en at 1.75 ATA, but th is does n o t su p p o rt the p en u m b ra theory. A p o ssib le learning, effect w as d iscounted, due to the specific co m p o sitio n and ad m in istra tio n o f the tests. T hey co n c lu d e d th a t the im p ro v e­ m ents w ere p ro b ab ly due to the p artici­ p atio n effect. T h e p are n ts w h o to o k part in the stu d y w ere all hig h ly m o tiv ated and sp en t tim e w ith th e ir ch ild ren in an e n ric h ed en v iro n m en t. T h e o u tc o m e o f the rese arch im p lies th at H B O m ay have a p laceb o effec t in CP. T h is w as a w e ll d e s ig n e d study. U sin g the g u id elin es p ro v id ed by G u y att et al (1993), it can be stated th a t the criteria fo r v alid ity w ere m et in the co n d u c t o f the study. D esp ite the d iffi­ culty in m atch in g p articip a n ts, d u e to the h etero g en ity o f CP, th ere w as a g ood sim ilarity in the d istrib u tio n o f ty p es o f C P b etw een the tw o g roups. S trict in c lu ­ sion and ex clu sio n c riteria w ere applied. T h e re w as ra n d o m a s s ig n m e n t o f the ch ild ren to e ith e r a h y p erb aric o x y ­ gen, o r a p ressu rise d air in terv en tio n . B oth in v estig ato rs an d p articip an ts w ere b lin d e d to th e tre a tm e n t b e in g a d m i­ n iste re d . T h e d ro p o u t ra te w as lo w - o n ly 4 ch ild ren did n o t co m p lete the study. B o th g ro u p s w ere treated equally e.g. physiotherapy w as discontinued from 6 w eek s b efo re the trial until the en d o f the trea tm e n t period. O u tc o m e s w e re m e a s u re d in all d im e n sio n s o f th e IC ID H 2 (W H O , 1997), nam ely im p airm en ts, functional lim ita tio n s an d so c ietal p a rtic ip a tio n , usin g v alid ated as se ss m e n t tools. T his study w o u ld be p la ce d at L ev el 1 (the hig h est level), ac co rd in g to S a c k e tt’s m eth o d fo r g rad in g rese arch ev id en ce. T h e s ig n ific a n t im p ro v e m e n ts in fu n ctio n o b ta in ed by p articip a tio n in the stu d y h av e w id er im p lica tio n s fo r o th e r th erap ies w here m uch tim e an d atten tio n is d ev o ted to c h ild re n w ith c e reb ral palsy, an d th e ir paren ts. T h e u nproven scien tific ratio n ale fo r the use o f H B O in the trea tm e n t o f ch ild ren w ith CP, and the o u tco m e o f the co n tro lled study, do no t su p p o rt the rec o m m en d a tio n o f this e x p e n siv e in terv en tio n . REFERENCES B utler C, C ham bers H, G o ldstein M , H arris S, Leach J, C am pbell S, A dam s R, D arrah J 1999 E v aluating research in de v elo p m en tal d is a b ilitie s : a c o n c e p tu a l fra m e w o rk fo r review ing treatm ent outcom es. D evelopm ental M edicine and C hild N eurology 4 1 :5 5 -5 9 C o lle t J, V anasse M , M arois P, A m a r M, G o ldberg J, L am b ert J, L assonde M , Hardy P, Fortin J, T rem elay S, M o ntgom ery D, L acroix J, R o b inson R, M a jn em er A 2001 H yperbaric o x ygen fo r c h ild ren w ith cerebral palsy: a random ised m u lticentre trial. T he L an c et 357: 582-586 G uyatt G H , S ackett D L, L ook DJ 1993 U s e r’s guide to the m edical literature. II How to use an article a bout therapy o r p re vention. A. A re the results o f the study v alid? Journal o f the A m erican M edical A ssociation 270: 2598-2601 M o n tg o m ery D, G o ldberg J, A m a r M , L acroix J, L ec o m te J, L am b ert J, V anasse M , M arois P T he e ffects o f h y p e rb aric o x ygen therapy on c h ild ren w ith spastic dip le g ic cere b ral palsy: a p ilot project. U n d e rse a H yperbaric M edicine 26:235-242 M utch L, A lberm an E, H a g b erg B, K odom a K, V elickovic P erat M 1992 C erebral palsy e pid e m io lo g y : w here are we now, and w here are w e g o in g ? D e v elopm ental M e dicine and C hild N eurology 34:547-555 N e u b au e r R, End E 1980 H yperbaric o x y g e ­ nation as an a d junct therapy in strokes due to th ro m b o sis - a review o f 122 patients. Stroke 11: 2 9 7-300 N e u b au e r R A , G otti ich SF, K agan R L 1990 E n h an c in g idling neurons T he L ancet 335: 542 (L etter) N ordm ark E, H agglund G , Jarnio GB 1997 R e lia b ility o f th e g ro ss m o to r fu n c tio n m e a su re in c e re b ra l palsy. S c a n d in a v ia n Journal o f R eh ab ilitatio n M edicine 29:25-28 S a c k ett Dl, R ichardon W S, R osenberg W, H aynes RB 1997 E v idence-based m edicine: how to p ractice and teach E B M . N ew York: C h urchill L iv in g sto n e S u k o ff M H 19 84 U pdate on the use o f HBO fo r the d iseases o f the central nervous system . H y perbaric O xy g en R eview 5:35-47 W orld H ealth O rg anization 1997 IC ID H -2. International C lassific a tio n o f Im pairm ents, A c tivities and P articipation. G eneva, S w itz er­ land. W H O 22 SA J o u r n a l o f P hysiotherapy 2001 V o l 57 No 4 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 3. )