Head-mounted display-based therapies for adults post-stroke: A systematic review and meta-analysis

senso s Re iew Head-Moun ed Display-Based The apies o Adul s Pos -S oke: A Sys ema ic Re iew and Me a-Analysis Guille mo Palacios-Na a o 1,2,* and Ne ille Hogan 2,3   Ci a ion: Palacios-Na a o, G.; Hogan, N. Head-Moun ed Display-Based The apies o Adul s Pos -S oke: A Sys ema ic Re iew and Me a-Analysis. Senso s 2021,21, 1111. h ps://doi.o g/10.3390/ s21041111 Academic Edi o : Y onne T an Recei ed: 8 Janua y 2021 Accep ed: 2 Feb ua y 2021 Published: 5 Feb ua y 2021 Publishe ’s No e: MDPI s ays neu al wi h ega d o ju isdic ional claims in published maps and ins i u ional a il- ia ions. Copy igh : © 2021 by he au ho s. Licensee MDPI, Basel, Swi ze land. This a icle is an open access a icle dis ibu ed unde he e ms and condi ions o he C ea i e Commons A ibu ion (CC BY) license (h ps:// c ea i ecommons.o g/licenses/by/ 4.0/). 1Depa men o Elec onic Enginee ing and Communica ions, Uni e si y o Za agoza, 44003 Te uel, Spain 2 Depa men o Mechanical Enginee ing, Massachuse s Ins i u e o Technology, Camb idge, MA 02139, USA; [email p o ec ed] 3Depa men o B ain and Cogni i e Sciences, Massachuse s Ins i u e o Technology, Camb idge, MA 02139, USA *Co espondence: Guille mo.palacios@uniza .es; Tel.: +34-978-618-179 Abs ac : Imme si e i ual eali y echniques ha e been applied o he ehabili a ion o pa ien s a e s oke, bu e idence o i s clinical e ec i eness is sca ce. The p esen e iew aims o ind s udies ha e alua e he e ec s o imme si e i ual eali y (VR) he apies in ended o mo o unc ion ehabili a ion compa ed o con en ional ehabili a ion in people a e s oke and make ecommenda ions o u u e s udies. Da a om di e en da abases we e sea ched om incep ion un il Oc obe 2020. S udies ha in es iga ed he e ec s o imme si e VR in e en ions on pos - s oke adul subjec s ia a head-moun ed display (HMD) we e included. These s udies included a con ol g oup ha ecei ed con en ional he apy o ano he non-imme si e VR in e en ion. The s udies epo ed s a is ical da a o he g oups in ol ed in a leas he pos es as well as ele an ou comes measu ing unc ional o mo o eco e y o ei he lowe o uppe limbs. Mos o he s udies ound signi ican imp o emen s in some ou comes a e he in e en ion in a o o he i ual ehabili a ion g oup. Al hough e idence is limi ed, imme si e VR he apies cons i u e an in e es ing ool o imp o e mo o lea ning when used in conjunc ion wi h adi ional ehabili a ion he apies, p o iding a non-pha macological he apeu ic pa hway o people a e s oke. Keywo ds: head-moun ed display; imme si e i ual eali y; mo o eco e y; ehabili a ion; s oke 1. In oduc ion In he pas decades, he e has been an sha p inc ease in he applica ion o i ual eali y (VR) ea men s o he ehabili a ion o a ange o diso de s esul ing om lesions o he ne ous sys em [ 1 , 2 ]. The a ea o ehabili a ion o pa ien s wi h s oke is he mos p oduc i e in e ms o echnology-based in e en ions in bo h uppe and lowe ex em- i ies [ 3 ]. VR he apies ha e been success ully used a e s oke [ 4 , 5 ] since hey apply concep s ha a e ele an o s oke ehabili a ion, such as high epe i ion, high in ensi y, and ask-o ien ed aining [6,7]. Vi ual eali y can p o ide an engaging and mo i a ional expe ience, allowing he use o p ac ice mo o mo emen s while manipula ing an in e ace de ice [ 5 ]. The i - ual en i onmen (VE) can be easily changeable, allowing he design o indi idualized he apies ha a e adap ed o pa ien needs. VR can p o ide unc ional, ich s imuli (cues) and mo i a ing con ex ( eedback), encou aging he mo e ac i e pa icipa ion o he sub- jec [ 8 ]. Fu he mo e, di e en s udies ha e epo ed imp o emen s in mo o abili ies, as well as a g ea le el o pa icipan mo i a ion a e including i ual eali y in s oke ehabili a ion [9–15] . In s oke ehabili a ion, p o iding an in e en ion ha is mo i a ing and engaging is c ucial o pa ien in ol emen and pa icipa ion. Semi-imme si e and non-imme si e VR sys ems ha e been widely used o s oke pa ien ehabili a ion. Senso s 2021,21, 1111. h ps://doi.o g/10.3390/s21041111 h ps://www.mdpi.com/jou nal/senso s Senso s 2021,21, 1111 2 o 24 Imme si e s. Non-Imme si e VR Weiss e al. de ined i ual eali y as “ he use o in e ac i e simula ions o p o ide he use s wi h oppo uni ies o engage in en i onmen s ha appea and eel simila o eal-wo ld objec s and e en s” [ 16 ]. Schul heis and Rizzo conside ed i ual eali y o be “an ad anced o m o human–compu e in e ace ha allows he use o in e ac wi h and become imme sed in a compu e -gene a ed en i onmen in a na u alis ic ashion” [ 17 ]. Rega dless o i s de ini ion, he mul isenso ial expe ience o e s a p ac ice en i onmen ha can be ecologically alid and has he po en ial o enhance pa ien enjoymen and compli- ance [ 18 ], impo an ac o s in success ul ehabili a ion [ 5 , 19 ]. The a ie y o echnologies ha a e conside ed VR is b oad. We conside echnologies anging om non-imme si e applica ions o comple ely imme si e applica ions, p og essing h ough semi-imme si e ones. I all depends on he deg ee o isola ion om he physical wo ld ha he echnology p o ides o he use when in e ac ing wi h he i ual en i onmen [7]. Lange e al. s a ed ha “imme si e VR can be p oduced by combining compu e s, head-moun ed displays (HMDs), body acking senso s, specialized in e ace de ices and eal- ime g aphics o imme se a pa icipan in a compu e -gene a ed simula ed wo ld ha changes in a na u al way wi h head and body mo ion” [ 20 ]. A ully imme si e VR sys em is an HMD in which he subjec sees only he compu e -gene a ed image, and he es o he physical wo ld is blocked om iew [ 21 ]. Imme si e VR sys ems o en ake ad an age o isual, audi o y, o hap ic de ices [ 22 , 23 ]. C osbie e al. also conside ed imme si e VR applica ions ha ypically use HMDs [24]. In addi ion o he imme si e mode, VR also comes in a “non-imme si e” o “semi- imme si e” o m. Bo h modes in ol e he use ’s pe cep ion o bo h he eal wo ld and he i ual one simul aneously, bu he use is no comple ely imme sed in he i ual en i on- men [ 25 , 26 ]. Acco ding o Lange e al., non-imme si e modes a e commonly gene a ed by using compu e s and console game sys ems (as well as nongame lab-gene a ed sys ems), and he de eloped he apies a e desc ibed as game-based ehabili a ion, he apy gaming, digi al game-based he apy, e c. [ 20 ]. He e, he isual aspec s o he compu e -gene a ed VR en i onmen a e p esen ed on a con en ional compu e moni o o p ojec ed on o sc eens. The subjec con ols his/he mo emen wi hin he en i onmen by means o a joys ick o o he con ol de ice. Imme sion and p esence a e wo impo an aspec s o a subjec ’s pe o mance o i ual asks [ 7 , 24 , 27 , 28 ]. Thus, whe eas imme sion is a “ echnology- ela ed” [ 16 ], objec i e aspec o VEs, p esence is a psychological, pe cep ual, and cogni i e consequence o imme sion. P esence is hough o as he psychological pe cep ion o “being in” o “exis ing in” he VE in which one is imme sed [ 29 , 30 ]. The use o HMDs may a ec he sense o p esence and imme sion [31] and, as a esul , impac pa icipan mo i a ion o exe cise. In spi e o he ac ha mos o he ecen ly conduc ed me a-analyses ha e shown im- p o emen s when compa ing non-imme si e VR sys ems o con en ional he apies [32–35] , he e a e s ill analyses ha showed a ema kable di e gence in he ou come measu es used in he included s udies [ 36 ]. Al hough some limi a ions o con en ional ehabili a ion may ha e been o e come by he ad an ages o VR aining, limi ed e idence is a ailable on he clinical e ec i eness o imme si e VR sys ems o s oke ehabili a ion. Fo he pu poses o his e iew, we ake in o accoun VR sys ems o s oke ha allow he use o be ully imme sed in he i ual en i onmen (VE) by means o an HMD. The ollowing me a-analysis sough o answe he ollowing ques ion: Do HMD-based i ual eali y he apies imp o e mo o unc ion mo e han he same du a ion o adi ional ehabili a ion in people a e s oke? 2. Me hods 2.1. Eligibili y C i e ia We included s udies ha examine he e ec s o imme si e VR on mo o ehabili a ion o pos -s oke adul s. In o de o be included in ou me a-analysis, he s udies had o ul ill he ollowing selec ion c i e ia: (a) he s udy had o apply a VR in e en ion o a sample Senso s 2021,21, 1111 3 o 24 o pos -s oke adul subjec s ia a ully imme si e de ice (HMD); (b) he s udy had o include a con ol g oup (con en ional he apy o ano he non-imme si e VR in e en ion, e en in e en ions applied o heal hy subjec s whene e hey se ed as con ols); he e o e, p e es –pos es one-g oup designs and N= 1 designs we e excluded; (c) he s udy had o include signi ican ou comes measu ing unc ional o mo o eco e y o ei he lowe o uppe limbs; (d) he s udy had o epo s a is ical da a o he g oups in ol ed in a leas he pos es (means, s anda d de ia ions, es s, ANOVAs, e c.); (e) he sample size o each g oup should no be less han 5 subjec s in he pos es ; ( ) he s udy had o be published in a pee - e iewed jou nal and w i en in English. Only andomized con olled ial (RCT) s udies we e included in an a emp o aise he s anda d me hodological quali y. We also excluded s udies in ended o pos -s oke cogni i e ehabili a ion despi e hei use o an HMD, as well as any kind o i ual- eali y-based con ibu ion de eloped o ec ea ional o educa ional pu poses. 2.2. Sea ch P ocedu e We sea ched he ollowing scien i ic da abases h ough hei online sea ch engines: MEDLINE (Medical Li e a u e Analysis and Re ie al Sys em Online, Be hesda, MD, USA) h ough PubMed, Coch ane CENTRAL (Cen al Regis e o Con olled T ials, Hoboken, NJ, USA), Coch ane Da abase o Sys ema ic Re iews, and Physio he apy E idence Da abase (PED o, New own, New Sou h Wales, Aus alia). S udies we e collec ed om incep ion up o 31 Oc obe 2020. In an a emp o iden i y u he ele an s udies, e e ence lis s om he iden i ied publica ions we e also e iewed o iden i y addi ional esea ch a icles o in e es o ele an a icles ha may ha e been missed du ing he ini ial da abase sea ches. We ini ially de eloped sea ch s a egies o Medline and hen we adap ed hem o use in o he da abases. The ollowing ou lines he comple e combina ion o sea ch e ms ha was used o sea ch he i les and abs ac s o po en ial pape s o MEDLINE (Be hesda, MD, USA) and adap ed o sea ch he o he da abases: (( i ual ehabili a ion OR i ual eali y OR augmen ed eali y OR compu e gam* OR i ual gam* OR se ious gam* OR ideo gam* OR augmen ed gam*) AND (S oke)) NOT cogni i e. 2.3. Me hodological Quali y Assessmen The me hodological quali y o he s udies was a ed wi h he PED o scale [ 37 , 38 ], which assesses 11 c i e ia. Speci ically, a s udy is gi en a poin o each o he ollowing: andom assignmen o subjec s; concealed alloca ion; measu es o subjec compa abili y p o ided a baseline; blinding o subjec s; blinding o clinicians adminis e ing he in e en- ions; blinding o he assesso s; ou come measu es ob ained om a leas 85% o subjec s; all subjec s o whom ou come measu es we e a ailable ecei ed ea men o con ol condi ions as alloca ed, o da a o a leas one ou come we e analyzed by “in en ion o ea ” analysis; esul s o be ween-g oup s a is ical compa isons epo on a leas one key ou come; and poin measu es and measu es o a iabili y in he ou comes we e p o ided o a leas one key ou come. The eligibili y c i e ion i em does no con ibu e o he o al sco e, so he PED o o al sco e a ies om 0 o 10, and he highe he sco e, he be e he me hodological quali y o he clinical ial. 2.4. Quan i a i e Analysis To compu e he e ec size ac oss he s udies, we used he s anda dized mean di e ence (d), de ined as he di e ence be ween he means o he expe imen al g oup and he con ol g oup, bo h aken in he pos es , di ided by a pooled es ima e o he wi hin-s udy s anda d de ia ion and co ec ed by a ac o o small samples, as s a ed by Hedges and Olkin [ 39 ]. The magni ude o an e ec size is an es ima e o he deg ee o which in e en ion and con ol g oups di e in e ms o hei he apeu ic e ec i eness [ 40 ]. Posi i e alues o d indica e a a o able ou come o he in e en ion. Acco ding o Cohen [ 41 ], an e ec size o d = 0.20 is seen as small, d = 0.50 is medium, and d = 0.80 is la ge. In he same way, an e ec size o d = 2.00 is conside ed e y la ge acco ding o Sawilowsky [42]. Senso s 2021,21, 1111 4 o 24 In each s udy, a di e en d index was calcula ed o he ou come measu es o he imed and up and go es (TUG), Be g balance scale (BBS), and o he measu es. The e o e, in he same s udy, we could calcula e mo e han one d index. The esul s om compa able ials we e pooled by means o he Re man so wa e 5.3 (Re Man; Coch ane, London, UK). Ou comes we e di ec ly ob ained om each a icle o con e ed o me e s pe second (m/s) om he epo ed esul s. Each d index was ea ed sepa a ely acco ding o he ou come measu e (by pe o ming sepa a ed me a-analyses). In each me a-analysis, a andom-e ec s model was applied, acco ding o which he d index in he pos es was weigh ed by i s in e se a iance. The p ocess o analysis consis ed o calcula ing he mean e ec size wi h i s 95% con idence in e al, assessing he e ogenei y (by means o he he e ogenei y es Q), and de e mining he I 2 index o e alua e he deg ee o homogenei y o he e ec sizes a ound he a e age e ec [ 43 ]. We ake in o accoun he classi ica ion o I 2 p oposed by Higgins and Thompson [ 43 ] by s a ing ha I 2 alues o a ound 25%, 50%, and 75% can be conside ed as e lec ing small, medium, and la ge he e ogenei y, espec i ely [ 44 ]. When he he e ogenei y Q es is s a is ically signi ican (p< 0.05) and he I 2 index is a leas 50%, hen we can assume ha he indi idual e ec sizes a e he e ogeneous. The in luence o mode a ing a iables should be aken in o accoun o explain his ac . Since we only included published s udies, we may ha e had impo an e ec sizes (ESs) due o publica ion bias. This p oblem occu s when s udies epo ing la ge ESs a e published and s udies epo ing null esul s o smalls ESs a e no . Publica ion bias was in es iga ed by inspec ing unnel plo s and eg ession asymme y es s. 2.5. Ou come Measu es The main ou comes ound in he s udies we e he ollowing. Fo he lowe limb: imed up and go (TUG) es , Be g balance scale (BBS), six-minu e walk es (6MWT), 10-m walk es (10MWT), unc ional each es (FRT), and ac i i ies-speci ic balance con idence (ABC). On he o he hand, he ou come measu es o he uppe limb we e he ac ion esea ch a m es (ARAT), he uppe ex emi y mo ici y index, and he Fugl-Meye uppe ex emi y es (FMUE). Fu he mo e, pa ame e s such as cadence, s ide leng h, eloci y, and s ep leng h we e included in some s udies. 3. Resul s 3.1. Sea ch Resul s The ini ial sea ch yielded 1436 a icles. We also iden i ied addi ional eco ds om o he sou ces (13). A e emo ing duplica es, 946 a icles ha po en ially in es iga ed imme si e VR in e en ions we e iden i ied. The au ho s independen ly e alua ed i les and abs ac s aking in o accoun he inclusion and exclusion c i e ia. Due o he ac ha , on many occasions, wo ds such as “imme si e” o “HMD” we e loca ed in nei he i les no abs ac s, we had o ca y ou a deepe sc eening o po en ial a icles (121). Finally, he popula ion o ou s udy consis ed o eigh a icles. All o hem e e o he impac o imme si e VR he apies in s oke popula ions. The de ails o he sea ch esul a e summa ized in Figu e 1. Senso s 2021,21, 1111 5 o 24 Senso s 2021, 21, x FOR PEER REVIEW 5 o 24 Figu e 1. Conso diag am o s udy selec ion. 3.2. Me hodological Quali y Assessmen The PED o sco es o each c i e ion a e p esen ed oge he wi h he cha ac e is ics o he s udies (Table 1). The ankings o all s udies bu one (Ögün [45]) a e a ailable in he PED o da abase [37]. The sco e o he s udy o Ögün [45] is no ye in PED o, bu he sco e was ob ained by consensus be ween he au ho s. The eligibili y c i e ia we e clea ly sa is- ied in all o he s udies, wi h he excep ion o he s udy o Lee [46], whe eas baseline compa abili y was sa is ied in all o he s udies. I has o be aken in o accoun ha , due o he na u e o his ype o s udy, he apis s and/o echnicians who adminis e and su- pe ise he in e en ions know which subjec s belong o bo h con ol and expe imen al g oups. This means ha i is no possible o apply some o he i ems in he PED o scale (blinding o subjec s and clinicians). In ac , none o he s udies ul illed hese wo equi e- men s simul aneously. The s udy o Ögün [45] had pa ien s masked by using sham VR he apy wi hin he con ol g oup. The same applies o i em 3 (concealed alloca ion), which was ul illed by only wo s udies [47,48]. Fo all o he abo e, s udies wi h PED o sco es o 4 o highe we e conside ed o be o a easonable quali y in his e iew. In addi ion, ou a e age PED o sco e o 5.75 sugges s ha he included s udies we e o mode a e me hodological quali y [49]. I is impo an o no e ha one s udy [47] eached he maxi- mum, and wo s udies eached 7 ou o 8 [46,48]. Fi e s udies epo ed ha he ou come assesso s we e blinded [45–48,50]. Fi e s udies epo ed wi hd awals and p o ided ea- sons o hese d opou s [45–48,51]. Figu e 1. Conso diag am o s udy selec ion. 3.2. Me hodological Quali y Assessmen The PED o sco es o each c i e ion a e p esen ed oge he wi h he cha ac e is ics o he s udies (Table 1). The ankings o all s udies bu one (Ögün [ 45 ]) a e a ailable in he PED o da abase [ 37 ]. The sco e o he s udy o Ögün [ 45 ] is no ye in PED o, bu he sco e was ob ained by consensus be ween he au ho s. The eligibili y c i e ia we e clea ly sa is ied in all o he s udies, wi h he excep ion o he s udy o Lee [ 46 ], whe eas baseline compa abili y was sa is ied in all o he s udies. I has o be aken in o accoun ha , due o he na u e o his ype o s udy, he apis s and/o echnicians who adminis e and supe ise he in e en ions know which subjec s belong o bo h con ol and expe imen al g oups. This means ha i is no possible o apply some o he i ems in he PED o scale (blinding o subjec s and clinicians). In ac , none o he s udies ul illed hese wo equi emen s simul aneously. The s udy o Ögün [ 45 ] had pa ien s masked by using sham VR he apy wi hin he con ol g oup. The same applies o i em 3 (concealed alloca ion), which was ul illed by only wo s udies [ 47 , 48 ]. Fo all o he abo e, s udies wi h PED o sco es o 4 o highe we e conside ed o be o a easonable quali y in his e iew. In addi ion, ou a e age PED o sco e o 5.75 sugges s ha he included s udies we e o mode a e me hodological quali y [ 49 ]. I is impo an o no e ha one s udy [ 47 ] eached he maximum, and wo s udies eached 7 ou o 8 [ 46 , 48 ]. Fi e s udies epo ed ha he ou come assesso s we e blinded [ 45 – 48 , 50 ]. Fi e s udies epo ed wi hd awals and p o ided easons o hese d opou s [45–48,51]. Senso s 2021,21, 1111 6 o 24 Table 1. Cha ac e is ics o he included s udies. Au ho (s)/Yea o Publica ion/ PED o Sco e Pa icipan s S oke Onse (Mon hs) S udy Design Con ol/Expe imen al G oup In e en ions Ou come Measu es Conclusions Age (y s ±SD) Gende (M, F) Ja e e al. (2004) [52]/ PED o: 4/10 N= 20 Con ol: 42.9 ±30.1 RCT Con ol: s epping o e eal oam objec s in a hallway (60 min, 3/week ×2 weeks) Gai endu ance: 6MWT The VR aining achie ed highe imp o emen s in eloci y compa ed o con ol aining OG g oup (N= 10) Subjec s showed clinically meaning ul changes in s ide leng h, eloci y, obs acle clea ance capaci y, and walking endu ance Age: 63.6 ±8.3 Gende : (7 M, 3 F) VR g oup (N= 10) Age: 58.2 ±11.2 Gai kinema ics: spa io empo al gai pa ame e s (walking eloci y, cadence, and s ide leng h) Gende : (5 M, 5 F) Exp: 47 ±27.5 Expe imen al: s epping o e i ual objec s on a eadmill (60 min, 3/week ×2 weeks) Obs acle clea ance es , balance es Jung e al. (2012) [50]/ PED o: 5/10 N= 21 Con ol: 15.4 ±4.7 RCT Con ol: eadmill walking aining (30 min, 5/week × 3 weeks) Balance (TUG) The e we e signi ican ly highe imp o emen s in TUG and ABC in he VR eadmill- aining g oup compa ed o he con ol g oup. Con ol g oup (N= 10) Signi ican inc eases in TUG and ABC in bo h g oups a e aining. Age: 63.6 ±5.1 Imp o emen s seen in he expe imen al g oup we e signi ican ly la ge han he con ol g oup. Gende : (6 M, 4F) Exp. g oup (N= 11) Age: 60.5 ±8.6 Gende : (7 M, 4 F) Exp: 12.6 ±3.3 Expe imen al: eadmill walking in a i ual ou doo en i onmen (30 min, 5/week ×3 weeks) Balance sel -e icacy (ABC scale) Senso s 2021,21, 1111 7 o 24 Table 1. Con . Au ho (s)/Yea o Publica ion/ PED o Sco e Pa icipan s S oke Onse (Mon hs) S udy Design Con ol/Expe imen al G oup In e en ions Ou come Measu es Conclusions Age (y s ±SD) Gende (M, F) Pa k e al. (2013) [53]/ PED o: 5/10 N= 16 Con ol: 135 ±54.4 RCT wi h ollow-up Con ol: wo adminis a ions o con en ional ehabili a ion (60 min, 5/week ×4 weeks) + (30 PT min, 3/week ×4 weeks) Func ional gai abili y (10MWT) Subjec s in he VR g oup showed a signi ican imp o emen (excep o cadence) a e aining and a he ollow-up (compa ed o he con ol g oup). Con ol g oup (N= 8) Wi hin g oups, he VR g oup demons a ed g ea e imp o emen s in s ide leng h (only) compa ed o he con ol g oup Age: 48.75±8.81 No signi ican di e ences ound in o he pa ame e s Gende : (5 M, 3 F) Exp. g oup (N= 8) Age: 46.25 ±6.84 Gende : (6 M, 2 F) Exp: 139.5 ±53.3 Expe imen al: con en ional ehabili a ion (60 min, 5/week × 4 weeks) + VR-based pos u al con ol exe cises (30 min, 3/week ×4 weeks) Spa io empo al gai abili y ( eloci y, cadence, s ep leng h, and s ide leng h) Kang e al. (2012) [48]/ PED o: 7/10 N= 30 TOF g oup: 14.1 ±4.4 RCT Con ol: Con en ional ehabili a ion (30 min ×5/week ×4 weeks) + s e ching added ROM exe cises (30 min, 3/week × 4 weeks) Balance (TUG, FRT) T eadmill using op ic low speed modula ion imp o ed he balance and gai signi ican ly compa ed o he con ol g oup TOF g oup (N= 10) T eadmill g oup: 13.5 ±4.0 Gai (6MWT, 10MWT) Age: 55.9 ±6.5 Gende : (6 M, 4 F) Con ol g oup: 15.1 ±7.4 T eadmill g oup (N= 10) Age: 56.3 ±7.6 Gende : (4 M, 6 F) Con ol g oup (N= 10) Age: 56.1 ±7.8 T eadmill g oup = Con en ional ehabili a ion (30 min ×5/week ×4 weeks) + eadmill aining (30 min, 3/week ×4 weeks) Gende : 6 M, 4 F TOF g oup (Exp.): Con en ional ehabili a ion (30 min ×5/week ×4 week) + eadmill walking wi h op ic low (30 min, 3/week × 4 weeks) Senso s 2021,21, 1111 8 o 24 Table 1. Con . Au ho (s)/Yea o Publica ion/ PED o Sco e Pa icipan s S oke Onse (Mon hs) S udy Design Con ol/Expe imen al G oup In e en ions Ou come Measu es Conclusions Age (y s ±SD) Gende (M, F) C osbie e al. (2012) [47]/ PED o: 8/10 N= 18 Con ol: 11.7 ±7.8 RCT wi h ollow-up Con ol: con en ional he apy (30–45 min, 3/week ×3 weeks) ARAT, uppe limb mo ici y index Nei he small no mode a e changes we e de ec ed by measu es Con ol g oup (N= 9) No signi ican imp o emen in ei he he con ol o in e en ion g oups Age: 66.4 ±7.4 T ansien dizziness and headache expe ienced by wo pa icipan s in he VR g oup Gende : (5 M, 4 F) VR g oup (N= 9) Age: 56.1 ±14.5 Gende : (5 M, 4 F) VR g oup: 10 ±6.4 Expe imen al: speci ic uppe limb VR asks ( each o a ge , each and g asp) (30–45 min, 3/week × 3 weeks) Lee e al. (2014) [46]/ PED o: 7/10 N= 21 Exp: 11.7 ±4.5 RCT Con ol: gene al physical he apy ocused on pos u al con ol aining (30 min, 5/week, 4 weeks) BBS, TUG, gai eloci y, s ide leng h, cadence, and s ep leng h The addi ion o VR-based aining con eyed o signi ican imp o emen in he ollowing gai a iables (s ep leng h, s ide leng h, and gai eloci y) compa ed o gene al physical he apy ea men only (con ol g oup) Con ol G oup (N= 11) Age: 54.0 ±11.9 Gende : (6 M, 5 F) No signi ican ime ×g oup e ec in bo h TUG and BBS. AR g oup (N= 10) Age: 47.9 ±12 Gende : (8 M, 2 F) Con ol: 11 ±4.7 Expe imen al: gene al physical he apy (30 min, 5/week ×4 week) + VR-based pos u al con ol aining (30 min, 3/week × 4 weeks) Senso s 2021,21, 1111 9 o 24 Table 1. Con . Au ho (s)/Yea o Publica ion/ PED o Sco e Pa icipan s S oke Onse (Mon hs) S udy Design Con ol/Expe imen al G oup In e en ions Ou come Measu es Conclusions Age (y s ±SD) Gende (M, F) Kim e al. (2012 [51])/ PED o: 4/10 N= 28 Con ol: 10.4 ±3.1 RCT Con ol: gene al physical he apy (30 min, 5/week, 8 weeks) + eadmill gai aining (20 min, 3/week, 8 weeks). TUG, BBS, muscle s eng h VR-FES and FES g oups showed g ea e imp o emen s in muscle s eng h han con ol g oup Con ol g oup (N= 9) FES g oup: gene al physical he apy (30 min, 5/week, 8 weeks) + eadmill gai aining + FES (20 min, 3/week, 8 weeks) G ea e imp o emen s in gai speed (assessed by TUG) in VR-FES g oup han con ol g oup Age: 49.11 ±11 Gende : (6 M, 3 F) VR + FES g oup: gene al physical he apy (30 min, 5/week, 8 weeks) + eadmill gai aining + VR + FES (20 min, 3/week, 8 weeks) Signi ican imp o emen s in BBS in all g oups FES g oup (N= 10) Age: 51.5 ±12.9 Gende : (5 M, 5 F) VR-FES g oup (N= 9) Age: 47.4 ±8.4 FES g oup: 9.2 ±2.7 Gende : (6 M, 3 F) VR-FES g oup: 9.7 ±4.2 Ögün e al. (2019) [45]/ PED o: 6/10 * N= 65 Con ol: 15.37 ±9.77 RCT Con ol: con en ional uppe ex emi y ac i e exe cises ocused on g ipping and handling (45 min, 3/week, 6 weeks) + passi e VR he apy (15 min, 3/week, 6 weeks) FMUE, ARAT, FIM, PASS-IADL, PASS-BADL Signi ican imp o emen s in FMUE, ARAT, FIM, and PASS sco es (compa ed o baseline) Con ol g oup (N= 32) Age: 59.75 ±8.07 Gende : (23 M, 9 F) VR g oup (N= 33) Age: 61.48 ± 10.92 Gende : (28 M, 5 F) VR g oup: 14.72 ±7.38 Expe imen al: ask-o ien ed games ocused on g ipping and handling (60 min, 3/week, 6 weeks) ABC: ac i i ies-speci ic balance con idence scale; ARAT: ac ion esea ch a m es ; BBS: Be g balance scale; FES: unc ional elec ical s imula ion; FIM: unc ional independence measu e; FRT, unc ional each es ; FMUE: Fugl-Meye uppe ex emi y scale; HMD: head-moun ed display; OG: eal obs acle aining; RCT: andomized con olled ial; ROM: ange o mo ion; PASS-BADL: Pe o mance Assessmen o Sel -Ca e Skills—basic ac i i ies o daily li ing; PASS-IADL: Pe o mance Assessmen o Sel -Ca e Skills—ins umen al ac i i ies o daily li ing; PE: physical en i onmen ; PT: physical he apy; 6MWT: six-minu e walk es ; 10MWT: 10-me e walk es ; TOF: eadmill wi h op ic low; TUG: imed up and go es ; VE: i ual en i onmen ; VR: i ual eali y; SPS: sc een p ojec o sys em. VR + FES: i ual eali y + unc ional elec ical s imula ion. (*) The sco e was ob ained by consensus be ween au ho s because i is no ye in he PED o da abase. Senso s 2021,21, 1111 16 o 24 4. Discussion The main goal o his sys ema ic e iew and me a-analysis was o e alua e he e i- dence ega ding he use o ully imme si e VR in e en ions o imp o e mo o unc ions on adul s oke popula ions. To he au ho s’ bes knowledge, his is he i s sys ema ic e iew o sepa a ely analyze he e ec s o imme si e VR ehabili a ion sys ems on s oke popula- ions. Resul s om he me a-analysis demons a e ha pa ien s who ecei ed imme si e VR ea men s la gely imp o ed compa ed o hose ecei ing adi ional o con en ional he apies. The e ec sizes in e ms o s anda d mean di e ences we e la ge [ 41 ] on mos scales o bo h lowe and uppe ex emi ies. The esul s ob ained o he TUG es showed an impo an o e all e ec size (0.82) [ 41 ], wi h an absolu e a e age alue o nea ly 5 scale poin s. This means ha pa ien s who ecei ed imme si e VR he apies had mo e impo an (and s a is ically signi ican ) im- p o emen s compa ed o he pa ien s who ecei ed con en ional he apies (con ol g oups). Ou indings a e compa able o and e en g ea e han he esul s ob ained in p e ious and ecen me a-analyses in which he majo i y o VR in e en ions we e non-imme si e. In hei me a-analysis, Liz e al. ound mode a e imp o emen s in subjec s ecei ing he VR in e en ion (absolu e mean di e ence o − 1.62, 95% con idence in e al o − 3.07 o − 0.16, p< 0.05, I 2 = 24%). The deg ee o homogenei y was compa able o ha ound in ou s udy [ 32 ]. Co be a e al. [ 33 ] also ound s a is ically signi ican bene i s o mobili y in he TUG es (absolu e mean alue o 2.3 s) when VR aining eplaced adi ional ehabili a ion (in pa o comple ely). I u haya ajah e al. [ 34 ] ound a mean di e ence in he o e all e ec size o 2.49 in hei me a-analysis. The o e all e ec size ob ained in ou me a-analysis is an absolu e alue o a ound 5, which doubles he p e ious esul . Ou esul s pa allel hese indings and add o he exis ing li e a u e e idence o s ong posi i e e ec s o using imme si e VR in e en ions. Howe e , his g ea e o e all e ec size showed by ou me a-analysis may ha e been o e es ima ed due o he smalle subjec sample used. 4.1. VR T eadmill and Feedback In gene al, in e en ions wi h eadmills ha e shown posi i e e ec s on gai and balance [ 48 , 50 – 52 ]. The ob ained esul s o 6MWT, 10MWT, and TUG sco es con i m his. T eadmill aining has p e iously been epo ed o be an e ec i e me hod o es o ing gai unc ion by p o iding a ask-o ien ed epe i i e p ac ice [ 34 , 56 ]. This ask-o ien ed and epe i i e ac i i y is belie ed o ac i a e he ce eb al co ex and, subsequen ly, o e oke mo o lea ning [ 50 ]. In addi ion, an imp o ed balancing abili y and e ec i e mo o lea ning wi h a as e gai speed occu [ 57 ]. In pa icula , VR eadmill aining has be e e ec s on balance skills compa ed o adi ional eadmill aining. Yang e al. compa ed adi ional eadmill and VR eadmill aining, and hey ound ha he VR eadmill p ac ice imp o ed balance skills in he medial-la e al di ec ion and du ing si - o-s and ans e s be e han adi ional aining did [58]. Ne e heless, VR eadmill aining usually in ol es he addi ion o cueing and eedback in di e en modali ies ( isual, audio, and ib o ac ile). The e o e, in addi ion o he e ec s o he eadmill, he in oduc ion o eedback and cueing o ea men s has been bene icial o he ou comes o s udies. VR allows use s o in e ac wi h a mul isenso y simula ed en i onmen and ecei e “ eal- ime” eedback on pe o mance [ 35 ]. All o his senso y in o ma ion allows he cen al ne ous sys em o be e con ol he posi ion and o ien a ion o body pa s, p omo ing he adap a ion o he ex e nal en i onmen [59]. P ac ice in VR en i onmen s has shown he impo ance o he pe cep ion o sel - mo ion in con olling di e en locomo ion pa ame e s, such as pos u e o gai . The eal- ime na u e o all eedback and cueing modali ies plays an impo an ole in imme si e VR in e en ions. In he s udy o Ja e [ 52 ], he isual ( he p esen a ion o he oo as i app oached he objec ), ib o ac ile (e o de ec ion), and audi o y eedback in he i ual en i onmen p o ided se e al ways o wa n he subjec o a collision. Fo example, la e al iews o he legs ga e subjec s isual cues, leading o a be e pe o mance. In he s udy Senso s 2021,21, 1111 17 o 24 o Kang [ 48 ], he modula ion o op ic low (OF) p o ided an e ec i e aining me hod o balance and gai ehabili a ion. Op ic low is he pa e n o he isual in o ma ion (di ec ion and speed) gene a ed by he ela i e mo ion be ween a pa ien ’s eye and he su ounding en i onmen [ 60 ], and when he pa ien iden i ies he incong ui y be ween op ic low and hei p op iocep i e in o ma ion om he lowe ex emi ies, walking speed is adjus ed o diminish he incompa ibili y [ 61 , 62 ]. The e o e, he manipula ion o op ical low cha ac e is ics can cause changes in locomo ion pa e ns. These good esul s a e in line wi h hose ob ained in p e ious s udies ha we e conduc ed o in es iga e he e ec s o he eloci y o op ic low on bo h pos u al con ol and gai a iabili y and walking speed. Pickhinke e al. in es iga ed he e ec s ha he a ia ion o op ical low speed may ha e on pos u al con ol du ing locomo ion. They sugges ed ha pos u al con ol may be a ec ed when he pe cep ion o sel -mo ion becomes unp edic able [ 63 ]. Some o he s udies ha e p e iously es ablished ha he modula ion o op ic low can change locomo o pe o mance by educing gai a iabili y [ 64 – 67 ]. Lamon agne e al. [ 68 ] compa ed he modula ion o walking speed in esponse o OF speed changes be ween pe sons wi h s oke and heal hy con ols and concluded ha VE manipula ion o he OF could be used o os e oli ional changes in walking speed. S oke pa ien s we e able o inc ease walking speed when p esen ed wi h slowe OFs. This is in line wi h p e ious s udies ha indica ed ha dec easing he a e o op ic low ela i e o no mal walking speed is co ela ed wi h an inc ease in walking speed in a heal hy indi idual [ 69 ]. The e o e, he manipula ion o op ic low speed using i ual eali y echnology could be implemen ed in a gai ehabili a ion in e en ion o p omo e as e walking speeds a e s oke. P e ious s udies ha e examined he e ec o isual eedback on b ain eo ganiza ions in s oke [ 70 ] and he ole i may play in he eco e y o locomo ion in pa ien s wi h ch onic s oke [ 71 ]. Fu he mo e, he li e a u e includes many s udies ha epo ha isual eedback mo i a es pa ien s o inc ease hei concen a ion [ 72 , 73 ] and imp o es he balance o s oke pa ien s [ 74 , 75 ]. This adds o he mo i a ion and psychological s abili y ha he use o VR p o ides by i sel o s oke pa ien s [13]. As a as imme si e VR in e en ions o uppe ex emi y ehabili a ion a e conce ned, he s udy o C osbie [ 47 ] is in line wi h he indings o he s udies by C osbie e al. [ 76 ] and Hende son e al. [ 7 ] since i epo s e y limi ed e idence o i ual eali y-based he apies. One possible explana ion o he poo esul s ob ained by C osbie e al. [ 47 ] in ol es he ac ha he equi emen o make objec s appea eachable is a big challenge in he c ea ion o VEs [ 77 ]. Vi ual spaces cha ac e is ically appea o he iewe as smalle han physical spaces [ 78 ]. This dec easing phenomenon has been p e iously epo ed [78,79] . Liebe - mann e al. epo ed such limi ed dep h-pe cep ion in he 2D p ojec ion o he en i onmen in hei s udy [ 80 ]. Piggo e al. epo ed some o he p oblems ha occu when using 2D VR sys ems [ 81 ], demons a ing ha all subjec s had a endency o dec ease hei w is ex ension (inc easing he elbow ex ension a he same ime). One plausible eason was ela ed o he missing dep h cues in a 2D en i onmen . They also sugges ed ha ully imme si e VR en i onmen s need o ake in o accoun dep h cues and he ype o hap ic eedback, p o ide hap ic cues o objec collision, and emula e he pe o mance o asks in na u al en i onmen s. Despi e he good esul s ob ained in he s udy o Ögun e al. [ 45 ], he au ho s also poin ed o he p o ision o mul isenso y eedback (audi o y, isual, and ac ile) in i ual eali y asks as a way o enhance co ical eo ganiza ion and, he e o e, esul in an imp o emen in mo o unc ion. Wi h ega d o p e iously epo ed ad e se incidences ela ed o he use o imme - si e VR equipmen ( isual dis u bances, nausea, and headache) [ 2 , 82 ], only one s udy epo ed some discom o s [ 47 ]. Two people expe ienced side-e ec s ( ansien dizziness and headache) in he s udy o C osbie e al. [ 47 ]. Ja e did no epo any HMD ad e se e - ec s in hei s udy, in spi e o he ac ha one subjec had p e iously expe ienced episodes o claus ophobia a home [ 52 ]. The d opou s epo ed in he s udy o Ögün e al. [ 45 ] we e he esul o compliance issues. In spi e o he ac ha isual dis u bances, nausea, headache, o o he discom o s in VR- ea ed subjec s seem o ha e been o e come [ 83 ], Senso s 2021,21, 1111 18 o 24 we s ill ind some examples whe e hey a e p esen . Tsoupiko a e al. [ 84 ] epo ed se e al occu ences, such as mild eyes ain and ansien nausea ha a ose du ing pilo s udies wi h an HMD. These occu ences, along wi h complain s abou com o , p omp ed hem o swi ch om he HMD o wo la ge displays. They ound ha en i onmen al cues could be a leas as e ec i e as s e eoscopic ision in p o iding pe cei ed size cons ancy o a i ual objec as i is mo ed o di e en dep hs in a VR en i onmen . Consequen ly, a ich sense o dep h was p o ided e en wi hou use o he HMD. 4.2. Limi a ions This e iew has limi a ions ha a e wo h men ioning. The inal numbe o s udies mee ing he inclusion c i e ia was modes . As a as he ou come measu es we e conce ned, he e was no uni o mi y among he s udies; as a esul , some gai pa ame e s we e no me a- analyzed. Among he analyzed s udies, we ound g ea a iabili y in bo h he du a ion and in ensi y o he ea men . La ge and mo e in ense ea men s do no always lead o g ea e imp o emen s, as in he s udy o Lee e al. [ 46 ]. Fu he mo e, he sample size was small in all o he included s udies (10 subjec s pe g oup on a e age), which may lead o educed s a is ical powe . Despi e he collec ion o RCTs o educe he bias isk, we hink i is necessa y o include a la ge numbe o pa icipan s, oge he wi h a wide ange o popula ion g oups. In ou e iew, mos o he s udies we e ca ied ou in one single coun y, which sugges s ha mul icen e s udies loca ed in di e en geog aphic loca ions a e needed in o de o ob ain esul s wi h a g ea e deg ee o gene alizabili y o any se ing o popula ion. In he same way, he esul s o he FRT, 6MWT, and 10MWT (Figu es 4–6, espec i ely) a e all based on publica ions om one g oup. A common ea u e s a ed in many e iews is he ac ha he powe and design o s udies a e limi ed, so he suppo ha hey o e emains weak o mode a e in quali y. The long- e m e ec s o imme si e VR in e en ions ha e no been e alua ed in mos o he included s udies. The esul s o his me a-analysis canno be gene alized o he acu e o sub-acu e s age o hemipa e ic s oke, since all o he in e en ions we e in ended o ch onic s oke pa ien s. 4.3. Implica ions o Resea ch Ou me a-analysis sugges s ha he e a e se e al impo an implica ions o u he esea ch. Fi s ly, he p ima y s udies show some de iciencies as a as he epo ing o gai and mo o unc ion pa ame e s is conce ned. Se e al s udies p esen he in o ma ion as a pe cen age a io o p e- and pos -in e en ion in some o he ou comes, which makes i di icul o in e p e he esul s and compa e hem o he e ec sizes o he es o he s udies. We s ongly ecommend epo ing he e ec size in e ms o s anda dized mean di e ences, since i is a mo e eliable measu e o he eal e ec o he in e en ions. Secondly, he sho pe iods o ime used in mos o he in e en ions sugges he need o ials wi h la ge ea men s pe iods o a be e e alua ion o he unc ional gains. I is impo an o bea in mind he ac ha di e ences in mo o se e i y and ch onici y should be ela ed o dose equi emen s. Fo ha eason, u he esea ch should be o ien ed o ha popula ion in acu e o sub-acu e s ages. Ano he aspec ha should be imp o ed in he design o hese s udies is he ob aining o ollow-up da a o he ea ed and con ol g oups. The long- e m e ec s o VR ha e no been explo ed ye , in con as o o he o ms o s oke ehabili a ion. In ac , only a small numbe o he s udies included in ou me a-analysis had es ablished ollow-up analyses [ 47 , 52 , 53 ], and he pe iods we e e y sho . This limi a ion o he p ima y s udies, limi s, in u n, he possibili ies o using a me a-analysis o in es iga e how he achie ed bene i s o imme si e VR he apies e ol e o e ime. Fo his pu pose, i would be sui able o ob ain compa isons be ween he con ol g oup and he expe imen al g oup o e long enough pe iods o ime o e alua e he bene i s o imme si e VR ea men s. The e o e, his necessa y quan i ica ion o he esidual bene i s in he sho and medium e m equi es Senso s 2021,21, 1111 19 o 24 u he s udies. This is o pa icula ele ance in ch onic s ages o he disease. Fo he abo emen ioned easons, u he s udies a e also needed o elucida e i be e pe o mance is due o la ge ea men s a he han he use o imme si e VR sys ems. Rega ding he lack o dep h-pe cep ion in uppe limb in e en ions, he e is so much wo k o be done, since he e is a conside able lack o ully imme si e VR in e en ions. Sub amanian and Le in compa ed he e ec s o iewing a i ual en i onmen ia HMD and la ge sc een p ojec ion sys ems (SPS) on uppe limb poin ing mo emen s. They ound ha he mo emen s pe o med by he s oke subjec s we e less p ecise. Fu he mo e, hey ealized ha he e was an impo an e ical di ec ional e o when using he HMD. The au ho s ema ked ha wea ing HMDs may esul in neck discom o , a ec ing dis ance es ima ion. Consequen ly, hey posi ed ha la ge sc een p ojec ion sys ems (SPS) a e mo e com o able and e ec i e han HMDs o ehabili a ion pos -s oke [85]. On he o he hand, p esence seems o be a e y impo an ea u e when dealing wi h imme si e VR sys ems as a as pe o mance is conce ned [ 27 , 28 ], bu i has been seldom assessed in he li e a u e. The e o e, he sense o p esence o pa icipan s in ol ed in imme si e VR in e en ions should be add essed o elucida e he e ec o wea ing an HMD in ehabili a ion p ocesses [85]. In a ecen s udy, Bo ego e al. [ 86 ] assessed p esence by means o wo ques ionnai es, he o iginal Sla e -Usoh-S eed Ques ionnai e [ 87 ] and a modi ied e sion o he P esence Ques ionnai e [ 88 ]. The au ho s e alua ed an HMD-based VR sys em (enabling head acking) ha was shown o elici a signi ican ly highe sense o p esence han Ca e Au oma ic Vi ual En i onmen (CAVE) sys ems. This p omo ion o a highe sense o p esence plays an impo an ole in enhancing he ecological alidi y o imme si e VR ehabili a ion applica ions. Fu u e esea ch in his di ec ion could gi e us some mo e in o ma ion abou he sense o p esence and i s impac on pa icipan compliance wi h exe cise and inal pe o mance. This would jus i y he use o HMDs in VR in e en ions. Ano he impo an issue ha has been poin ed ou by di e en au ho s is ela ed o he ans e o posi i e esul s achie ed by subjec s o ac i i ies o daily li ing (ADL) [ 89 ]. Al hough some p og ess has been made in he demons a ion o he ans e o abili ies and skills acqui ed wi hin VE o eal-wo ld pe o mance [ 5 , 90 , 91 ], se e al s udies (non- imme si e) in ended o he s oke popula ion ha e epo ed an inhe en di icul y in achie ing such a ans e [ 92 , 93 ]. The e o e, i is e y impo an o asce ain i he induced imp o emen s a e ecologically alid a home o in communi y en i onmen s [94]. Finally, due o he di icul y o inco po a ing unpublished s udies in o a me a-analysis in his ield, i is highly ecommended o ou inely examine whe he publica ion bias may be a h ea o he alidi y o esul s. 4.4. Implica ions o P ac ice The indings om ou e iew sugges ha he use o imme si e VR in mo o i ual ehabili a ion is a p omising in e en ion when used in s oke popula ions. VR has he abili y o c ea e a ich i ual en i onmen by modula ing bo h he in ensi y o he ask and senso y eedback o p o ide he mos app op ia e and indi idualized mo o aining [ 15 , 95 ]. Vi ual cueing and eedback a e impo an in he sense ha hey no malize he in e nal cueing de ici o p epa e he pa ien o he nex mo emen while compensa ing o any mal unc ioning senso y in eg a ion [96]. The ichness o s imuli p o ided by imme si e VR (cueing and eedback) has been success ully exploi ed by some o he in e en ions [ 48 , 51 – 53 ], which has led o e y la ge e ec sizes in he TUG, FRM, and 10MWT es s. The TUG o e all e ec size is g ea e han he esul s ob ained in p e ious and ecen me a-analyses in which he majo i y o VR in e en ions we e non-imme si e. On he o he hand, in spi e o he ac ha he s udy o Lee e al. [ 46 ] used isual eedback, he addi ion o VR-based aining did no esul in a be e pe o mance on he TUG es compa ed o con ols (who ecei ed con en ional he apy only). A ela i ely sho ea men du a ion as well as he small sample size could lead o his lack o signi ican Senso s 2021,21, 1111 20 o 24 ea men e ec on he TUG es . This is in line wi h p e ious s udies, like he one de eloped by Walke e al. [ 14 ], who ound no signi ican be ween-g oup di e ences when isual eedback was added in he expe imen al g oup in a balance aining in e en ion o acu e s oke pa ien s. I is wo h aking in o accoun he p e e ed modali y o he cue o eedback o e e y pa ien in o de o imp o e he ehabili a ion p ocess [ 97 ], as well as he poin a which i should be applied in he ehabili a ion p og am. Fo hese easons, g ea e imp o emen s migh be achie ed by u he cus omizing he applied cueing and eedback o e e y single pa ien [ 98 ]. Clinicians should ake in o accoun ha he app op ia eness o he use o hese s imuli depends on he pe son’s ehabili a ion goals and p e e ences, in he in e es o imp o ing he pa ien pe o mance [89]. Al hough he e a e se e al s udies ha ha e claimed ha he HMD is e ec i eness in inducing es ibulo-ocula e lex (VOR) gain adap a ion in subjec s wi h ch onic dizzi- ness [ 99 ] o in p o iding op okine ic s imula ion and isual– es ibula in e ac ion o subjec s wi h balance diso de s [ 100 ], he e some o he semi-imme si e in e en ions ha ha e ques ioned he use o HMDs. Kim e al. [ 94 ] used an IREX VR sys em o enhance he mo i a ion and s a ic and dynamic balance pe o mance associa ed wi h gai in pa ien s wi h s oke. Wi hin his sys em, subjec s we e ee o mo e in he eal wo ld while manip- ula ing i ual objec s in he 3D i ual en i onmen wi hou equi ing a hea y HMD o o he pe iphe al de ices. This g ea e eedom o mobili y, as well as he non-necessi y o hea y and expensi e de ices, was ema ked upon in [ 70 , 94 ]. Fische e al. ound ha i was di icul o some subjec s o li hei a ms while looking a he i ual en i onmen due o he limi ed ield o iew (FOV) o he HMD used. The au ho s ema ked ha an HMD wi h a wide ield o iew could educe hese demands on mo o con ol [ 101 ]. These limi a ions on FOV, oge he wi h he weigh o he HMD, a e ac o s ha can lead o an inco ec dis ance es ima e, and i could be a con ounding ac o ha impac s dis ance pe cep ion when uppe limb mo emen s a e pe o med [102]. Finally, in e ms o p ac ical conside a ions, we a e no able o s a e whe he he cos o he imme si e echnology jus i ies he bene i s. We ha e seen ha he use o imme si e VR in e en ions p o ides imp o emen s in some gai pa ame e s, bu we canno s a e ha imme si e sys ems pe o m be e han non-imme si e o semi-imme si e sys ems. The e o e, he e is s ill wo k o be done o de e mine whe he he bene i s we a e a ge ing a e clinically wo hwhile. 5. Conclusions This e iew and me a-analysis has shown some imp o emen s in balance and gai in pos -s oke pa ien s when imme si e VR in e en ions a e applied and compa ed o con en ional ehabili a ion he apies. The esul s con i m he e ec s o in e en ions and jus i y u he clinical ials (posi i e e ec s bu wi h limi a ions). Al hough he numbe o RCTs using imme si e VR sys ems o s oke ehabili a ion is g owing, he e a e s ill un esol ed ques ions o add ess o de e mine whe he he bene i s a e clinically wo hwhile. This ac should encou age u u e imme si e in e en ions wi h la ge and mul icen e popula ions o elucida e whe he his kind o imme si e he apy could pe o m be e han non-imme si e he apies. Despi e i s limi a ions, his e iew encou ages he use o imme si e VR in e en ions in conjunc ion wi h adi ional he apies o he eco e y o mo o impai men s in s oke subjec s. Fu u e s udies a e needed wi h a la ge numbe o subjec s o imp o e he in e nal and ex e nal alidi ies. Au ho Con ibu ions: Concep ualiza ion, G.P.-N. and N.H.; da a cu a ion, G.P.-N.; o mal analysis, G.P.-N. and N.H.; unding acquisi ion, G.P.-N.; in es iga ion, G.P.-N. and N.H.; me hodology, G.P.-N. and N.H.; p ojec adminis a ion, G.P.-N. and N.H.; esou ces, G.P.-N. and N.H.; so wa e, G.P.-N.; supe ision, N.H.; alida ion, G.P.-N. and N.H.; isualiza ion, G.P.-N.; w i ing—o iginal d a , G.P.- N.; W i ing— e iew and edi ing, G.P.-N. and N.H. All au ho s ha e ead and ag eed o he published e sion o he manusc ip . Senso s 2021,21, 1111 21 o 24 Funding: This esea ch was suppo ed by he Minis y o Educa ion, Cul u e and Spo o he Go e nmen o Spain, unde g an PRX16/00365 (p og am o mobili y s ays o academic s a and esea che s in o eign ins i u ions o highe educa ion and esea ch). Ins i u ional Re iew Boa d S a emen : No applicable. In o med Consen S a emen : No applicable. Da a A ailabili y S a emen : No applicable. Acknowledgmen s: This wo k was concei ed and de eloped o he mos pa du ing he esea ch s ay o Palacios as a acul y isi o in he E ic P. and E elyn E. Newman Labo a o y o Biomechanics and Human Rehabili a ion a he Massachuse s Ins i u e o Technology (MIT), wi hin he Depa men o Mechanical Enginee ing. Palacios wan s o hank bo h Hogan and MIT o hei suppo o de elop his wo k. Con lic s o In e es : The au ho s decla e no con lic o in e es . Re e ences 1. Rose, F.D.; B ooks, B.M.; Rizzo, A.A. Vi ual Reali y in B ain Damage Rehabili a ion: Re iew. Cybe Psychology Beha . 2005 ,8, 241–262. [C ossRe ] 2. Holden, M.K. Vi ual En i onmen s o Mo o Rehabili a ion: Re iew. Cybe Psychology Beha . 2005,8, 187–211. [C ossRe ] 3. Iosa, M.; Mo one, G.; Fusco, A.; B agoni, M.; Coi o, P.; Mul a i, M.; Ven u ie o, V.; De Angelis, D.; P a esi, L.; Paolucci, S. Se en Capi al De ices o he Fu u e o S oke Rehabili a ion. S oke Res. T ea . 2012,2012, 1–9. [C ossRe ] [PubMed] 4. C osbie, J.H.; Lennon, S.; McNeill, M.D.J.; McDonough, S.M. Vi ual Reali y in he Rehabili a ion o he Uppe Limb a e S oke: The Use ’s Pe spec i e. Cybe Psychology Beha . 2006,9, 137–141. [C ossRe ] 5. S eis up, H. Mo o Rehabili a ion Using Vi ual Reali y. J. Neu oeng. Rehabil. 2004,1, 10. [C ossRe ] 6. Langho ne, P.; Coupa , F.; Pollock, A. Mo o Reco e y a e S oke: A Sys ema ic Re iew. Lance Neu ol. 2009 ,8, 741–754. [C ossRe ] 7. Hende son, A.; Ko ne -Bi ensky, N.; Le in, M. Vi ual Reali y in S oke Rehabili a ion: A Sys ema ic Re iew o I s E ec i eness o Uppe Limb Mo o Reco e y. Top. S oke Rehabil. 2007,14, 52–61. [C ossRe ] 8. Paolucci, S.; Di Vi a, A.; Massicci, R.; T aballesi, M.; Bu eca, I.; Ma ano, A.; Iosa, M.; Gua iglia, C. Impac o Pa icipa ion on Rehabili a ion Resul s: A Mul i a ia e S udy. Eu . J. Phys. Rehabil. Med. 2012,48, 455–466. [PubMed] 9. Sis o, S.A.; Fo es , G.F.; Glendinning, D. Vi ual Reali y Applica ions o Mo o Rehabili a ion A e S oke. Top. S oke Rehabil. 2002,8, 11–23. [C ossRe ] 10. B oe en, J.; Claesson, L.; Goude, D.; Rydma k, M.; Sunne hagen, K.S. Vi ual Rehabili a ion in an Ac i i y Cen e o Communi y- Dwelling Pe sons wi h S oke. The Possibili ies o 3-Dimensional Compu e Games. Ce eb. Dis. 2008 ,26, 289–296. [C ossRe ] [PubMed] 11. Housman, S.J.; Sco , K.M.; Reinkensmeye , D.J. A Randomized Con olled T ial o G a i y-Suppo ed, Compu e -Enhanced A m Exe cise o Indi iduals wi h Se e e Hemipa esis. Neu o ehabil. Neu al Repai 2009,23, 505–514. [C ossRe ] 12. Ya uze , G.; Senel, A.; A ay, M.B.; S am, H.J. “Plays a ion Eye oy Games” Imp o e Uppe Ex emi y-Rela ed Mo o Func ioning in Subacu e S oke: A Randomized Con olled Clinical T ial. Eu . J. Phys. Rehabil. Med. 2008,44, 237–244. 13. Yang, Y.-R.; Tsai, M.-P.; Chuang, T.-Y.; Sung, W.-H.; Wang, R.-Y. Vi ual Reali y-Based T aining Imp o es Communi y Ambula ion in Indi iduals wi h S oke: A Randomized Con olled T ial. Gai Pos u e 2008,28, 201–206. [C ossRe ] [PubMed] 14. Walke , C.; B ouwe , B.J.; Culham, E.G. Use o Visual Feedback in Re aining Balance Following Acu e S oke. Phys. The . 2000 , 80, 886–895. [C ossRe ] 15. Me ians, A.S.; Jack, D.; Boian, R.; T emaine, M.; Bu dea, G.C.; Adamo ich, S.V.; Recce, M.; Poizne , H. Vi ual Reali y-Augmen ed Rehabili a ion o Pa ien s Following S oke. Phys. The . 2002,82, 898–915. [C ossRe ] 16. Weiss, P.L.; Kizony, R.; Fein uch, U.; Ka z, N. Vi ual eali y in neu o ehabili a ion. In Tex book o Neu al Repai and Rehabili a ion; Selze , M., Cla ke, S., Cohen, L., Duncan, P., Gage, F., Eds.; Camb idge Uni e si y P ess: Camb idge, UK, 2006; pp. 182–197. ISBN 978-0-511-54507-8. 17. Schul heis, M.T.; Rizzo, A.A. The Applica ion o Vi ual Reali y Technology in Rehabili a ion. Rehabil. Psychol. 2001 ,46, 296–311. [C ossRe ] 18. Schul heis, M.T.; Himels ein, J.; Rizzo, A.A. Vi ual Reali y and Neu opsychology: Upg ading he Cu en Tools. J. Head T auma Rehabil. 2002,17, 378–394. [C ossRe ] [PubMed] 19. Weiss, P.L.T.; Ka z, N. The Po en ial o Vi ual Reali y o Rehabili a ion. J. Rehabil. Res. De . 2004,41, ii–x. 20. Lange, B.; Koenig, S.; Chang, C.-Y.; McConnell, E.; Suma, E.; Bolas, M.; Rizzo, A. Designing In o med Game-Based Rehabili a ion Tasks Le e aging Ad ances in Vi ual Reali y. Disabil. Rehabil. 2012,34, 1863–1870. [C ossRe ] [PubMed] 21. She man, W.R.; C aig, A.B. Unde s anding Vi ual Reali y: In e ace, Applica ion, and Design; Mo gan Kau mann Se ies in Compu e G aphics and Geome ic Modeling; Mo gan Kau mann Publishe s: Ams e dam, The Ne he lands; Bos on, MA, USA, 2003; ISBN 978-1-55860-353-0. Senso s 2021,21, 1111 22 o 24 22. Ri a, G. Vi ual en i onmen s in clinical psychology. Psycho he apy 2003,40, 68–76. [C ossRe ] 23. Oujamaa, L.; Rela e, I.; F oge , J.; Mo e , D.; Pelissie , J.-Y. Rehabili a ion o a m unc ion a e s oke. Li e a u e e iew. Ann. Phys. Rehabil. Med. 2009,52, 269–293. [C ossRe ] 24. C osbie, J.; McDonough, S.; Lennon, S.; McNeill, M. De elopmen o a i ual eali y sys em o he ehabili a ion o he uppe limb a e s oke. S ud. Heal h Technol. In o m. 2005,117, 218–222. [PubMed] 25. Peñasco-Ma ín, B.; Reyes-Guzmán, A.D.L.; Gil-Agudo, Á.; Be nal-Sahún, A.; Pé ez-Aguila , B.; De La Peña-González, A.I. [Applica ion o i ual eali y in he mo o aspec s o neu o ehabili a ion]. Re is a de Neu ología 2010 ,51, 481–488. [C ossRe ] [PubMed] 26. La e , K.E.; Geo ge, S.; Thomas, S.; Deu sch, J.E.; C o y, M. Vi ual eali y o s oke ehabili a ion. In Coch ane Da abase o Sys ema ic Re iews; The Coch ane Collabo a ion, Ed.; John Wiley & Sons, L d.: Chiches e , UK, 2011; p. CD008349.pub2. 27. Rizzo, A.A.; Schul heis, M.; Ke ns, K.A.; Ma ee , C. Analysis o asse s o i ual eali y applica ions in neu opsychology. Neu opsychol. Rehabil. 2004,14, 207–239. [C ossRe ] 28. Being The e: Concep s, E ec s and Measu emen s o Use P esence in Syn he ic En i onmen s; Ri a, G.; Da ide, F.; IJssels eijn, W.A. (Eds.) Eme ging Communica ion: S udies in New Technologies and P ac ices in Communica ion; IOS P ess: Ams e dam, The Ne he lands; Washing on, DC, USA; Tokyo, Japan, 2003; ISBN 978-1-58603-301-9. 29. Hee e , C. Being The e: The Subjec i e Expe ience o P esence. P esence Teleope a o s Vi ual En i on. 1992 ,1, 262–271. [C ossRe ] 30. D ape , J.V.; Kabe , D.B.; Ushe , J.M. Telep esence. Hum. Fac o s 1998,40, 354–375. [C ossRe ] [PubMed] 31. McNeill, M.; Pokluda, L.; McDonough, S.; C osbie, J. Imme si e Vi ual Reali y o Uppe Limb Rehabili a ion Following S oke. In P oceedings o he IEEE In e na ional Con e ence on Sys ems, Man and Cybe ne ics, The Hague, The Ne he lands, 10–13 Oc obe 2004; Volume 3, pp. 2783–2789. 32. Li, Z.; Han, X.-G.; Sheng, J.; Ma, S.-J. Vi ual Reali y o Imp o ing Balance in Pa ien s a e S oke: A Sys ema ic Re iew and Me a-Analysis. Clin. Rehabil. 2016,30, 432–440. [C ossRe ] 33. Co be a, D.; Ime i, F.; Ga i, R. Rehabili a ion Tha Inco po a es Vi ual Reali y Is Mo e E ec i e han S anda d Rehabili a ion o Imp o ing Walking Speed, Balance and Mobili y a e S oke: A Sys ema ic Re iew. J. Physio he . 2015,61, 117–124. [C ossRe ] 34. I u haya ajah, J.; McIn y e, A.; Co oi, A.; Macaluso, S.; Teasell, R. The Use o Vi ual Reali y o Balance among Indi iduals wi h Ch onic S oke: A Sys ema ic Re iew and Me a-Analysis. Top. S oke Rehabil. 2017,24, 68–79. [C ossRe ] [PubMed] 35. Saposnik, G. Vi ual Reali y in S oke Rehabili a ion. In Ischemic S oke The apeu ics: A Comp ehensi e Guide; Sp inge In e na ional Publishing: New Yo k, NY, USA; pp. 225–233. ISBN 978-3-319-17749-6. 36. Boo h, V.; Masud, T.; Connell, L.; Ba h-Hex all, F. The E ec i eness o Vi ual Reali y In e en ions in Imp o ing Balance in Adul s wi h Impai ed Balance Compa ed wi h S anda d o No T ea men : A Sys ema ic Re iew and Me a-Analysis. Clin. Rehabil. 2014,28, 419–431. [C ossRe ] 37. Physio he apy E idence Da abase (PED o). A ailable online: h ps://ped o.o g.au/ (accessed on 28 Decembe 2020). 38. Moseley, A.M.; He be , R.D.; She ing on, C.; Mahe , C.G. E idence o Physio he apy P ac ice: A Su ey o he Physio he apy E idence Da abase (PED o). Aus . J. Physio he . 2002,48, 43–49. [C ossRe ] 39. Hedges, L.V.; Olkin, I. S a is ical Me hods o Me a-Analysis; Academic P ess: O lando, FL, USA, 1985; ISBN 978-0-12-336380-0. 40. Law, M.C.; MacDe mid, J. E idence-Based Rehabili a ion: A Guide o P ac ice; SLACK Inco po a ed: Tho o a e, NJ, USA, 2008; ISBN 978-1-55642-768-8. 41. Cohen, J. S a is ical Powe Analysis o he Beha io al Sciences, 2nd ed.; L. E lbaum Associa es: Hillsdale, NJ, USA, 1988; ISBN 978-0-8058-0283-2. 42. Sawilowsky, S.S. New E ec Size Rules o Thumb. J. Mod. App. S a . Me h. 2009,8, 597–599. [C ossRe ] 43. Higgins, J.P.T.; Thompson, S.G. Quan i ying He e ogenei y in a Me a-Analysis. S a . Med. 2002 ,21, 1539–1558. [C ossRe ] [PubMed] 44. In oduc ion o Me a-Analysis; Bo ens ein, M. (Ed.) John Wiley & Sons: Chiches e , UK, 2009; ISBN 978-0-470-05724-7. 45. Ögün, M.N.; Ku ul, R.; Ya¸sa , M.F.; Tu koglu, S.A.; A ci, ¸S.; Yildiz, N. E ec o Leap Mo ion-Based 3D Imme si e Vi ual Reali y Usage on Uppe Ex emi y Func ion in Ischemic S oke Pa ien s. A q. Neu o-Psiquia . 2019,77, 681–688. [C ossRe ] 46. Lee, C.-H.; Kim, Y.; Lee, B.-H. Augmen ed Reali y-Based Pos u al Con ol T aining Imp o es Gai Func ion in Pa ien s wi h S oke: Randomized Con olled T ial. Hong Kong Physio he . J. 2014,32, 51–57. [C ossRe ] 47. C osbie, J.; Lennon, S.; McGold ick, M.; McNeill, M.; McDonough, S. Vi ual Reali y in he Rehabili a ion o he A m a e Hemiplegic S oke: A Randomized Con olled Pilo S udy. Clin. Rehabil. 2012,26, 798–806. [C ossRe ] 48. Kang, H.-K.; Kim, Y.; Chung, Y.; Hwang, S. E ec s o T eadmill T aining wi h Op ic Flow on Balance and Gai in Indi iduals Following S oke: Randomized Con olled T ials. Clin. Rehabil. 2012,26, 246–255. [C ossRe ] [PubMed] 49. Foley, N.C.; Teasell, R.W.; Bhogal, S.K.; Speechley, M.R. S oke Rehabili a ion E idence-Based Re iew: Me hodology. Top. S oke Rehabil. 2003,10, 1–7. [C ossRe ] 50. Jung, J.; Yu, J.; Kang, H. E ec s o Vi ual Reali y T eadmill T aining on Balance and Balance Sel -E icacy in S oke Pa ien s wi h a His o y o Falling. J. Phys. The . Sci. 2012,24, 1133–1136. [C ossRe ] 51. Kim, I.-C.; Lee, B.-H. E ec s o Augmen ed Reali y wi h Func ional Elec ic S imula ion on Muscle S eng h, Balance and Gai o S oke Pa ien s. J. Phys. The . Sci. 2012,24, 755–762. [C ossRe ] 52. Ja e, D.L.; B own, D.A.; Pie son-Ca ey, C.D.; Buckley, E.L.; Lew, H.L. S epping o e Obs acles o Imp o e Walking in Indi iduals wi h Pos s oke Hemiplegia. JRRD 2004,41, 283. [C ossRe ] Senso s 2021,21, 1111 23 o 24 53. Pa k, Y.-H.; Lee, C.; Lee, B.-H. Clinical Use ulness o he Vi ual Reali y-Based Pos u al Con ol T aining on he Gai Abili y in Pa ien s wi h S oke. J. Exe c. Rehabil. 2013,9, 489–494. [C ossRe ] 54. C osbie, J.H.; McNeill, M.D.J.; Bu ke, J.; McDonough, S. U ilising Technology o Rehabili a ion o he Uppe Limb Following S oke: The Uls e Expe ience. Phys. The . Re . 2009,14, 336–347. [C ossRe ] 55. Duncan, P.W.; Weine , D.K.; Chandle , J.; S udenski, S. Func ional Reach: A New Clinical Measu e o Balance. J. Ge on ol. 1990 ,45, M192–M197. [C ossRe ] 56. Ha is-Lo e, M.L.; Macko, R.F.; Whi all, J.; Fo es e , L.W. Imp o ed Hemipa e ic Muscle Ac i a ion in T eadmill e sus O e g ound Walking. Neu o ehabil. Neu al Repai 2004,18, 154–160. [C ossRe ] 57. Baya , R.; Ba beau, H.; Lamon agne, A. Speed and Tempo al-Dis ance Adap a ions du ing T eadmill and O e g ound Walking Following S oke. Neu o ehabil. Neu al Repai 2005,19, 115–124. [C ossRe ] [PubMed] 58. Ha ey, R.L. Imp o ing Pos s oke Reco e y: Neu oplas ici y and Task-O ien ed T aining. Cu . T ea . Op ions Ca dio asc. Med. 2009,11, 251–259. [C ossRe ] [PubMed] 59. Yang, S.; Hwang, W.-H.; Tsai, Y.-C.; Liu, F.-K.; Hsieh, L.-F.; Che n, J.-S. Imp o ing Balance Skills in Pa ien s Who Had S oke h ough Vi ual Reali y T eadmill T aining. Am. J. Phys. Med. Rehabil. 2011,90, 969–978. [C ossRe ] [PubMed] 60. Pailhous, J.; Fe andez, A.M.; Flückige , M.; Baumbe ge , B. Unin en ional Modula ions o Human Gai by Op ical Flow. Beha . B ain Res. 1990,38, 275–281. [C ossRe ] 61. P okop, T.; Schube , M.; Be ge , W. Visual In luence on Human Locomo ion. Modula ion o Changes in Op ic Flow. Exp. B ain Res. 1997,114, 63–70. [C ossRe ] 62. Va aine, E.; Bonna d, M.; Pailhous, J. In e ac ion be ween Di e en Senso y Cues in he Con ol o Human Gai . Exp. B ain Res. 2002,142, 374–384. [C ossRe ] 63. Pickhinke, J.; Chien, J.H.; Mukhe jee, M. Va ying he Speed o Pe cei ed Sel -Mo ion A ec s Pos u al Con ol du ing Locomo ion. S ud. Heal h Technol. In . 2014,196, 319–324. 64. Hollman, J.H.; B ey, R.H.; Bang, T.J.; Kau man, K.R. Does Walking in a Vi ual En i onmen Induce Uns able Gai ? Gai Pos u e 2007,26, 289–294. [C ossRe ] 65. Ka sa elis, D.; Mukhe jee, M.; Decke , L.; S e giou, N. The E ec o Vi ual Reali y on Gai Va iabili y. Nonlinea Dyn. Psychol. Li e Sci. 2010,14, 239–256. 66. Mukhe jee, M.; Siu, K.-C.; Ka sa elis, D.; Fayad, P.; S e giou, N. The In luence o Visual Pe cep ion o Sel -Mo ion on Locomo o Adap a ion o Unila e al Limb Loading. J. Mo . Beha . 2011,43, 101–111. [C ossRe ] 67. Mendelson, D.N.; Red e n, M.S.; Nebes, R.D.; Richa d Jennings, J. Inhibi o y P ocesses Rela e Di e en ly o Balance/Reac ion Time Dual Tasks in Young and Olde Adul s. Aging Neu opsychol. Cogn. 2009,17, 1–18. [C ossRe ] 68. Lamon agne, A.; Fung, J.; McFadyen, B.J.; Faube , J. Modula ion o Walking Speed by Changing Op ic Flow in Pe sons wi h S oke. J. Neu oeng. Rehabil. 2007,4, 22. [C ossRe ] [PubMed] 69. Powell, W.A.; Hand, S.; S e ens, B.; Simmonds, M. Op ic Flow wi h a S e eoscopic Display: Sus ained In luence on Speed o Locomo ion. Annu. Re . Cybe The apy Telemed. 2006,4, 65–70. 70. Jang, S.H.; You, S.H.; Halle , M.; Cho, Y.W.; Pa k, C.-M.; Cho, S.-H.; Lee, H.-Y.; Kim, T.-H. Co ical Reo ganiza ion and Associa ed Func ional Mo o Reco e y A e Vi ual Reali y in Pa ien s wi h Ch onic S oke: An Expe imen e -Blind P elimina y S udy. A ch. Phys. Med. Rehabil. 2005,86, 2218–2223. [C ossRe ] 71. You, S.H.; Jang, S.H.; Kim, Y.-H.; Halle , M.; Ahn, S.H.; Kwon, Y.-H.; Kim, J.H.; Lee, M.Y. Vi ual Reali y-Induced Co ical Reo ganiza ion and Associa ed Locomo o Reco e y in Ch onic S oke: An Expe imen e -Blind Randomized S udy. S oke 2005 , 36, 1166–1171. [C ossRe ] 72. Banz, R.; Bollige , M.; Colombo, G.; Die z, V.; Lünenbu ge , L. Compu e ized Visual Feedback: An Adjunc o Robo ic-Assis ed Gai T aining. Phys. The . 2008,88, 1135–1145. [C ossRe ] [PubMed] 73. Ho lings, C.G.C.; Ca pen e , M.G.; Küng, U.M.; Honegge , F.; Wiede hold, B.; Allum, J.H.J. In luence o Vi ual Reali y on Pos u al S abili y du ing Mo emen s o Quie S ance. Neu osci. Le . 2009,451, 227–231. [C ossRe ] 74. Keshne , E.A.; Kenyon, R.V. Pos u al and Spa ial O ien a ion D i en by Vi ual Reali y. S ud. Heal h Technol. In . 2009 ,145, 209–228. [C ossRe ] 75. Van Peppen, R.P.S.; Ko smi , M.; Lindeman, E.; Kwakkel, G. E ec s o Visual Feedback The apy on Pos u al Con ol in Bila e al S anding a e S oke: A Sys ema ic Re iew. J. Rehabil. Med. 2006,38, 3–9. [C ossRe ] 76. C osbie, J.H.; Lennon, S.; Bas o d, J.R.; McDonough, S.M. Vi ual Reali y in S oke Rehabili a ion: S ill Mo e Vi ual han Real. Disabil. Rehabil. 2007,29, 1139–1146. [C ossRe ] 77. Du gin, F.H.; Li, Z. Con olled In e ac ion: S a egies o Using Vi ual Reali y o S udy Pe cep ion. Beha . Res. Me hods 2010 ,42, 414–420. [C ossRe ] [PubMed] 78. Knapp, J.; Loomis, J. Visual Pe cep ion o Egocen ic Dis ance in Real and Vi ual En i onmen s. In Vi ual and Adap i e En i onmen s; He inge , L., Haas, M., Eds.; CRC P ess: Boca Ra on, FL, USA, 2003; pp. 21–46. ISBN 978-0-8058-3107-8. 79. Mon-Williams, M.; Bingham, G.P. On ological Issues in Dis ance Pe cep ion: Cue Use unde Full Cue Condi ions Canno Be In e ed om Use unde Con olled Condi ions. Pe cep . Psychophys. 2008,70, 551–561. [C ossRe ] [PubMed] 80. Liebe mann, D.G.; Be man, S.; Weiss, P.L.; Le in, M.F. Kinema ics o Reaching Mo emen s in a 2-D Vi ual En i onmen in Adul s wi h and Wi hou S oke. IEEE T ans. Neu al Sys . Rehabil. Eng. 2012,20, 778–787. [C ossRe ] Senso s 2021,21, 1111 24 o 24 81. Piggo , L.; Wagne , S.; Zia , M. Hap ic Neu o ehabili a ion and Vi ual Reali y o Uppe Limb Pa alysis: A Re iew. C i . Re . Biomed. Eng. 2016,44, 1–32. [C ossRe ] 82. Schul heis, M.T.; Rebimbas, J.; Mou an , R.; Millis, S.R. Examining he Usabili y o a Vi ual Reali y D i ing Simula o . Assis . Technol. 2007,19, 1–10. [C ossRe ] 83. Tu olla, A.; Dam, M.; Ven u a, L.; Tonin, P.; Agos ini, M.; Zucconi, C.; Kipe , P.; Cagnin, A.; Pi on, L. Vi ual Reali y o he Rehabili a ion o he Uppe Limb Mo o Func ion a e S oke: A P ospec i e Con olled T ial. J. Neu oeng. Rehabil. 2013 ,10, 85. [C ossRe ] 84. Tsoupiko a, D.; S oyko , N.S.; Co igan, M.; Thielba , K.; Vick, R.; Li, Y.; T ianda ilou, K.; P euss, F.; Kampe , D. Vi ual Imme sion o Pos -S oke Hand Rehabili a ion The apy. Ann. Biomed. Eng. 2015,43, 467–477. [C ossRe ] [PubMed] 85. Sub amanian, S.K.; Le in, M.F. Viewing Medium A ec s A m Mo o Pe o mance in 3D Vi ual En i onmen s. J. Neu oeng. Rehabil. 2011,8, 36. [C ossRe ] 86. Bo ego, A.; La o e, J.; Llo ens, R.; Alcañiz, M.; Noé, E. Feasibili y o a Walking Vi ual Reali y Sys em o Rehabili a ion: Objec i e and Subjec i e Pa ame e s. J. Neu oeng. Rehabil. 2016,13, 68. [C ossRe ] [PubMed] 87. Sla e , M.; S eed, A. A Vi ual P esence Coun e . P esence Teleope a o s Vi ual En i on. 2000,9, 413–434. [C ossRe ] 88. Wi me , B.G.; Singe , M.F. Measu ing p esence in i ual en i onmen s. Meas. P esence Vi ual En i on. 1994,53. [C ossRe ] 89. Palacios-Na a o, G.; Albiol-Pé ez, S.; Ga cía-Maga iño Ga cía, I. E ec s o Senso y Cueing in Vi ual Mo o Rehabili a ion. A Re iew. J. Biomed. In o m. 2016,60, 49–57. [C ossRe ] 90. Viau, A.; Feldman, A.G.; McFadyen, B.J.; Le in, M.F. Reaching in Reali y and Vi ual Reali y: A Compa ison o Mo emen Kinema ics in Heal hy Subjec s and in Adul s wi h Hemipa esis. J. Neu oeng. Rehabil. 2004,1, 11. [C ossRe ] 91. Lam, Y.S.; Man, D.W.K.; Tam, S.F.; Weiss, P.L. Vi ual Reali y T aining o S oke Rehabili a ion. Neu o ehabili a ion 2006 ,21, 245–253. [C ossRe ] 92. Lee, G. E ec s o T aining using ideo games on he muscle s eng h, muscle one, and ac i i ies o daily li ing o ch onic s oke pa ien s. J. Phys. The . Sci. 2013,25, 595–597. [C ossRe ] [PubMed] 93. Kwon, J.-S.; Pa k, M.-J.; Yoon, I.-J.; Pa k, S.-H. E ec s o i ual eali y on uppe ex emi y unc ion and ac i i ies o daily li ing pe o mance in acu e s oke: A double-blind andomized clinical ial. Neu o ehabili a ion 2012 ,31, 379–385. [C ossRe ] [PubMed] 94. Kim, J.H.; Jang, S.H.; Kim, C.S.; Jung, J.H.; You, J.H. Use o i ual eali y o enhance balance and ambula ion in ch onic s oke: A double-blind, andomized con olled s udy. Am. J. Phys. Med. Rehabil. 2009,88, 693–701. [C ossRe ] 95. Reid, D. The use o i ual eali y o imp o e uppe -ex emi y e iciency skills in child en wi h ce eb al palsy: A pilo s udy. Technol. Disabil. 2002,14, 53–61. [C ossRe ] 96. Azulay, J.-P.; Mesu e, S.; Blin, O. In luence o isual cues on gai in Pa kinson’s disease: Con ibu ion o a en ion o senso y dependence? J. Neu ol. Sci. 2006,248, 192–195. [C ossRe ] [PubMed] 97. Nieuwboe , A.; Kwakkel, G.; Roches e , L.; Jones, D.; Van Wegen, E.; Willems, A.M.; Cha e , F.; He he ing on, V.; Bake , K.; Lim, I. Cueing aining in he home imp o es gai - ela ed mobili y in Pa kinson’s disease: The RESCUE ial. J. Neu ol. Neu osu g. Psychia y 2007,78, 134–140. [C ossRe ] 98. G i in, H.J.; G eenlaw, R.; Limousin, P.; Bha ia, K.P.; Quinn, N.P.; Jahanshahi, M. The e ec o eal and i ual isual cues on walking in Pa kinson’s disease. J. Neu ol. 2011,258, 991–1000. [C ossRe ] 99. Vii e, E.; Si a z, R. Ves ibula ehabili a ion using isual displays: P elimina y s udy. La yngoscope 2002 ,112, 500–503. [C ossRe ] [PubMed] 100. Suá ez, H.; Sua ez, A.; La insky, L. Pos u al adap a ion in elde ly pa ien s wi h ins abili y and isk o alling a e balance aining using a i ual- eali y sys em. In . Tinni us J. 2006,12, 41–44. 101. Fische , H.C.; S ubble ield, K.; Kline, T.; Luo, X.; Kenyon, R.V.; Kampe , D.G. Hand ehabili a ion ollowing s oke: A pilo s udy o assis ed inge ex ension aining in a i ual en i onmen . Top. S oke Rehabil. 2007,14, 1–12. [C ossRe ] 102. Willemsen, P.; Col on, M.B.; C eem-Regeh , S.H.; Thompson, W.B. The e ec s o head-moun ed display mechanical p ope ies and ield o iew on dis ance judgmen s in i ual en i onmen s. ACM T ans. Appl. Pe cep . 2009,6, 8. [C ossRe ]