Ankstyvo neurologinio pagerëjimo po intraveninës trombolizës, gydant ûminá iðeminá insultà, klinikinë reikðmë ir prognostiniai veiksniai

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1 Ankstyvo neurologinio pagerëjimo po intraveninës trombolizës, gydant ûminá iðeminá insultà, klinikinë reikðmë ir prognostiniai veiksniai A. Vilionskis* O. Knoknerienë** M. Ðeðeikaitë*** D. Jatuþis**** V. Budrys**** *Respublikinë Vilniaus universitetinë ligoninë, Neurologijos skyrius; Vilniaus universiteto Medicinos fakultetas, Neurologijos ir neurochirurgijos klinika **Klaipëdos Jûrininkø ligoninë, Neurologijos skyrius ***Vilniaus universiteto Medicinos fakultetas, Neurologijos ir neurochirurgijos klinika ****Vilniaus universiteto Medicinos fakultetas, Neurologijos ir neurochirurgijos klinika; Vilniaus universiteto ligoninës Santariðkiø klinikos, Neurologijos centras Santrauka. Ávadas. Intraveninë trombolizë yra pirmo pasirinkimo iðeminio insulto gydymo me to das, ta èiau re ka na li za ci ja po jos pa sie kia ma ne daþ nai. Pas ta ruo ju me tu dau gë ja in ter - ven ci niø pro ce dûrø, kuriomis daþniau pavyksta atverti uþsikimðusià smegenø arterijà. Jos ga li bû ti at lie ka mos ligoniams, kuriems intraveninë trombolizë neduoda laukiamo efekto, to - dël svar bu at rinkti ligonius, kuriems tokia procedûra bûtø naudinga. Taigi svarbu ávertinti veiks nius, lei dþianèius prognozuoti trombolizës efektyvumà iki jos pradþios. Mûsø darbo tiks las áver tin ti ryð kaus anks ty vo neu ro lo gi nio pa ge rë ji mo reikð mæ il ga lai kei ið ei èiai ir nu - sta ty ti jo prog nostinius veiksnius. Me to dai, medþiaga. Á prospektyviná tyrimà buvo átraukti ligoniai, sergantys ûminiu iðemi niu in sul tu ir gy dy ti tai kant in tra ve ni næ trom bo li zæ. Ver tin ti de mo gra finiai ir kli ni ki niai pra di niai ro dik liai. Reikðmingu ankstyvu neurologiniu pagerëjimu laikytas neurologinio de - fi ci to su ma þë ji mas 4 ir dau giau ba lø pa gal NIHSS, ar ba 0 1 ba las pa gal NIHSS pra ëjus 2 val. po trom bo li zës. Puiki iðeitis apibûdinta kaip funkcinë bûklë 0 1 pagal mrs po 3 mën. Re zul ta tai. Á tyrimà buvo átraukti 136 ligoniai, gydyti Vilniaus miesto ligoninëse. Ryðkus anks ty vas neu rologinis pagerëjimas buvo stebëtas 70 (51,5 %) ligoniø, o puiki iðeitis po 3-jø mën. bu vo nu statyta 49 ligoniams (36,0 %). Tarp ryðkaus ankstyvo neurologinio pagerëjimo ir pui kios ið ei ties po 3 mën. bu vo ras ta vi du ti nio laips nio ko re lia ci ja (r = 0,445, p < 0,001). Ryð kus anks ty vas neurologinio deficito pagerëjimas buvo susijæs su ligoniø jaunesniu am - þiu mi (ðan sø san ty kis (ÐS) 0,956, 95 % PI 0,918 0,996, p = 0,03) ir vi du ri nës sme ge nø arte ri jos hi per densinio signalo nebuvimu pradinëje galvos smegenø KT (ÐS 0,238, 95 % PI 0,089 0,637, p = 0,004). Ið va dos. Ankstyvas neurologinës bûklës pagerëjimas daþnai leidþia numatyti palankià funk ci næ ið ei tá po insulto, gydyto trombolize. Nepalankiais prognostiniais veiksniais anksty - vam neu ro lo gi niam pa ge rë ji mui ir funk ci nei ið ei èiai lai ky ti ni VSA hi per den si nis sig na las pra di në je gal vos smegenø KT ir vyresnis ligoniø amþius. Rak ta þo dþiai: intraveninë trombolizë, ûminis iðeminis insultas, ankstyvas neurologinis pa - ge rë ji mas, prognostiniai veiksniai. Neurologijos seminarai 2013; 17(57): ÁVADAS Adresas: A. Vilionskis Respublikinë Vilniaus universitetinë ligoninë, Neurologijos skyrius Ðiltnamiø g. 29, LT Vilnius Tel El. paðtas aleksandras.vilionskis@gmail.com Ðiuo me tu in tra ve ni në trom bo li zë yra pa tvir tin ta pir mo pa - si rin ki mo ið emi nio in sul to gy dy mo me to du nuo simp to mø at si ra di mo pra ëjus ne dau giau kaip 4,5 val. [1, 2]. Vie nas svar biau siø veiks niø, le mian èiø ge rà trom bo li zës re zul ta - tà, yra uþsikimðusios arterijos atvërimas rekanalizacija, ir gal vos sme ge nø krau jo ta kos at sta ty mas ið emi jos zo no je, nors lai ko fak to rius ið lie ka svar bus [3]. Re ka na li za ci ja, at - liekant áprastinæ intraveninæ trombolizæ, pasiekiama palygin ti ne daþ nai apie %, pri klau so nuo ok liu zi jos vie tos [4 6]. Pas ta ruo ju me tu li go niams, ku rie at vy ko vë - liau kaip 4,5 val. nuo simp to mø at si ra di mo ar ba in tra ve ni - në trom bo li zë ne ga li ma dël esan èiø kon train di ka ci jø, vis daþniau atliekama intervencinë procedûra mechaninis trombo iðtraukimas per ávestà kateterá (trombektomija). Pirmosios trombektomijos jau atliktos ir Lietuvoje. Ji taip pat ga li bû ti tai ko ma li go niams, ku riems in tra ve ni në trom - bo li zë bu vo ne efek ty vi, t. y. ne gau ta re ka na li za ci ja. To dël la bai svar bu at rink ti li go nius, ku riems to kia pro ce dû ra bû - tø nau din ga. Tam svar bu áver tin ti veiks nius, lei dþian èius prog no zuo ti trom bo li zës efek ty vu mà iki jos pra dþios. Kas - die në je kli ni ki në je prak ti ko je ûmi niu in sul tu ser gan tiems li go niams krau jo ta ka trom bo li zës me tu ir ið kar to po jos në ra ver ti na ma (krau jo ta kos at si sta ty mas ne do ku men tuo - ja mas), ta èiau yra duo me nø, kad anks ty vas neu ro lo gi nio deficito sumaþëjimas patikimai atspindi uþsikimðusios ar - terijos rekanalizacijà [7]. 217

2 A. Vilionskis, O. Knoknerienë, M. Ðeðeikaitë, D. Jatuþis, V. Budrys DAR BO TIKS LAS Mû sø dar bo tiks las nu sta ty ti ry ðá tarp reikð min go anks ty - vo neu ro lo gi nës bûk lës pa ge rë ji mo ir vë les nës ið ei ties ir nu sta ty ti pa ge rë ji mo prog nos ti nius veiks nius. ME DÞIA GA IR ME TO DAI Á pros pektyviná ste bi mà já ty ri mà átrauk ti li go niai, ser gan - tys ûmi niu ið emi niu in sul tu ir gy dy ti tai kant in tra ve ni næ trom bo li zæ Vil niaus uni ver si te ti në je res pub li ki në je li go - ni në je ir Vil niaus uni ver si te to li go ni nës San ta rið kiø kli ni - ko se nuo 2002 iki 2011 me tø. Á ty ri mà bu vo átrauk ti vi si li - go niai, ku riems in tra ve ni në trom bo li zë bu vo at lik ta lai - kan tis ðiuo me tu Lie tu vo je ga lio jan èiø ûmi nio in sul to gy - dy mo re ko men da ci jø [8], ið sky rus am þiø (da lis li go niø bu vo vy res ni nei 80 me tø) ir lai kà nuo simp to mø at si ra di - mo iki trom bo li zës pra dþios (da liai li go niø in tra ve ni në trom bo li zë at lik ta per 3 4,5 val. nuo simp to mø at si ra di - mo pra dþios; iki 2012 m. te ra pi nis lan gas trom bo li zei, pa - gal Lie tu vo je ga lio jan èias re ko men da ci jas, bu vo pir mo - sios 3 val. nuo in sul to pra dþios). At vy ki mo me tu bu vo ver ti na mi ben dri de mo gra finiai ir kli ni ki niai ro dik liai. Li - go niø neu ro lo gi në bûk lë bu vo ver ti na ma nau do jant Na - cio na li nio svei ka tos ins ti tu to in sul to ska læ (angl. Na - tional In sti tute of Health Stroke Scale, NIHSS) li go niui at vy kus ir pra ëjus 2 val. nuo in tra ve ni nës trom bo li zës pra dþios. Li go niø funk ci në bûk lë ato kiu pe ri odu bu vo ver ti na ma pra ëjus 3 mën. nuo in sul to pra dþios nau do jant mo di fi kuo tà Ran ki no ska læ (mrs). Vi siems li go niams, prieð pra de dant trom bo li zæ, bu vo at lik ta na ty vi në gal vos sme ge nø KT, ku rià ver ti no ra dio lo gas ar ba bu din tis neu - ro lo gas. Tais at ve jais, kai gal vos sme ge nø KT bu vo ver ti - na ma bu din èio neu ro lo go, vë liau ji bu vo ap ta ria ma su ra - dio lo gu. Reikð min gu anks ty vu neu ro lo gi niu pa ge rë ji mu lai ky - tas neu ro lo gi nio de fi ci to su ma þë ji mas 4 ir dau giau ba lø pa - gal NIHSS (ly gi nant bûk læ at vy kus ir pra ëjus 2 val. nuo in - tra ve ni nës trom bo li zës pra dþios), ar ba 0 1 ba las pa gal NIHSS pra ëjus 2 val. po trom bo li zës (neat si þvel giant á tai, ko kia bûk lë bu vo at vy kus). Pui ki ið ei tis api bû din ta kaip funk ci në bûk lë 0 1 pa gal mrs po 3 mën. Dar bui at lik ti bu vo gau tas Vil niaus re gio ni nio bio me - dicininiø tyrimø etikos komiteto leidimas. Statistinë analizë. Statistinë analizë atlikta naudojant sta tis ti ná pro gra mø pa ke tà SPSS 16.0 (ver sion for Win - dows). Pa ra met ri niams kin ta mie siems api bû din ti nau do tas vi dur kis ir stan dar ti nis nuo kry pis ar ba me dia na ir 25 bei 75 kvar ti liai, ne pa ra met ri niams ab so liu tûs ir san ty ki niai daþniai. Normaløjá pasiskirstymà atitinkantiems kintamie - siems palyginti taikytas Studento t kriterijus nepriklausomoms im tims. Ne pa ra met ri niams kin ta mie siems tar pu sa - vy je pa ly gin ti nau do tas 2 ir Fiðerio testas. Koreliacijai tarp at ski rø ro dik liø áver tin ti bu vo tai ko mas Spe ar ma no me to das. Ti riant ry ðá tarp anks ty vo neu ro lo gi nio pa ge rë ji - mo ir funkcinës iðeities su rizikos veiksniais bei kliniki - 1 lentelë. Ligoniø demografiniai ir klinikiniai duomenys Rodiklis Amþius, m. (vidurkis ± SD) 66,3 ± 15,0 Lytis, vyras (%) 50 PAH (%) 63,2 CD (%) 11,9 PV áskaitant paroksizminá, (%) 32,4 Buvæs insultas (%) 13,2 Ðirdies nepakankamumas (%) 13,2 Pradinis neurologinis deficitas, NIHSS (vidurkis ± SD) Pradinis neurologinis deficitas, NIHSS (mediana, IQR) Laikas nuo simptomø atsiradimo iki gydymo pradþios, min. (vidurkis ± SD) Iðeminiai pakitimai pradinëje galvos smegenø KT (%) niais ro dik liais, tai ky tas dau gia ly pës re gre si jos me to das. Tai ky tas þings ni nis for ward kin ta mo jo at ran kos me to - das. Kintamasis buvo átrauktas á regresijos lygtá, jei jo reikð min gu mas ne vir ði jo 0,1. REZULTATAI 15,0 ± 5,4 14 (11 19) 146,9 ± 43,9 16,2 Simptominës VSA hiperdensinis signalas (%) 26,2 PAH arterinë hipertenzija, CD cukrinis diabetas, PV prie ðir - dþiø virpëjimas, NIHSS Nacionalinio sveikatos instituto in sul - to skalë (angl. Na tional In sti tute of Health Stroke Scale), KT kom piu te ri në tomografija, VSA vidurinë smegenø arterija. Vilniaus mieste intraveninë trombolizë ûminiu iðeminiu insultu sergantiems ligoniams atliekama dviejose ligoni - në se Vil niaus res pub li ki në je uni ver si te ti në je li go ni në je ir Vilniaus universiteto ligoninës Santariðkiø klinikose. Nuo 2002 m. jo se in tra ve ni në trom bo li zë bu vo at lik ta 209 ið emi niu in sul tu ser gan tiems li go niams. 35 li go niai ne bu vo átrauk ti á ty ri mà dël ne pil tø pra di niø duo me nø ir ne áver tin tos neu ro lo gi nës bûk lës po 2 val. nuo gy dy mo pra dþios. Dar 26 li go niai bu vo pa ða lin ti ið ty ri mo dël gal - vos sme ge nø ne pil no vaiz di nio áver ti ni mo. 12 li go niø ne - bu vo átrauk ti á ty ri mà dël ne þi no mos funk ci nës bûk lës, pra - ëjus 3 mën. po pa tir to in sul to. Á ga lu ti ná ty ri mà bu vo átrauk - ti 136 li go niai. Li go niø vi du ti nis am þius 66,3 ± 15,0 m. Li go niai, vy - res ni kaip 80 m., su da rë 8,8 % vi sø li go niø. Vi du ti nis neu - ro lo gi nis de fi ci tas, pa gal NIHSS, at vy kus bu vo 15,0 ± 5,4. Vi du ti nis lai kas nuo simp to mø at si ra di mo iki trom bo li zës pra dþios bu vo 146,9 ± 43,9 min. 23 li go niams (16,9 %) trom bo li zë bu vo at lik ta per 3 4,5 val. nuo simp to mø at si - ra di mo. Pra di në je na ty vi në je gal vos sme ge nø KT vi du ri - nës sme ge nø ar te ri jos (VSA) hi per den si nis sig na las, su - tam pan tis su ûmi nio in sul to ba sei nu, ste bë tas 34 li go niams (26,2 %). Ið sa mûs li go niø de mo gra finiai ir kli ni ki niai duo - menys pateikti 1 lentelëje. 218

3 Ankstyvo neurologinio pagerëjimo po intraveninës trombolizës, gydant ûminá iðeminá insultà, klinikinë reikðmë ir prognostiniai veiksniai 2 lentelë. Ryðkus ankstyvas neurologinis pagerëjimas ir atoki iðeitis, praëjus 3 mën. po trombolizës Ryðkus ankstyvas neu ro - lo gi nis pagerëjimas (%) Visi ligoniai Amþius 80 m. Amþius > 80 m. p ONT 180 min. ONT > 180 min. p 51,5 % 44,4 % 33,3 % 0,55 42,5 % 47,8 % 0,65 mrs 0 1 (%) 36,0 % 39,3 % 25,0 % 0,53 37,3 % 41,9 % 0,81 ONT laikas nuo simptomø atsiradimo iki gydymo pradþios (angl. on set to nee dle time). 3 lentelë. Demografiniø ir klinikiniø veiksniø átaka ankstyvam neurologiniam pagerëjimui Poþymis ÐS 95 % PI p Vyresnis amþius 0,956 0,918 0,996 0,03 Vyriðka lytis 1,338 0,595 3,007 0,48 Laikas nuo simptomø pradþios iki gydymo pradþios 0,995 0,985 1,005 0,32 PAH 1,094 0,452 2,649 0,84 Cukrinis diabetas 1,238 0,309 4,960 0,76 Buvæs insultas 0,993 0,301 3,273 0,99 Prieðirdþiø virpëjimas 0,582 0,235 1,441 0,24 Ðirdies nepakankamumas 1,476 0,366 5,954 0,58 Didesnis pradinis neurologinis deficitas 0,982 0,910 1,060 0,65 VSA hiperdensinis signalas natyvinëje galvos smegenø KT 0,238 0,089 0,637 0,004 ÐS ðansø santykis, PI pasikliautinieji intervalai, PAH pirminë arterinë hipertenzija, VSA vidurinë smegenø arterija, KT kom - piu te ri në tomografija. Ryð kus anks ty vas neu ro lo gi nis pa ge - rë ji mas bu vo ste bë tas 70 (51,5 %) li go - niø, o pui ki ið ei tis po 3 mën. nu sta ty ta 49 li go niams (36,0 %). Tarp li go niø, ku - riems IVT bu vo at lik ta pra ëjus min. nuo li gos pra dþios, reikð - min gas anks ty vas neu ro lo gi nis pa ge rë ji - mas ir pui ki ið ei tis po 3 mën. bu vo nu sta - ty ti ati tin ka mai 47,8 % ir 41,9 % pa cien tø. Ðie ro dik liai ne si sky rë nuo re zul ta tø, gau - tø li go niams, ku riems IVT bu vo at lik ta per 180 min. nuo li gos pra dþios. Vy res nio am þiaus (> 80 m.) li go niø gru pë je ryð kus anks ty vas neu ro lo gi nis pa ge rë ji mas bu vo nu sta ty tas 33,3 % li go niø, o pui ki ato ki ið - ei tis 25 % li go niø. Ðie ro dik liai taip pat ne si sky rë nuo jau nes niø li go niø (iki 80 m. amþiaus) grupës (2 lentelë). Tarp ryð kaus anks ty vo neu ro lo gi nio pa ge rë ji mo ir pui kios ato kios ið ei ties bu - vo ras ta vi du ti nio laips nio ko re lia ci ja (r = 0,445, p < 0,001) (Pav.). Lo gis ti në re - gre si në ana li zë pa ro dë, kad li go niø reikð - min gas anks ty vas neu ro lo gi nës bûk lës pa ge rë ji mas bu vo su si jæs su li go niø jau - nes niu am þiu mi (ðan sø san ty kis (ÐS) 0,956, 95 % pa si - kliau ti nie ji in ter va lai (PI) 0,918 0,996, p = 0,03) ir vi du - ri nës sme ge nø ar te ri jos hi per den si nio sig na lo ne bu vi mu pra di në je gal vos sme ge nø KT (ÐS 0,238, 95 % PI 0,089 0,637, p = 0,004). Ki ti de mo gra finiai ir kli ni ki niai ro dik liai reikð min gam anks ty vam neu ro lo gi niam pa ge rë ji - mui áta kos ne tu rë jo (3 len te lë). Pav. Koreliacija tarp ankstyvo neurologinio pagerëjimo ir funkcinës bûklës po 3 mën. r - Spearman koreliacijos koeficientas. DISKUSIJOS Ðiame darbe pirmà kartà Lietuvoje analizuojamos reikð - min go anks ty vo neu ro lo gi nës bûk lës pa ge rë ji mo sà sa jos su in sul to ið ei ti mi po 3 mën. ir nu sta to mi prog nos ti niai veiks niai. Tai yra svar bu, ka dan gi Lie tu vos gy ven to jai pa - tiria sunkesnius insultus. Be to, jie turi daugiau gretutiniø 219

4 A. Vilionskis, O. Knoknerienë, M. Ðeðeikaitë, D. Jatuþis, V. Budrys li gø. Dar vie nas svar bus mo men tas li go niø ið ty ri mø ga li - my bës. Ðiuo me tu jos yra ri bo tos, to dël tiks li nës gru pës nu - sta ty mas yra la bai svar bus, lei dþian tis pa ge rin ti gy dy mo efek ty vu mà veiks nys. In sul to ato kiø jø re zul ta tø prog no za - vimas yra svarbus klinikinëje praktikoje. Jis leidþia, tik pra dë jus gy dy mà, kar tais ir iki jo, nu ma ty ti to li mes ná li go - nio iðtyrimà, ávertinti jo skubumà ir apimtá, o esant reika - lui ap svars ty ti ir tai ky ti pa pil do mus gy dy mo me to dus. Ti kë ti na, kad tai pa ge ri na gy dy mo re zul ta tus, su ma þi na in - sulto sukeltà negalià ir mirtingumà. Mû sø dar bo re zul ta tai ro do, kad ryð kus anks ty vas neu - ro lo gi nës bûk lës pa ge rë ji mas ko re liuo ja su ge ra funk ci ne bûk le po 3 mën. Pa na ðûs re zul ta tai gau ti ir ki tø au to riø ty ri - muo se. T. M. Hem men ir T. Cha ri to no va nu ro do, kad neu - ro lo gi nio de fi ci to su ma þë ji mas 20 %, ly gi nant su pra di niu, pra ëjus 2 val. po trom bo li zës, yra pa ti ki mas ge ros funk ci - nës bûk lës po 3 mën. prog nos ti nis veiks nys [7, 9]. I. P. Mu - re sa no at lik tas ty ri mas pa ro dë, kad la bai anks ty vas neu ro - lo gi nës bûk lës pa ge rë ji mas (api bû din tas kaip pa ge rë ji mas 5 ba lais ir dau giau pa gal NIHSS ska læ ar ba neu ro lo gi nio de fi ci to vi sið kas ar be veik vi sið kas ið ny ki mas (0 1 ba las pa gal NIHSS), pra ëjus 1 val. po trom bo li zës, stip riai su si - jæs su gera ilgalaike iðeitimi [10]. Kitø autoriø duomeni - mis, neu ro lo gi nës bûk lës ne ge rë ji mas, pra ëjus 24 val. po in tra ve ni nës trom bo li zës, su si jæs su blo ga vë les ne prog no - ze [11]. Tai lei dþia teig ti, kad reikð min gas anks ty vas neu - ro lo gi nës bûk lës pa ge rë ji mas lei dþia nu ma ty ti to li mes ná neu ro lo gi nës bûk lës ge rë ji mà ir at rink ti li go nius, ku riems tikëtina nepalanki ilgalaikë iðeitis. Manoma, kad anksty - vas neu ro lo gi nës bûk lës pa ge rë ji mas ne tie sio giai at spin di uþsikimðusios kraujagyslës rekanalizacijà. Tai patvirtino ty ri mas, ku ris pa ro dë pra di nio neu ro lo gi nio de fi ci to su ma - þëjimo 40 %, pra ëjus 2 val. po in tra ve ni nës trom bo li zës, sà sa jà su re ka na li za ci ja [12]. Ðio ty ri mo au to riai siû lo neu - ro lo gi nës bûk lës pa ge rë ji mà ver tin ti kaip ne tie sio gi ná re - ka na li za ci jos po þy má. Ka dan gi sa vo dar be ne tu rë jo me ga - li my biø do ku men tuo ti re ka na li za ci jà, at lie kant trom bo li zæ ir po jos, pa si rin ko me reikð min gà anks ty và neu ro lo gi nës bûk lës pa ge rë ji mà, kaip re ka na li za ci jos su ro ga ti ná po þy - má, ir ty rë me jo prog nos ti næ reikð mæ ato kiai neu ro lo gi nei iðeièiai po insulto. Ðiuo me tu ne abe jo ja ma, kad kuo anks èiau bus pra dë ta in tra ve ni në trom bo li zë, tuo pa svei ki mo re zul ta tai yra ge - res ni [13], to dël iki jos pra dþios grieþ tai re ko men duo ja ma atlikti tik bûtiniausius tyrimus [8]. Pradëjus trombolizæ, ligonio iðtyrimas gali bûti tæsiamas (tuo metu galima atlikti gal vos sme ge nø KT an giog ra fi jà, per fu zi jà, gal vos sme ge - nø MRT), sie kiant gau ti pa pil do mos in for ma ci jos apie jo gal vos sme ge nø ir sme ge nø krau ja gys liø bûk læ. Ka dan gi ðiuo me tu Lie tu vo je ty ri mø pri ei na mu mas daþ niau siai yra ri bo tas, svar bu nu sta ty ti tiks li næ li go niø gru pæ, ku riems to - kie ty ri mai gal bû ti ypaè nau din gi op ti mi zuo jant jø gy dy - mà. Mû sø ty ri mas pa ro dë, kad tik jau nes nis am þius ir simp to mi nës VSA (ati tin kan èios ûmi nio in sul to ba sei nà) hi per den si nio sig na lo ne bu vi mas pra di në je gal vos sme ge - nø KT yra ne pri klau so mi anks ty vos neu ro lo gi nës bûk lës pa ge rë ji mo prog nos ti niai veiks niai. Am þiaus áta ka anks ty - vam neu ro lo gi nës bûk lës pa ge rë ji mui rei ka lau ja pa pil do - mø ty ri mø ar ba di des nës im ties, ka dan gi gau tas ðan sø san - ty kis yra ar ti mas 1. Tai ro do, kad jo áta ka yra mi ni ma li, nors ir pa ti ki ma. Ádo mu tai, kad ne ra do me ry ðio tarp pra di - nës neu ro lo gi nës bûk lës sun ku mo ir anks ty vo pa ge rë ji mo. Panaðûs rezultatai gauti ir kitame tyrime, taèiau jame ligoniams su kar dio em bo liu in sul tu anks ty vas pa ge rë ji mas bu - vo ste bë tas re èiau [14]. Mû sø ty ri me ne bu vo ana li zuo ja - mas ry ðys tarp in sul to po ti pio ir anks ty vo pa ge rë ji mo daþ - nio, ta èiau ne ga vo me duo me nø, kad prie ðir dþiø vir pë ji mas tu ri áta kos neu ro lo gi nës bûk lës pa ge rë ji mui. Rei kia pa mi - në ti, kad SITS-EAST duo me ni mis, ryð kaus anks ty vo neu - ro lo gi nio pa ge rë ji mo daþ nis li go niams su kar dio em bo li niu insultu ir insultu dël stambiø precerebriniø arterijø stenozës yra pa na ðus (A. Vi lions kis ir kt., SITS-EAST ty rë jai, ne pub li kuo ti duo me nys). E. T. As ke vold su ben dra au to riais nu ro dë, kad re ka na - li za ci ja re èiau ávyks ta li go niams su di des niu pra di niu neu - rologiniu deficitu, turintiems prieðirdþiø virpëjimà, daugiau ri zi kos veiks niø ir di des næ gli ke mi jà at vy ki mo me tu [15]. Mû sø ty ri mo duo me ni mis, gli ke mi ja ne tu rë jo reikð - mës anks ty vam pa ge rë ji mui. Ta èiau E. T. As ke vold ty ri me ul tra gar si niu me to du bu vo ver ti na mas re ka na li za ci jos daþ - nis, o ne anks ty vas neu ro lo gi nës bûk lës pa ge rë ji mas, kaip mû sø dar be. Mû sø ty ri mas pa ro dë, kad VSA hi per den si nio sig na lo ne bu vi mas pra di në je gal vos sme ge nø KT yra la bai reikð - min gas anks ty vo pa ge rë ji mo prog nos ti nis veiks nys. Tai ati tin ka ki tø au to riø pa ste bë ji mus dël VSA hi per den si nio sig na lo reikð mës neu ro lo gi nës bûk lës di na mi kai ir ið ei tims po in sul to. Anks èiau at lik ti ty ri mai ro do, kad VSA hi per - den si nis sig na las ko re liuo ja su VSA ok liu zi ja [16] ir yra su si jæs su blo ges ne prog no ze [17]. Ki ta me ty ri me bu vo nu - sta ty tas tei gia mas ry ðys tarp VSA hi per den si nio sig na lo ne bu vi mo ir anks ty vo neu ro lo gi nio pa ge rë ji mo [18]. Pas ta ruo ju me tu in tra ve ni në trom bo li zë vis daþ niau tai ko ma li go niams, vy res niems nei 80 me tø am þiaus, nors tai prieðtarauja oficialioms gamintojo rekomendacijoms. Ty ri mai ro do, kad in tra ve ni nës trom bo li zës efek ty vu mas ið lie ka ir to kiems li go niams [19, 20]. Mû sø ty ri mas taip pat pa ro dë, kad am þius > 80 m. ne tu ri áta kos nei anks ty vam neu ro lo gi nës bûk lës pa ge rë ji mui, nei funk ci nei bûk lei ato - kiu pe ri odu po 3 mën. Toks pa ste bë ji mas ga li tu rë ti ke lis pa aið ki ni mus. Pir ma, mû sø ty ri me tik 11 li go niø bu vo vy - res ni nei 80 m. am þiaus ir tai ga li bû ti per ma þa im tis, lei - dþian ti da ry ti ið va das. An tra, ben dras li go niø skai èius yra per ma þas, kad bû tø ga li ma juos skirs ty ti á at ski ras am þiaus gru pes, to dël mû sø dar be á re gre si jos mo de lá am þius bu vo átrauktas tik kaip diskretusis kintamasis. Kaip jau minëta, ðan sø san ty kis yra ar ti mas vie ne tui, ir tai pa aið ki na, ko dël ne gau tas skir tu mas tarp li go niø iki ir dau giau kaip 80 me tø amþiaus. Mû sø ty ri mas tu ri tam tik rø trû ku mø. Sa vo dar be re ka - na li za ci jos ro dik liu nau do jo me neu ro lo gi nës bûk lës po ky - tá po 2 val. Nors anks tes niuo se ty ri muo se bu vo pa ro dy ta, kad anks ty va neu ro lo gi nës bûk lës di na mi ka ge rai ko re - liuoja su kitais metodais, taèiau juose buvo tiriama tik stambiø galvos smegenø arterijø rekanalizacija. Tikëtina, kad da liai mû sø ty ri mo li go niø, ypaè su ma þes niu pra di niu 220

5 Ankstyvo neurologinio pagerëjimo po intraveninës trombolizës, gydant ûminá iðeminá insultà, klinikinë reikðmë ir prognostiniai veiksniai neu ro lo gi niu de fi ci tu, in sul tas ávy ko dël smul kes niø ar te ri - jø ok liu zi jos. To kio je li go niø gru pë je anks ty vo neu ro lo gi - nës bûklës pagerëjimo ir rekanalizacijos ryðiai iki ðiol ne - buvo vertinti. Todël ateityje reikëtø atlikti papildomà tyrimà, á at ski rus po gru pius ið ski riant li go nius su di de liu ir ma - þu pra di niu neu ro lo gi niu de fi ci tu. Be to, mû sø ty ri me ne - bu vo at ski rai ana li zuo ja mi po gru piai su skir tin gu lai ku nuo simp to mø at si ra di mo pra dþios iki trom bo li zës pra dþios, kas taip pat galëtø turëti átakos rekanalizacijos daþniui ir neu ro lo gi nës bûk lës ki ti mui. Api ben dri nant, mû sø ty ri mo duo me nys ro do, kad anks ty vas neu ro lo gi nës bûk lës pa ge rë ji mas lei dþia nu ma - ty ti pa lan kià funk ci næ ið ei tá. Li go niams, ku riems ran da mas VSA hi per den si nis sig na las pra di në je gal vos sme ge nø KT, ir gal bût vy res nio am þiaus li go niams ga li bû ti tiks lin gi pa - pil do mi ty ri mai gal vos sme ge nø ir gal vos sme ge nø krau ja - gys liø bûk lei áver tin ti (gal vos sme ge nø KT an giog ra fi ja, perfuzija), atliekami nelaukiant intraveninës trombolizës pa bai gos. Ti kë ti na, kad to kiems li go niams ga li bû ti re ko - men duo ja mas pa pil do mas in ter ven ci nis gy dy mas, ta èiau tam reikalingi tolimesni iðsamûs tyrimai. Gauta: Priimta spaudai: Literatûra 1. The Na tional In sti tute of Neu ro log i cal Dis or ders and Stroke rt-pa Stroke Study Group: tis sue plasminogen ac ti va tor for acute ischaemic stroke. N Engl J Med 1995; 333: Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al; ECASS In ves ti ga tors. Thrombolysis with alteplase 3 to 4.5 hours af ter acute ischemic stroke. N Engl J Med 2008; 359: Labiche LA, Al-Senani F, Woiner AW, Grotta JC, Malkoff M, Alexandrov AV. Is the ben e fit of early recanali - zation sus tained at 3 months? A pro spec tive co hort study. Stroke 2003; 34: Rha JH, Saver JL. The im pact of recanalization on ischemic stroke out come: a meta-anal y sis. Stroke 2007; 38: Wolpert S, Bruckmann H, Greenlee R, Wechs ler L, Pessin M, del Zoppo G. Neuroradiologic eval u a tion of pa - tients with acute stroke treated with re com bi nant tis sue plasminogen ac ti va tor. The rt-pa Acute Stroke Study Group. AJNR Am J Neuroradiol 1993; 14: Lee KY, Han SW, Kim SH, Nam HS, Ahn SW, Kim DJ, et al. Early recanalization af ter in tra ve nous ad min is tra tion of re - com bi nant tis sue plasminogen ac ti va tor as as sessed by preand post-throm bo lytic angiography in acute ischemic stroke pa tients. Stroke 2007; 38: Kharitonova T, Mikulik R, Roine OR, Soinne L, Ahmed N, Wahlgren N; for the Safe Im ple men ta tion of Thrombolysis in Stroke (SITS) In ves ti ga tors. As so ci a tion of early National In sti tutes of Health Stroke Scale im prove ment with ves sel recan a li za tion and func tional out come af ter in tra ve nous thrombolysis in ischemic stroke. Stroke 2011; 42: Galvos smegenø insulto diagnostikos, gydymo, profilaktikos ir reabilitacijos metodika. Neurologijos seminarai 2012; 16: Hemmmen TM, Ernston K, Raman R. Two-hour im prove - ment of pa tients in the na tional In sti tute of Neu ro log i cal Dis - or ders and Stroke tri als and pre dic tion of fi nal out come. Stroke 2011; 42: Muresan IP, Favrole P, Levy P, Andreux F, Marro B, Alamowitch S. Very early neu ro logic im prove ment af ter in - tra ve nous thrombolysis. Arch Neurol 2010; 67: Saposnik G, Young B, Sil ver B, Legge SD, Web ster F, Beletsky V, et al. Lack of im prove ment in pa tients with acute stroke af ter treat ment with throm bo lytic ther apy pre dic tors and as so ci a tion with out come. JAMA 2004; 292: Mikulik R, Ribo M, Hill MD, Grota JC, Malkoff M, Molina C, et al. Ac cu racy of se rial Na tional Health In sti tute Stroke Scale scores to indentify ar tery sta tus in acute ischemic stroke. Cir cu la tion 2007; 115: Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treat ment with in tra ve nous alteplase and out come in stroke: an up dated pooled anal y sis of ECASS, ATLANTIS, NINDS, and EP I THET tri als. Lan cet 2010; 375: Cho KH, Lee H, Kwon SU, Choi CG, Kim SJ, Suh DC, et al. Fac tors and out comes as so ci ated with recanalization tim ing af ter thrombolysis. Cerebrovasc Dis 2012; 33: Askevold ET, Naess H, Thomassen L. Pre dic tors for recana - lization af ter in tra ve nous thrombolysis in acute ischemic stroke. J Stroke Cerebrovasc Dis 2007; 16: Marsman JWP, Feenstra-Holtkamp M. Dense mid dle ce re - bral artery computed tomography sign: confirmation by mag - netic res o nance (MR) im ag ing and MR angiography. Australasian Radiol 1996; 40: Manelfe C, Larrue V, von Kummer R, Bozzao L, Ringleb P, Basitanello S, et al. As so ci a tion of hyperdense mid dle ce re - bral ar tery sign with clin i cal out come in pa tients with tis sue plasminogen ac ti va tor. Stroke 1999; 30: Agarwal P, Kumar S, Hariharan S, Eshkar N, Verro P, Cohen B, et al. Hyperdense mid dle ce re bral ar tery sign: can it be used to select intra-arterial versus intravenous throm - bolysis in acute ischemic stroke? Cerebrovasc Dis 2004; 17: Ford GA, Ahmed N, Azevebo E, Grond M, Lamue V, Lindsberg P, et al. In tra ve nous alteplase for stroke in those older than 80 years old. Stroke 2010; 41: Mishra N, Ahmed N, Andersen G, Egdo JA, Lindsberg PJ, Ringleb PA, et al for the VISTA and SITS col lab o ra tors. Thrombolysis in very el derly peo ple: con trolled com par i son of SITS In ter na tional Stroke Thrombolysis Reg is try and Vir - tual In ter na tional Stroke Tri als Ar chive. BMJ 2010; 341: c6046. A. Vilionskis, O. Knoknerienë, M. Ðeðeikaitë, D. Jatuþis, V. Budrys CLINICAL RELEVANCE AND PREDICTORS OF EARLY SIGNIFICANT NEUROLOGICAL IMPROVEMENT AFTER INTRAVENOUS THROMBOLYSIS FOR ACUTE ISCHEMIC STROKE Summary Background and objective. In tra ve nous thrombolysis is first line treat ment for acute stroke pa tients, how ever, it s po ten tial for recanalization is not high. Interventional pro ce dures of fer ing better chances for open ing of oc cluded ce re bral ar tery be come more pop u lar within the last years and could be rec om mended for acute stroke pa tients who re spond poorly to in tra ve nous thrombolysis. It is im por tant to es ti mate the out come and its pre - 221

6 A. Vilionskis, O. Knoknerienë, M. Ðeðeikaitë, D. Jatuþis, V. Budrys dic tors be fore in tra ve nous thrombolysis started. The objective of our study was to es ti mate the rel e vance of sig nif i cant early neu ro - log i cal im prove ment for out come and to iden tify the pre dic tors of early im prove ment. Meth ods, ma te ri als. Patients with acute ischemic stroke and treated with in tra ve nous thrombolysis were in cluded in the pro - spec tive study. De mo graphic and clin i cal char ac ter is tics were an a lyzed. Sig nif i cant early neu ro log i cal im prove ment was de - fined as de crease of neu ro log i cal def i cit 4 and more points or 0 1 score on NIHSS af ter 2 hours af ter in tra ve nous thrombolysis. The ex cel lent out come was de fined as 0 1 score on mrs af ter 3 months from stroke on set. Results. 136 pa tients were in cluded in this study. 70 pa tients (51.5%) had significant early neurological improvement, and 49 pa tients (36.0%) had ex cel lent out come af ter 3 months. The mod er ate cor re la tion (r=0.445, p<0.001) was found be tween early significant neurological improvement and outcome after 3 months. The independent predictors of significant early neurological im - prove ment were youn ger age (odds ra tio (OR) 0.956, 95% CI , p=0.03) and ab sence of MCA hyperdense sign on ini tial brain CT (OR 0.238, 95% CI , p=0.004). Conclusions. Early im prove ment of neu ro log i cal def i cit is of ten as so ci ated with fa vour able out come of stroke, treated with thrombolysis. MCA hyperdense sign on ini tial CT and older age are poor prognostic factors of early neurological improvement and func tional out come. Keywords: in tra ve nous thrombolysis, acute ischemic stroke, early significant neurological improvement, predictors. 222

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