Ersifa Fatimah, dr.

| Neurologi | 2013

Hemorrhagic Conversion
Anatomy of the Brain Blood Vessels of the Brain Atherosclerosis and Thrombus Formation Cerebral Embolism Formation o o o Formation Cardiac Sources Hemorrhagic Conversion

Cellular Injury During Ischemia Additional Resources

In this exam le there is a gross arenchymatous hematoma !ith intra"entricular extension# midline shift# and herniation$

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Ischemic infarction can be di"ided into 'bland( infarction associated !ith secondary bleeding)referred to as hemorrhagic con"ersion or transformation *+T,)in ischemically infarcted areas -.ohr /0 and Sacco R1# 23345 Teal 0A and 0essin .S# 23345 0essin .S# In6 +ac%e et al *eds,# 23327$ Bland infarction is characteri8ed by bland !ides read leu%ocyte infiltration and macro hage in"asion# !ith only scattered red cells being found$ +emorrhagic con"ersion may ta%e the form of infarction *+I, or# less commonly# arenchymatous infarction *0+,$ The occurrence of hemorrhagic con"ersion is ' redominantly a natural tissue conse9uence of embolism( -Teal 0A and 0essin .S# 23347$ At auto sy# +I may "ary from atchy etechial bleeding to more confluent hemorrhages# re resenting multifocal extra"asation of blood from ca illaries or "enules -Teal 0A and 0essin .S# 23347$ +I and 0+ ha"e different incidences# athogenesis# and clinical outcome# but distinguishing +I and 0+ on CT may be difficult -Teal 0A and 0essin .S# 23347$ Although +I and 0+ ha"e often been grou ed together# there are certain features on CT that hel characteri8e these t!o ty es of hemorrhagic transformation$ :n CT# +I a ears as a discontinuous heterogeneous mixture of high and lo! densities occurring !ithin the "ascular territory of the infarct$ In contrast# 0+ a ears as a discrete# homogeneous collection of blood that often exerts mass effect and may extend beyond the original infarct boundaries or e"en into the "entricles$

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+I occurs regularly in the natural e"olution of acute embolic stro%e -0essin .S# In6 +ac%e et al *eds,# 23327$ In auto sy studies# the occurrence of +I has ranged from ;2< to =2< of recent embolic stro%es -Teal 0A and 0essin .S# 23347$ +o!e"er# CT studies ha"e

Ersifa Fatimah, dr. | Neurologi | 2013

sho!n a lo!er incidence# !ith studies of con>coagulated atients !ho ha"e redominantly embolic infarcts indicating an o"erall incidence of 4?< to @A<$ According to another estimate# a roximately 4B< of atients !ith cardioembolic stro%e ha"e hemorrhagic transformation in the infarcted 8one# usually occurring !ithin @C hours -1eonard AD# De!burg S$ / Deurosci Durs$ 233454@6?37$ Transformation of a bland embolic infarct to +T is rare in the first ? hours$ .ost +Is are asym tomatic# and it is not uncommon to detect +I on CT atients !ho are stable or im ro"ing$ The athogenesis of +T a ears to relate to re erfusion of bleeding from recanali8ed but ischemically injured "essels by the natural# dynamic dissolution of thrombi -Teal 0A and 0essin .S# 23347)i$e$# an embolus that re resents all or art of a thrombus has a s ontaneous tendency to lyse and dis erse$ Re erfusion into the ischemically injured "essels can therefore result in "arying degrees of blood extra"asation through the damaged blood>brain barrier$ As noted by .ohr and Sacco *2334,# +I has been often ex lained as a result of re erfusion of the "ascular bed of the infarct# such as !ould occur after fragmentation and distal migration of an embolus or after early reo ening of a large "essel occlusion in the setting of a large infarction5 the full ressure of arterial blood into hy oxic ca illaries results in a dia edesis or red cells through their hy oxic !alls$ The conce t of restored lumen atency is consistent !ith greater fre9uency of hemorrhagic infarction in atients !ith cardioembolic infarcts$ The occurrence of 0+ in areas of ischemic infarction is less common that that of +I -Teal 0A and 0essin .S# 23347$ 0+ a ears to be associated !ith anticoagulation thera y# !ith a lo! incidence of s ontaneous 0+ in areas of ischemic infarction *on the order of 4< to 3<, in atients no recei"ing anticoagulation thera y$ In contrast to +I# clinical deterioration is often associated !ith 0+$ It has been ro osed that the athogenesis of 0+ may in"ol"e 'ischemic necrosis resulting in the ru ture of small enetrating "essels analogous to hy ertensi"e hemorrhage# leading to massi"e bleeding rather that the multifocal dia edesis of blood through ca illary !alls# as seen in +I( -Teal 0A and 0essin .S# 23347$

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The obser"ation that some hemorrhagic infarctions de"elo distal to the site of a ersisting occlusion suggests that re erfusion is not al!ays a necessary condition$ In"estigators from /a an examined the brains of 2@ atients !ho died from herniation of the brain after cardioembolic stro%e !ith ersistent occlusion of the internal carotid>middle arterial axis -:gata /# et al$ Stro%e$ 23C354B6C=?>CA7$ The finding of hemorrhagic infarct in = of the atients contradicts the conce t that reo ening a re"iously occluded "essel is the only atho hysiologic mechanism for the de"elo ment of hemorrhagic infarct$ Analysis of blood ressure after stro%e has re"ealed on or more surges of arterial hy ertension or ra id rise of blood ressure in atients !ith hemorrhagic stro%e !ithout a reo ening of the occluded artery5 it has been s eculated that these blood ressure rises might ex lain hemorrhagic infarction in many cases$ A relationshi bet!een hy erglycemia and hemorrhagic transformation has also been suggested by the obser"ation that occluding the middle cerebral artery of mar%edly hy erglycemic cats !as associated !ith ;>fold more fre9uent and 4;>fold more extensi"e hemorrhage into infarcts than in normoglycemic animals -de Courten>.yers E.# et al$ 23347$ Com ared !ith ermanent occlusion# tem orary restoration of blood flo! after @ hours caused the most extensi"e hemorrhage into infarcts$ It !as concluded that hy erglycemia and restoration of blood flo! to ischemic territories !ere strong ris% factors for hemorrhagic infarct con"ersion$ The e"idence suggests that the mar%ed tissue energy de letion accom anied by acidosis damages brain "essels# causing lea%age of edema fluid and red blood cells -de Courten>.yers E.# et al# 23347$ Diffuse +I associated !ith mar%ed hy erglycemia has been re orted in t!o atients -Broderic% /0# et al# 233;7$

Ersifa Fatimah, dr. | Neurologi | 2013

In summary# +I occurs regularly in the natural e"olution of acute embolic stro%e and is usually asym tomatic -0essin .S# In6 +ac%e et al *eds,# 23327$ 0+s occur less fre9uently# but are often sym tomatic due to extension and mass effect beyond the original infarct territory$ Interest in these issues has been further generated by trials of thrombolytic thera y for acute ischemic stro%e$

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Hemorrhagic transformation of ischemic stroke
Etiology
Article section 5 of 16. Previous Next
By Nivedita U Jerath M a!d "ha!da! #eddy M

$emorrhage after a! is%hemi% i!sult is thought to &e multifa%torial, i!volvi!g o'idative stress, leu(o%yte i!filtratio!, vas%ular a%tivatio!, a!d dysregulated e'tra%ellular )roteolysis *+a!g a!d ,o 2003-. $emorrhage i! a! area of is%hemi% i!far%tio! o%%urs .he! &lood e'travasates through vessel .alls damaged &y is%hemia. /he o%%urre!%e of &leedi!g, therefore, re0uires a! is%hemi% i!sult of suffi%ie!t severity a!d duratio! to alter vessel .all )ermea&ility a!d i!tegrity, )lus the restoratio! of ade0uate re)erfusio!, dire%t or %ollateral, to the site of i!1ury *$ai! et al 12324 ,yde! a!d 5ivi! 12234 $ama!! et al 1222-. 6e%o!dary &leedi!g may o%%ur .ith most stro(e me%ha!isms, &ut several studies have demo!strated the s)e%ial )redile%tio! of em&oli% i!far%tio! to u!dergo hemorrhagi% tra!sformatio! *Fisher a!d 7dams 12314 8amagu%hi et al 129:4 $or!ig et al 129;4 Bo<<ao et al 1221-. 6ystemi% i!flammatio! %a! also i!%rease the ris( of hemorrhagi% tra!sformatio! .ith a 3=fold i!%rease i! MM>=2, .hi%h is i!volved i! disru)ti!g the %ere&rovas%ular tight 1u!%tio!4 i!hi&itio! of MM>=2 i! mi%e has resulted i! a redu%ed i!%ide!%e of hemorrhagi% tra!sformatio! *M%"oll et al 2009-. Pathogenesis and pathophysiology
Article section 6 of 16. Previous Next
By Nivedita U Jerath M a!d "ha!da! #eddy M

Fisher a!d 7dams )ro)osed the theory of ?migratory em&olism,? .ith se%o!dary re)erfusio! &leedi!g from is%hemi%ally i!1ured %a)illaries as the )atho)hysiologi% &asis res)o!si&le for the evolutio! of hemorrhagi% i!far%tio! *Fisher a!d 7dams 1231-. /his %o!%e)t, derived from their )athologi%al o&servatio!s, )ro)oses that a! em&oli% o%%lusio! results i! a distal is%hemi% i!1ury that is i!itially )ale. /he em&oli% material is su&1e%t to fragme!tatio!, dissolutio!, or lysis leadi!g to distal migratio! a!d re)erfusio! of the is%hemi% tissue &ed. $emorrhage is the result of e'travasatio! a!d dia)edesis of &lood through is%hemi%ally damaged vessels. More re%e!tly, loss of %ere&ral mi%rovas%ular i!tegrity se%o!dary to )lasmi!=ge!erated lami!i! degradatio!, matri' metallo)rotease a%tivatio!, vas%ular adhesio! )rotei!=1 a%tivity *$er!a!de<=@uillamo! et al 2010-, high serum ferriti! level *"hoi et al 2012-, a!d tra!smigratio! of i!flammatory leu(o%ytes through the vessel .all have also &ee! im)li%ated *$ama!! et al 1222-. /he duratio! a!d the severity of is%hemia are im)orta!t determi!a!ts of hemorrhagi% tra!sformatio!. 7!giogra)hi% studies sho. that )artial or %om)lete s)o!ta!eous re%a!ali<atio! o%%urs i! u) to 20A of em&oli% o%%lusio!s *8amagu%hi et al 129:-. /he hy)othesis that early re%a!ali<atio! may &e )rote%tive agai!st re)erfusio! &leedi!g remai!s u!)rove! *,yde! a!d 5ivi! 1223-. ,oh a!d %olleagues fou!d that amo!g )atie!ts .ith M#B )atter! of adva!%ed &asal ga!glio!i% i!1ury, su%%essful re%a!ali<atio! )redi%ts a higher ris( of hemorrhagi% tra!sformatio! &ut &etter out%ome *,oh et al 2010-. 7lso, re)erfusio! after stro(e so!othrom&olysis .ith mi%ro&u&&les may )redi%t i!tra%ere&ral &leedi!g &ut does !ot seem to i!%rease the ris( of sym)tomati% i!tra%ra!ial hemorrhage * i!ia et al 2002-. E')erie!%e to date sho.s that the i!%ide!%e of se%o!dary &leedi!g is a%%e)ta&ly lo. if throm&olysis is give! .ithi! 190 mi!utes of stro(e o!set, .hereas the fre0ue!%y of &leedi!g %om)li%atio!s i!%reases .he! treatme!t is delayed *Brott et al 12224 del 5o))o et al 12224 $a%(e et al 12234 12294 NBN 6 rt=>7 6tro(e 6tudy @rou) 12234 "lar( et al 2000-. Usi!g tra!s%ra!ial o))ler, Moli!a demo!strated that delayed *lo!ger tha! ; hours- s)o!ta!eous

Ersifa Fatimah, dr. | Neurologi | 2013

arterial re%a!ali<atio! follo.i!g %ardioem&oli% stro(e .as a! i!de)e!de!t )redi%tor of hemorrhagi% tra!sformatio! *odds ratio 9.2, 23A %o!fide!%e i!terval 2.1 to 33.3- *Moli!a et al 2001-. /he severity of is%hemia is determi!ed &y the amou!t of residual %ere&ral &lood flo. .ithi! the territory of the o%%luded vessel. /he )rese!%e of hy)ode!se %ha!ges o! "/ s%a!s )erformed .ithi! 3 hours of sym)tom o!set, )resuma&ly refle%ti!g severe is%hemia, is a )redi%tor of hemorrhagi% tra!sformatio! */o!i et al 122;4 Moli!a et al 2001-. B! a %a!i!e stro(e model, a redu%tio! of the %ere&ral &lood flo. to less tha! 30A .as %riti%al for the develo)me!t of hemorrhagi% i!far%tio! *6e(i et al 1293-. 6>E"/ has &ee! utili<ed to evaluate )retreatme!t %ere&ral &lood flo. i! )atie!ts u!dergoi!g su)ersele%tive i!traarterial throm&olyti% thera)y *Ueda et al 122:-. "ere&ral &lood flo. values .ere sig!ifi%a!tly lo.er i! the 3 )atie!ts .ho develo)ed hemorrhagi% i!far%tio! %om)ared to 13 )atie!ts .ho did !ot develo) hemorrhage. $emorrhagi% i!far%tio! may also o%%ur i! throm&oti% stro(es a!d other !o!em&oli% stro(e me%ha!isms &ut is u!%ommo! %om)ared to em&oli% i!far%tio! *8amagu%hi et al 129:-. $emorrhage tra!sformatio! has &ee! re%orded follo.i!g early %arotid e!dartere%tomy for re%e!t stro(es. $emorrhage is also %ommo!ly !oted i! )osterior %ere&ral artery territory i!far%tio! asso%iated .ith her!iatio! of the tem)oral lo&e, .hi%h %om)resses the artery )erha)s i!%om)letely or i!termitte!tly agai!st the te!torial edge. B!far%tio! due to vasos)asm may &e%ome hemorrhagi%. /erada re)orted hemorrhagi% tra!sformatio! i! 33A *13 of 3C- of i!far%ts due to vasos)asm i!du%ed &y a!eurysmal su&ara%h!oid &leedi!g */erada et al 129;-. >resuma&ly, the %ommo! theme of vessel o%%lusio! leadi!g to %a)illary is%hemia a!d altered )ermea&ility follo.ed &y re)erfusio! a!d su&se0ue!t &leedi!g is o)erative i! ma!y of these e'am)les. $emorrhagi% tra!sformatio! %a! o%%ur distal to )ersisti!g arterial o%%lusio! due to &lood flo. )rovided &y %ollateral %ha!!els, although the fre0ue!%y of hemorrhages se%o!dary to this me%ha!ism remai!s u!%ertai! *$or!ig et al 129;4 Dgata et al 12924 Bogousslavs(y et al 1221-. Ba!g a!d asso%iates fou!d that a!giogra)hi% grade of %ollateral flo. stro!gly i!flue!%es the rate of hemorrhagi% tra!sformatio! after thera)euti% re%a!ali<atio! for a%ute is%hemi% stro(e *Ba!g et al 2011-. Dgata a!d %olleagues re)orted %li!i%al a!d auto)sy data o! C )atie!ts .ith hemorrhagi% tra!sformatio! distal to )ersiste!t em&oli% o%%lusio! *Dgata et al 1292-. /he authors )ro)osed that tra!sie!t surges of arterial )ressure a!d the )rese!%e of effi%ie!t &lood flo. through le)tome!i!geal %ollateral vessels may lead to re)erfusio! &leedi!g. >ersisti!g arterial o%%lusio! .as dete%ted i! : of 10 %ases of )athologi%ally verified hemorrhagi% i!far%tio! re)orted &y 8amagu%hi a!d %olleagues *8amagu%hi et al 129:-. Evide!%e from several a!imal stro(e models )rovides e')erime!tal su))ort for the role of %ollateral %ir%ulatio! i! the ge!esis of se%o!dary &leedi!g *$ai! et al 12324 Faris et al 12;34 ,yde! a!d 5ivi! 1223-. /he late develo)me!t of hemorrhagi% tra!sformatio!, o%%urri!g after the first .ee(, may &e due to the develo)me!t of %ollateral %ir%ulatio! a!d the re)erfusio! of i!1ured %a)illaries that reo)e! as i!far%t edema su&sides *Faris et al 12;34 $art a!d Easto! 129;4 $or!ig et al 129;4 Bo<<ao et al 1221-. 7%ute is%hemi% stro(e treatme!t i!volves throm&olysis, .hi%h i!%reases the ris( of hemorrhage &y u) to 10 times .he! %om)ared to %o!trols *$ama!! et al 1222-. "ere&ral is%hemia %a! result i! a loss of &asal lami!a of %ere&ral mi%rovas%ulature through me%ha!isms su%h as )lasmi!=ge!erated lami!i! degradatio!, a%tivatio! of matri' metallo)rotei!ases, or tra!smigratio! of leu(o%ytes through vessel .alls *$ama!! et al 1222-. t>7 %a! %ause hemorrhagi% tra!sformatio! i! is%hemi% stro(e through various me%ha!isms that have &ee! )ro)osed. Bt has !euroto'i% side effe%ts4 it lyses %lots, is a! e'tra%ellular )rotease, a!d may i!%rease e'%itoto'i% %al%ium %urre!ts &y &ei!g a! NM 7 ty)e glutamate re%e)tor *+a!g et al 200:-. +a!g a!d %olleagues me!tio! ho. t>7 may degrade e'tra%ellular matri' i!tegrity &y i!%reasi!g matri' metallo)rotei!ase dysregulatio!4 this %a! i!%rease the ris( of hemorrhage *+a!g et al 200:-. /he )athoge!esis of )are!%hymal hematoma follo.i!g is%hemi% i!1ury has !ot &ee! thoroughly studied. $art a!d Easto! )ro)osed that o!ly 0ua!titative differe!%es e'ist &et.ee! )are!%hymal hematomas a!d hemorrhagi% i!far%tio! *$art a!d Easto! 129;-. B! some i!sta!%es, ho.ever, )are!%hymal hematomas must result from the ru)ture of small )e!etrati!g arterioles a!alogous to me%ha!isms of hy)erte!sive hemorrhages or the ru)ture of larger arteries rather tha! &y e'travasatio! of &lood through disru)ted %a)illary e!dothelial 1u!%tio!s.

Ersifa Fatimah, dr. | Neurologi | 2013

Epidemiology
Article section 7 of 16. Previous Next
By Nivedita U Jerath M a!d "ha!da! #eddy M

$emorrhagi% tra!sformatio! is a %ommo! a!d !atural %o!se0ue!%e of em&oli% i!far%tio!. /he true i!%ide!%e of hemorrhagi% tra!sformatio! remai!s u!%ertai!, a!d re)orted fre0ue!%ies vary de)e!di!g o! the methodology used a!d the u!derlyi!g )athoge!esis of the is%hemi% i!sult *Mouli! et al 122:-. 7uto)sy series have re)orted se%o!dary &leedi!g i! 31A to C1A of re%e!t em&oli% i!far%tio!s as %om)ared to a 2A to 21A i!%ide!%e i! !o!em&oli% stro(es *Fisher a!d 7dams 12314 ,odder a!d va! der ,ugt 1293-. /he high i!%ide!%e of hemorrhagi% tra!sformatio! re)orted i! these studies refle%ts, i! )art, the as%ertai!me!t &ias to.ard large i!far%t si<e a!d &rai! her!iatio! i! auto)sy series. "/ studies have re)orted hemorrhagi% i!far%tio! i! 2;A to :3A of !o!a!ti%oagulated )atie!ts .ith )redomi!a!tly em&oli% i!far%ts *+eis&erg 12934 $or!ig et al 129;4 D(ada et al 1292-. $emorrhagi% i!far%tio! .as dete%ted i! 29 *:3A- of ;3 )atie!ts .ith )redomi!a!tly %ardioem&oli% stro(e studied )ros)e%tively .ith serial "/s over : .ee(s *$or!ig et al 129;-. B! most "/ series i!volvi!g %o!se%utive !o!a!ti%oagulated )atie!ts .ith i!far%ts of all ty)es, the overall i!%ide!%e refle%ts the i!%lusio! of all stro(e ty)es i!%ludi!g small vessel i!far%ts as .ell as a !o!serial !euroimagi!g methodology. 6)o!ta!eous hemorrhagi% tra!sformatio! rates .ere fou!d to &e 39A to C1A i! auto)sy studies a!d 13A to :3A i! "/ studies *Jaillard 1222-. /hrom&olysis i!%reases ris( of hemorrhagi% stro(e &y a&out CA as %om)ared to grou)s that did !ot re%eive throm&olysis *Jaillard 1222- *6ee also /a&le 2-. M#B is highly se!sitive for the dete%tio! of &lood degradatio! )rodu%ts. $emorrhagi% tra!sformatio! .as re)orted i! 2: *;9.;A- of 33 %o!se%utive %ardioem&oli% stro(es studied &y M#B at 3 .ee(s after the eve!t, a )er%e!tage %om)ara&le to auto)sy data *$or!ig et al 1223-. /he !atural i!%ide!%e of )are!%hymal hematoma i! !o!a!ti%oagulated )atie!ts has !ot &ee! %learly esta&lished. "/ studies have re)orted a 2.0A to 9.;A i!%ide!%e of )are!%hymal hematoma i! !o!a!ti%oagulated )atie!ts .ith a%ute em&oli% stro(e *Fisher et al 129:-. /he i!%ide!%e of hemorrhagi% stro(e i! u!treated )atie!ts i! the B!ter!atio!al 6tro(e /rial .as o!ly 0.:A4 ho.ever, serial "/s .ere !ot routi!ely o&tai!ed *B!ter!atio!al 6tro(e /rial "olla&orative @rou) 122C-. /he i!%ide!%e of s)o!ta!eous )are!%hymal hematoma or se%o!dary &leedi!g severe e!ough to &e sym)tomati% i! %o!trol or )la%e&o=treated )atie!ts i! throm&olyti% trials ra!ged from 0.;A to ;.3A */a&le 1-. 7lthough the i!%lusio! a!d e'%lusio! %riteria for these trials are rigid a!d, therefore, do !ot re)rese!t %o!se%utive )atie!ts, the defi!itio!s for hemorrhagi% tra!sformatio! .ere %learly stated a!d %arefully loo(ed for &y )roto%ol. $emorrhagi% tra!sformatio! o%%urred i! 30A of %hildre! .ith arterial is%hemi% stro(e .ithi! 30 days. Most hemorrhages .ere )ete%hial a!d asym)tomati% *Beslo. et al 2011-. Prevention and risk factors
Article section 8 of 16. Previous Next
By Nivedita U Jerath M a!d "ha!da! #eddy M

#elia&le %li!i%al a!d radiologi% )redi%tors are !eeded to ide!tify those )atie!ts at highest ris( for hemorrhagi% tra!sformatio! i! order to guide the safe use of a!ti%oagula!ts or throm&olyti% thera)y. "ardioem&oli% stro(e me%ha!isms, large i!far%ts, o%%lusio! of the middle %ere&ral artery stem, a&se!%e of %ollateral flo., hy)ergly%emia, a!d dete%tio! of early hy)ode!se %ha!ges o! "/ may hel) )redi%t hemorrhagi% tra!sformatio! *Broderi%( et al 12234 $a%(e 12234 7le'a!drov et al 122C4 @orter et al 122C4 Moli!a et al 2001-.

Ersifa Fatimah, dr. | Neurologi | 2013

7 !euro)athologi% la& study evaluated 2:3 auto)sies a!d fou!d that age older tha! C3 years is a ris( for hemorrhagi% tra!sformatio! i! em&oli% i!far%ts. Bt also fou!d that dia&etes mellitus *&ut !ot serum glu%ose levels-, alo!g .ith i!far%t si<e greater tha! 10 %m3 are i!de)e!de!t )redi%tors of hemorrhagi% tra!sformatio! of is%hemi% stro(e *Eere!yi et al 200;-. Em&oli% stro(es, )arti%ularly those due to %ardioge!i% em&olism, are )arti%ularly )ro!e to u!dergoi!g hemorrhagi% tra!sformatio! *Fisher a!d 7dams 12314 $art a!d Easto! 129;4 7le'a!drov et al 122C-. ,arge i!far%t si<e, the )rese!%e of mass effe%t, %ere&ral edema, a!d &rai! her!iatio! all sig!ifi%a!tly i!%rease the ris( of se%o!dary &leedi!g *"ere&ral Em&olism 6tudy @rou) 129:4 $or!ig et al 129;4 Dtt et al 129;4 ,aure!o et al 129C4 "hamorro et al 1223-. #e)orts %o!fli%t o! the %o!tri&utio! of hy)erte!sio!, adva!%ed age, a!d dia&etes or hy)ergly%emia i! )romoti!g hemorrhagi% tra!sformatio! *Faris et al 12;34 "ere&ral Em&olism 6tudy @rou) 12934 Broderi%( et al 12234 Bru!o et al 1222-. /he dete%tio! of early hy)ode!se %ha!ges o! "/ )erformed .ithi! hours of stro(e o!set may )redi%t su&se0ue!t &leedi!g *8amagu%hi et al 129:4 Bo<<ao et al 12214 /o!i et al 122;-. ,o.er a))are!t diffusio! %oeffi%ie!t values a!d )ersiste!t )erfusio! defi%its demo!strated o! diffusio!F)erfusio!=.eighted M#B imagi!g have &ee! li!(ed to i!%reased ris( for hemorrhagi% tra!sformatio! */o!g et al 2001-. #egio!al very lo. %ere&ral &lood volume )redi%ts hemorrhagi% tra!sformatio! after throm&olysis &etter tha! diffusio!=.eighted imagi!g volume a!d thresholded a))are!t diffusio! %oeffi%ie!t *"am)&ell et al 20104 Eim et al 2010-. 7lso, &lood=&rai! &arrier )ermea&ility assessed &y )erfusio! "/ s%a! )redi%ts sym)tomati% hemorrhagi% tra!sformatio! *$om et al 20114 ,ee et al 2012-. /he early use of a!ti%oagula!ts has &ee! asso%iated .ith hemorrhagi% tra!sformatio! *"ere&ral Em&olism 6tudy @rou) 129C4 Ba&i(ia! et al 12924 B!ter!atio!al 6tro(e /rial "olla&orative @rou) 122C-. B! %o!trast, several re)orts have !ot demo!strated %li!i%al .orse!i!g asso%iated .ith early a!ti%oagulatio!, a!d .ides)read %li!i%al usage )ersists. >ro)osed treatme!t guideli!es for em&oli% stro(e ra!ge from immediate a!ti%oagulatio! to a delay of 2 or more .ee(s for large i!far%ts *"ere&ral Em&olism 6tudy @rou) 129:4 129C4 "ere&ral Em&olism /as( For%e 1292-. /hese re%omme!datio!s are largely em)iri%al, a!d a!ti%oagulatio! is ge!erally delayed or avoided i! )atie!ts .ith severe !eurologi% defi%its, im)aired level of %o!s%ious!ess, large i!far%ts .ith mass effe%t o! "/, or u!%o!trolled severe hy)erte!sio! */eal a!d >essi! 1222-. 7 study of 1C1 )atie!ts a!ti%oagulated follo.i!g a%ute stro(e, i!%ludi!g 93 )atie!ts .ith em&oli% hemis)heri% i!far%tio! treated .ithi! C2 hours after sym)tom o!set, fou!d that e'%essive )rolo!gatio! of the a%tivated )artial throm&o)lasti! time *greater tha! 2 times %o!trol- .as the o!ly sig!ifi%a!t fa%tor asso%iated .ith hemorrhagi% .orse!i!g *"hamorro et al 1223-. /he )rese!%e of large i!far%ts, severe %li!i%al defi%its, a!d age, although related to the fre0ue!%y of hemorrhagi% %o!versio!s, did !ot )redi%t a higher ris( of sym)tomati% &leedi!g. >atie!ts .ith small or moderate %ardioem&oli% i!far%ts .ho are at high ris( for re%urre!%e may &e safely a!ti%oagulated early or immediately if !o hemorrhage is )rese!t o! the i!itial "/ *"ere&ral Em&olism 6tudy @rou) 12934 "ere&ral Em&olism /as( For%e 1292-. >redi%tors of hemorrhagi% tra!sformatio! asso%iated .ith throm&olyti% thera)y have also &ee! ide!tified. /he Natio!al B!stitute of Neurologi%al iseases a!d 6tro(e /rial re)orted a! i!%reased ris( of hemorrhage asso%iated .ith the )rese!%e of a severe i!itial !eurologi% defi%it or the )rese!%e of mass effe%t o! the i!itial "/ s%a! *NBN 6 rt=>7 6tro(e 6tudy @rou) 12234 122C-. 7!other study also i!di%ated that elevated &aseli!e serum glu%ose greater tha! 300 mgFd, .as a! i!de)e!de!t )redi%tor of hemorrhagi% tra!sformatio! i! t>7=treated )atie!ts * em%hu( et al 1222-. 7! a!alysis of the Euro)ea! "oo)erative 7%ute 6tro(e 6tudy data also sho.ed a! asso%iatio! &et.ee! severity of i!itial !eurologi% defi%it a!d the )rese!%e of early is%hemi% %ha!ges o! "/ .ith su&se0ue!t hemorrhagi% i!far%tio! *,arrue et al 122C-. Furthermore, &lood )ressure varia&ility .ithi! the first 2: hours of a! a%ute stro(e %a! lead to i!%reased ris( of hemorrhagi% tra!sformatio! *8o!g a!d Easte 2009-. B! fa%t, )ost=throm&olysis &lood )ressure elevatio! a!d &lood )ressure varia&ility more tha! the a&solute level of &lood )ressure are asso%iated .ith hemorrhagi% tra!sformatio! i! a%ute is%hemi% stro(e *But%her et al 20104 Eo et al 2010-. 7!alysis of data from Euro)ea! "oo)erative 7%ute 6tro(e 6tudy BB %o!firmed these fi!di!gs, a!d also suggested that i!%reasi!g )atie!t age, &aseli!e systoli% &lood )ressure, %o!gestive heart failure, a!d treatme!t .ith as)iri! )rior to throm&olysis .ere )redi%tors of hemorrhagi% tra!sformatio! *,arrue et al 20014 orado et al 2010-. B!vestigators have also &ee! evaluati!g various M#B te%h!i0ues, i!%ludi!g M# diffusio! a!d )erfusio! s%a!!i!g, i! a! attem)t to assess hemorrhagi% tra!sformatio! ris( after throm&olysis *6elim et al 2002-. 7 study a!aly<i!g throm&olyti% thera)y .ith i!trave!ous t>7 a!d ris(s of hemorrhagi% tra!sformatio! dis%overed treatme!t time after 3 to ; hours, a larger lesio! volume, a!d a high Natio!al B!stitutes of $ealth 6tro(e 6%ale s%ore o! admissio! .ere sig!ifi%a!t i!de)e!de!t )redi%tors of hemorrhagi%

Ersifa Fatimah, dr. | Neurologi | 2013

tra!sformatio! */homalla et al 200C-. Dld age, ho.ever, .as the mai! sig!ifi%a!t )redi%tor of )are!%hymal hemorrhage after i!trave!ous t>7 */homalla et al 200C-. D!e study, ho.ever, em)hasi<ed that old age *older tha! 90 years old- does !ot i!%rease the ris( of sym)tomati% hemorrhagi% tra!sformatio! after admi!istratio! of throm&olyti% thera)y4 thus, old age should !ot deter o!e from admi!isteri!g throm&olyti% thera)y *>u!di( et al 2009-. >are!%hymal hematoma has &ee! (!o.! to have a more adverse out%ome4 it is )redi%ted &y larger lesio!s %aused &y %ardioem&oli% disease, high &lood glu%ose, or throm&olysis *>a%iaro!i et al 2009-. Be%ause hemorrhagi% tra!sformatio! is related to e!dothelial damage after a! is%hemi% stro(e, al&umi!uria, a mar(er of %hro!i% e!dothelial damage, %a! &e used to )redi%t hemorrhagi% tra!sformatio! *#odrigue<=8a!e< et al 200;-. 7 study fou!d that al&umi!uria is a sig!ifi%a!t i!de)e!de!t )redi%tor of hemorrhagi% tra!sformatio!, es)e%ially i! the most severe hemorrhagi% tra!sformatio!s, es)e%ially the )are!%hymal hemorrhage ty)e 1 a!d 2 i! )atie!ts .ho have had a! a%ute is%hemi% stro(e *#odrigue<=8a!e< et al 200;-. 7 study assessed 2C2 )atie!ts via M#B a!d evaluated .hether %ere&ral mi%ro&leeds are related to early hemorrhagi% tra!sformatio! after throm&olyti% thera)y for hy)era%ute is%hemi% stro(e. /he results )roved that mi%ro&leeds, .hether fe. or ma!y, .ere !ot i!de)e!de!t ris( fa%tors for early hemorrhagi% tra!sformatio! of is%hemi% stro(e or for a!y sym)tomati% hemorrhagi% after throm&olyti% thera)y for hy)era%ute is%hemi% stro(e *Eim et al 200;-. >redi%tors for i!traarterial throm&olysis have also &ee! evaluated. 7 study demo!strated that higher Natio!al B!stitutes of $ealth 6tro(e 6%ale s%ores, lo!ger times to re%a!ali<e, lo.er )latelet %ou!ts, lo.er %oated=)latelet levels, a!d higher glu%ose levels .ere i!de)e!de!t )redi%tors of hemorrhagi% tra!sformatio! after i!traarterial throm&olysis *Eid.ell et al 20024 >roda! et al 2010-. Bt has also &ee! fou!d that after re%a!ali<atio! thera)y for is%hemi% stro(e, lo. , , levels *i!de)e!de!t of stati! usage-, smo(i!g, a!d a! i!%rease i! stro(e severity i!%reased the ris( of sym)tomati% hemorrhagi% tra!sformatio! *Ba!g et al 200C-. ,o. level of , , %holesterol i!%reases hemorrhagi% tra!sformatio! i! large artery atherothrom&osis stro(e &ut !ot i! %ardioem&oli% stro(e *Eim et al 20024 >a%iaro!i et al 2002-. /he BM6 study )u&lished i! 200; fou!d that atrial fi&rillatio! a!d i!ter!al %arotid artery o%%lusio! as o))osed to middle %ere&ral artery o%%lusio! .ere sig!ifi%a!tly asso%iated .ith hemorrhagi% tra!sformatio! of stro(e.

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