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Cuvinte cheie : atac ischemic tranzitor cerebral, diagnostic prespitalicesc, factori de risc vascular, terapie AIT, profilaxie AVC.
DATE DIN LITERATURA
Incadrarea nosologica si definirea conceptului de AIT
Definitia clasica a AIT presupune existenta unui deficit neurologic, brusc instalat, care dureaza mai putin de 24 ore, presupus a fi de origine vasculara si care este limitat la o arie cerebrala (focala) sau oculara, tributare unei anumite artere cerebrale.
Datele actuale estimeaza ca numarul celor care sufera un episod de AIT in SUA este aproximativ cuprins intre 200,000 si 500,000 oameni/an (2002), in timp ce in Europa Occidentala apar 500 cazuri noi de AIT la fiecare 1 milion locuitori (1999). Aproximativ 5 milioane de adulti din SUA au suferit deja un episod de AIT, in timp ce multi altii sunt nediagnosticati (Johnston si colab, 2003).
AIT face parte din clasa maladiilor cerebrovasculare, fiind incadrat ca sindrom cerebrovascular acut ischemic. Se defineste ca tranzitor, pentru ca are o durata limitata in timp (mai frecvent 5-10 minute), si ischemic, pentru ca se datoreste intreruperii de scurta durata a fluxului sanguin cerebral (practic consta intr-o tromboza tranzitorie pe fondul unor stenoze vasculare preexistente si in prezenta unor factori de risc vascular).
Aceste episoade scurte de deficit neurologic focal, cu debut brusc, erau considerate anterior ca avand un caracter relativ benign; in 2002 insa, secundar unor observatii asupra relatiei durata episode - aspect imagistic - prognostic caz, a fost propusa o noua definitie a AIT-lui, bazata pe criterii fiziopatologice. Exista un consens la ora actuala, conform caruia AIT nu reprezinta un eveniment benign, lipsit de gravitate, in consecinta necesitand o atentie, evaluare si tratare in regim de urgenta (Daffertshofer, Mielke, Pullwit, Felsenstein, & Hennerici, 2004). Practic, in prezent, expertii pe problematica AIT, considera ca un episod de AIT ar trebui tratat si evaluat cu promptitudinea si agresivitatea cu care se intervine in cazul sindroamelor coronariene acute.
Notiuni de etiopatogeneza privind producerea unui episod de AIT
Ateroscleroza cerebrala, asociata sau nu complicatiilor sale (stenoza, tromboza, embolie) are o semnificatie patologica majora prin compromiterea fluxului sanguin cerebral (FSC), rezultand leziuni ischemice cerebrale. Relatia intre stenoza/ocluzie si patologia reprezentata de AIT/AVC este inca incerta si variabila, de vreme ce stenoze relativ reduse pot induce uneori simptomatologie clinica evidenta, in timp ce stenozele avansate/ocluziile nu se asociaza, intotdeauna, cu un tablou clinic relevant de ischemie cerebrala (Danaila si Pais, 2004).
Astfel, la pacientii cu stenoze si ocluzii trombotice ale vaselor cerebrale, AIT este rezultatul emboliilor cu punct de plecare din leziunea ateromatoasa (cel mai adesea la nivelul arterei carotide externe - principala cale de circulatie colaterala).
Caracterul tranzitor si variabil al manifestarilor din AIT se datoreste restabilirii starii hemodinamice initiale, cu intreruperea conditiei patologice ce a generat episodul de AIT - normalizarea valorilor TA, fragmentarea/dizolvarea embolului, disparitia vasospasmului, interventia eficace a circulatiei colaterale in vederea restabilirii FSC.
Consideratii asupra factorilor de risc vascular
Producerea unui episod de AIT reprezinta un semnal de alarma asupra prezentei unor factori de risc vascular, pentru care trebuie demarata o terapie specifica si corecta, cat mai precoce, cu scopul final de evitare a unui AVC constituit. Conform recomandarilor EUSI (2005), conditiile si obiceiurile de viata care se pot constitui ca si factori de risc pentru AVC sunt : hipertensiunea arteriala, fibrilatia atriala, diabetul zaharat, patologia carotidiana, infarctul de miocard, hipercolesterolemia, hiper-homocisteinemia, fumatul, abuzul de alcool, sedentarismul si obezitatea.
In afara de situatiile care comporta o asociere de mai multi factori de risc (asa numitele cazuri cu multipli factori de risc vascular), o atentie deosebita se pare ca trebuie acordata acelor cazuri care prezinta o asociere a factorilor de risc rezultand dintr-un stil de viata nesanatos, cum sunt - obezitatea, fumatul si etilismul cronic. S-a semnalat, de asemenea, ca interventia terapeutica asupra tuturor factorilor de risc depistati este mai benefica pentru reducerea incidentei AVC decat corectarea doar a unora dintre ei.
Terapia episodului de AIT si profilaxia AVC-lui ischemic
Plecand de la consideratia ca orice episod de AIT poate fi urmat la scurta distanta de un AVC ischemic constituit, aplicarea de urgenta a unei terapii pare mai mult decat indicata. Practic vorbind, terapia unui episod de AIT consta in : corectia rapida, eficienta si prompta a tuturor factorilor de risc vascular identificati, demararea unei terapii antitrombotice in functie de caz (antiagreganta plachetara sau anticoagulanta), evaluarea oportunitatii efectuarii unei endarterectomii carotidiene, precum si elaborarea unui plan de regim igieno-dietetic cu modificarea stilului de viata, adaptat la noua conditie de boala si de risc cerebrovascular crescut.
Valoarea TA peste 140/90 mmHg reprezinta cel mai important si mai frecvent intalnit factor de risc corectabil, printre pacientii cu AIT/AVC (EUSI, 2005). O meta-analiza a evidentiat ca scaderea TA cu 5-6 mmHg, induce o scadere cu 35-40% a incidentei AVC. Totodata, riscul de AVC continua sa scada pe masura ce valorile TA sunt coborate, astfel ca se pledeaza pentru atingerea celor mai reduse valori tensionale pe care pacientul le poate tolera, in vederea optimizarii preventiei. In prezent, nu exista un regim terapeutic standard antihipertensiv pentru folosirea in cadrul preventiei primare sau secundare a AIT/AVC. IECA, diureticele si beta-blocantele s-a demonstrat ca amelioreaza prognosticul vital al pacientului, scazand semnificativ riscul de AVC.
In ceea ce priveste terapia antiagreganta, cele doua aspecte importante care trebuie precizate sunt a) tipul si doza optima de preparat care sa fie administrat; si b) indicatiile de adminstrare. Agentii antiagreganti care sunt unanim acceptati astazi pentru scaderea riscului de AVC sunt Aspirina, Dipiridamolul si Clopidogrelul. In practica clinica curenta insa, Aspirina este antiagregantul plachetar cel mai extensiv folosit.
Aplicarea terapiei anticoagulante este indicata la pacientii cu afectiuni ce comporta un risc crescut de embolism cardiogenic - FiA, o sursa cardioemboligena cunoscuta (confirmare tromb), sau o sursa cardioemboligena banuita (infarct miocardic recent extins, valve mecanice, CMP, SM reumatismala). In ceea ce priveste tratamentul FiA si indicatiile de administrare ale terapiei anticoagulante, recomandarile EUSI pe 2005 stipuleaza : Warfarina reduce rata de AVC ischemic cu 60-70% (la un INR de 2-3), anticoagularea cu un INR sub 2,0 nu este eficace, cresterea riscului de complicatii hemoragice la un INR peste 3,5, Aspirina (300 mg/zi) scade riscul relativ cu 21%;
In final putem conchide spunand - factorii de risc vascular pentru AVC ar trebui evaluati la pacientii care au suferit un prim episod de AIT. HTA, dislipidemia, FiA si DZ ar trebui corectati in sensul ameliorarii acestora. Atunci cand este cazul, renuntarea la fumat si reducerea ponderala trebuie avute in vedere. Terapia cu IECA poate ajuta la preventia AVC (conform studiilor clinice). Aspirina reprezinta tratamentul de electie pentru prevenirea AVC-lui la pacientii care nu au indicatie de anticoagulare. Clopidogrelul reprezinta o alternativa pentru cei care nu tolereaza Aspirina. Daca este identificata FiA sau alte cauze cardiace cu risc mare emboligen (infarct miocardic recent extins, cardiomiopatie dilatativa, valve mecanice sau SM reumatismala), ele reprezinta indicatii de anticoagulare.
CONTRIBUTII PERSONALE
Ipoteza de lucru
Problematica terapiei AIT-lui reprezinta, la ora actuala, un aspect de maxima importanta in domeniul maladiilor cerebrovasculare, avand in vedere cresterea alarmanta a numarului de AVC-uri ischemice in populatia generala; astfel, importanta notiunii si problematicii legate de AIT rezida din faptul ca, practic, reprezinta singura posibilitate de a reduce semnificativ, la nivel populational, incidenta producerii AVC-lui ischemic. Plecand de la o relativa precaritate a informatiei teoretice referitoare la problematica AIT printre medicii din cadrul altor specialitati, coroborata cu o lipsa aproape completa a educatiei medicale a populatiei referitoare la acest subiect, am considerat ca o punere in valoare, cu evidentierea caracterului de urgenta medicala majora, pe care patologia reprezentata de AIT o implica, tototdata cu punctarea limitelor si posibilitatilor terapeutice de care dispunem la ora actuala, nu poate sa fie decat in avantajul reducerii, la nivel populational, a morbiditatii si mortalitatii patologiei cerebrovasculare ischemice acute.
Obiective
Redactand teza de doctorat mi-am propus urmatoarele obiective : 1) sa evaluez datelele clinico-anamnestice ale pacientilor cu elaborarea unei fise originale de diagnostic prespitalicesc a cazurilor suspectate a fi suferit un AIT; 2) sa cuantific si sa prezint factorii de risc vascular la pacientii cu AIT; 3) sa prezint metodele de corectie terapeutica a factorilor de risc vascular modificati, ce se constituie intr-o terapie de urgenta a unui caz cu AIT; 4) sa evaluez metodele terapeutice si de regim igieno-dietetic menite sa previna producerea unui AVC ischemic.
Material si metode
Am luat in studiu un numar de 180 pacienti, internati in Clinica de Neurologie din Cluj-Napoca intre anii 2003-2006, care au avut stabilit diagnosticul clinic de AIT cerebral. Criteriile de includere in studiu a pacientilor sunt - existenta unui diagnostic formulat de AIT, dorinta pacientului de a fi inclus in studiu, existenta unei documentatii cantitativ/calitativ suficiente in foaie de observatie clinica referitor la parametrii cardio-metabolici pe baza carora s-a analizat lotul de pacienti, precum si posibilitatea pacientilor de a se prezenta la 2 vizite consecutive, la 6 luni si, respectiv, 12 luni fata de momentul externarii din serviciul nostru. Studiul a fost gandit ca si o metoda de analizare a cazurilor cu AIT internate in Clinica Neurologie, pe baza unor parametrii clinico-anamnestici si cardio-metabolici definiti, in vederea redactarii unei fise originale de evaluare prespitaliceasca a cazurilor suspectate a fi suferit un AIT (informatie necesara mai ales serviciilor de asistenta primara a starii de sanatate - servicii de urgenta sau cabinete ale medicilor de familie), precum si a unui algoritm de terapia acuta a episodului de AIT si de profilaxie primara a unor evenimente cerebrale vasculare ischemice (AVC).
Cazurile au fost studiate in mod prospectiv, luandu-se ca si parametrii de urmarit - datele clinice (tipul si calitatea simptomelor enuntate de bolnavi, cu descrierea episodului de AIT, pe baza criteriilor semiologice clasice; teritoriul vascular afectat), factorii de risc vascular, datele cuprinse in anamneza (varsta, sex, ocupatie, consum de toxice, istoric familial de boala cardio- sau cerebrovasculara). Ca si metoda de analiza statistica a datelor am folosit testul χ² si testul exact Fisher.
I. Evaluarea datelor clinico-anamnestice ale pacientilor : acest prim capitol a fost gandit sa analizeze parametrii obtinuti din anamneza (sex, varsta, consum de toxice, istoricul episodului de AIT cu descrierea pe baze semiologice a acestuia).
Rezultate
. s-a constatat predominanta sexului masculin [115 pacienti (63,88%)];
. pentru barbati, decada de varsta mai frecvent afectata a fost 51-60 ani, iar pentru femei 61-70 ani;
. pacientii au acuzat ca si motive ale internarii - deficitul motor (mono- si hemipareza), tulburare de sensibilitate (parestezii, amorteala), tulburari vizuale (orbire monoculara tranzitorie, hemianopsie, diplopie), tulburari de vorbire (afazie, disartrie), simptome asociate (de teritoriu vertebro-bazilar); cel mai frecvent simptom a fost deficitul motor (74 cazuri, 41,1%);
. cele doua teritorii vasculare afectate, in timpul episoadelor de AIT, au fost cel carotidian intern [123 pacienti (68,33%)] si cel vertebro-bazilar [57 pacienti (31,66%)];
. 44 pacienti (24,4%) au prezentat un istoric familial pozitiv pentru o boala cardio- sau cerebrovasculara ischemica. Astfel, in 37 cazuri boala cardiaca ischemica, in 40 cazuri HTA, in 23 cazuri AVC, 11 cazuri DZ;
. in ceea ce priveste stilul de viata al pacientilor luati in studiu, acestia au fost supraponderali (67 cazuri) sau obezi (52 cazuri), au declarat ca nu fac exercitii fizice regulate (153 pacienti, 85%), nu consuma legume/fructe mai des de 1-2 x/saptamana (135 pacienti, 75%), fumeaza (57 pacienti, dintre care 38 fumeaza mai mult de 15 tigari/zi) sau consuma alcool mai mult de 1x/zi si in cantitate mai mare de 100 ml/zi (34 pacienti);
. descrierea episodului clinic de AIT releva in mod caracteristic urmatoarele - debut brusc in 148 cazuri (82,2%), aparitie dimineata la trezire (19,4%) sau in timpul desfasurarii unor activitati casnice (47,7%), evolutie fara agravare a simptomelor in 166 cazuri, doar in 13 cazuri deficitul neurologic a fost total, 115 cazuri au avut o durata a episodului intre 1-10 min (63,88%).
Studiind asocierea cu semnificatie statistica, intre simptome si durata episodului de AIT a rezultat ca hemipareza s-a asociat cu o durata de 1-10 min la 85,1% dintre pacientii cu deficit motor (p<0,001), in timp ce tulburarea vizuala s-a asociat cu o durata a episodului intre 10-60 min (p<0,005).
. timpul mediu de prezentare la medic a fost crescut, astfel ca doar 21 pacienti (10,66%) s-au prezentat in primele 10 ore;
Discutii
Multi din parametrii luati in discutie nici nu pot fi comparati cu literatura de specialitate (varsta, sex, conditii de viata si munca, sa) pentru ca datele teoretice adesea lipsesc. Evaluarea parametrilor clinico-anamnestici ai pacientilor cu AIT luati in studiu indica o varsta de producere a atacului apropiata de cea a AVC, dar cu 3-5 ani mai mica. Faptul ca teritoriul carotidian intern este cu predilectie implicat se poate explica prin mai marea specificitate a simptomatologiei care rezulta in aceste cazuri (deficit motor, senzitiv sau tulburari ale functiilor elaborate cortical), spre deosebire de simptomele nespecifice din afectarea teritoriului vertebro-bazilar, fapt ce conduce la o prezentare in procent mai mare a cazurilor cu afectare de teritoriu carotidian intern. De notat este gradul crescut de incarcare vasculara in familia pacientilor cu AIT, cu un procent ridicat de afectare vasculara pe linie paterna, mortalitatea din cauze vasculare fiind, intr-un procent foarte mare, distribuita in randul ambilor genitori. Descrierea episodului clinic este de natura sa orieteze categoric diagnosticul spre un episod de AIT, mai ales daca : debutul este brusc, simptomele nu fluctueaza in intensitate, nu apar simptome asociate, remisia simptomelor se produce in 1-10 min, este descris un deficit motor, senzitiv sau vizual, la un pacient cunoscut sau identificat cu factori de risc vascular si care nu urmeaza o terapie constanta pentru afectiunile comorbide
Concluzii de etapa
1. nu se poate trasa un pattern clar de simptomatologie clinica a episodului de AIT, in schimb, ca si o concluzie la acest prin capitol putem spune ca persoana care se prezinta pentru un episod presupus a fi AIT - este mai frecvent barbat (63,8%), cu varsta medie cuprinsa intre 61-70 ani, din mediul urban, prezentand un istoric familial de boala cardio- si cerebrovasculara (in 24,4% cazuri), este sedentar si hipertensiv, obez sau fumator (in 31,6% cazuri), se prezinta, cel mai adesea, pentru un singur episod de deficit motor sau sindrom senzitiv unilateral, in teritoriul carotidian, cu durata de 1-10 minute, cu debut brusc, in timpul unei activitati sau dimineata la trezire, mai frecvent pe fondul sau asociat unui puseu de HTA, cu intensitate maxima de la debut, fara insa ca deficitul neurologic sa aiba caracter total, are un timp mediu de prezentare la spital intre 2-3 zile, cel mai adesea nu a auzit de AIT, durata medie a internarii fiind de 3,6 zile.
2. datele obtinute si analizate mi-au permis elaborarea unei fise de diagnostic prespitalicesc a cazurilor suspectate a fi suferit un episod de AIT, fisa care se afla la finalul capitolului corespunzator din teza de doctorat.
II. Evaluarea factorilor de risc vascular care determina producerea episodului de AIT : pornind de la conderatiile teoretice referitoare la implicarea diferitilor factori de risc vascular in promovarea simptomelor din cadrul AIT/AVC am evaluat pacientii luati in studiu si din acest punct de vedere.
Rezultate
. HTA a reprezentat cel mai frecvent intalnit factor de risc la pacientii luati in studiu (153 pacienti - 85%). Astfel, din cele 153 cazuri, 23 pacienti (15%) au avut forma de preHTA (TAs intre 130-140mmHg si TAd intre 80-90 mmHg), 47 pacienti (30,7%) au avut HTA forma usoara (TAs intre 140-160 mmHg si TAd intre 90-100 mmHg), 51 pacienti (33,3%) au avut o HTA forma moderata (TAs intre 160-180 mmHg si TAd intre 95-110 mmHg), iar 32 pacienti (20,9%) au avut HTA forma severa (TAs intre 180-240 mmHg si TAd peste 115 mmHg);
. 57 pacienti au fost fumatori activi (41 barbati si 16 femei); anamnestic am mai decelat un numar de 24 pacienti care au fost fumatori in antecedente (15 barbati si 9 femei) si care fumau in medie 10-20 tigari/zi;
. 58 pacienti (32,2%) au prezentat o forma clinica de dislipidemie, astfel ca 22 au avut hipertrigliceridemie, 28 hipercolesterolemie iar 8 pacienti o forma mixta de dislipidemie. Din cei 58 pacienti cu dislipidemie, la 18 dintre ei (31%), prezenta acesteia a fost diagnosticata in serviciul nostru; Din cei 22 pacienti cu hipertrigliceridemie, cei mai multi, 14 (63,63%) au avut valori peste 220 mg/dl (valorile normale fiind considerate sub 150 mg/dl), iar, dintre cei 28 cu hipercolesterolemie, cei mai multi, 18 (64,28%) au avut valori peste 250 mg/dl (valorile considerate normale fiind sub 200 mg/dl);
. din totalul celor 180 pacienti, repartitia pe procente a diferitelor afectiuni cardiace, se prezinta astfel : 68 pacienti (38%) cu boala cardiaca ischemica, 27 pacienti (15%) cu insuficienta cardiaca, 12 pacienti (6,66%) cu fibrilatie atriala, 12 pacienti (6,66%) cu stenoza mitrala, 17 pacienti (9,4%) cu alte afectiuni - semne de HVS, cardiomiopatie, tromboza intracavitara;
. valori modificate ale glicemiei au fost identificare la un numar de 82 pacienti (45,5%). 48 pacienti (27%) au avut DZ tip 2 cu valori ale glicemiei la internare cuprinse intre 162-360 mg/dl. Pe lotul studiat, inafara celor 48 cazuri cunoscute cu DZ, au mai fost inregistrate alte 12 cazuri cu valori ale glicemiei cuprinse intre 140-189 mg/dl, cu o medie a glicemiei de 160,9 mg/dl. Aceste cazuri au fost considerate ca posibil avand alterarea tolerantei la glucoza si au fost indrumate spre Clinica de Diabet in vederea stabilirii unui diagnostic clinic. Alte 22 cazuri au fost evidentiate cu valori ale glicemiei cuprinse intre 111-139 mg/dl, cu o medie a valorilor glicemiei de 127,11 mg/dl. Aceste cazuri au fost interpretate ca hiperglicemie reactiva, avand in vedere ca, in lipsa unei terapii hipoglicemiante (orale sau injectabile), valorile au atins intervalul de normalitate in urmatoarele 5 zile de la internare.
. alti factori de risc vascular identificati au fost - supraponderea (67 pacienti), obezitatea (52 pacienti), alcoolism cronic (34 pacienti), istoric familial de boala vasculara (44 pacienti), boala aterosclerotica a arterelor carotide (17 cazuri).
Discutii
Pe lotul studiat, 85% dintre pacienti au prezentat valori ale TA care se incadrau la diagnosticul de HTA, fiind astfel cel mai frecvent factor de risc vascular la pacientii luati in studiu. Pe lotul studiat, din cei 153 pacienti depistati cu HTA, doar 102 pacienti (66,6%) se cunoasteau ca avand HTA, restul au fost diagnosticati la prezentarea in serviciul nostru. Pe lotul studiat, asocierea cea mai puternica cu HTA au avut-o diabetul, fumatul si consumul cronic de alcool, in timp ce pentru varsta, diferenta nu a fost atat de marcanta; in functie de sex, pe lotul studiat, nu s-a observat o diferenta in favoarea sexului masculin, fapt ce poate fi explicat prin procentul destul de mare de femei cu 4, 5 sau mai multi factori de risc vascular. 34 de pacienti (41,5%) din cei 82 identificati cu valori crescute ale glicemiei nu stiau de existenta acestei anomalii, iar dintre pacientii cunoscuti cu DZ doar 29 (60,4%) aveau o forma echilibrata terapeutic. Pentru cei 12 pacienti cu FiA din lotul studiat, evaluarea riscului de AVC pe baza scorului CHADS2 indica un risc mediu de 8,5%/an. 6 pacienti (35,3%) dintre cei identificati cu patologie carotidiana au avut un grad de stenoza peste 70%. In ceea ce priveste fumatul, as adauga ca asocierea mare intre cazurile de alcoolism, fumat si obezitate, reprezinta un indiciu asupra unui comportament social si alimentar viciat, astfel ca, in final, se obtine un efect sinergic al unora dintre factorii de risc.
Concluzii de etapa
1. prevalenta cazurilor de HTA printre pacientii cu AIT este mult crescuta fata de populatia generala si fata de alte grupuri la risc, totodata 1/3 din cazuri fiind reprezentate de cazuri nou diagosticate; din totalul cazurilor deja cunoscute cu HTA (101), doar 39 cazuri urmau un tratament consecvent la domiciliu, cu atingerea unor valori optime ale TA in doar 24 cazuri; astfel, trebuie intensificate eforturile de depistare, evaluare si tratare a cazurilor cunoscute sau aflate la risc de a dezvolta HTA;
2. se observa o tot mai mare asociere a factorilor de risc vascular, in special pentru diabetul zaharat, HTA, fumat, dislipidemie, obezitate si alcoolismul cronic, cu asocierea frecventa a multora dintre acestia, fapt ce poate explica, pe de-o parte, numarul crescut de cazuri de AIT si, pe de alta parte, progresia frecventa a acestora spre un AVC ischemic constituit;
3. inafara factorilor de risc vascular mai sus mentionati, analiza cazurilor luate in studiu, arata ca existenta cardiopatiei ischemice sau a afectiunilor cardiace cu potential emboligen (FiA, ICC, SM sau tromboza intracavitara) este depistata in procent mare la cazurile cu AIT, motiv pentru care, aceste cazuri necesita o evaluare cardiologica cat mai prompta si mai amanuntita, pentru efectuarea unui bilant cardiovascular global.
III. Terapia acuta a unui episod de AIT si profilaxia AVC-lui ischemic : au fost evaluate datele de la lotul in studiu, in ceea ce priveste clasele de agenti terapeutici folositi, precum si strategiile de ameliorare a factorilor de risc vascular, la fiecare caz in parte.
Rezultate
. terapia valorilor crescute ale TA a fost realizata cu preparate din clasa IECA, blocanti ai canalelor de Ca, diuretice, beta-blocante si inhibitori adrenergici centrali. Din cei 153 de pacienti cu HTA, 127 pacienti (83%) au fost tratati cu agenti din clasa IECA (Enalapril, Captopril, Perindopril si Quinapril); din totalul de 127 pacienti tratati cu agenti IECA, la 94 pacienti (74%) IECA s-au folosit in monoterapie;
diureticele au reprezentat a doua clasa de agenti hipotensori folositi pentru pacientii luati in studiu. De departe, cel mai frecvent folosit agent diuretic a fost Furosemidul, utilizat la 37 pacienti (90,24%), in timp ce, pentru restul de 5 pacienti (9,76%) a fost folosita Indapamida; Folosirea diferitelor preparate, in dozele si asocierile care au fost mentionate, s-a facut cu respectarea consideratiilor teoretice in vigoare si pe baza experientei colectivului nostru in manuirea diferitelor preparate cu efect de scadere a TA;
. terapia celor 48 cazuri identificate cu o forma de dislipidemie, a constat in : statine (Simvastatina, Fluvastatina si Atorvastatina) la un numar de 25 cazuri, fibrati in 6 cazuri si adoptarea unui regim alimentar hipolipemiant si hipocaloric in 27 cazuri.
. terapia cazurilor cu DZ sau cu valori alterate ale glicemiei (hiperglicemie reactiva sau scaderea tolerantei la glucoza) a presupus continuarea terapiei antidiabetice orale sau insulinice pentru cazurile care la domiciliu nu au atins valoarea optima a glicemiei, in timp ce, pentru cele 34 cazuri noi identificate cu valori crescute ale glicemiei, cei 12 pacienti, care au fost identificati ca avand o toleranta alterata la glucoza, cu valori ale glicemiei intre 140-189 mg/dl la 2 ore post prandial, au fost tratati, in 9 cazuri, cu terapie antiadiabetica orala (cazurile cu glicemia peste 160 mg/dl), ajungandu-se la o reducere medie a valorilor glicemiei cu 30-55 mg/dl; in cazul celor 22 pacienti, care au prezentat hiperglicemie evaluata ca si reactiva, cu valori cuprinse intre 110-139 mg/dl, s-a optat, in toate cazurile, pentru o terapie non-farmacologica, cu modificarea regimului alimentar, in functie de necesitatile conditiei nou aparute;
. terapia antiagreganta aplicata cazurilor luate in studiu a inclus folosirea Aspirinei (75-100 mg/zi) si Clopidogrelului (75 mg/zi), pentru cazurile cu factori de risc protrombotici, cu risc cardioembolic considerat mediu sau scazut (scor CHADS2 sub 3 puncte) sau in caz de AIT in repetitie. S-a administrat la un numar de 162 pacienti, impartiti in 4 loturi, dupa cum urmeaza : 1) primul lot a inclus pacientii tratati doar cu Aspirina, in doza de 75 mg/zi (148 pacienti); 2) al doilea lot a inclus 4 pacienti la care s-a optat pentru o terapie, de scurta durata, pe perioada internarii cu Aspirina + Clopidogrel (ambele in doza de 75 mg/zi); 3) al treilea lot a inclus un numar de 6 pacienti care au primit doar Clopidogrel; 4) al patrulea lot a inclus 4 pacienti cu episoade repetitive de AIT (3 sau 4) si la care s-a optat pentru o asociere a Aspirinei (75 mg/zi) cu HMMM (pe termen scurt).
. terapia anticoagulanta a fost aplicata unui numar de 22 cazuri, astfel ca : 12 pacienti cu FiA cronica sau paroxistica, cu AIT presupus cardioembolic, cu scor CHADS2 mai mare sau egal cu 3 puncte, au fost tratati folosindu-se heparine cu masa moleculara mica (Dalteparina, Enoxaparina si Reviparina); 6 pacienti cu AIT repetitive (3-4 episoade) au fost tratati cu HMMM si anticoagulante orale; 4 pacienti, cu AIT repetitive, cu factori de risc vascular protrombotici au fost tratati prin combinatia Aspirina + HMMM.
. profilaxia primara a AVC-lui ischemic a presupus : 1) continuarea terapiei antihipertensive, prin modificarea dozelor sau asocierea altor clase de agenti antihipertensivi pentru cei 29 pacienti care au continuat sa prezinte valori crescute ale TA la externare; pentru pacientii cu valori stabile ale TA s-a continuat terapia antihipertensiva demarata in spital; 2) pentru cazurile cu dislipidemie, la 25 pacienti s-a continuat tratamentul cu statine initiat la internare sau la domiciliu (aceleasi preparate mentionate la terapia acuta), la 6 pacienti s-au administrat fibrati, in timp ce, la restul de 27 pacienti, s-a optat doar pentru o modificare a regimului igieno-dietetic; 3) din cei 82 pacienti, depistati cu valori crescute ale glicemiei la internare, doar la 54 pacienti s-au mentinut valori ale glicemiei compatibile cu diabetul zaharat (48 cazuri cunoscute + cele 6 cazuri cu valori crescute ale glicemiei la externare, considerate pe baza consultului diabetologic, ca avand diabet zaharat). Astfel, dintre acesti 54 pacienti, un numar de 13 pacienti (22,4%) inca au mai prezentat la externare valori crescute ale glicemiei (in ciuda tratamentului administrat); restul de 41 pacienti, au fost stabilizati, atingand la externare valori acceptabile ale glicemiei; 4) pentru pacientii cu stenoza carotidiana, acesti pacienti au fost trecuti pe anticoagulant injectabil subcutanat pe perioada internarii (heparine cu molecule mica, 60-100 mg/zi), iar la externare au fost trecuti antiagregant plachetar (Aspirina in 5 cazuri si Clopidogrel intr-un caz). Pentru restul de 11 cazuri, cu stenoza vasculara mai mica de 70%, s-a optat inca de la inceput pentru tratament antiagregant plachetar cu Aspirina, 1 tb 75 mg/zi; 5) cei 148 pacienti, care au inceput pe parcursul internarii o terapie cu Aspirina 75 mg/zi, au continuat cu acelasi preparat si doza si la externare; alti 6 pacienti, care luau Clopidogrel 75 mg/zi, au continuat tratamentul si dupa externare; 4 pacienti considerati cu risc crescut pentru stroke si care luau Aspirina 75 mg/zi si Clopidogrel 75 mg/zi, au continuat terapia si la domiciliu, recomandandu-se ca in primele 3 luni sa ia cele doua medicamente in asociere, urmand ca apoi, sa ramana pe Aspirina 75 mg/zi, cu monitorizarea riguroasa a factorilor de risc vascular asociati; ultimul lot, il reprezinta cei 4 pacienti care pe parcursul internarii au luat Aspirina 75 mg/zi si HMMM si care, la externare, au ramas pe Aspirina 75 mg/zi si Warfarina orala 2 mg/zi (cu recomandarea monitorizarii regulate a INR); 6) schema finala de terapie anticoagulanta, cu rol profilactic pentru stroke-ul ischemic, la aceste cazuri, a inclus - 17 cazuri la care s-a recomandat folosirea anticoagulantelor orale la domiciliu, 2 cazuri care au fost trecute pe Aspirina (considerandu-se ca riscul imediat de stroke a fost depasit prin corectarea de faza acuta a factorilor de risc vascular prezenti) si 4 cazuri au fost lasate pe o terapie de asociere, anticoagulant oral in doza mica + Aspirina, considerandu-se riscul ca fiind intermediar, urmand ca la urmatoarea vizita, terapie sa fie, eventual, reconsiderata.
Discutii
Terapia antihipertensiva a fost initiata in situatia in care valorile TA au depasit valoarea de 140/90 mmHg (153 cazuri), chiar daca pacientii nu erau toti cunoscuti cu HTA in antecedente, pentru ca, asa cum prevede si literatura de specialitate, chiar si cazurile de pacienti non-hipertensivi, beneficiaza in urma aplicarii unei terapii antihypertensive. Principalele cauze identificate, pentru prezentarea in serviciul nostru cu valori crescute ale TA au fost - lipsa unei terapii HTA consecvente la domiciliu, consumul crescut de alcool, lipsa adoptarii unui regim igieno-dietetic corespunzator, lipsa prezentarii la controale medicale periodice, precum si managementul inadecvat al afectiunilor medicale asociate. Am urmarit modul de evolutie a valorilor TA de la internare, la 3 zile si, respectiv 5 zile. Considerand o valoare medie a TA la internare de 170-180/90-100 mmHg, la 3 zile valorile au scazut la 160-170/100 mmHg, in timp ce, la 5 zile de la aplicarea unei terapii hipotensoare, valorile TA scazusera pana la 140-150/90 mmHg. Am observat o tendinta mai buna de reducere a valorilor TA pentru pacientii care au urmat o terapie hipotensoare consecventa la domiciliu, la cei cu valori foarte crescute ale TA la internare (peste 190 mmHg), precum si la cei care nu au prezentat factori de risc vascular care sa promoveze sau sa intretina fenomenul de ATS si, secundar, sa promoveze HTA (obezitate, sedentarism, istoric familial de CICr si HTA, dislipidemie).
Terapia antiagreganta plachetar a reprezentat principalul mod de protectie antitrombotica la pacientii cu AIT luati in studiu, a inclus 4 grupe diferite de pacienti, cu factori de risc vascular non-cardioembolici sau considerati a avea un risc emboligen scazut.
Terapia anticoagulanta a fost aplicata unui numar de 22 cazuri, evaluati ca avand risc embolic si de promovare a unui AVC crescut - prezenta unor factori de risc inalt emboligeni (cu sau fara FiA, la un scor CHADS2 mai mare sau egal cu 3 puncte), cu multipli factorii de risc vascular asociati, consumatorii de toxice, cu o varsta inaintata (peste 70 ani), precum si cei care la domiciliu nu au prezentat o corectie constanta si judicioasa a afectiunilor medicale asociate.
Concluzii de etapa
1. corectia factorilor de risc vascular reprezinta primul pas in tratarea cazurilor cu AIT si presupune, din punct de vedere practic, corectia valorilor crescute ale TA (coborarea lor la valori de 140-160/80-90 mmHg), demararea unei terapii hipolipemiante (pentru a se atinge o valoarea a colesterolului de maxim 220 mg/dl si a trigliceridelor de maxim 150 mg/dl), scaderea valorilor glicemiei, atat pentru pacientii cunoscuti cu DZ, cat si pentru cei fara un istoric de hiperglicemie (spre o glicemie medie de 110-120 mg/dl), precum si incadrarea spre o terapie anticoagulanta sau antiagreganta plachetar a tuturor cazurilor identificate cu afectiuni cardiace cu potential emboligen;
2. asociat corectiei factorilor de risc vascular, trebuie demarata o terapie cu agenti antitrombotici, fie din clasa agentilor antiagreganti plachetari - Aspirina 75-100 mg/zi, fie Clopidogrel 75 mg/zi; cazurile care se preteaza pentru o terapie folosind agentii antiagreganti plachetar, cuprind - cazurile cu factori de risc trombotici cunoscuti, fara evidente de afectiuni cu potential cardioembolic sau, daca exista, sa aiba potential emboligen apreciat ca si redus (ex. Scor CHADS-2 sub 3 puncte); pacientii care prezinta stenoze catorotidiene eligibile pentru interventia chirurgicala dar pentru care pacientii refuza operatia;
3. terapia cu preparate anticoagulante trebuie demarata pentru cazurile cunoscute cu afectiuni cardiace cu potential emboligen cu risc crescut (punctaj CHADS2 peste 3), la cazurile care prezinta mai mult de 2 episoade clinice de AIT, la pacientii considerati a avea deficit de protectie antitrombotica, la pacientii a caror profil de risc vascular ii incadreaza pentru un risc crescut de stroke si pentru cazurile care prezinta un INR mai mic de 1,5;
4. preventia unui AVC ischemic constituit presupune continuarea masurilor active de corectie farmacologica sau igieno-dietetica luate pe parcursul spitalizarii, in vederea corectiei factorilor de risc vascular; alegerea unei scheme de terapie antitrombotica adecvata fiecarui caz in parte (antiagregare cu 1 sau 2 preparate, asocierea unui preparat antiagregant cu altul anticoagulant, folosirea doar a unui preparat anticoagulant oral sau injectabil); realizarea unui plan individual de terapie corectoare a factorilor de risc vascular + un regim de viata si alimentar menit sa promoveze starea de sanatate si sa combata dezechilibrarea statusului neurologic actual;
Concluzii
Teza mea face parte din categoria lucrarilor cu caracter de cercetare clinica, evaluata pe baza unor parametrii luati in discutie, cu obtinerea in final a unui ghid propriu de diagnostic diferential a episodului de AIT si prezentare a masurolor active de terapie si profilaxie care trebuie aplicate unui caz cu AIT pentru evitarea producerii unui AVC ischemic constituit.
. AIT-ul necesita o evaluare diagnostica si terapeutica de maxima urgenta, intr-un timp cat mai scurt, deoarece o proportie semnificativa a pacientilor cu AIT pot suferi un AVC ischemic, la intervale de timp variabile, dupa primul episod de AIT;
. Terapia acuta a unui episod de AIT presupune o identificare a tuturor factorilor de risc vascular, cu corectarea consecutiva a acestora, asociata cu elaborarea unei scheme de tratament antitrombotic adaptata fiecarui caz in parte;
. Corectia factorilor de risc vascular reprezinta primul pas in tratarea cazurilor cu AIT si presupune, din punct de vedere practic, in primul rand, corectia valorilor crescute ale TA (cu mentinerea acestora la valori de maxim 140-160/80-90 mmHg), dat fiind faptul ca, cel mai frecvent, pacientii cu AIT asociaza hipertensiunea arteriala, in toate gradele de severitate;
. Terapia antiagreganta plachetara la pacientii cu AIT, presupune folosirea Aspirinei (in doza de 75-100 mg/zi) sau Clopidogrel (in doza de 75 mg/zi); cazurile care beneficiaza de aceasta terapie includ - pacientii cu AIT cu factori de risc trombotici cunoscuti, fara evidente de afectiuni cu potential emboligen crescut;
. Terapia anticoagulanta, la pacientii cu AIT, presupune folosirea heparinelor cu masa moleculara mica sau a preparatelor anticoagulante orale; indicatiile de administrare includ cazurile cunoscute cu afectiuni cardiace cu potential emboligen crescut, care prezinta mai mult de 2 episoade clinice de AIT sau pacientii considerati a avea un deficit de protectie antitrombotica;
. Profilaxia unui accident vascular cerebral ischemic, la pacientii cu AIT, presupune continuarea masurilor active de corectie farmacologica sau de regim igieno-dietetic demarate pe parcursul spitalizarii, in vederea ameliorarii factorilor de risc vascular, precum si alegerea unei scheme de terapie antitrombotica adecvate fiecarui caz de AIT in parte; indicatiile de terapie a unui episod de AIT si profilaxie a unui AVC ischemic sunt incluse in fisa proprie din teza;
Rezultatele, discutiile precum si concluziile cuprinse in teza mea de doctorat au ca si obiectiv aducerea in atentia pacientilor si a colegilor din alte specialitati a patologiei reprezentate de AIT si care, din cauza frecventei crescande, a implicatiilor fiziopatologice si a intercurentei cu multe alte afectiuni medicale sistemice, constituie o piatra de hotar in evaluarea de prima intentie a cazurilor suspectate ca avand o afectare cerebrovasculara acuta, permitand, consecutiv, aplicarea unei terapii si profilaxii prompte si eficiente, cu scopul final de scadere a incidentei AVC-lui ischemic, care, in prezent, se situeaza pe al doilea loc ca mortalitate populationala si pe primul loc ca si cauza de sechelaritate neurologica.
Articole publicate :
1. Kory-Calomfirescu Stefania, Stanca Delia, Marge C, Manzat Ivona : Manifestari paroxistice diurne si nocturne neepileptice. Acta Neurologica Transilvaniae, nr. 2, 2003, pag. 3-6;
2. Kory-Calomfirescu Stefania, Marge C, Kory-Mercea Marilena. Sindromul Melkersson-Rosenthal. Acta Neurologica Transilvaniae, nr. 2, 2003, pag. 29-32;
3. Marge C. Diagnosticul clinico-paraclinic al atacului ischemic tranzitor cerebral. Acta Neurologica Transilvaniae nr. 3, 2003, pag. 20-23;
4. Marge C, Stefania Kory-Calomfirescu. Existenta predispozitiei ereditare in epilepsie. Acta Neurologica Transilvaniae, nr. 3, 2003, pag. 36-39;
5. Marge C. Sindroamele neurocutanate. Viata Medicala, nr. 42, 2003, pag. 3;
6. Marge C. Profilaxia primara si secundara in atacul ischemic tranzitor cerebral. Acta Neurologica Transilvaniae, nr. 4, 2003, pag. 43-50;
7. Marge C. Tratamentul modern in AIT. Acta Neurologica Transilvaniae, nr. 3-4, 2004, pag. 20-28;
8. Marge C. Etiopatogenia si diagnosticul atacului ischemic tranzitor cerebral. Clujul Medical, nr. 2, vol. LXXVIII, 2005, pag. 364-369;
Lucrari stiintifice comunicate :
1. Kory-Calomfirescu Stefania, Zegreanu I, Marge C, Stanca Delia, Manzat Ivona. Forme clinice de epilepsie in tumorile cerebrale. Reuniunea de Neurooncologie, Cluj-Napoca, 21 Aprilie 2003;
2. Marge C Existenta predispozitiei ereditare in epilepsie. Reuniunea de Neurologie, Psihiatrie si Neurochirurgie, Cluj-Napoca, 27 Mai 2003;
3. Kory-Calomfirescu Stefania, Stanca Delia, Marge C. Managementul epilepsiei. Reuniunea de Neurologie, Psihiatrie si Neurochirurgie, Cluj-Napoca, 27 Mai 2003;
4. Kory-Calomfirescu Stefania, Marge C. Profilaxia secundara la atacul ischemic tranzitor cerebral. Consfatuirea - Accidentele vasculare cerebrale; Problema de sanatate publica, Baile Felix, 3-5 Octombrie 2003;
5. Marge C, Marinescu C. Managementul diagnostico-terapeutic in hipotensiunea ortostatica de cauza neurogena. Primul Congres National de Medicina Interna, Targu Mures, 15-17 Aprilie, 2004;
6. Stanescu Ioana, Marge C, Marginean I, Perju-Dumbrava Lacramioara, Bulboaca A. Date epidemiologice privind Stroke-ul in Municipiul Cluj-Napoca in perioada 2003-2004. A VII-a Conferinta Nationala de Stroke (AVC), Bucuresti, 14-15 Octombrie 2004;
7. Marginean I, Vacaras V, Marcu G, Marge C, Popescu D, Vicas Alina. Abordarea clinico-terapeutica in boala Charcot-Marie-Tooth. Al V-lea Congres al Societatii de Neurologie din Romania, Bucuresti, 9-12 mai 2007;
Key words : transient ischemic attack, prehospital evaluation, vascular risk factors, therapy TIA, prevention stroke.
Theoretical knowledge
Nosological approach and defining of the term TIA
The classical definition of TIA requires the presence of a neurological deficit, of sudden onset, which lasts less than 24 hours, presumed of vascular origin, which is limited to a certain brain area (focal) or ocular, supplyied by a cerebral artery.
Current data suggest that the real number of TIAs in the United States is between 200,000 and 500,000 episodes per year (2002), while in Western Europe, there are 500 new cases of TIA for every 1 milion people (1999). About 5 milion people in America have suffered a TIA and many other are out of diagnosis (Johnston, 2003).
TIA is part of the cerebrovascular pathology, being defined as an acute ischemic vascular event. It is declared as transient because it's limited duration (usually 5-10 minutes) and as ischemic because it implies a short, sudden decrease of the cerebral blood flow (practically it consists of a transient trombosis due to previous vascular stenosis in the presence of multiple vascular risk factors).
These short episodes of focal neurological dysfunction, with sudden onset, were previously thought to have a benign character; but, in 2002, the members of the TIA Working Group, in the light of the many new clinical and physiopathological proofs decided that a TIA is no longer to be considered as a benign event, without affecting the brain functionning, but as a condition, of a severity compaired with that of an acute coronary event (Daffertshofer, Mielke, Pullwit, Felsenstein, & Hennerici, 2004).
Etiology and pathogenesis of a TIA episode
Cerebral atherosclerosis, with or without it's complications (stenosis, ulceration and embolism) implies a major pathological significance by altering the cerebral blood flow, with consequent ischemic brain damage. It is important to note that the degree of an atherosclerotic stenosis is not a firm basis for evaluating the vascular risk, since low grade stenosis have been shown to promote a TIA episode, while other lesions of high grade stenosis don't imply the same clinical manifestations (Danaila and Pais, 2004).
Thus, within patients with trombotic stenosis/oclusion of the cerebral blood vessels, a TIA is the result of embolism from the atherosclerotic plaque (most often from the external carotid artery). The transient and changeable features of a TIA patient is dued to the restoration of the cerebral blood flow, while it's possible cause wears off (normalization of blood pressure, breaking up of the embolus, the dissapereance of vasospasm or the take over by the collateral circulation.
Knowledge about the vascular risk factors
The existence of a TIA episode is a warning sign for the presence of many hidden vascular risk factors, which must be holistically and efficiently evaluated, while starting an early treatment, for preventing the occurrence of an ischemic stroke. The 2005 EUSI recommendations state that the life style habits or conditions that may proove to be vascular risk factors are represented by - arterial hypertension, atrial fibrillation, diabetes mellitus, the carotid disease, heart attack, hypercolesterolemia, smoking, heavy alcoholism, fatness and sedentary life.
Besides the situations that imply the presence of more vascular risk factors (so called multiple risk factors), another situation that needs a close attention is represented by the existence of vascular risk factors, that come from an unhealthy life style, including sedentary, fatness, smoking and heavy drinking. It has also been mentioned that the treatment for all vascular risk factors, not just for some, is useful in decreasing the rate of occurrence for ischemic stroke.
Treatment of a TIA episode and prevention of stroke
Considering that almost 1/3 of the TIA episodes can be closely followed by an ischemic stroke, starting of an early treatment seems reasonably enough. Practically speaking, the treatment of a TIA episode consists of - the quick, vigorous and efficient intervention on all the identified vascular risk factors, the start of an antithrombotic therapy (antiplatelet agents or anticoagulants), the evaluation for the opportunity of a carotid endarterectomy as well as the setting up of a comprehensive life style modification plan, adapted to the new condition of illness and of increased cerebrovascular risk.
The values of blood pressure over 140/90 mmHg represent the most consistent and frequently met treatable risk factor among the patients with TIA/stroke (EUSI, 2005). A recent meta-analysis has proved that the descrease by only 5-6 mmHg of blod pressure will lower the incidence for ischemic stroke by 35-40%. At the same time, the risk for stroke continue to diminish as the blood pressure levels are being decreased, thus it's recommended for the patient to aquire the lowest blood pressure levels that he can tolerate, for enhancing the chance of prevention. Currently, there is no standard antihypertensive treatment regimen to be used in the primary and secondary prevention of an ischemic stroke or TIA. AIEC, diuretics and beta-blocants have been shown to improve the patient life expectancy, with a consequent reduction of the stroke risk.
As for the antiplatelet therapy, the 2 important features thast must be brought to disscution are a) the type of agent and the optimal dose that can be administred and b) conditions of administering. The antiplatelet agents that are nowadays considered to reduce the risk of ischemic stroke are Aspirin, Clopidogrel and Dipiridamol. In daily clinical practice, Aspirin is the most frequent used antiplatelet agent.
The use of anticoagulation therapy is indicated to those cases that imply a high risk of cardiac embolism, including - atrial fibrillation, a documented cardiac source of embolism (thromb), or a suspected cardiac source (largely recent myocardic infarct, prothetic valves, cardiomiopathy, reumatismal mitral stenosis). For the treatment of atrial fibrillation and use of anticoagulant therapy, current data suggests - Warfarin reduces the rate of ischemic stroke by 60-70% (INR mean 2-3); under the level of 2,0 anticoagulantion efficacy cannot be validated, while above an INR of 3,5 the risk for bleeding increases.
Finally we can conclude that the vascular risk factors for ischemic stroke should be closely evaluated in patients with a prior TIA. Arterial hypertension, hyperlipaemia, atrial fibrillation and diabetes mellitus should be corrected in order to improve the lab disturbances. When needed, the smoke quick and the reduction of body mass is indicated. Therapy with AIEC can proove useful for preventing stroke (according with some clinical trials). Aspirin remains the leading antithrombotic therapy for patients that do not have an indication for anticoagulantion. Clopidogrel may be an alternative for those who cannot take Aspirin (intolerance). If atrial fibrillation or other cardiac source of embolism is confirmed, they represent strong indications for anticoagulation.
Personal contribution
Work hypothesis
The problems concerning the TIA represent a major concern worldwide, due to the increase of number of cases with cerebrovacular pathology in the general population (especially with ischemic stroke). Thus, the importance and relevance of the TIA problems can be found in the real possibility of reducing the number of ischemic strokes by better evaluating and treating the patients identified with a prior TIA. Due to a relative powerty of knowledge among the doctors from other medical specialities concerning the problems of TIA, and taking into consideration the total lacq of information on this subject in the general population, I considered that bringinng out the latest data on TIA with pointing out the emergency feature of TIA pathology, can only proove beneficial for reducing the stroke rates, through a better prevention and evaluation of the cases that are at greater risk.
Study objectives
By taking the subject into discussion I intended the followings : 1) to analyse the clinical and historical data from the patient, aiming to make up a personal record on the pre-hospital diagnosis of suspected TIA patients; 2) to assess the presence of vascular risk factors; 3) to discuss the possible treatment for the disturbed risk factors that can represent an emergency approach for TIA patients; 4) to assess the possible therapeutical means and life style changes that cand help prevent an ischemic stroke.
Means of evaluation
The present study included a number of 180 patients, who were admitted to the Neurological Clinic in Cluj-Napoca, during 2003-2006, with the diagnosis of transient ischemic attack (TIA). The inclusion criteria consisted of - the established diagnosis of TIA, the verbal consent of the patients about joining the study, the existence of enough written material about the clinical and biological parameters that were used for analysis and the real possibility for the patient to appear for two succesive visits (at 6 and 12 months from the original TIA episode). The study was also meant to assess the clinical and historical data of the patients, as well as the cardiometabolic parameters, in order to build up an original record on the pre-hospital diagnosis make up for suspected TIA patients.
This is a prospective study, that used the following parametres - clinical data (the type of symptoms related by the patients, with an holistic approach for the TIA episode, based on classical semiological criteria; the vascular territory affected), vascular risk factors, historical data (age, sex, occupation, toxic abuse, family history of cardio- or cerebrovascular pathology). For the analysis of data we used the Fisher and exact χ² tests.
I. The evaluation of historical and clinical data : this first chapter was meant to assess both the historical and clinical aspects of TIA patients.
Results
. there was a predominance of masculin gender [115 patients (63,88%)];
. the main decade of disease was 51-60 years (for men) and 61-70 years (for women);
. the most often symptoms met for admittance were - muscular weakness (mono- or hemiparesis), sensitive impairment (numbness, tickling), visual disturbances (transient monocular blindness, double vision, hemianopsia), speech disturbances (slurred speak, aphasia), associated symptoms (in the vertebrobasilar territory); the most common symptom was the muscular weakness (74 cases, 41,1%);
. the two vascular territories that were affected are the carotidian [123 patients (68,33%)] and the vertebrobasilar [57 patients (31,66%)];
. 44 patients (24,4%) presented with a positive family history for an ischemic cardio- or cerebrovascular disease. Thus, there were 37 cases of ischemic cardiac disease, 40 cases of arterial hypertension, 23 cases of ischemic stroke and 11 cases of diabetes mellitus;
. the assessment of the patients's life style revealed that 67 patients were overweighted, 52 had obesity, 153 patients (85%) stated that they don't do regular physical exercise, 57 patients were smokers (with 38 of them smoking more then 15 cigarettes/day), while 34 patients were heavy drinkers (with more then 100 ml/day or more then 1 drink/day);
. the description of the TIA episode revealed that most often - the onset was sudden for 148 cases (82,2%), mostly in the morning (19,4%) or during a house activity (47,7%), the evolution of symptoms was steady for 166 cases, only for 13 cases the degree of neurological deficit was complete, while 115 of the cases had a lifetime between 1-10 minutes (63,88%).
When studying the relationship between the type of symptoms and the duration of an TIA episode, we found out that there can be a valid statistically association between the muscular weakness and the duration of 1 to 10 minutes for the episodes (p<0,001, in 85,1% of cases), while the vision impairment was linked to a duration of the episode between 10-60 minutes (p<0,005).
. the mean time for presenting to a doctor was quite long, thus only 21 patients (10,66%) were noted with a time under 10 hours from the start of the episode.
Discussions
Many of the evaluated parameters cannot even be compaired with the foreign literature (age, sex, life style or working conditions, and so forth), because theoretical data often lack. The assessment of the clinical and hystorical data from the patients with TIA (from the study) indicate an age for TIA onset around the age for stroke, with only 3-5 years earlier. The higher incidence for carotid TIAs can partially be explained by the more specific symptoms in this territory (such as muscular weakness, sensitive impairment or alteration of the cortical elaborated functions), compaired with those of the vertebrobasilar territory, who are less specific, leading the patient to a later presenting to a doctor. One aspect that should be pointed out is the high burden of vascular pathology within the patient's family, especially from the father's line, so that many vascular deaths are being noted. There is a higher chance for establishing the TIA episode diagnosis, in case of - sudden onset, steady symptoms, there are none associated symptoms, the symptoms go off in 1 to 10 minutes, a muscular weakness or sensitive/visual impairment is noted, with a patient with recently discovered or known history of vascular risk factors, for whom he follows no therapy.
Stage conclusions
1. there is no pattern for TIA symptoms that can clearly state the diagnosis, but the evidence suggests that more often we meet a patient of male gender (63,8%), mean age between 61-70 years, with a positive family history for cardio- or cerebrovascular disease (24,4% of cases), being hypertensive or sedentary, with obesity or smoking (31,6% of cases), who will present himself for a transient unilateral episode of muscular weakness or sensitive impairment, in the carotid territory, with a duration between 1-10 minutes, of sudden onset, in the morning or while doing house activities, often associated with high values of arterial pressure, with a maximum intensity within the onset, with less frequent complete degree of neurological deficit, has a mean time for presenting to a hospital between 2 to 3 days, usually never heard of TIA;
2. the analysis and evaluation of the data taken from the studied patients allowed me to make up an original record concerning the prehospital diagnosis management, of a real clinical use;
II. The assessment of vascular risk factors that trigger the TIA episode : starting from the theoretical considerations about the implication of vascular risk factors in the TIA pathology, I also made an analysis of the patients's data concerning this issue.
Results
. arterial hypertension was the most frequently met vascular risk factors for the TIA patients from the study (153 patients, 85%). The distribution of patients, based on the degree of hypertension revealed that - 23 patients had a pre-hypertensive state (15%), 47 patients had mild hypertension (30,7%), 51 patients had moderate hypertension (33,3%), and 32 patients had severe hypertension (20,9%);
. 57 of the patients were actual smokers (41 men and 16 women); from the historical data I've noted another 24 ex-smokers, who used to smoke between 10 and 20 cigarettes/day, and who quited smoking because of different considerations;
. 58 patients (38,8%) presented with a form of dyslipidaemia, so that 22 patients had hypertrigliceridemia, 28 patients had hypercolesterolemia, while 8 had a mix form of dyslipidaemia. Of all 58 patients, for 18 (31%) of them the dyslipidaemia diagnosis was established in our medical center; for the patients with hypertrigliceridemia, the majority (14 patients, 63,63%) had levels over 220 mg/dl, while for those with hypercolesterolemia, 18 patients (63,8%) had levels over 250 mg/dl;
. as for the cardiac diseases that were met within the studied patients, the results show that - 68 patients (38%) had ischemic cardiac disease, 27 patients had cardiac insufficiency, 12 patients had atrial fibrillation, 12 patients had mitral stenosis, and other 17 patients had different cardiac diseases (with emboligenic effect);
. altered values of glycemia were met within 82 patients (45,5%), while only 48 of them were known with diabetes mellitus (mean values for glycemia at presentation moment between 162-360 mg/dl). Besides the cases with already known diabetes, another 12 cases were identified with mean high values for glycemia between 140-189 mg/dl, that were considered states of hyperglicemia; these cases had been considered as cases with altered tolerance for oral glucosis and were directed for The Clinical Center of Diabetes, Nutrition and Metabolic Diseases in Cluj-Napoca, for further analysis; the last cases, with mean hyperglicemia values between 111-139 mg/dl were considered reactive states of hyperglicemia, who eventually came back to normal values within 5 days, without any kind of treatment;
. other identified vascular risk factors were - overweight (67 patients), obesity (52 patients), cronic alcoholism (34 patients), family history of vascular disease (44 cases), carotid artery disease (17 cases).
Discussions
From the studied patients, 153 of them presented with high values of arterial pressure, that were compatible with a diagnosis of arterial hypertension. Only 102 of the patients (66,6%) were known with hypertension, the rest of cases being diagnosed in our medical center. The strongest link for hypertension was noted for diabetes mellitus, smoking and chronic alcoholism, while the link with age was not so persistent; there were no greater incidence for hypertension with men over women, that could explained by the great number of women presenting with more than 3 vascular risk factors. 34 patiens (41,5%) with high levels of glycemia were unaware of this condition, while from the 48 patients knwon with diabetes, only 29 (60,9%) had a stabilised form of disease. Among the 12 patients with atrial fibrillation, the assessment of ischemic stroke risk was made using the CHADS2 scale, showing an average risk of 8,5%/year. 6 patients (35,3%) of those with carotid artery disease had a degree of stenosis over 70 percent. The high link between the cases of smoking, heavy drinking and obesity represent, in my own vue, a sign for an altered life style (social and food), with a final synergic effect, that needs to be accurately assessed.
Stage conclusions
1. the prevalence of hypertension, among TIA patients, is higher than in general population, with almost one third of the cases being diagnosed when presenting for a TIA episode; from the 101 patients with kown hypertension, only 39 of them followed a steady treatment at home, with only 24 cases of stabilised arterial pressure values. Thus, this calls for a better evaluation, diagnose make-up and treatement of all cases with known hypertension or being at high risk for it;
2. there can be noted a higher rate of association between the different type of risk factors, including hypertension, diabetes, smoking, dyslipidaemia, obesity and chronic alcoholism, which cand explained, on one hand, the great number of TIA episodes in the general population and, on the other hand, the high rate of ischemic stroke occurrence for these patients;
3. besides the above mentioned vascular risk factors, the presence of cardiac ischemic diasease or that of other cardiac source of embolism (atrial fibrillation, cardiac insufficency, mitral stenosis or intracavitar thrombosis) is higly noted for TIA patients, which motivates an early and complete cardiological evaluation for these cases, in order to establish the precise degree of vascular risk.
III. The acute therapy of an TIA episode and the prevention of ischemic stroke : I've taken into consideration the therapeutical agents used for improving the disturbed vascular risk factors, with notice for the type, dose and indication of these agents.
Results
. the antihypertensive agents that were used for the evaluated patients included - the ACE inhibitors, diuretics, beta-blockers, calcium channel blockers and central adrenergic inhibitors. Of the 153 patients, a number of 127 were treated using the ACE inhibitors (including Enalapril, Captopril, Perindopril si Quinapril); within the 127 patients treated with ACE inhibitors, in 94 cases (74%) the treatment was based on monotherapy; the second used class of antihypertensive agents was the diuretics, with Furosemid being administred for 37 patients (20,55%); the use of different types of antihypertensive agents, with the specified dose and association was done considering the latest recommendations on the therapy of hypertesive patients with TIA and taking note of the experience of my own and of the medical center I work in;
. the therapy for the 48 cases with diagnosed dyslipidaemia consisted of - Statins in 25 cases, Fibrates in 6 cases, and adjusting of the dietary and life style, to the new condition;
. the therapy for the known cases of diabetes or recently discovered states of hyperglicemia consisted of - continuing therapy with oral antidiabetic agents or Insulin for the known cases of diabetes that have not yet reached the normal values of glycemia at home, while for the other 34 cases, recently discovered with impaired glycemia, for the 12 patients identified with altered tolerance for oral glucose , with mean values of 140-189 mg/dl, 9 of them were given oral antiadiabetic agents (in case of glycemia over 160 mg/dl), with a mean lowering of values between 30-55 mg/dl; for the 22 cases with a state of reactive hyperglicemia, for all cases it was recommended a non-pharmacological therapy, including dietary changes, with target for glycemia lowering;
. the antiplatelet therapy used for the TIA cases included the use of Aspirin (75-100 mg/day) and Clopidogrel (75 mg/day), for known cases with prothrombotic vascular risk factors, in case of newly identified emboligen causes considered of moderate or low risk (=< 3 points with CHADS2 scale) or for reccurrent TIAs. 162 patients were given antiplatelet therapy, divided into 3 subgroups : 1) first group included patients treated only with Aspirin; 2) second group included patients that were treated with both Aspirin + Clopidogrel (75 mg/day), for a short period of time; 3) third group included patients that were treated only with Clopidogrel; 4) fourth group included 4 patients that had repetitive TIAs and received Aspirin + Low Molecular Heparins;
. the anticoagulation therapy was used for 22 cases, so that : 12 patients with known atrial fibrillation (acute or paroxistic), with presumed cardioembolic TIA, with more than 3 points with CHADS2 scale, were treated using low molecular heparins; 6 patients with repetitive TIAs (3 or 4 episodes) were treated using low molecular heparins + oral anticoagulantion; 4 patients with known prothrombotic risk factors were treated with a combination of Aspirin + low molecular heparins;
. the primary prevention of an ischemic stroke included - 1) the continuation of the antihypertensive therapy, by adjusting doses or decided to go for other combination of antihypertensive agents, for the 29 patients who continued to have high levels of arterial pressure at hospital discharge; for the patients who acquired normal values of arterial pressure the therapy was maintained the same as before; 2) for the patients with dyslipidaemia, in 25 cases the treatment included the use of statins, for 6 patients fibrates were used, while for the last 27 patients it was decided to change inly the patients's life and dietary style; 3) from the 82 patients identified with high values of glycemia at hospital admittance, only for 54 cases the diagnosis of diabetes mellitus stood up finally (48 cases with known diabetes + 6 new cases with stable high levels of glycemia at hospital discharge); 4) for the 6 patients with high degree of carotid stenosis it was decided to follow a short time treatment with injectable low molecular heparins (60-100 mg/daily) during hospitalization; after the patients were discharged, they continued treatment with Aspirin (5 cases) or Clopidogrel (1 case). For the other 11 cases with a lower degree of stenosis the treatment consisted of Aspirin from the very beginning; 5) the 148 patients that were given Aspirin while being hospitalized in the neurological clinic, continued to take Aspirin home as well; the 6 patients that took Clopidogrel remained on the same agent after discharge; the 4 patients that were considered as being at high risk for stroke and were given a combination of Aspirin + Clopidogrel ar discharge, remained with this combination for 3 months, after this they only took Aspirin, but with a closely care for monitoring tha vascular risk factors; the last group is represented by the patients that were given the combination of Aspirin + low molecular heparins and who, after hospital discharge were given Aspirin (75 mg/daily) + oral Warfarin (2 mg/daily), with a constant recommendation for INR follow up; 6) as for the anticoagulation therapy, 17 cases were left on oral anticoagulants at home, 2 cases were given Aspirin (it was considered that the high immediate risk for stroke was partially cancelled by correcting the vascular risk factors), with the last 4 cases being left on a combination of Aspirin + oral anticoagulants (low doses) with a recommendation for stroke risk reevaluation at the next visit;
Discussions
The antihypertensive therapy was initiated when blood pressure levels were above 140/90 mmHg (153 cases), even for patiens who were not known with a history of hypertension (because the literature states the benefit of an antihypertensive therapy no matter if the patients is known with hypertension or not); the main indentified causes for presenting with high values of blood pressure (for the patients with TIA) consisted of - the lack for a steady antihypertensive treatment at home, heavy alcoholism, the lack of adopting a proper dietary and life style changes, lack of presenting to regular medical visits, as well as the insufficient management of the associated diseases. I try to make an analysis regarding the evolution of blood pressure values, from the first day of admittance and the last day of hospitalizing. Considering a mean value for blood pressure of 170-180/90-100 mmHg at admittance moment, after 3 days of treatment the mean values were about 160-170/100 mmHg, while after 5 days the values decreased till 140-150/90 mmHg. I noticed a better tendency of blood pressure values lowering within patients with a steady home antihypertensive treatment, for patients with very high values of blood pressure ar admittance day (over 190 mmHg), as well as for those who didn't associate vascular risk factors that could maintain or promote the atherosclerosis process, and thus, induce hypertension (obesity, sedentary life, family history of vascular diseases, dyslipidaemia).
The antiplatelet therapy represented the main way for antithrombotic protection for the patients with TIA, included 4 different groups of patients, with non-cardioembolic risk factors or with low emboligen risk assessment.
The anticoagulantion therapy was an option for 22 cases, who were considered at high risk for emboligen manifestations, and thus for ischemic stroke occurrence - presence of emboligen risk factors (with or without atrial fibrillation, with a total score of 3 points or above with the CHADS2 score), with multiple associated vascular risk factors, including smoking and heavy drinking, old patients (over 70 years), as well as those who, at home, didn't acquire a reasonable value of the cardiometabolic parametres.
Stage conclusions
1. the correction of vascular risk factors represent the first step in the acute treatment of a TIA patient, and practically implies the lowering of high values of blood pressure (till values around 140-160/80-90 mmHg), initiating of an hipolipemiant therapy (to acquire maximum cholesterol values around 220 mg/dl and trigliceridemia around 150 mg/dl), lowering of glycemic values (for both diabetic patients and those with reactive hyperglycemia or with altered tolerance for oral glucose);
2. besides the therapy for vascular risk factors, there is a need for the use of antiplatelet therapy, using Aspirin 75-100 mg/day or Clopidogrel 75 mg/day; the antiplatelet therapy is indicated for - cases with known thrombotic risk factors, with no evidence for emboligen cardiac sources or with low assessed risk cardiac emboligen sources (less than 3 points with CHADS2 score), patients with tight carotid stenosis and for which patients refuse to undergo surgery;
3. the anticoagulation therapy is recommended for all cases with known cardiac emboligen sources, with high assessed risk for ischemic stroke (3 points or above with CHADS2 score), for cases with more than 2 episodes of TIA, for patients considered of having an insufficient antithrombotic therapy, with estimated high risk for ischemic stroke, or for patients with an INR unde 1,5;
4. prevention of an ischemic stroke consists of - accurate and early treatment of all identified vascular risk factors (by adjusting the doses, change the possible associations between the different classes of agents or look for relative causes of vascular risk maintenance), the use of antiplatelet or anticoagulation therapy (1 or 2 agents, monotherapy or in association), setting up an individual record for dietary and life style changes, who is meant to promote health and wipe out the risk for a future major ischemic event.
Conclusions
My doctoral thesis is part of the clinical based works, evaluated by the means of some chosen cardiometabolic parametres with the final goal for setting up a personal record on the differential diagnosis of a TIA episode and on the acute therapy that should be initiated in order to further prevent the occurrence of an ischemic stroke.
. a TIA episode calls for an emergency approach, as soon as possible, because a TIA patient can undergo, after a certain period of time, an ischemic stroke of variable severity;
. the acute therapy for a TIA episode includes the correction of all identified vascular risk factors, with consecutive improving of them, with the set up of an antithrombotic regime (that must be individualised accordingly to the patient own personal conditions);
. the correction of the vascular risk factors represent the first step in the treatment of a TIA episode and practically includes, first of all, the lowering of the high values of blood pressure (they should be kept at maximum 140-160/80-90 mmHg), because hypertension is the most frequent met risk factor for patients with TIA;
. the antiplatelet therapy for patients with TIA includes the use of Aspirin (75-100 mg/daily) or Clopidogrel (75 mg/daily); the cases that benefit from this therapy include - patients with known prothrombotic vascular risk factors, with no evidence for emboligen sources of high risk;
. the anticoagulantion therapy for TIA patients involves the use of low molecular heparins or of oral anticoagulants; the indication schedule includes - known emboligen cardiac sources at high risk, patients with more than 2 clinical episodes or patients that are considered of having a deficit of antithrombotic protection;
. the prevention of an ischemic stroke, among the TIA patients involves - the continuing of the therapeutical measures or of life style changes that were initiated during hospitalization, with the aim of alleviating the altered vascular risk factors, besides an antithrombotic schedule of administering (adapted after the clinical features); the indications for an acute therapy of the TIA episode + the prevention of an ischemic stroke for TIA patients are included in the personal record that I issued at his chapter.
The results, discussions and conclusions that are being presented in my doctoral thesis aim to bring to life, for both patients and fellow colleagues, the meaning of a TIA case, which, due to its increasing frequence, of its pathological implications and intercurrence with other medical conditions stands for a major issue in the internal medicine field, having a direct relevance in lowering the number of ischemic strokes, by administering an early and accurate treatment and prevention for all TIA cases, thus lowering the burden of this terrible disease in the general population.
List of published papers :
1. Calomfirescu Kory-Stefania, Stanca Delia, Marge C, Manzat Ivona. Paroxysmal diurn and nocturn non-epileptic manifestations. Acta Neurologica Transilvaniae, nr. 2, 2003, pg. 3-6;
2. Calomfirescu Kory-Stefania, Marge C, Kory-Mercea Marilena. Melkersson-Rosenthal syndrome. Acta Neurologica Transilvaniae, nr. 2, 2003, pg. 29-32;
3. Marge C. The clinical and investigational diagnosis in transient ischemic attack. Acta Neurologica Transilvaniae, nr. 3, 2003, pg. 20-23;
4. Marge C, Calomfirescu Kory-Stefania. The hereditary propensity in epilepsy. Acta Neurologica Transilvaniae, nr. 3, 2003, pg. 36-39;
5. Marge C. Neurocutaneous syndromes. Medical Life, nr. 42, 2003, pg. 3;
6. Marge C. The primary and secondary prevention in the transient ischemic attack. Acta Neurologica Transilvaniae, nr. 4, 2003, pg. 43-50;
7. Marge C. Modern treatment in transient ischemic attack. Acta Neurologica Transilvaniae, nr. 3-4, 2004, pg. 20-28;
8. Marge C. Etiopathogenesis and clinical diagnosis in transient ischemic attack. Clujul Medical, nr. 2, vol. LXXVIII, 2005, pg. 364-369;
List of scientifical oral communications and posters :
1. Calomfirescu Kory-Stefania, Zegreanu I, Marge C, Stanca Delia, Manzat Ivona. Clinical types of epilepsy in cerebral tumors. Neurooncology Reunion, Cluj-Napoca, April 2003;
2. Marge C. The existence of hereditary propensity in epilepsy. Neurology, Psychiatry and Neurosurgery Reunion, Cluj-Napoca, May 2003;
3. Calomfirescu Kory-Stefania, Stanca Delia, Marge C. The management of epilepsy. Neurology, Psychiatry and Neurosurgery Reunion, Cluj-Napoca, May 2003;
4. Calomfirescu Kory-Stefania, Marge C. Secondary prevention in transient ischemic attack. Conference - The cerebral strokes; Public Health Problems, Felix Baths, Octomber 2003;
5. Marge C, Marinescu C. The diagnosis and therapy management in orthostatic hypotension of neurological cause. First Congress of Internal Medicine, Targu-Mures, April 2004;
6. Stanescu Ioana, Marge C, Marginean I, Perju-Dumbrava Lacramioara, Bulboaca A. Epidemiological data on Stroke in Cluj-Napoca between 2003 and 2004. The VII-th National Stroke Conference, Bucharest, Octomber 2004;
7. Marginean I, Vacaras V, Marcu G, Marge C, Popescu D, Vicas Alina. The clinical and therapeutical approach in Charcot-Marie-Tooth disease. The V-th Congress of the Romanian Neurological Society, Bucharest, May 2007;
