AVM rep re sent a set of ab nor mal di rect com mu ni ca - ...

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1 /STRUÈNI RAD UDK : DOI: /ACI R Epilepsy as an initial factor of the clinical presentation of arteriovenous mal for ma tions of the brain - nat u ral his tory and risk fac tors... Ma rina Radosavljeviæ 1, Nikola R. Repac 1, Igor M. Nikoliæ 1,3, Igor B. Djoriæ 2, Aleksandar M. Janiæijeviæ 1, Siniša P. Matiæ 1,Vuk D. Šæepanoviæ 1, Vladi mir T. Jovanoviæ 1,3, Ivan S. Miliæ 1, Goran M. Tasiæ 1,3 1 Department of Neurosurgery, Clinical Center of Serbia, Belgrade 2 Center for Radiology, Clinical Center of SErbia, Belgrade 3 Faculty of Medicine, University of Belgrade, Belgrade We pres ent the re sults of treat ment of 15 pa tients with brain arteriovenous malformacijon ini tially pre sented by ep i lepsy in Neu ro sur gery, Clin i cal Cen ter of Ser bia in Bel grade, in the pe riod year. Re sults: Most of the pa tients had a grand mall type of ep i lepsy, 14 of them, while one was pres - ent pe tit mall ep i lepsy. The at tacks are man i - fested in di vid u ally in 14, and in 1 case se ries. Re - sponse to treat ment was good in 11 and 4 pa tients with re frac tory. In 26.7% of cases, sei zures al ter nated with bleeding. Anatomical features of malformations did not show a sig nif i cant dif fer ence in the pre dis po si - tion to ep i lepsy treat ment re sponse. Conclusion: Good control of epilepsy by medication sup ports the view that there is no need for ur gent sur - gi cal treat ment of brain AVM so we can gen er ally con clude that brain AVM in re la tion to a wide range of neurosurgical pa tients are in be nign le sions, which re quires pa tience and good work man ship and stra te - gic therapeutic approach. Key words: AVM of the brain, ep i lepsy, the nat u ral course rezime INTRODUCTION AVM rep re sent a set of ab nor mal di rect com mu ni ca - tion be tween the ce re bral ar ter ies and veins and are con gen i tal in or i gin. They emerge in the third week of ges ta tion, with the de vel op ment of prim i tive blood ves - sels. Ter mi na tion in the de vel op ment of prim i tive blood ves sels re sults in the for ma tion of di rect com mu ni ca tion be tween ar ter ies and veins by in sert ing a pri mor dial cap - il lary plexus be tween them 1,2. They con sist of a cen tral angiomatous nidus, feed ing ar ter ies and drain age veins. When the AVM is pro jected into the ventricul, the ves - sels which pro trudes into the ventricul are cov ered only with ependymal tis sue. AVM is usu ally fed by the branches of the mid dle ce re bral ar tery, and then the an te - rior and pos te rior ce re bral ar tery 3-5. AVM in 50-75% of cases is pre sented by hem or rhage, which is usu ally parenchymal and is more com mon in small mal for ma - tions (Par kin son et al. 1980, Co hen et al. 1982). The risk of hem or rhage in AVM is 3-4% per year while the risk of re-hem or rhage slightly higher in the first year and is about 6%. Mor tal ity from hem or rhage 10-15%, and the mor bid ity is about 30% af ter each ep i sode of bleed ing. Ep i lep tic sei zures (EPI) is the sec ond sig nif i cant as pect of the pre sen ta tion of AVM and they are the ini tial symp - tom in 24.2%, AVM has equal fre quency in men and women and they oc cur most of ten be tween 10 and 40 years of age. Most of ten fo cal sei zures oc curred and they aret gen er al ized in 55.8% of cases. In 27% cases grand mall sei zures (GM) are re frac tory to med i cal ther apy. The risk of hem or rhage in pa tients with ep i lepsy as the ini tial symp tom is about 1 to 2.3% per an num. Ev ery fourth pa tient with sei zures as an ini tial symp tom will have hem or rhage MA TE RI ALS AND METH ODS We pres ent a group of 15 pa tients with AVM of the brain in which the mal for ma tions was ini tially pre sented by ep i lepsy and CT/NMR find ings of brain pointed to ce - re bral lo cal iza tion of the AVM could cause ep i lep tic sei - zures, and ex cluded the sec ond patho log i cal sub strate that could cause ep i lepsy. Pa tients were treated at the Clinic of Neu ro sur gery (NHK), Clin i cal Cen ter of Ser bia in the pe riod from Oc to ber 2006 to May The anal - y sis clas si fies pa tients with AVM of the brain that have not been sub jected to any of the modes of treat ment: sur - gery, embolization and/or ra dio ther apy, ex clud ing symp - tom atic ther apy. The di ag no sis of ce re bral AVM is set panangiography (stan dard or dig i tal substractional). The pa tients were not treated be cause the the Collegium of Neu ro sur geons le sion as sessed in op er a ble or un suit able

2 28 M. Radosavljevic et al. ACI Vol. LXI for other forms of causal treat ment, be cause the pa tient or his fam ily re fused treat ment or be cause it is es ti mated that sur gi cal treat ment is bur dened higher risk of post op - er a tive dis abil ity than if left to the nat u ral course dis ease, and the AVM un suit able for other ther a peu tic mo dal i ties. The cri te rion for in clu sion in the study was the mo ment of di ag no sis, in which sin gle at tacks GM type dom i nate. All pa tients were fol lowed for an av er age of four years. Clin i cal fol low-up com pleted with the de fin i tive es tab - lish ment of the se ries and the start of data pro cess ing def - i nitely un treated cases or the time of ini ti a tion of the causal treat ment of AVM. To eval u ate the clin i cal and an a tom i cal char ac ter is tics of the AVM was used widely ac cepted sys tem ac cord ing to Spetzler-Mar tin (SM in - dex-score). For each AVM was made the fol low ing as - sess ment: mea sur ing the size, es ti ma tion of gen eral and neu ro log i cal sta tus, as well as work ing and liv ing skills of pa tients with AVM was per formed ac cord ing to Karnofsky index. RE SULTS The group with ep i lepsy as the ini tial mode of clin i cal pre sen ta tion AVM in cluded 15 pa tients, of whom 7 or 46.7% were male and 8 or 53.3% were fe male. The youn - gest pa tient was 11 years old and the old est 54, the av er - age age of all pa tients was 32.8 ± 11.5 years. The larg est num ber of pa tients stud ied had a grand mall (GM) type of ep i lepsy, 14 of them or 93.3%, and in one pa tient or 6.7% was pres ent pe tit mall (PM) ep i lepsy. Sei zures are in di - vid u ally man i fested in 14 or 93.3%, and in 1 case se ries, or 6.7%. Re sponse to treat ment was good in 11 or 73.3% and the re frac tory at 4 or 26.7% of the sub jects (Ta ble 1). Karnofsky in dex was lower in pa tients with re frac tory re - sponse to ther apy and sig nif i cantly lower at the end of fol low-up (p<0.05). Type of blood sup ply and the man ner of pre sen ta tion (right-left) showed no sig nif i cant dif fer - ence be tween pa tients with good and re frac tory re sponse to ther apy. Pa tients who had a re frac tory re sponse to treat ment had higher val ues of to tal AVM Mar tin-spetzler's score com pared to pa tients whose ep i lepsy is well con trolled by med i ca tion, and in these pa tients the com - bined type of drain age was dom i nated. Dur ing fol low-up in 4 pa tients there was bleed ing from the AVM, which made 26.7% of all pa tients with ep i lepsy as an ini tial sign, rep re sent ing an an nual risk of 0.14%. One (6.67%) pa tient who had AVM MS in dex 5 died two days af ter hem or rhage due to de vel oped in farc tion of ce re brum hemi sphere, due to throm bo sis of the in ter nal ca rotid ar - tery at the level of the cav ern ous si nus. Other three pa - tients had the fol low ing val ues of the in dex MS: 2 in one pa tient, 3 in one pa tient and 1 pa tient had a value of MS in dex 5. The first two pa tients were op er ated on one pa - tient reg is tered ab sence sei zures dur ing the three years of op er a tion, while were in an other ep i lep tic sei zures oc - curred with the same fre quency as be fore surgery. DIS CUS SION Crawford and as so ci ates in 1986 based on the re sults of twenty years of fol low-up of pa tients with AVM found that the risk of bleed ing, 42%, 18% of ep i lepsy, neu ro - log i cal def i cit, 27%, and death is about 29%. They also pres ent a model of a pa tient with brain AVM with gen er - ally poorer prog no sis. This is a man older than 40 years, which has sig nif i cant neu ro log i cal def i cit on ad mis sion, as well as large and deep placed AVM pre vi ously pre - sented subarachnoid hem or rhage as well as AVM lo cal - ized in the func tional zone of the brain.. Forster mak ing a cross-sec tion in the treat ment of AVM of the brain at the Karolinska Hos pi tal, Uni ver sity of Stock holm, in the pe riod year, found that there is hem or rhage as the ini tial symp tom of brain AVM in 71% of cases, ep i lepsy in 47% of cases, a si mul ta neous pre sen ta tion of ep i lepsy and hem or rhages in 23% of cases. The av er age age of pa tients at the time the ini tial bleed ing was 30 years old, and ep i lepsy 25 years. Pa tients with ep i lepsy as an ini tial sign of hav ing a chance to bleed 25% over the next 15 years, while pa tients who ex pe ri enced one hem or rhage have a chance to re-bleed of 25% over the next four years. Post op er a tively, there was a re duc tion in the fre quency of ep i lep tic sei zures in 14% of cases, while in 22% of pa tients post op er a tively de vel oped ep i lepsy, and that they had pre op er a tively. Guidetii and Delitala sum ma rize their ex pe ri ence in 145 pa tients with AVM treated con ser va tively or sur gi cally. 12 The fol low up pe - riod was 2-25 years. Male to fe male ra tio was 1.6: 1. Age of the re spon dents ranged from 5-67 years, with a peak in ci dence be tween 20 and 30 years. Over all op er a tive mor tal ity was 6.3%. The mor tal ity rate among con ser va - tively treated pa tients was 20%. These au thors em pha size that the op er a tion showed no ther a peu tic ef fect on ep i - lepsy, but ep i lepsy main tained post op er a tively, and that in four cases oc curred im me di ately af ter the op er a tion so that they came to the con clu sion that con ser va tive treat - ment is re served for pa tients with ep i lepsy that is well con trolled by med i ca tion, el derly pa tients and pa tients with un ac cept ably high sur gi cal risk. Mingrino states hem or rhage as a cause of hos pi tal iza tion for brain AVM in 5.8% of cases, while 21.6% is the ten dency to rehemorrhage 13. Hem or rhage as so ci ated with sei zures reg is ter as an ini tial symp tom in 5.8% of pa tients, whereas the coma as the ini tial symp tom is reg is tered in 17.2% of cases. Ep i lepsy as an ini tial symp tom in large AVM in 26.7% in sec ond ary AVM at 17.6% in small AVM in 10.2% of cases. Par kin son gives ab so lute pri or - ity to the sur gi cal treat ment of AVM of the brain com - pared to con ser va tive treat ment 14. Of the 100 pa tients di - ag nosed with brain AVM, 90 were op er ated with di rect op er a tive mor tal ity of l2%. 8% of pa tients who did not have ep i lepsy pre op er a tively gained ep i lepsy post op er a - tive, and neu ro log i cal def i cit were pres ent in 35%. Pellettieri in di cates that su per fi cially lo cal ized AVM are mainly pres ent by ep i lep tic sei zures while deep have a greater ten dency to bleed 15.

3 Br. 4 Ep i lepsy as an ini tial fac tor of the clin i cal pre sen ta tion of arteriovenous mal for ma tions 29 of the brain - nat u ral his tory and risk fac tors Also, he first de scribes the phe nom ena of ret ro grade flow ("back-flow") from the drain age vein AVM in the veins of the nor mal brain, which is more com mon in veins with a large shunt (high flow), and this very phe - nom e non re duces the ten dency to bleed from the AVM. The prob lem of post op er a tive ep i lepsy is at trib uted to di - rect intraoperative ma nip u la tion. It is be lieved that it is oc cur ring in an av er age of 7% of pa tients who did not have ep i lepsy be fore sur gery, while pa tients who had pre - op er a tive ep i lepsy in 54%, the im prove ment of the sta tus re mains un changed 32%, and worse find ing is reg is tered in 12% of cases 16,17. Janicijevic and col leagues sug gest that the cur rent AVM sur gery in volves the use of microsurgical tech niques, and the only sur gi cal pro ce dure that leads to a de fin i tive cure is com plete ex ci sion of the mal for ma tion with out res i dues 18. Any res i due the mal for - ma tion, which may not be greater than 1/10 of the to tal vol ume of the le sion in terms of pro pen sity to re-and per - haps cat a strophic hem or rhage is as dan ger ous as the whole mal for ma tion. Dom i nance of GM sei zures, as con - firmed by our re sults, is due to chronic hypoxia of the brain around the AVM and he mo sid erin de pos its clin i - cally si lent hem or rhage and the pres ence of deep ve nous drain age, which com presses the blood cir cu la tion in the basal gan glia 3-5,19,20. The sig nif i cance of the sup ply ing ar - tery was high lighted in the lit er a ture, be cause the feed ing ar ter ies eas ily iden ti fied on arteriography. These ar ter ies are ab nor mal in terms of an a tom i cal and phys i o log i cal char ac ter is tics, and can be re lated to the AVM in three forms: as the ter mi nal ar ter ies that end at the AVM, the tran sit ar ter ies un der go ing AVM giv ing branches par tic i - pat ing in its ir ri ga tion and tran sient ar ter ies pass ing through the mal for ma tion is not tak ing part in its ar chi - tec ture. Yasargil an a lyz ing AVM states that there are 60 pos si ble com bi na tions of ar te rial feeder ves sels for each le sion 21. Big gest drop in sys tem pres sure co mes when the sup ply ing ar te rial ves sels are cross ing in the AVM, and as a sure in di ca tion of the pres ence of steal ing blood ("steal" phe nom e non) iden ti fies the length of the ar te rial sup ply is greater than 8 cm, mea sured from the level of Wilis's hexa gon Ar te rial sup ply in the con text of the re sults of our se ries could not be sin gled out as a fac tor that af fects the qual ity of reg u la tion of ep i lep tic sei zures. Pa tients who had a re frac tory re sponse to treat ment had higher val ues of to tal AVM Spetzler-Mar tin score com - pared to pa tients whose ep i lepsy is well con trolled by med i ca tion, and in these pa tients dom i nated the com - bined type of drain age. Drain age veins have 6-10 times greater distensibility of the sup ply ing ar tery and may con tain three times the vol ume of blood from the ar tery, and the com pli ance of their times higher than in the ar ter ies. Spetzler-Mar tin's gra da tion is a sta tis ti cal con fir ma tion of har mo niz ing po si tions neu ro sur geons and neuroradiologists with re spect to an a tom i cal fea tures of the brain AVM that were pre dic tors of poor out come in pa tients if it were left to the nat u ral course of the dis - ease How ever, this grad ing sys tem has re cently been sub ject to crit i cism. Spe cif i cally, in terms of size mal for ma tions neu ro sur geons are likely to pre op er a tive di am e ter mal for - ma tions and over all value SM re cent es ti mates higher com pared to neuroradiology. Dis agree ment also man i fest in as sess ing the type of drain age, es pe cially in cases of mal for ma tion, which has a small deep drain age vein and com mand ing ex ten sive su per fi cial vein. Lo cal iza tion of the AVM is also dif fi cult to as sess in bor der line cases, ie, in ar eas that are in the im me di ate vi cin ity so. el o quent ar - eas - the somatosensory and mo tor cor tex, a cen ter for speech, vi sual cor tex, hy po thal a mus, tha- lamus, in ter nal cap sule, brainstem, cer e bel lar peduncle and deep cen tral nu clei 5. In ter est ingly, the age of the pa tient at the time of di ag no sis of AVM ini tially pre sented ep i lepsy has no im - pact on the fre quency and type of at tack and on the ther a - peu tic re sponse 23. On the other hand the re sults of sur gi - cal treat ment does not fa vor sur gery as the method of choice for the treat ment of ep i lepsy was un der AVM brain or gen u ine ep i lepsy. 24 In large AVM ep i lepsy oc - curs in 26.7%, sec ond ary 17.6% and 10.2% of small 6 Radiosurgical treat ment of brain AVM smaller than 3 cm in di am e ter ini tially pre sented by ep i lepsy, only af ter three years of treat ment sug gests that the 65% can ex pect a good med i ca tion con trol ep i lepsy and its cure. The un - re li abil ity of these re sults is re flected in the method it self (com plete oc clu sion of the AVM can be ex pected only af ter 4 years of treat ment, gamma knife in cluded), dis ad - van tages of the pro posed clas si fi ca tion sys tem AVM (es- pe cially for AVM lo cal ized in the basal gan glia and brain stem) and a tough and long se lec tion of symp toms, due to the ten dency that pa tients with AVM ini tially the pre - sented later ep i lepsy may ex pe ri ence bleed ing and vice versa 19,25,26. CON CLU SION Our re sults in di cate that ep i lepsy as an ini tial symp tom of AVM of the brain in most cases, ie, 93.3% pre sented a GM type and in 73.3% of cases had a good ther a peu tic re sponse to one of the AEDs. In 26.7% of cases, GM at - tacks are cou pled com bi na tion of sev eral antiepileptic drugs. In 26.7% of cases of ep i lep tic sei zures took turns with bleed ing, with di rect an nual risk of 0.14%. Poorly con trolled ep i lepsy ac com pa nied by a re duc tion of work - ing abil ity, Karnofsky in dex was sig nif i cantly lower in pa tients with ep i lepsy re frac tory to treat ment, while higher val ues of Spetzler Mar tin's in dex and combination with ve nous drain age pre dom i nantly found in poor treat ment re sponse. A good med i ca tion con trol of ep i - lepsy sup ports the view that there is no need for ur gent sur gi cal treat ment of brain AVM so we can gen er ally con clude that brain AVM in re la tion to a wide range of neurosurgical pa tients fall into be nign le sions, which re - quires pa tience and stra te gic good work man ship in ther a - peu tic ap proach.

4 30 M. Radosavljevic et al. ACI Vol. LXI SUM MARY EPILEPSIJA KAO INICIJALNI FAKTOR KLINIÈKE PREZENTACIJE ARTERIOVENSKIH MALFORMACIJA MOZGA PRIRODNI TOK I FAKTORI RIZIKA U radu prikazujemo rezultate leèenja 15 pacijenata sa arteriovenskom malformacijon mozga inicijalno prezentovanih epilepsijom na Neurohirurškoj klinici Klinièkog Centra Srbije u Beogradu u periodu godine. Rezultati: Najveæi broj ispitivanih bolesnika imao je grand mall tip epilepsije, njih 14, dok je kod jednog bila je prisutna pe tit mall epilepsija. Napadi su se pojedinaèno ispoljavali kod 14, a u serijama kod 1 bolesnika. Odgovor na terapiju bio je dobar kod 11 i refrakteran kod 4 ispitanika. U 26,7% sluèajeva epileptièki napadi su se smenjivali sa krvarenjem. Anatomske karakteristike malformacije nisu pokazale znaèajnu razliku u pogledu predispozicije za terapijski odgovor epilepsije. Zakljuèak. 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