Gamma Knife Radiosurgeryin Medium-sized Arteriovenous Malformations: Preliminary Report
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1 Original Article Gamma Knife Radiosurgeryin Medium-sized Arteriovenous Malmations: Preliminary Rept Masaaki YAMAMOTO, M.D.,1 Mitsunobu IDE, M.D.,1 Minu JIMBO, M.D.,1 Kintomo TAKAKURA, M.D.,2 Tatsuo HIRAI, M.D.,3 Christer LINDQUIST, M.D.,4 and Bengt KARLSSON, M.D.4 Summary: Six patients with medium-sized arteriovenous malmation (AVMs, cm in maximum diameter), treated by gamma knife radiosurgery without preceding embolization, are repted. The AVM manifested with intracranial hemrhage in three cases and with seizure in three. The maximum nidus diameter ranged from 3.4 cm to 5.7 cm, with a mean and a median 4.0 cm and 4.1 cm, respectively. Although total AVM coverage at time dose planning was feasible in four patients, selected dose at periphery nidus was limited to Gy (total coverage and non-optimal dose treatment). The two remaining patients had only partial coverage; part nidus adjacent to maj feeding artery was covered and a dose Gy was given within this limited area, although remaining part nidus was irradiated with a dose Gy less (partial coverage and optimal dose treatment). Neir hemrhage n significant radiation-induced complications occurred in any six cases during postradiosurgical follow-up period which ranged from 18 to 85 months (mean 48 months). Complete nidus obliteration was angiographically confirmed 38 months after radiosurgery in one case, me than 90% obliteration treated nidus, respectively, 36 and 70 months after radiosurgery, in two cases. Magnetic resonance (MR) angiography demonstrated disappearance nidus in one case and remarkably decreased nidus volume in one, respectively, 30 and 18 months after radiosurgery. In one remaining case, MR imaging obtained at 24 months after treatment showed a significantly diminished flow signal void, as well as appearance a gadolinium enhanced area within treated nidus. In addition, a T2-weighted image showed hyperintense edema surrounding AVM. These results indicate that single irradiation a medium-sized AVM using a gamma knife, though not optimal, can produce complete nidus obliteration, significant nidus shrinkage, two-six years, me, after radiosurgery. Even in latter instance, shrunken AVM can easily be re-treated using a gamma knife. Introduction Radiosurgery using a gamma knife, a linear accelerat system a system incpating Bragg peak proton beam, is nowadays an established treatment alternative small volume arteriovenous malmations (AVMs) located in critical brain structures.3) `7)10)11)14) `19)21)22)23)25)26)28) `31)36) In Department Neurosurgery, 1 Dai-ni Hospital and 2 Neurological Institute, Tokyo Women's Medical College, 3 Heisei Memial Hospital, 4Karolinska Hospital, Stockholm (Sweden) (Received May 23, 1996) kmailing address: Masaaaki YAmAmoTo, M.D., Department Neurosurgery, Tokyo Women's Medical College Dai-ni Hospital, Nishiogu, Arakawa-ku, Tokyo 116, Japan l
2 Table 1 Preradiosurgical clinical characteristics, angiographic features, dose planning and neuro-imaging follow-up results gamma knife radiosurgery, 80-90% AVMs not exceeding 3.0 cm in any diameter can be expected to undergo complete obliteration after a two- threeyear latency period, with relatively low incidences radiation-induced complications.14) `17)21)23)25)29)30)31) 36) On contrary, although it is technically feasible to treat larger AVMs, rapeutic radiation doses cannot be safely delivered. Theree, pre-radiosurgical embolization has generally been carried out relatively large AVMs, to achieve volume reductions so as to be acceptable gamma knife treatment, and good results this staged approach have recently been repted.1)12) However, because po accessibility caterization feeding arteries, not all patients are good candidates Preradiosurgical embolization. Guo et al.12) repted that, even among 144 AVMs in which volume reduction by embolization had been attempted subsequent gamma knife radiosurgery, 80 (56%) nidi were still too large radiosurgery. Furrme, a number central questions as to this combination treatment modalities remain unanswered. In particular, furr long-term follow-up results are necessary to assess wher obliterated nidus has any potential recanalization which could, eventually, lead to rebleeding. Meover, most appropriate interval between embolization and radiosurgery remains to be determined. Herein, we rept six patients whose mediumsized AVMs ( cm in maximum diameter, by Spetzler-Martin grading system 27)) were treated with gamma knife radiosurgery without preceding embolization. These results indicate that single irradiation a medium-sized AVM using a gamma knife, even when less than optimal, can induce complete nidus obliteration, significant nidus shrinkage, two-six years, me, after radiosurgery. Even in latter instance, shrunken AVM can easily be re-treated using a gamma knife. Materials and Methods I. Patient Population Among 41 patients with AVMs treated by means gamma knife radiosurgery during period from 1978 to 1994, six patients whose nidi were 3.0 cm larger in maximum diameter were selected this study. Preradiosurgical clinical characteristics are shown in Table 1. The patients ranged in age from 14 to 54 years (mean, 27 years) at time radiosurgery. There were two females and four males. The AVM manifested with intracranial hemrhage in three cases and with seizure in three. At time radiosurgery, five patients had no neurological deficits, while one patient had left hemiparesis. Two AVMs were located in parietal lobe, two in thalamus basal ganglia, one in frontal lobe and one in tempal lobe. The maximum nidus diameter ranged from 3.4 cm to 5.7 cm, with a mean and a median 4.0 cm and 4.1 cm, respectively. None patients had previously 466
3 undergone eir fractionated external beam radiation interventional radiology. However, a cerebrospinal fluid shunt operation had been carried out in one (Case 5) and an unsuccessful clipping feeding artery in an (Case 2). II. Gamma Knife Treatment Two patients (Cases 1 and 2) underwent gamma knife radiosurgery at Karolinska Hospital, Stockholm, one (Case 3) at Heisei Memial Hospital, Fujieda and three at Tokyo Women's Medical College. Dose planning data se six patients are shown in Table 1. Stereotactic angiography was mainly used dose planning in all cases, computed tomographic (CT) scan and magnetic resonance (MR) imaging were also used in four cases (Cases 3, 4, 5 and 6). Although four patients (Cases 3, 4, 5 and 6) had total AVM coverage at time dose planning, optimal dose (20 Gy me) could not be given (total coverage and non-optimal dose treatment). The two remaining patients had only partial coverage; part nidus adjacent to maj feeding artery only was partially covered and an optimal dose was given within this limited area (partial coverage and optimal dose treatment), although remaining part nidus was irradiated with a dose Gy less. Results I. Clinical Outcomes All patients returned to ir previous employment activity level after gamma knife radiosurgery. Although one patient (Case 2) experienced two generalized convulsive seizures on first postradiosurgical day, no subsequent changes in his seizure frequency have thus far been repted. Neir hemrhage n significant radiation-induced complications occurred in any six cases during follow-up period ranging from 18 to 85 months (mean, 48 months), although transient hair loss developed in a 2 cm in diameter irradiated area in one case (Case 6). II. Neuro-imaging Assessment Complete nidus obliteration was angiographically confirmed 38 months after radiosurgery in one case (Case 2) and me than 90% obliteration treated nidus in two (Cases 1 and 3) 70 and 36 months after radiosurgery, respectively. MR angiography demonstrated disappearance nidus in one case (Case 4) and remarkably decreased nidus volume in one case (Case 6), 30 and 18 months after radiosurgery, respectively. In one remaining case (Case 5), MR imaging obtained 24 months after treatment showed significant decreases in flow signal void and appearance a gadolinium enhanced area within treated nidus, as well as adjacent parenchymal changes appearing as a hyperintense area on T2- weighted image. Case 1: A 25-year-old female underwent gamma knife radiosurgery an AVM located in left parietal lobe, which had manifested with seizure, at Karolinska Hospital on October 12, Because nidus was too large total coverage and optimal dose treatment, lower half nidus, which was adjacent to two maj feeding arteries, was partially covered with a 50% isodose volume using two target points with an 18-mm collimats (Figs. 1, A and B). A central dose 50 Gy was used. Although angiography showed minimal changes 21 months after treatment, 70 month postradiosurgical angiography demonstrated only a small residual nidus; me than 99% treated nidus had been obliterated (Figs. 1, C and D). Following radiosurgery, this patient became pregnant and experienced a nmal delivery following an uncomplicated pregnancy. She has experienced neir rebleeding, complications related to irradiation, n subsequent changes in her seizure frequency over seven years since gamma knife radiosurgery. However, 57 month postradiosurgical MR imaging revealed appearance a cyst within target volume surrounded by hypointense edema. Subsequent MR imaging follow-up demonstrated a gradual increase in cyst volume through 79th. postradiosurgical month (Figs. 2, A and B). This patient has thus far had no difficulty daily life as a house wife, though meticulous examinations focusing on left parietal lobe functions have not yet been permed. The residual AVM was re-treated using a gamma knife on October 5, The nidus was covered with a 55% isodose volume using seven target points, one with a 14-mm collimat and six with an 8-mm collimat. A central dose 34 Gy was used to obtain a marginal dose 18.7 Gy Case 2: Because his pri refusal to undergo surgical resection, this 28-year-old male, who had Surgery Cerebral Stroke 24 :
4 Fig. 1 Sequential angiograms in Case 1 obtained at time (A; carotid [upper] and vertebral [lower] angiograms and B; isodose gradient superimposed on carotid angiogram) and 70 months (C; carotid and D; vertebral angiograms) after radiosurgery. Seventy month postradiosurgical angiography demonstrates that me than 99% treated nidus has been obliterated. The residual nidus (C; arrow) is not included within target volume. undergone unsuccessful clipping feeding artery, underwent gamma knife radiosurgery a ruptured left parietal lobe AVM at Karolinska Hospital on December 14, The nidus was too large to be totally covered and irradiated with an optimal dose. Theree, lower half nidus, which was adjacent to maj feeding artery, was partially covered with a 30% isodose volume using two target points with an 18-mm collimats (Fig. 3, 468 脳 卒 中の 外 科24:1996 A). A central dose 70 Gy was used. On day after radiosurgery, generalized convulsive seizure occurred twice. However, re were no subsequent changes in his seizure frequency over six years following gamma knife radiosurgery. Complete obliteration was angiographically confirmed 38 months after radiosurgery (Fig. 3, B). He has thus far experienced neir rebleeding n complications related to irradiation.
5 Fig. 2 Postgadolinium, T1-weighted magnetic resonance images Case 1 obtained 70 (A) and 79 (B) months after radiosurgery showing an enlarging hypointense cyst with surrounding edema. Case 3: A 20-year-old male underwent gamma knife radiosurgery an AVM located in right frontal lobe, which had manifested with seizure, at Heisei Memial Hospital on August 11, Because nidus was diffusely filled with numerous small tributaries from two maj feeding arteries (pericallosal and callosomarginal arteries), nidus could not divided into compartments. Theree, nidus was totally covered with 40% isodose volume using seven target points, three with an 18-mm collimats, three with a 14-mm collimats and one with an 8-mm collimat (Fig. 4, A). A central dose 35 Gy was used to obtain a marginal dose 14 Gy, based on dose-volume curve repted by Kondziolka et al.19) A gradual decrease in nidus volume was demonstrated by one-, two- and threeyear postradiosurgical MR angiography. Three-year postradiosurgical angiography demonstrated only a small residual nidus (Fig. 4, B, me than 90% obliteration); this residual AVM was re-irradiated using a gamma knife on August 11, The nidus was covered with a 60% isodose volume using two target points, one with a 14-mm collimat and one with an 8-mm collimat. A central dose 33.3 Gy was used to obtain a marginal dose 20 Gy. The patient has experienced neir rebleeding, complica- Surgery Cerebral Stroke 24 :
6 Fig. 3 tions Sequential angiograms in Case 2 obtained at time (A; isodose gradient superimposed) and 38 months after radiosurgery (B). Complete nidus obliteration was angiographically confirmed three years after treatment, although upper part AVM had not been included within target volume. related his to seizure irradiation, n frequency gamma knife subsequent over changes three that only in years since radiosurgery. Discussion It is widely accepted total coverage treatment; peripheral isodose described cure by and with a peripheral Steiner,29) small can AVMs be keep reduced 10% two less, is rates latency small as 3) that patients been are following total carried out, observed continue remarkable several a gamma second obliteration ment can from a po knife to 1, recommended 3-6). as this 脳 卒 中 の外 科24:1996 1, treat- expected if se years,,32) nidus treated treatment induced me, elsewhere, although by place irradiation by Even end if "non-optimal" treat- with a medium-sized AVM good shown et al, treatment candidate by in five ir gamma our recent method cases article, com- obtained, a relatively Steiner, (Cases obliteration repted taken a patient that here year.21)23)31)35) radiosurgery, (Cases 470 have is not change However be after changes knife obliteration non-optimal in years radiosurgical plete we 5 ` treatment three-six As changes most "a can radiosurgery. to to postradiosurgical subtotal which dose AVMs, repted in radiosurgery-induced using cases after successful same as years rate AVMs.8)35) Gy", chance larger with AVMs, has small indicate medium-sized ment" with compared three 25 three complication within period, outcomes 2 and cases chance obtained, higher While radiation-related results a 90% radiosurgery.10)11)17)21)22)23)25)29)30)31) should optimal dose achieve within "an 50% large Fig. 4 Sequential angiograms in Case 3 obtained at time (A; isodose gradient superimposed) and 36 months after radiosurgery (B). The nidus was covered with a 40% isodose volume at time irradiation and three-year postradiosurgical angiography demonstrated remarkable nidus shrinkage.
7 In Case 1, MR imaging demonstrated that enlargement cystic degeneration including treated nidus had been ongoing through fifth and seventh postradiosurgical year. Lindquist 20) experienced three patients with delayed cyst mation; all three had been asymptomatic. Fster 9) also experienced three patients with this type complication. Although all three patients were asymptomatic, one three patients underwent surgery to exclude possibility neoplastic changes. However, pathological study disclosed nothing special but gliosis and spongy state. Tanaka et al. experienced one patient with symptomatic cyst mation three years after radiosurgery. In this patient, aspiration followed by placement Ommaya's reservoir was carried out (Tanaka T, Kobayashi T, Kida Y, Department Neurosurgery, Komaki City Hospital, Komaki, personal communication, April, 1995). As we repted elsewhere,33) among 40 AVM patients who underwent gamma knife radiosurgery abroad between 1978 and 1991, we experienced three patients with delayed cyst mation within target volume, which were demonstrated by MR imaging five, seven and ten years after treatment, respectively. Although mechanism delayed cyst mation has not yet been known thoughly, a breakthrough blood brain barrier can be considered to play a maj role. Furrme, relatively high blood flow volumes and increased permeability through incompletelyinjured blood vessel walls within treated nidus, despite angiographically visible invisible, may enhance cyst mation within area radiosurgically-induced degeneration; coagulation necrosis to liquefaction necrosis continues several years after radiosurgery.32) As we repted previously,36) an autopsy study a patient with an AVM treated with gamma knife radiosurgery, in which postmtem studies were permed following AVM-unrelated death 24 months after treatment, disclosed exudation albuminous fluid within treated nidus. Theree, this patient (Case 1) recently underwent second course gamma knife radiosurgery. Acknowledgement The auths would like to thank Masatake HAMASAKI, M.D. second course gamma knife radiosurgery in one patient (Case 1) and Bierta E. Barfod, M.D., University Washington School Medicine, her assistance in pro reading English manuscript. AVMs not be discarded and that research aimed at refining techniques used be continued.31) The Mayo Clinic group recently repted that six eight larger AVMs (volume 11 `30 cm3) showed complete obliteration between one and three years after gamma knife treatment 37) In a patient with an unruptured AVM presenting with epilepsy headache, with an accidentally discovered asymptomatic AVM, we advise radiosurgery using this method, even if nidus is 3.0 ` 6.0 cm in maximum diameter. In an AVM which has never bled, re is relatively little risk interim bleeding during post-irradiation latency period which precedes nidus obliteration.2) Preradiosurgical embolization, though generally used as a treatment alternative, is not advisable se conditions. As we repted elsewhere,34) radiosurgery is me advantageous than embolization in which it is impossible to occlude arteries selectively and in which, ree, risk bleeding during, immediately after, procedure is rar high. Bleeding in a residual nidus after embolization has been repted in 7% to 11% cases.1)24) In contrast, we cannot recommend radiosurgery a ruptured, medium-sized AVM unless both surgery and embolization are contraindicated; same is true patients who refuse surgery, as with Case 2 in this rept. Debate continues as to which type treatment is me effective AVM obliteration, "total coverage and non-optimal dose treatment" "partial coverage and optimal dose treatment". Occasional AVM obliterations have been experienced following latter type treatment, which has also been described as "compartment treatment" by Inoue et a1.13) Steiner et al.31) have repted that nidus obliteration can occur if embryologically determined strategic site pathological shunt is accidentally included within target volume. Thus, "partial coverage and optimal dose treatment" can be used in a case in which an AVM is fed by a one two artery system, as in Cases 1 and 2 repted here. In contrast, only "total coverage and non-optimal dose treatment" is applicable an AVM diffusely fed by several, small arteries, as in Case 3 repted here. These preliminary results suggest that this type treatment can, at least, reduce volume a medium-sized AVM from unsuitable to suitable gamma knife radiosurgery. Surgery Cerebral Stroke 24 :
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