Long-term results of radiosurgery for arteriovenous malformation: Neurodiagnostic imaging and histological studies of angiographically confirmed nidus obliteration

Surg Neurol 1992 ;37 :219-30

219

Long-Term Results of Radiosurgery for Arteriovenous Malformation : Neurodiagnostic Imaging and Histological Studies of Angiographically Confirmed Nidus Obliteration Masaaki Yamamoto, M .D., Minoru Jimbo, M.D ., Makio Kobayashi, M .D ., Chisato Toyoda, M .D ., Mitsunobu Ide, M .D., Noriko Tanaka, M.D., Christer Lindquist, M.D., Ph .D., and Ladislau Steiner, M.D ., Ph.D . Department of Neurosurgery, Dai-ni Hospital, and Department Pathology, Tokyo Women's Medical College, Tokyo, Japan ; Department of Neurosurgery, Karolinska Hospital, Stockholm ; and Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia

Yamamoto M, Jimho M, Kohayashi M, Toyoda C, Ide M, Tanaka N, Lindquist C, Steiner L . Long-corm results of radiosurgery for arteriovenous malformation : neurodiagnostic imaging and histological studies of angiographically confirmed nidus obliteration. Surg Neurol 1992 ;37 :219-30 . Detailed follow-up results for 25 patients treated for cerebral arteriovenous malformation (AVM) with a gamma unit are presented . Complete nidus obliteration was angiographically confirmed in 16 (73cc) of 22 cases receiving full-dose irradiation . There were no radiation- or AVMrelated mortalities . However, we did experience one case of radiation-related morbidity and one of angiographyrelated mortality, the autopsy findings of which are discussed . Computed tomography scan and magnetic resonance imaging follow-up studies of radiosurgically treated AVMs indicated that increased enhancement of the nidus after contrast or gadolinium administration could persist even after obliteration of the AVM was angiographically confirmed . Arteriovenousmalfortnation ;Radiosurgery ;Stereotactic neurosurgery ; Magnetic resonance image ; Computed tomography ; Autopsy KEYWORDS :

Stereotactic radiosurgery with a gamma unit may be the treatment of choice for some cerebral arteriovenous malformations (AVMs) [2,7-9,12,17,18,22], acoustic neurinomas [14,23], and adrenocorticotropic hormoneproducing pituitary tumors [3,16] . The results of this procedure for AVM have been reported by Lindquist and Steiner [12], Lunsford [13}, and Steiner [18] . How-

ever, few reports analyzing the long-term results in detail, including histological study and investigations with computed tomography (CT) scans anti magnetic resonance (MR) imaging, have been published [6,22] . Since 1978, some 26 patients with AVM have been taken from Tokyo to foreign facilities to undergo stereotactic radiosurgery with a gamma unit . In this article the long-term follow-up results in 25 of the 26 cases are presented in detail, with special reference to CT and MR findings in AVMs angiographically confirmed to have been obliterated . One autopsy case is also discussed_

Summary of Cases

Patient Population Between 1978 and 1989, 25 patients with AVMs (24 Japanese and one Indonesian) were treated radiosurgically with a gamma unit (Table 1) : 22 cases at Karolinska Hospital, Stockholm ; 2 cases (cases 11 and 12) at Clinica Del Sol, Buenos Aires ; and I case (case 13) at Presbyterian University Hospital of Pittsburgh . The patients ranged in age from 9 to 54 years (mean 25 years) at the time of radiosurgery . There were 14 males and 11 females . None of the patients had undergone either radical surgery for the AVMs or interventional radiology before radiosurgery . However, a cerebrospinal fluid shunt operation had been carried out in five cases and a craniotomy for another intracranial condition in one- Case 3 was the only patient who had received prior irradiation .

Clinical Presentation Masaaki Yamamoto, M .D ., Department of Neurosurgery, Tokyo Women's Medical College, Dai-ni Hospital, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, Japan . Received July 22, 1991 ; accepted October 3, 1991 . Addrett reprint requertr to .

9 1992 by

Hlse.iec5„cnce

Publishing Co ., Inc .

The AVM manifested with seizure in I patient and with intracranial hemorrhage in the other 24 . The number of hemorrhages was one in 18 patients, two in 4 patients, and three in 2 patients . At the time of radiosurgery 16 0090-3019i92./S5 .00



220

Table

Neurol 1992 ;37 :219-30

Yamamoto

Surg

et

at

1 . Summary of Clinical Data of 25 Cases of AVM Treated by Radiosurgey Clinical symptoms

Case

Age ./sex

Onset

1 2 3

54/M 11/F 19/F

SAH SAH' SAH 2

4 5 6 8 9 10

22/M 22/M 10/F 32/F 19/M 16/F 11/M

SAH SAH SAH SAH SAH SAW SA11 2

11 12 13 14 15 16

39/M 14/M 43/M 27/M 30/F 9/F

SAH 2 SAH SAH SAH SAH SAH

P 18 19 20 21 22 23 24 25

9/M 43/F 19/F 13/F 14/M 25/F 28/M 47/M 26/M

SAH SAIL SAH SAW SAH Seizure SAH SAH SAH

7

Convulsion

Neurological deficits"

Interval between onset and radiosurgery.) (m '6

154 133 123

35 4

111 98 97

6 57 122

67 66 58

12

52 50

Mental list Balance dist Diplopia

Hemiparesis,

+

+

+

Monoparesis Diplopia Hemiparesis, Dysmetria . It

it

it

37 37 36

Facial paresis Mental ret Hemiparesis, It

Hemiparesis, rt

i +

Follow-up period after radiosurgery (ino)

35 15 6 72 12 120 84 336 20

36 26' 35 31 33 32 30 29 29

Abbreviation ... disc, disturbance; It. left, wt retardation, a, right : SAH. scharachuo,d hemorrhage once . SAH'-, SAH twice; SAH' . SAH three times . Before radiosurgery . Died of pulmonary embolism .

(64%) of the 25 patients had no neurological deficits, while the other nine (36%) had mild neurological symptoms . The interval between onset and radiosurgery ranged from 4 to 336 months, with a median of 14 months . The follow-up period after radiosurgery was 26-154 months, the mean and median being 61 and 45 months, respectively (Table 1) . Angiographic findings . The location and size of the nidus, feeding arteries, and draining veins are presented in detail in Table 2 and summarized in Table 3 . The size of the nidus was calculated from the stereotactic angiogram obtained during radiosurgery, with correction for magnification . The maximum nidus diameter ranged from 8 mm to 43 mm, with a mean of 20 mm . The location of the nidus was supratentorial in 21 cases and infratentorial in four .

Stereotactic Radiosurgery

In cases 22 and 23, in which AVMs were too large to be covered completely at the optimal dose, partial

coverage by irradiation was accomplished by using two target points with an 18-mm collimator . In the other 23 cases the AVMs were completely covered with a 50% 90% isodose volume . The selected target dose given by the gamma unit was 15-35 Gy (mean 25 Gy) at the periphery and 24-70 Gy at the center of the nidus (Table 2) . Following radiosurgery, 23 cases were periodically examined by means of angiography until total obliteration of the nidus was confirmed . In the other two cases follow-up angiography has not yet been performed because the patients have refused it . Among the 23 patients, 9 had been examined by CT scan and MR imaging, 1 only by CT scan, and 1 only by MR imaging more than 19 months after radiosurgery . Serial CT scans of the nidus in the horizontal plane and MR images in horizontal and frontal planes were obtained in 5-mm slices . For MR imaging a 1 .5-Tesla 200 FX unit was used . TI-weighted images were obtained at SE 500 ms/20 ms and T2-weighted images at SE 2500 ms/80 ms . In the first study in case 15 only, a 0 .5Tesla G50 unit was used for MR imaging . Contrast



54/M

14/F

19/F 22/M

22/M

10/F

32/F 19/M

16/F

11/M 39/M 14/M 43/M 27/M 30/F 9/F

9'M 43/F

19/F 13/F

14/M 25/F

28/M 47/M 26/M

I

I

3 4

5

6

7 8

9

10 11 12 13 14 15 16

17 18

19 20

21 22

23 24 25

Parietal, I It Lingual g ., It Thalamus, rr

Temporal I ., It Parietal .I, It

Midbrain, It Thalamus (pulvinar), 1t Splenium of core . cal . Pineal area, It Thalamus, It Cerebellum, It Parietal I ., It Thalamus, It Pons, tt Parahippocampal g ., tt Pons, rt Lat. occipitotemp . g ., It Thalamus, rr Thalamus, It

Parahippocampal g ., It Splenium of Corp . cal . Thalamus . It Parahrppocampal g., It Post. corona radiata, rt Uucalg ., rt

touation"

x 12 x 8 x 10 x 10 x 12 x 12

x 16 x 11 x 15 x 10

43 x 36 x 30 12 x 11 x 8 8 x 6 x 6

15 x 13 x 14 34 x 28 x 27

10 x 10 x 10 28 x 17 x 15

21 x 18 x 16 30 x 20 x 20

13 16 20 21 16 13 14

22 x 12 x 11

15 x 10 x 10 23

27 x 111 x 10

AICA MTA (via PCeA) PChA AChA,PChA, ThP MTA PPA, AA, CMA PCA, CMA CA ThP CV VG ICV

18 mm x 2 14 min x 1 14 mm x 1

2 1, I 1 2

14 mm x 1 18 Into x 7

x x x x x

CV CV

ICV ICV

mm mm mm mm mm

14 18 14 14 18

x 1 x 1 x 1 x 1 x 1 x 1 x 1

VG IVV

mm mm mm mm mm mm mm

VG VG PCV CV BV PV BV

PCeA, SCA PChA SCA PPA, PCeA PChA AICA PChA

14 11 14 18 14 14 14

14 mm x 2

VG

7(110-35/ 30/27 27/25

40/20 50/0-20-/

28/25 45/23

32/16 50/25

35/30 40/20 36/25 50/25 32/22 24/22 38/25

50/25

50/35 50/25

PChA, PCA

SCA AChA

BV BV

30/15

x 1, x 1 x 2 x 1

14 min 8 nmi 4 mm 14 mm

50/25 50/25

ICV

AChA

VG

14 mm x 1 14 mm x I

ICV BV

50/25

50/25

Dose tmax/peri) a

50/25

AA

9 x 9 x 9

14 mm x I

14 mm x I

I(-V

BV

Draining vein`

14 turn x I

PCIsA, ThP AChA

PCLA, PCA

PChA

Feeding artery'

15 x 15 x 14 12 x 12 x 8

26 x 15 x 15

25 x 15 x l5

Size (mm)

Collimator size X no . of targets

Radiosurgery

Total Partial

Partial Partial

Partial Partial

No change Partial

Partial Partial Total

Partial

Partial

Total

Total

Total

No change

1

Partial Total

Total Partial

Partial`

Partial Partial

Total Total

Partial Total

Total Total Total

-

-

Partial - -

Partial

Total

3

Partial

Partial Total

Total

Partial

total

Partial

2

Angiographic, follow-up' (years after radiosurgery)

Partial^

Total

Location : Corp . cal ., corpus ndL u ; g., atru.s : I ., lobe; Lt_ lateral. It, Ictt, teed . . medial ; occ p a e ,p ., o pt t - mpntal ; posy, pasteri . ; t net, Feeding artery : a, artery ; AA . angular a ; AChA,anterior churoidal a : AICA, anterior interior cerebella, a : CA . cAcarine a ; CMA, callosomarginal a ; MTA, middle temporal a : PCA ; pericallosal a ; PCeA, posterior cerebral a : PChA, posterior churoidal a: PPA, posterior parietal a ; SCA, superior cerebellar a ; ThP, thalami perforating arteries . Draining vein : BV, basilar vein v ; CV, cortical (v) : ICV, internal cerebral v ; IVV, inferior ventricular v ; VG . v of Galen; PCV, precentral cerebellar v ; PV . petrosal v . ° Maximurn dose/peripheral dose . ' Angiographic folLrw-up : partial ; partial obliteration ; total ; total obliteration . /Nidus was partially covered . ' Neatly coral .

Agei sex

Case

Angiographi( features

Table 2 . Angiographic Features, Dote-Planning Data, and Results of Angiographic Follow-up



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Surg Neurol 1992 ;37 : 2 1 9-30

Table 3 .

Yamamoto et al

Summary of Angiographic Findings of AVM

Finding Location Temporal lobe Parietal lobe Occipital lobe Thalamus Corpus callosum Pineal area

No . of cases

2

I

Brain stem Cerebellum Size -10 mm 10 mm
Feeding artery and draining vein Perforating artery 12 Deep vein Cortical vein I Corneal artery 4 Deep vein 5 Cortical vein Both of the above Deep vein

18 supratentorial lesions were shown to have been completely obliterated . In particular, complete obliteration was obtained in six of seven thalamic AVMs, and more than 95% obliteration was confirmed in the one remaining case (case 25) . In contrast, among four infratentorial lesions, only two were shown to have been completely obliterated ; the rate was one of three for brain stem AVMs . of

9

material and gadolinium diethylene-triamine-pentaacetic acid (Gd-DTPA) were given as bolus injections, and scanning was begun immediately .

Results of Treatment Angiographic follow-up . The results of follow-up angiography in each patient are shown in Table 2 . A total of 43 angiographies were carried out in 23 (92%) of 25 patients between 1 and 5 years after irradiation . In case 22 total obliteration of the nidus could not be expected because only partial coverage was achieved . Among the other 22 patients, total obliteration was confirmed in five (29%) of 17 patients who underwent angiography 1 year after irradiation . At 2 years the other five patients underwent angiography and the AVM was shown to have been completely obliterated in three patients . Complete obliteration of the AVM was also angiographically confirmed at 2 years in six of the 12 patients in which the AVMs had been shown to be partially obliterated or unchanged at the previous examination . Therefore the AVM was successfully obliterated in 14 (64%) patients within 2 years after irradiation . Complete obliteration of the AVM was also angiographically demonstrated in one patient each at 3 and 5 years, bringing the total to 16 (737) . In the other six cases angiography showed that the AVM had decreased in size . With regard to the location of the nidus, 14 (78%)

Outcome . No hemorrhages occurred in any of the 25 patients during the follow-up period after radiosurgery . There has been no aggravation of clinical symptoms in any of the patients except for one who has been suffering from facial nerve paresis since 19 months after irradiation (case 15) [21 ) . Although there were no deaths related to the irradiation itself, one patient died as a result of pulmonary embolism following cerebral angiography performed 26 months after irradiation . Consequently, the morbidity rate after radiosurgery and the management mortality rate were both 47 . All eight patients who were less than 15 years of age at the time of radiosurgery showed normal physical development but mental development was subnormal in two . In these two cases mild mental disturbance that had existed before radiosurgery persisted, but neither patient experienced any exacerbation . In cases 6, 9, and 21, static hormonal levels measured 8, 5, and 2 years, respectively, after irradiation were all within normal limits .

CT scans and MR imaging . The results of enhancement studies in CT scans and MR images are presented in Table 4 . Follow-up angiography showed complete obliteration in 7, nearly complete obliteration in 2, and partial obliteration in 2 cases . After contrast administration CT scans showed significant enhancement of the AVM in all 11 cases . None of the cases showed a flow signal void related to the AVM, except for one case in which the AVM was shown to have been partially obliterated (case 17) . In all cases, except 17 and 21, MR images demonstrated significant enhancement of the AVM after administration of gadolinium, diffusely in live cases and partially in three ; in case 15, significant enhancement was demonstrated once during the follow-up period, but thereafter it disappeared [21) . In case 6, in which the nidus was angiographically shown to have been obliterated 1 year after radiosurgery, significant gadolinium enhancement of the nidus was apparent as long as 8 years after radiosur gery, as presented below . Report of Three Cases Three cases worthy of special consideration are presented .



Surg Neurol 1992 ;37 :219-30

Radiosurgery for Arteriovcnous Malformation

Table 4 .

Suinm

y of CT Scan and MR Imaging Findings (I ] Cases) MR

Interval between radiosurgery and CT and MRI (mo)

6

I0%F

96

Obliteration on angiography Total

9

16/F

62

Nearly total

Case

30i F

15

19

Not performed

28

Total

16

9iF

24

Total

17

9/M

24

Partial

18

4 ;/F

26

Total

19

191E

25

Total

20

13/F

24

Total

21

14/M

33

Partial

24

4'!M

24

Total

25

26%M

24

Nearly total

The

area

of

223

enhancement was smaller

them

CT

Flow

contrast enhancement

signal void

+ (partial)

-

4

(partial) + (diffuse) + (partial)' i (partial) + (diffuse) + (diffuse) (partial) + (partal) (partial) + (partial) + (partial)

image Gd-DTPA

enhancement + (diffuse) + (partial) + (diffuse) + (partial)

+ + (diffuse) + (partial) + (diffuse) Not performed + (diffuse)

that of the previous examination .

Case 6 : Significant Gadolinium Enhancement 7 Years After Angiographically Confirmed Nidus Obliteration A 9-year-old girl was admitted to our facility following the sudden onset of headache and frequent vomiting on January 20, 1983 . A CT scan demonstrated intraventricular hemorrhage, and angiography revealed an AVM located in the medial temporal lobe (Figure 1, top) . Radiosurgery was performed on May 9, 1983 . The nidus was covered with a 50(~(' isodose volume administered at two target points with 14-mm and 8-mm collimators . A central dose of 30 Gy was used to obtain a marginal dose of 15 Gy . Complete obliteration of the AVM was angiographically confirmed 1 year after radiosurgery (Figure 1, bottom) . The patient was seen on March 3, 1991, for a routine medical examination following an uncomplicated postirradiation course . She showed normal mental and physical development, and static hormonal measurements were all within normal limits . When CT scanning and MR imaging were carried out 9 years after irradiation, contrast and gadolinium administration enhanced the

nidus slightly and significantly, respectively (Figure 2 A-D) .

Case 18 : Autopsy Case A 42-year-old woman was admitted to a local clinic on May 15, 1987, following the abrupt onset of severe headache. A CT scan showed a hematoma in the left temporal lobe . Angiography demonstrated an AVM, fed by the vertebrobasilar and internal carotid artery systems, in the lower part of the left temporal lobe (Figure 3, left and right) . She was subsequently referred to our facility . Radiosurgery was carried out on August 2, 1988 . The nidus was covered with a 50% isodose volume administered at two target points with 18-mm and 14-mm collimators . A central dose of 50 Gy was used to obtain a marginal dose of 25 Gy . Angiography showed nearly total obliteration of the nidus 1 year after irradiation, and complete obliteration was confirmed by reexamination carried out on October 18, 1990 (Figure 4, left and right) . On CT scans and MR images examined at the same time, the nidus was



224

Surg Neurol 1992 ;37 :219-30

Yamamoto et al

ventricle (Figure 6, left). A change caused by old hemorrhage was seen in the white matter of the left temporal lobe . Many meandering blood vessels had obstructed lumina owing to intimal hypertrophy (Figure 7 A-C) . Within the obstructed vessels elastic laminae were not discernible, or they were fragmented when they did exist (Figure 7 C), and occasional clusters of lymphocytes (Figure 7 B) were identified . These thickened blood vessels were immunohistochemically demonstrated to be strongly positive for collagen type III, while collagen type I findings were equivocal . However, some of the vessels had patent lamina ; remaining patent vessels (Figure 7 C) and recanalizing vessels (Figure 7 B), Only these patent blood vessels had endothelial cells, which were shown immunohistochemically to he positive for factor VIII . There was evidence of exudation of albuminous fluid in the nidus (Figure 7 C) . Although necrosis, demyelination, and gliosis existed in the temporal lobe surrounding the nidus, no other abnormal, radiationinduced changes appeared in any part of the brain distant from the nidus, including the pituitary lobe and the basal ganglia . Case 25 : Nearly Total Obliteration and Gadolinium Enhancement

Figure 1 . Left oertehral angiograms in care 6 before (top) and after (bottom) radiosurgical treatment . Complete obliteration of the AVM (arrou an s demonstrated t year after treatment.

markedly enhanced after contrast or gadolinium administration (Figure 5, left and right) . On the day after angiography, the patient suffered angor pectoris of sudden onset when she began to walk after the 24 hours of rest required after the examination . Cardiopulmonary arrest occurred within a few minutes . There was no response to resuscitation procedures . An autopsy revealed that death was due to pulmonary arterial embolism . Neuropathological findings . The weight of the brain was 1263 g . Macroscopically, there were no abnormal findings on the surface of the brain ; there was no evidence of adhesion, turbidity, or thickening of the arachnoid membrane . In coronal sections of the brain including the mamillary bodies, the AVM was located in the subcortex of the lateral occipitotemporal gyrus, extending to the wall of the inferior horn of the lateral

A 24-year-old man experienced sudden deterioration in his level of consciousness and was transported to the nearest emergency clinic on June 2, 1986 . A CT scan demonstrated subarachnoid hemorrhage with ventricular dilatation, and angiography revealed an AVM located in the right thalamus (Figure 8, left) . His consciousness recovered following cerebrospinal shunt surgery . Radiosurgery was performed on January 18, 1989 . The nidus was

Figure 2 . CT scans and MR images in case 6 taken 8 years after radiasnrgery . Complete obliteration of the nidus war demonstrated by angiography, as shown in Figure 1 . Contrast and gadolinium administration enhanced the nidus slightly and significantly, respectively . (A) Plain and (S) enhanced CT scan; TI-weighted MR image (SE 500/20 . 1 .5 TeslaJ (C) without and (D) with gadolinium administration .



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1992 ;37 :219-30

covered with a 90% isodose volume administered at one target point with a 14-mm collimator . A central dose of 27 Gy was used to obtain a marginal dose of 25 Gy . Angiography showed a significant change in the size of the AVM at 1 year and nearly total obliteration at 2 years (Figure 8, middle and right) . When CT scanning and MR imaging were carried out 2 years after irradiation, contrast and gadolinium administration enhanced the nidus slightly and significantly, respectively (Figure 9 A-D) .

Figure 3 . Preoperative (left) left vertebral and (right) left carotid angiograms in care 18 demonstrated an AVM fed by the vertebral and carotid artery systems (arrows) .

Figure 4. (Left) Left vertebral and (right) left carotid angiograms in case 18 demonstrated complete obliteration of the AVM 26 months after treatment .



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Surg Neurol 1992 ;37 :219-30

Figure 5 . MR Images in case I S taken 26 month, of er radiosnrgeryr TI-

weighted MR images ( .SE 5001)0, 1 .5 Teslal (left) without and (right) with gadolinium administration . Significant enhancement avas demonstrated even after complete obliteration of the nidus u ai angiographiealli confirmed, as prevented in Figure 4 .

Discussion Systems of Stereo tactic Radiosurgery

Among systems for stereotactic radiosurgery, the gamma unit using 60 Co as the radiation source is currently considered to be the most advanced system from the viewpoints of operative simplicity and reliability, because both the patient's head and the ionizing beams are fixed [11,13} . In contrast, a patient must be moved during treatment with linear accelerators or systems using the Bragg peak proton beam or the neutron beam, both of which have a number of mechanical and operative disadvantages and are uncomfortable for the patient compared with the gamma unit [4,10] .

Outcome and Risks of Stereotactic Radiosurgery

The efficacy of radiotherapy for cerebral AVM was disputed until recently [15] . However, stereotactic radiosurgery as developed by Leksell [11) is clearly distinct from conventional radiotherapies and has a number of advantages compared with the alternatives of either nonsurgical therapy or direct surgical excision, as Lunsford reported [13] . Complications associated with gamma

Yamamoto et al

unit treatment for AVM, although not frequent, include (1) hemorrhage and both (2) temporary and (3) permanent radiation effects . In Steiner's most recent report [ 17], a 3 .1 % incidence of permanent and a 3 .1 % incidence of temporary radiation-induced disorders were noted- In our present study facial nerve paresis developed in only one case [21], the overall morbidity being 494; . Complete obliteration of the nidus was angiographically confirmed in 73% of the subjects, with a marked decrease noted in the remaining patients .

Rebleeding After Treatment

There has been no report, to our knowledge, of hemorrhage occurring after obliteration of the AVM was angiographically confirmed . However, an interval of 1-2 years is usually needed to obtain obliteration of the nidus ; it is possible for hemorrhages to occur during this interim period . Although no such hemorrhages occurred in our patients, rebleeding occurred before completion of total obliteration of the AVM in 17 (8 .5%) of 199 patients with ruptured, deep-seated AVMs treated by radiosurgery at Karolinska Hospital during the period from 1970 to 1984 [20] . Five of them died as a result of these episodes . Thus, the incidence of rebleeding during the year just after radiosurgical treatment for an AVM is thought to be 2%-4% . This is comparable to the incidence of rebleeding during the natural course of an AVM [19},



Radiosurgere' for Arteriovcnous Malformation

Sing Neurol 1992 :37 :219-30

Y=100 .0

227

CRAN L E F T

Z

R

110

130

150 X

thus indicating no particular increase in the risk of rebleeding after stereotactic radiosurgery .

Figure 6 . (Left) MacroccopecpostmortemJinding, and the (right) percentage isodose volume gradient in case 18 shown at the same magnification .

Reirradiation We previously recommended that reirradiation be considered when the AVM is still present on angiograms obtained 2 years after radiosurgery . However, we recently experienced a case of total obliteration obtained 5 years after irradiation (case 3) [81 . Furthermore, a time-related decrease in the nidus size was observed more than 2 years after irradiation in three other cases . Therefore, we now think it advisable to follow the patient without reirradiation as long as decrease in the size of the nidus is angiographically verified to be ongoing, regardless of the results of examination at 2 years . In case 9, there was a consistent decrease in the size of the nidus until 3 years after irradiation, but no changes were found on subsequent angiograms . In such a case it would be reasonable to consider reirradiation .

Brain Stem AVMs Among the cases described in this study, only one case of brain stem AVM was successfully treated by

radiosurgery . According to Steiner's recent report [171, the efficacy rate of radiosurgery was 63% (20 of 32 cases) for brain stem AVMs, lower than the corresponding rates for lesions in other sites. This seems to be related to the fact that the safety of irradiation to the brain stem has not vet been fully established, which necessitates special modifications such as lowering the irradiation dose, as in case 17, or using a collimator with a smaller focus, as in case 7 . In addition, unexpected radiation-induced edema may occur, as in case 15 [21} . We believe that the estimated maximum dose of 22 Gy given to the brain stem in this case was not particularly dangerous, given our experience with radiosurgery for acoustic neurinoma [14,23) .

CT and MR Findings Changes in CT scan or MR image findings of radiosurgically treated AVMs have only rarely been followed . To our knowledge no report referring to gadolinium



228

Surg Neurol 1992 ;37 :219-30

Figure 7 . Hittological fondings in case 18 . (A) Matron-Trichrome x 25 .

(B) Elastica Van Gieson x 20 . (C) Elastica hematoxylin-'eosin x 13 .2 . The majority of vessels were obliterated by intimal hypertrophy . Lv ,nphocytic aggregation eras seen in the otter layer of a thickened vessel ¢call Ghost arrows in B) . However, son, of the vessels had patent lamina ; remanalizing vessels (long arrows in Bi and remaining patent vessels . E. Exudation of albumenous fluid.

enhancement of the nidus on MR imaging has been published . Ito et al [6] reported that contrast enhancement of the AVM on CT scans was not observed 6-28 months after radiosurgery in four patients in whom the AVMs were shown to have been completely obliterated on angiograms obtained 1 year or 2 years after treatment . However, in the present study seven AVMs with such obliteration were enhanced as long as 24-96 months after radiosurgery . In addition, gadoliniumenhanced MR images showed significant increases in signal intensity in five of the six AVMs . Significant gadolinium enhancement was apparent on the previous MR image even in the remaining case (case 15) in which the AVM appeared, on the basis of its clinical

Yamamoro et at

course, to have been obliterated . Gadolinium enhancement was not seen, however, in a later study of this case [211 . It is likely that increased permeability of the vessel wall is involved in the mechanism underlying enhancement by contrast medium or Gd-DTPA [I] . However, slow blood flow, which cannot be identified on angiography, may also play a role, as the autopsy findings of case 18 suggested the presence of patent blood vessels that could not be observed angiographically .

Role of MR Imaging in Follow-up The significance of MR imaging in the follow-up of patients with AVM after radiosurgery is an important issue . At present angiography is the only method available for confirming complete obliteration of the nidus . However, we experienced one death related to angiography . Steiner [17] also reported angiography-relaced morbidity in two of 625 patients . In addition, annual examination by cerebral angiography places physical, psychological, and financial burdens on the patient .



Surg Neurol 1992 :37 :219-30

Radiosurgery for Arteriovenous Malformation

2 29

Figure 9 . 0 scars and MR images in case 25 taken 2 years after radio eergery . .tieeerly complete obliteration of the nidus was demonstrated by angiography, as shown in Figure 8 . Contrast and gadolinium administration enhanced the nidus slightly and significantly, respectively . (A) Plain and (B) enhancedCT saw ; T I-weighted MR image(SE 500/20, t .5Tes/a) (C) it ithout and (D) ndth gadolinium administration .

figure

Figure

7 (Continueel)

8 . Vertebra! angiogramr in care 25 (left) before, (middle) I year, and (right) 2 years after radiorurgecal treatment . Although complete ob!iteration of the AVM was not demonstrated, the major part of the nidns appeared to fine been obliterated 2 years after treatment . Arrow, earA opacifrcatiou of the tein of Galen .

Debate continues as to which factor, increased permeability or patent vessels, as mentioned above, is primarily responsible for the gadolinium enhancement seen in angiographically confirmed obliteration of an AVM . Nevertheless, an increase in signal intensity of the nidus following administration of gadolinium, with the disappearance of flow signal void, is seldom observed in either partially obliterated or untreated AVMs . Therefore, we think it better to use MR imaging as a first step in the follow-up of a radiosurgically treated AVM . Thus, angiography can be postponed until the flow signal void, reportedly characteristic of AVM f5], is eliminated and enhancement by Gd-DTPA is obtained . As the results reported by Ito et al [6} and our findings indicate, angiographic obliteration is unlikely in patients that show flow signal void . Moreover, it seems that enhancement by Gd-DTPA in MR imaging cannot be obtained until the AVM has been angiographically confirmed to have been completely obliterated, or nearly so, as in cases 9 and 25 .

Autopsy Findings

Postmortem examination has been performed in a limited number of patients who died of massive intracranial hemorrhage before obliteration of the AVMs was angiographically confirmed (L-D . Lunsford, personal communication, 1991) . However, as death was not due to the AVM itself in the present case, this may he the first



2 30

Surg Neurol 1992 ;37 :219-30

Yamamoto et al

instance in which autopsy findings have revealed the natural postirradiation course

of nidus

obliteration . An-

giographically confirmed disappearance

of the

nidus, at-

teriovenous fistula, and draining vein has been generally accepted as the goal in radiosurgical treatment

of AVM

patients . However, this autopsy case disclosed the presence

of

a number

of

6 . Ito S, Ham M, Maemura E, Maeda T, Konishi Y, Shiogai T, Kadowaki C, Takeuchi K . Evaluation of therapeutic effects of stereotacric radiosurgery for AVM based on angiography, CT and MRI . Surg Cereb Stroke (Tokyo) 1990 ;18 :429-35 . Jimbo M . Radiosurgery for cerebral arteriovenous malformation . Mt Fuji Workshop on CVD 1984 ;2 :167-72.

patent blood vessels that could

not be observed angiographically . Nevertheless, debate continues as to whether these patent vessels have the potential to rebleed . Furthermore, the immunohistochemical findings, as mentioned above, and the presence

of

far diseases . In : Wilkins RH, Rengachary SS, eds . Neurosurgery update 1 . New York : McGraw-Hill, 1990 :69-87 .

8 . Jimbo M . Radiotherapy for cerebral arteriovenous malformation by gamma knife . In : Takakura K, ed . Treatment of cerebral and spinal arteriovenous malformations . Tokyo : Gendai-Iryo, 1988 :117-28 . 9 . Jimbo M, Kitamura K, Steiner L . Radiotherapy to cerebral arteriovenous malformation . Neurosurgeons (Tokyo) 1987 ;6 :254-7 .

lymphocytic infiltration may indicate that recon-

structive and destructive processes continue within a thrombosed vessel wall.

10 . Kjellberg RN, Abe M . Stereotactic Bragg peak proton beam therapy . In : Lunsford LD, ed . Modern stereoractic neurosurgery . Boston : Nijhoff, 1988 :481-9 . 11 . Lekssell L . Stereotaxis and radiosurgery . An operative system . Springfield, IL : Charles C Thomas, 1971 .

The authors thank Hernan J. Bunge, M .D ., Ph .D., Centro de Radiocirugia Neurologica, Clinica Del Sol, Buenos Aires, and L . Dade Lunsford, M .D ., Ph.D., Department of Neurological Surgery . University of Pittsburgh School of Medicine, Pittsburgh, for stereotactic radiosurgical treatment, and Bierta E . Barfod, M .D ., University of Washington School of Medicine, for her assistance in the preparation of this manuscript . The authors are also very grateful to Kuniaki Matsumori, M .D., Department of Neurosurgery, Sagamihara National Hospital, Mau Nan Chen, M .D ., Department of Neurosurgery, Kousei General Hospital, Kazuo Watanabe, M .D ., Department of Neurosurgery, Southern Touhoku Research Institute for Neuroscience, and Sadahiko Ban, M .D., Department of Neurosurgery, Koube City Central Hospital, for their collaboration in following the patients, and Mr . Masaro Gore, Department of Radiology, Toda Chuo Hospital, for his collaboration in the MR imaging study . This study was supported by scholarships from the Royal Swedish Academy of Sciences, the Japanese Society for the Promotion of Science, the Japan Private School Promotion Foundation, and the Dr . lice Okamoto International Exchange Fund .

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12 . Lindquisr C, Steiner L . Stereoractic radiosurgical treatment of arteriovenous malformations . In : Lunsford LD, ed . Modern stereotactic neurosurgery. Boston : Nijhoff, 1988 :491-505 . 13 . Lunsford LD. Srereotactic radiosurgery of intracranial arteriovenous malformations. In : Wilkins RH, Rengachary SS, eds. Neurosurgery Update II . New York : McGraw-Hill, 1990 :175-85 . 14 . Nor€n G, ArndtJ, Hindmarsh T, Hirsch A . Srereotactic radiosurgical treatment of acoustic neurinomas . In : Lunsford LD, ed . Modern stereotacric neurosurgery . Boston : Nijhoff, 1988 :481- 1) . 15 . PatersonJH,McKissockW .Aclinical survey ofintracranialangiomas with special reference m their mode of progression and surgical treatment . A report of 110 cases . Brain 1956 ;79 :233-66 . 16. Rahn T, Thor€n M . Hall K, Backlund EO . Stereoracric radiosurgery in Cushing's syndrome : acute radiation effects . Surg Neurol 1980 ;14 :85-92 . 17 . Steiner L. Possibilities and limits of radiosurgery in the treatment of intracranial tumors and arteriovenous malformations . Abstr Annu Meet Jpn Neurosurg Soc 1990 :1-IL-4 . 18 . Steiner L. Treatment of arteriovenous malformation by radiosurgery . In : Wilson CB, Stein BM, eds . Intracranial arrerinvenous malformations . Baltimore : Williams & Wilkins, 1984 :295-313 . 19. Toya S, Kawase T . Natural history of cerebral arteriovenous malformations: summarized data of 10 presentations . Surg Cereb Stroke (Tokyo) 1990 ;18 :477-81 . 20- Yamamoto M. Arrotegui Jl, Fedorsak l, Lindquist C, Jimbo M . Stereotactic radiosurgery in cerebral arrerinvenous malformations . Abstr Annu Meet Jpn Neurosurg Soc 1989 :1-D0100 . 21 . Yamamoto M, Jimbo M, Lindquist C . Radiation-induced edema after radiosurgery for poaatine arteriovenous malformation : a case report and detection by magnetic resonance imaging . Surg Neurol 1991 ;37 :15-21 . 22 . Yamamoto M,Jimbo M, Lindquist C, Steiner L . Stereotactic radiosurgery of arteriovenous malformations in children . Nerv Syst Children (Tokyo) 1991 ;16 :167-72 . 23 . Yamamoto M, Nor€n G . Srereotactic radiosurgery in acoustic neurinomas . Neurol Surg (Tokyo) 1990 ;18 :1101-6 .