Brain Necrosis D elay after Stereotactic Radiosurgery

A D if f u s e

W

h it e

a t t e r

Is c h e m

ic

L e s io n

Y e a r s

a f t e r

S t e r e o t a c t ic

C A S E D E S C R IP T IO N
A fte r h is p r e v io u s r e fu s a l to u n d e r g o

A p p e a r in g

7

s u r g ic a l r e s e c tio n , th is 2 8 -y e a r -o ld m a n ,
in

R a d io s u r g e r y

f o r

C e r e b r a l

A r t e r io v e n o u s

w hom

c lip p in g

o f th e

fe e d in g

ar­

te ry h a d b e e n u n s u c c e s s fu l, u n d e rw e n t
g a m m a k n ife r a d io s u r g e r y fo r ru p tu r e d

' M a lf o r m a t io n s :

C a s e

R e p o r t

le ft p a r ie ta l lo b e A V M s a t th e K a r o lin ska

H o s p ita l

on

D ecem ber

14,

1988

(Fig. 1). A t t h e t i m e o f t r e a t m e n t , h e h a d
n o n e u r o lo g ic a l d e fic its . T h e n id u s w a s

Masaaki Yamamoto, M .D ., Sadahiko Ban, M .D .,
Mitsunobu Ide, M .D ., Minoru Jimbo, M .D.

to o

la r g e

( 2 4 .1

c m 3, a s

c a lc u la te d

by

m u l t ip l y i n g t h e t h r e e d ia m e t e r s , 4 .3 , 3 .6 ,

: : Departments of N eurosurg ery, T o k yo W o m e n 's M ed ical C ollege D ai-ni Hospital (M Y, M l, MJ),
J Tokyo, Japan, and Kobe C ity C entral H ospital (SB), Kobe, Japan

I -------------------------------------------------------------------------------------------------------------------------------------------

d

a n d 3 .0 , b y 0 .5 2 , a s r e p o r te d b y P a s q u a lin
e t a l. [1 5 ]) to b e t o t a lly c o v e r e d a n d ir ­
r a d ia te d w ith a p e r ip h e r a l d o s e o f 2 0 to
2 5 G y , c o n s id e r e d a t th a t tim e to b e th e
o p tim a l d o s e . T h e r e fo r e , th e lo w e r h a lf o f

OBJECTIVE

AND

IM P O R T A N C E :

Little

in fo rm atio n

is

a v a ila b le

about

t h e n id u s , w h ic h w a s a d ja c e n t to t h e m a ­

radiatio n -in du ced c o m p lic a tio n s o c c u rrin g m o re than 5 y e ars after ra d io ­

jo r fe e d in g a r te r y , w a s p a r t ia lly c o v e r e d

surgical tre a tm e n t fo r a rte rio v e n o u s m a lfo rm a tio n s.

w ith a 3 0 %

CLINICAL P R E S E N T A T IO N : W e p resen t a patient w ith a rte rio v e n o u s m a l­

is o d o s e v o lu m e u s in g tw o

ta r g e t p o in ts w ith a n 1 8 -m m c o llim a to r

form ations w h o e x p e rie n c e d h e m im o to r w ea k n e ss ca u se d by a diffuse

(Fig. 2 ) . A c e n t r a l d o s e o f 7 0 G y w a s u s e d

white m atter n e c r o tic le sio n d e ve lo p in g 7 y e ars after gam m a knife ra d io ­

to o b ta in 2 1 G y a t th e p e r ip h e r y ; th e re a l

surgery. T h e o rig in a l n id u s had been too large (24.1 c m 3) to be to tally

v o lu m e in c lu d e d w ith in t h e 3 0 % (2 1 .0 G y )

covered and irra d ia te d w ith a p e rip h e ra l dose o f 20 to 25 G y . T h e re fo re ,
the lo w e r h a lf o f the n id u s, w h ic h w a s a d ja c e n t to the m ajo r feeding
artery, had been p a rtia lly c o v e re d w ith a 3 0 % isodose vo lu m e using tw o
target po ints w ith an 1 8-m m c o llim a to r. A c e n tra l dose o f 70 G y w as used

is o d o s e g r a d ie n t w a s e s tim a te d to b e
1 2 .6

c m 3 o n th e b a s is o f th e d o s e -v o lu m e

h is to g r a m o b ta in e d u s in g a K U L A s y s ­
te m (E le k ta In s tr u m e n t A B , S to c k h o lm ,
S w e d e n ) a t th e tim e o f tr e a tm e n t. O n th e

to obtain 21 G y at the p e rip h e ry . C o m p le te n id us o b lite ra tio n w as an-

d a y a fte r r a d io s u r g e r y , tw o g e n e r a liz e d

g iographically c o n firm e d 3 8 m on th s after rad io su rg e ry . A fter a 6-year

c o n v u ls iv e s e iz u r e s o c c u r r e d . H o w e v e r ,

un co m p licated p e rio d , th is patient e x p e rie n c e d a c o n v u lsiv e se iz u re and

th e re w e re n e ith e r s u b s e q u e n t c h a n g e s

then m ild right h e m ip a re sis.
IN T ER V EN T IO N : C o m p u te d to m o g rap h y d em o n strated a diffuse h yp od en se

in s e iz u r e fr e q u e n c y , s u b s e q u e n t b le e d ­

area in the left w h ite m atte r, w h ic h had not been rev e ale d by the p revio u s

d u r in g th e 6 y e a rs a fte r g a m m a k n ife

exam ination. W ith stero id tre atm e n t, this patient a c h ie v e d c lin ic a l im ­

r a d io s u r g e r y . C o m p le te o b lite r a tio n w a s

provem ent, alth o u g h th e re w a s no sig n ifican t im p ro vem en t in the c o m ­
puted to m o g ra p h y -d e m o n stra te d w h ite m atter lesio n .
C O N C L U S IO N : A lth o u g h the e valu a tio n o f this patient m ay not be su fficien t
and fu rth er e x a m in a tio n s m ay be n e c e ssa ry , w e te n tative ly c o n c lu d e that

in g , n o r r a d ia tio n -r e la te d c o m p lic a tio n s

a n g io g r a p h ic a lly c o n fir m e d 3 8 m o n th s a f­
t e r r a d i o s u r g e r y (Fig. 3 ) .
T h is p a tie n t p r e s e n te d to o u r fa c ility
w ith m ild r ig h t h e m ip a r e s is , w h ic h h a d
d e v e lo p e d a f te r a c o n v u ls iv e s e iz u r e in

the co m p u ted to m o g rap h y-d em o n stra te d h yp o d en se lesion in this patient

m id -D e c e m b e r o f 1 9 9 5 . C o m p u te d

is a rad iatio n -re late d n e c ro tic le sio n . Long-term fo llo w -u p is c ru c ia l, even

m o g r a p h y (C T ) d e m o n s t r a t e d a d iffu s e

to ­

after the "tre a tm e n t g o al" has been a c h ie v e d . ( N e u r o s u r g e r y 4 1 : 1 4 0 5 -

h y p o d e n s e a r e a in th e le ft w h it e m a tte r ,

1409, 1997)

w h ic h h a d n o t b e e n r e v e a le d b y th e p re ­

Keywords: A rterio veno us m alfo rm ations, D elayed co m p licatio n , G am m a knife, Radiation necro-

v i o u s e x a m i n a t i o n (Fig. 4). W i t h s t e r o i d
tr e a tm e n t, th e p a tie n t s h o w e d

S|s, Radiosurgery

c lin ic a l

im p r o v e m e n t w ith in 2 m o n th s , d e s p ite
th e la c k o f a n y s ig n ific a n t im p r o v e m e n t
w e p r e s e n t a n o th e r p a tie n t w ith A V M s

in th e w h it e m a t t e r le s io n r e v e a le d b y

tim e , p o s tr a d io s u r g ic a l

w ho

C T . T h e p a t ie n t w a s in g o o d c o n d it io n

o c c u r rin g

5

c a u s e d b y a d iffu s e w h ite m a tte r is c h e m ic

u n til Ju ly 4 , 1 9 9 6 , w h e n h e e x p e r ie n c e d

ye a rs a f t e r i r r a d i a t i o n f o r c e r e b r a l a r t e r i o -

le s io n d e v e lo p in g 7 y e a r s a fte r g a m m a

a n o th e r c o n v u ls iv e

Ven o u s m a l f o r m a t i o n s ( A V M s ) . H e r e i n ,

k n ife r a d io s u r g e ry .

in g s o f p r e c o n tr a s t-e n h a n c e d C T w e r e

I n a p r e v io u s r e p o r t (2 4 ), w e d e s c r ib e d ,
fo r t h e

fir s t

c o m p lic a tio n s

m o re

th a n

e x p e r ie n c e d

h e m im o to r w e a k n e s s

Neurosurgery, Vol. 41, No. 6, December 1997

s e iz u r e . T h e

fin d ­

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M

1405

1406

Yamamoto et al.

D IS C U SSIO N

FIGURE 2. Anteroposterior (A) and lateral (B ) views of stereotactic angiograms
obtained at the time of radiosurgery. The thick lines (white in the anteroposterior view
and hlack in the lateral view) show the nidus configuration. The dotted lines (white in
the anteroposterior view and hlack in the lateral view) show the essential part of the
nidus to be included within a target volume. The lines were drawn by a neuroradiolo­
gist. The isodose gradient is superimposed 90, 70, 50, 30, 20, and 10% from the
center.

FIGURE 3. Anteroposterior (A) and lateral (B) views of angiograms obtained 38
months after radiosurgery. Complete nidus obliteration was angiographically con­
firmed, despite the upper part of the AVMs not having been included within the target
volume.

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FIG U R E 1. Anteroposterior (A) and lateral (B) views of angiograms obtained
before radiosurgery.

unchanged, and postcontrast-enhanced
CT demonstrated only a slightly en
hanced area w ithin a part of the treated
nidus (Fig. 4 0 ; this type of abnormal
enhancem ent is usually observable for
many years after angiographically con
firmed obliteration of AVMs, as we re­
ported previously (26). Single photon
em ission computed tomography using
94mTc-ethyl cysteinate daimer showed a
hypoperfused area in the left parietal
region, which was surrounded by a
slightly hyperperfused area (Fig. 5). Postictally, mild right hemiparesis persisted
and was still persisting as of the end of
August, 1996.

Delayed radiation-induced complica­
tions after radiosurgical treatment for
AVMs, rates of which reportedly range
from 3.2 to 12.5%, have been described
by all investigators using gamma knives
(8, 9, 12, 14, 16, 19-22), linear accelerator
systems (1-3, 6, 7, 13, 17), or particle
beam system s (4, 5, 10, 18). The majority
of such com plications occurred by the
third postradiosurgical year. Previously,
there were no reports of series of AVlVb
in which delayed radiation-induced com­
plications occurring more than 5 years
after irradiation w ere described. How­
ever, as we recently reported (24) in
our series of 38 patients with AVMs
who have been follow ed for more than
5 years after gam m a knife radiosur­
gery, we experienced two patients
(5.0% ) w ith sym ptom atic complica­
tions that developed 5.5 and 7 years,
respectively, after irradiation. Herein,
another patient w ith a late complica­
tion, w hich developed 7 years after
irrad iation, is presented.
Based on the neuroimaging fin d in g s
for this patient, the C T - d e m o n s t r a t e d
hypodense area, which although d iffu se
was limited to the white matter, was
considered to be a radiation-induced ne­
crotic lesion. The mechanism o f this
type of com plication has yet to b e fully
clarified. We have elsewhere r e p o r t e d
an autopsy case with AVMs treated by
gamma knife radiosurgery, in which
postm ortem studies after death that was
unrelated to the AVMs were c o n d u c t e d
after angiography performed at 2 years

Neurosurgery , Vol. 41, No. 6, D ecem ber 1997

mo7

Brain Necrosis D elay after Stereotactic Radiosurgery

d e m o n s tr a te d c o m p le te n id u s o b lite r a ­
tio n (2 5 ). T h is s tu d y d is c lo s e d th a t in tim a l h y p e r t r o p h y c a n o c c u r in a n o r m a l
p ia l a r te r y th a t is u n r e la te d

to A V M s

and

th a t m o r e r e m a r k a b le in tim a l h y ­

p e rtro p h y

w ith

fr a g m e n ta tio n

of

th e

e la s tic la m in a e , o r e v e n c o m p le te o c c lu ­
s io n , c a n o c c u r in th e s e a r te r ie s w ith 2 5
G y . In a d d itio n , w e h a v e e ls e w h e r e r e ­
p o r te d th e c a s e o f a p a tie n t w ith A V M s
in w h o m

s e v e re , a lth o u g h a s y m p to m ­

a tic , s te n o s is o f th e m id d le c e re b r a l a r ­
te ry tru n k h a d b e e n c a u s e d b y re la tiv e ly
lo w -d o s e

ir r a d ia tio n

3

y ea rs

a fte r

g a m m a k n ife r a d io s u r g e r y (2 3 ). F o r th e
p r e s e n t p a tie n t, th e ir r a d ia tio n d o s e to
th e a ffe c te d a r te r y w a s r e tr o s p e c tiv e ly
e s tim a te d to b e 1 0 G y o r le s s . W e th in k
th a t

th e

changes

had

p ro g re sse d

in

s m a ll a r te r ie s o f th e w h ite m a tte r fo r
m a n y y e a r s a fte r ir r a d ia tio n a n d th a t th e
d iffu s e w h ite m a tte r h y p o d e n s ity e v e n ­
tu a lly d e v e lo p e d .
A lth o u g h , b e c a u s e o f th e p a r tia l ir r a ­
d ia tio n c o v e r a g e in th e p r e s e n t p a t ie n t,
th e d o s e -v o lu m e

a n a ly s is m a y

a d e q u a t e , t h e 2 1 .0 G y - 1 2 .6
u sed

exceed s

be

in ­

c m 3 p o in t

th e e s ta b lis h e d

3%

r is k

o f p e r m a n e n t s y m p t o m a t ic b r a in in ju r y
r e p o r te d b y K o n d z io lk a e t a l. (1 1 ). S im ­
i la r ly , t h e d o s e - d i a m e t e r p o i n t ( 2 1 .0 G y 3 .5

c m , w h ic h is th e m a x im u m d ia m e te r

o f a 3 0 % is o d o s e g r a d ie n t) is fa r a b o v e
th e 1%

r is k le v e l fo r r a d io n e c r o s is r e ­

p o r te d b y F r ie d m a n a n d B o v a (6 ). T h e
ir r a d ia tio n d o s e o f 7 0 G y s e le c te d a t th e
ta r g e t c e n t e r is c o n s id e r e d to b e h ig h ;
to d a y , th e c e n tr a l d o s e u s e d fo r p a tie n ts
w ith A V M s d o e s n o t e x c e e d 5 0 to 5 5 G y
in t h e m a jo r it y o f c e n t e r s u s in g g a m m a
k n iv e s

or

lin e a r

a c c e le r a to r

sy ste m s

(3 , 6 , 7 , 1 3 , 1 4 , 1 6 , 1 7 , 2 2 ). F u r th e r m o r e ,
w hen

th is

k n ife

ra d io s u r g e ry ,

p a tie n t u n d e r w e n t g a m m a
o n ly

a n g io g ra m s

w e r e u s e d fo r d o s e p la n n in g . In r e c e n t
y e a r s , h o w e v e r , th r e e -d im e n s io n a l im ­
a g in g e x a m in a tio n s h a v e b e e n
u sed

fo r

r a d io s u r g ic a l

w id e ly

tre a tm e n t

A V M s . T h e r e fo r e , it is n o w

of

e x p e c te d

th a t r a d io s u r g e r y , e v e n fo r p a tie n ts w ith
r e la t iv e ly la r g e A V M s , is r e la t iv e ly s a fe
(2 2 ). L o n g -te r m

f o llo w - u p , h o w e v e r , is

c r u c ia l, e v e n a f te r th e " tr e a t m e n t g o a l,"

FIGURE 4. Sequential computed tomographic scans obtained 38 (A ), 91 (B), and 92
IC) months after radiosurgery; with (C ) and without (A and B) contrast tn ancement
N eu rosurgery , Vol. 41, No.

a s d e s c r ib e d b y L in d q u is t a n d S te in e r
(1 2 ), h a s b e e n a c h ie v e d .

6, December 1997

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b e c a u s e o f ir r a d ia tio n o f 1 0 G y o r m o r e

1408

Yam amoto et al.
10. Kjellberg RN, Hanam ura T, Davis KR, Lyons
SL, Adam s RD: Bragg-peak proton-beam ther
apy for arteriovenous malformations of tht
brain. N Engl J Med 309:269-274, 1983.
11. Kondziolka

D,

Lunsford

LD,

Coffey R|

Bissonette DJ, Flickinger JC: Stereotactic radio­

Downloaded from https://academic.oup.com/neurosurgery/article-abstract/41/6/1405/2846189 by University of Western Sydney user on 11 January 2019

surgery of angiographically occult vascular
malformations: Indications and preliminary ex­
perience. N eurosurgery 27:892-900, 1990.

12. Lindquist C , Steiner L: Stereotactic radiosur
gical treatm ent of arteriovenous malforma

tions, in Lunsford LD (ed): Modern Stereotactic
N eurosurgery. Boston, Martinus Nijhoff, 1988
pp 4 9 1 -5 0 5 .

13. Loeffler JS, Rossitch E Jr, Siddon R, Moore MR
Rockoff MA, Alexander E III: Role of stereotac­
tic radiosurgery with a linear accelerator in
treatment of intracranial arteriovenous malfor­
mations and tumors in children. Pediatrics 85:
774-784, 1990.
14. Lunsford LD, Kondziolka D, Flickinger |C,
Bissonette DJ, Jungreis CA, Maitz AH, Horton
JA, Coffey RJ: Stereotactic radiosurgery for ar

teriovenous m alformations of the brain. J Neu­
rosurg 75:512-524, 1991.

15. Pasqualin A, Barone G, Cioffi F, Rosta R,
Scienza R, Pian RD: The relevance of anatomic
and hem odynam ic factors to a classification of
cerebral arteriovenous malformations. Neuro­
surgery 28:370-379, 1991.

FIG U R E 5. Coronal views of single photon emission computed tomographic scans
using ,,,,mTc-ethyl cysteinate daimer obtained 92 months after radiosurgery, show­
ing a hypoperfused area in the left parietal region, which was surrounded by a
slightly hyperperfused area.

16. Pollock BE, Lunsford LD, Kondziolka D, Maitz A,
Flickinger JC: Patient outcomes after stereotactic
radiosurgery for "operable" arteriovenous mal­
formations. Neurosurgery 35:1-8, 1994

17. Souhami L, Olivier A, Podgorsak EB, Pia M,
Pike GB:

A CK N O W LED G M EN TS
W e t h a n k B e n g t K a r ls s o n , M .D ., P h .D .,
D e p a r tm e n t o f N e u r o s u r g e r y , K a r o lin s k a
H o s p ita l, S to c k h o lm , fo r g a m m a

k n ife

t r e a t m e n t a n d B ie r ta E . B a r f o d , M .D ., U n i­
v e r s ity o f W a s h in g to n S c h o o l o f M e d i­
c in e , f o r a s s is t a n c e in t h e p r e p a r a t i o n o f
th e m a n u s c r ip t.
R eceived, S e p tem b e r 17, 1996.
A ccepted, July 16, 1997.
R e p rin t re q u e sts: M asaaki Y am am oto, M .D.,
D e p a rtm e n t of N e u ro su rg e ry , T okyo W o m ­
e n 's M edical C ollege D ai-ni H o sp ita l, 2-1-10
N ish io g u , A ra k aw a-k u , T okyo, 116 Japan.

REFEREN CES
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2. Colombo F, Benedetti A, Pozza F, Marchetti C,
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20. Steiner L, Lindquist C, Adler JR, Torner JC,

6. Friedman WA, Bova FJ: Linear accelerator ra­
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J N e u r o s u r g 77:832-841, 1992.

21

timore, Williams & Wilkins, 1984, pp 295-313.

Alves W, Steiner M: Clinical outcome of radio­
surgery for cerebral arteriovenous malforma
tions. J N eurosurg 77:1-8, 1992.
Steiner L, Lindquist C, Steiner M: Radiosurgery

7. Friedman WA, Bova FJ, Mendenhall WM: Lin­

in Symon L (ed): Advances and Technical Star
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22. Yam am oto Y, Coffey RJ, Nichols DA, Sha"
EG: Interim report on the radiosurgical treat­

1992, vol 19, pp 19-102.

8. Jimbo M, Kitamura K, Steiner L: Radiotherapy

ment of cerebral arteriovenous m alform ations

to cerebral arteriovenous malformation Jin Japa­
nese, English abstr], in Hirakawa K (ed): Neuro­

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