Central nervous system hemangiomatosis in early childhood

ELSEVIER

the vascular spaces. resultin, ‘1 in a more solid cellular appearance.with foci of increased mitoses 131. Two

syndromes of more widespread hemangioma in-

volvement, or hemangiomatosis, are seen in the newborn period: benign neonatal hemangiomatosis and diffuse neonatal hemangiomatosis. In benign neonatal hemangiomatosis, there are many small cutaneous hemangiomas. In diffuse neonatal hemangiomatosis, any organ can be affected; most commonly involved are skin, liver, central nervous system (CNS). gastrointestinal tract. lungs, eyes. oral cavity, spleen, and kidneys. Such systemic involve-

Donna M. Capin, M Steven M. Gottlie

ment cannot be predicted based 011 the number of cutaneous hcmangiomas [ I ,2]. Two cases of hemangiomatosis with CNS involvement are prksented. In the first, the CNS lesions were asymptomat;c. while in the second there was progressive ma-

Two cases of hemangiomatosis are reported, a girl of 3 years of age and a boy 2 years of age, both with central nervous system (CNS) involvement. In the first, the CNS lesions were asymptomatic; in the second, symptomatic. Magnetic resonance imaging was used both to identify the lesions and to follow their evolutions. In the first case, the CNS lesions involuted in parallel with those in skin arid liver. In the second, while there was no obvious resolution of the CNS lesions, there was a decrease in the level of urine basic fibroblast growth factor, indicating ‘9aelesions were probably.involloting. Serial magnetic ~esslnance hnaging studies and urine assays of basic fibroblastic growth factor have important roles to plny in following CNS involvement in Irralnngiomatosis. Q 1997 by Elsevicr Science Inc. All rights reserved. Capin DM.

Gottlieb SM.

crencephaly, i.e., brain size exceeding the mran by more than 2 standard deviations expressive

(S.D.), with accompanying

language delay. Serial

magnetic resonance

imaging (MRI) studies showed resolution of the CNS lesions in the first case, following treatment with steroids and interferon (IFN)-alpha-2a.

The IeGons failed to rc-

solve on

MRI in the second case despite treatment with

steroids,

but decreasing serial assays of urinary

fibroblast growth factor (bFGF)

basic

revealed that they weI?

probably involuting.

Case

Reports

Rosman NP. Ccnlral IICI’VOUS

system hcmi~ngior~~;~~r)sis in early chilcihood. Pediatr NWrol 1997; 17*3(,5-17r). .. - .

Introduction Hemangiomas. the most common tumors of infancy. are benign neoplasms composed of proliferating endotheli m. mast cells.

fibroblasts.

found in IO-12%

and macroph;tges 1I 1. They arc

of children, and 7040%

of these arc

noted by 1 month of age. Most are solitary, with IS-20% involving two sites. and
involving

three or more

sites [ I .21. Hem~ngioendothclion~as also are benign lcsions. but with denser cellularity than that needed to line

_--l+<:n thu Dqxrruncnts ol’ Pediatrics and Ncurolopy: IX\ iris ol Rdinlric Neurology; Floaling Hospital for U~ildren: Nrw Enpld Medical Center: Hos~trn. Massacl~uw~~x. C~~mmunicnlic~nxdwulJ be addrcshcd lo:

0 1997 by Elsevier Science Inc. All right!, rest-ved. PII S0887-8994(97)001h9-O .0887-8994/97/S I7.00

Dr. Rorman: Division d Pcdi:mk Nc~trology.NI:M(‘ tt3 \I): ‘I hc t:lwiting Hospil;il liw ChilJr~n: 7.40 W:d~in~tmI Sfrcel: ibW~ MA 02 I I I. Rrccived June 2.5. IWi:

accepkd July IS. 1’107.

(4

(Cl CLII;~IUIU~ nntl liver hemangirm~usby 3 years. 6 lmmlha of ;I~u. The rhild’~ lockedgrowlh and cc@ivc developnien~ remniiird nmliil.

Al I nk~~~llr ol’ qt. 111~child’* head ciruumfcrcnre wuh :II the WIII prrcciitils \SO%ltrr ill1 inlniii 2 mnnthh of age).Uy 7 mondis of aEc. hr was rolling o\cr in both dirc&mh. hc could nramlge io sh up. and he had

366

PEDIATRIC

NEUROLOGY

Vol. I7 No. 4

hegun to play peck-n-ho0und patlyakc and wuvc goodhyt!.During hi% lirht ycur of nge. his hcud circumfcrcnrr grew inurcnhingly lu il si/c ahovethe Wh percealilc.At 13%mondl* rrf upc. Ire hcgunIO walk with ~pprrrl. Hy 14’2 iii~ilih of age.hc could respond 111bimplr: commands. five” or “give me lhe hnll.” He was vocal. hul huch ah “slop 111~’ pr”duccd ~CIwlml~. ‘Thcrc ucrc no IllCnl ;rhnorm;dilich on ncurolclgic cxuminu~ion. including normul mubclelom2. sWcnglh. illld tendon reflex ucllvity. wiL tlesrrr plunlur responses. His headsire was dull of u child IO yours of uge(Fig 2). hut lie had no aymplomsof increuscdinlracrunial prc~surc. MRI of ~hchuh showctl four discrctr pnrcnchymallesions: lcfi inferior frontal loh (?I. Icfl occipilnl lohe ( I ). ;Ind rigIll banporn lohc (I ). Nonu cxhibirud P signific;mt muss rffccl (Fig 3A. 38). The lesions were hypcrinlenseor isoinlense on T,-weighrcd imngc\.and hyprrintcnsc

l-lead circumference growth (patient 2)

proliferative stage

ary, and then an involutional

stage. The

lasts 6-10

this stage, the hemangioma

months.

During

grows more rapidly than does the infant. During the stationary stage, the growth of the hemangioma initially parallels that of the child, then slows. The hemangioma then involutes with fibrosis and diminished cellularity, with complete resolution of 5( 96 of the lesions by the time the child reaches 5 years of age and of 90% by 10 years of age [ 1,2]. Hemangiomas

can cause significant

pressing normal structures.

morbidity

Respiratory

by com-

distress or strider

can accompany 2y

on T,-weighted

4

6

images. with punctate enhancement

6

10 12 14 16 16y

after gadoiinium

administration. as seen in Case I. The subarachnoid space was normal and there was no hydrocephalus. Complete blood count, platelet count. plasma thrombopiastin.

partial

thromboplastin time, and cerebrospinal fluid examination were normal. Urine assay for bFGF

was elevated I6 times above normal.

The child was treated with oral

prednisone 2 mg/kg/day for 6 weeks.

Serial MRI showed no progression of the lesions. which were

unchnnped

of age. but levels of urinary bFGF had fallen to OIIC eighth

iIt 24 months

their previous level. indicating the lesions were involuting. At 24 months of age, the child’s head circumference had grown to that of a child of

a subglottic lesion. Deprivation amblyopia, strabismus, glaucoma, or proptosis result from lesions near the eye. Hepatic lesions can cause fatal high output cardiac failure from arteriovenous shunting. In some hemangiomas, there is platelet sequestration and destruction, causing rapid enlargement of the hemangioma, thrombocytopenia, and a consumptive coagulopathy (Kasabach-Merritt syndrome). Also, hemorrhage from these lesions can cause significant morbidity and mortality [ 1,2]. In I97 I, Folkman proposed that the growth of tumors, including

ment membrane

cell proliferation,

genie

factors

proliferation lization

with a vocabulary of 20 to 30 words and five

factors

gljlle" illlll"get

out."

hut

his

2-word phrases, such

as

receptive Ianguapc. cognitive

development. and motor \hills were normal and there were no

focal

neurologic deficits.

is a benign

endothcl~al

ncoplasnl

COI~I~OSC~

weeks of life 1I ,21. Vascular

llll!

malthrmations,

by

are hamartomas, composed of mature endothelial proliferate

congenital,

nor involute.

Although

they may not become clinically

after the newborn

period. Their growth

that of the child’s, port-wine

Vascular

nevus

stain,

flammeus,

phangioma,

and arteriovenous to see extracranial with

intracranial

most often

manifested

malformation

involves

that are innervated

salmon

vascular

cells that

parallels

include patch,

malformation

when

contrast.

apparent until

generally

vascular

fit%1 t*CW

they are aL,o

malformations

uncommon associated

01

cells. mast cells. fibroblasts.

Ill~lClW~~ll~l~CS, USUiLlly il~~~XUk!i~l within

neither

the lym-

121. It is not malformations

anomalies;

the extracranial

this is vascular

those portions of the scalp and face

by the first division

of the fifth cranial

nerve [41. into three categories: ( I ) only the dermis; (2) mixed capillary/ cavernous, involving the dermis and subcutaneous tissues: and (3) cavernous, involving the panniculus and deeper Hemangiomas

capiiiary,

been

bFGF,

cell growth

base-

of the parent venule,

endo-

identified

IS]. Angiothat

of endothelial

of macrophages angiogenin,

and migration,

are divided

involving

structures. They evolve

through

a proliferative,

a station-

for growth

nohistochemical

growth

it is probably of hcmangiomas

analysis

hemangiomas high

growth

that have been studied

platelet-derived

al. looked at nine indcpcndent markers’ oxprcssion

stimulate

cells and mobi-

to release endothelial factors

factor, and transforming

responsible

AII hcmangioma and

include

have

and migration

of

that involved

and differentiation

161. Angiogenic

liferation

dividing

on the formation

endothelial factors alpha

and beta. Because bFCF stimulates endothelial

iscussion

rapidly

depended

degradation

thelial

I3’/2 years of age (Fig 2). He exhibited a mild expressive language delay.

“ill1

hemangiomas,

new blood vessels (“angiogenesis”)

cellular

cell pro-

the main facto1 121. Takahashi

ct

markers by immu-

to SW whcthcr the dcgrcc of the

would

and vascular

hc1p to distinguish malformations.

bctwccn

They

found

expression of proliferating cell nuclear antigen, type

IV collagenase, vascular endothclial factor. urokinasc, and and stationary phases of hcmbF;GC-;,in the proliferative angiomas [ 71. By contrast, vascular malformations showed little or no expression of these proliferative cell markers. They concluded that these data rellected basic biologic differences between proliferating hemangiomas and wscular malformations 171. Therefore, a urinary assay for bFGT= can help the clinician to differentiate between a proliferating hemangioma and a vascular malformation in the CNS, may help design therapy, and can aid in the evaluation of response to that therapy. Burke et al.. in 1964, first described CNS inwkmcnt in newborns with hemangiomatosis 181. When hemangiomas involve the CNS, they most commonly involve the cerebellum, but they have also been found in the cerebral hemispheres, brainstem, and spinal cord 18- 15I. Additimally, IeptomeningeaI involvement in the region of the optic

Capill et al: CNS Hemangiomatosis

in Childhood

367

Ilc’rvcs. optic

ClliilSIlI, illld pitliilil~y j$lillld IlilVL! blXll dL!-

scrilxd 191. In ii rcvicw ot’lllc Iitc‘ruturc, of

CNS

involvcmcnt

clinical

WC limllcl X lxxliilllk

by hc\t~li~t~~iol~lat~~~is (‘l’ublc

signs Wcrc

V~Niilhl~. with

highly

CilSCS

I ). The

IlydlIkX!l~llillllS

cilscs ol’ disscminutcd cuusc many

Icsions

ing

CNS

ol’ the

with

lip all

children

with

ins) most liqucntly

und later can bleed

the

CNS

lesions

‘ulurming

were

in 2 ol’ 8 Cuscs,

C!iKCS):

III 25 cases ot

asylnptonlutic.

hemi\ngiomas”

lesions), which

(3 ol’ t(

(f’unclion-

or life-threatening

wi\s done in only

neuroimaging

seizures had OCCLI~I-cd, and computed

these 3 Cilses was normal. by the hypcrdynamic directly

und acidosis

curdi(~vi~sculi~r

1l6!.

Causes

involve

brain

omntosis

tomography

The authors postulnted

of the seizures to be brain hypoxia of

when

irritation

local

ot’ 5 fatal GISCS of hemangiomatosis

&oroid

Hospital

hemorrhage.

for Sick Children,

plexus invr,lvcment

IIO colmxmt about the CNS

at

Riley

of

the absence

and the small

reported

macrencephaly,

a family

multiple

without

involvement

was evident

in only

the study

does

not indicate

whether iieuroimaging

and if so, how many of the patients of involvement

36X PEDlATRlCNEUROLOGYVol. 17No.-I

I case; was

were tested

of the CNS

in

diffuse

angiomatosis

lipomatosis,

ities at autopsy family clinically

(involving

with

[ IS]. Zonana

multiple

similar

to the patient

of the

) must be postulated. with

syndromes. (a mother

ma-

In 1960,

and four of and

hemangiomas or other

ncuro-

was autosomal the with

domi-

a sporadic

cast ot

neck

limbs),

no CNS

et al. in 1076

hemangiomus

is

an absolute

in children

described

and macrcncephaly,

case

or external

enlargement

hydroccphulus

the inheritance

muy

prognosis.

lesions,

cutuneous

nant I I Xl. In i 97 I. Bannayan

CNS

of bony

size of the bruin

ir? c;everal well-described with

lesions

internal

have been described

and Smith

initially,

and hydro-

in our second

in brain size (mucrencephaly

her children)

silent

CNS

of

MRI

Iiciiiaii~ioiiiat~~Sis

and can aft&t

the absence

in the other 4 114). In u scrics Hospital

these

of therapy

logic abnormalities:

from Chilclren’s

is important

rise to seizures

of macrocephaly

Given

crencephaly

and

in Boston,

(171. Thus, the true extent

skull,

detection

presence

hydrocephalus,

and give

wils prcscnt in 1 of the 5. with

of 20 CiIsCs of hcmangiomutosi!,

performed.

The

increase

and mass

leptomeningeul

Also,

noteworthy.

or

imaging

iicoiiulal

dit’l’usc

be-

screen-

tomography

CNS

in bruin citn be clinicully

the choice

Hemangiomas

of surrounding

brain parenchyma. Toronto’s

on

hemangiomas

effect.

In a review

ischemia,

the cause

st;\tc OF the hcmangi-

seizures

include

in

brought

cephalus. influence

the 3 cases in

computed

hiIs not bcctn pcrli~rmcd.

l>Cci\llscIcsions

is unknown,

i~SylllptOllliltiC and routine

u~uillly

(SCCr)lltl~~~y to illtl’ilV~lltl’iClllil~ illltl/O~ Sllbi~lY~ChllOid blWdcited

hcotianliomiltosis ilW

and

abnormaldescribed

a

and macrencephaly,

described

by Bannayan,

but

Table I.

Pediatric cusw of CNS involvement by hemangionwtosis Author

Locution

Burke et

Signs and Symptoms

13il~ltt!l~ill frontal. tt!nl~~l~rill, illld pilriCt;ll lohe~. right OCCipitiil lik.

Aqueductul obstruction 1%ith

kti

hydrocephalua, sci/ures,

hippOCiullpUS. corpus CilllOSUl1~.

et ill..

lYh.5 IYI

Lcptomeningwl

yCilr\

niolor dcli~y Opi4hcaanu~

lesions of optic

Deuth; prwumonirr and cardiac

nervc/chiasn~ and pituitary, right

Burnlanet ill.. I967 1IO] Holden et al.. lY70

Ii I I

!ililUrC ilt 1 months

ccrt2hcllun~ Right cerebellar hemisphere (hemorrhagic)

CNS Ieion asymptomatic

Death; cardiac failure at 3

Biluterul

Aqueductill obstruction with

days Death: hydroccphalus and

ccrehral henkpheres.

midbrain.

Ill~dUllil. cervical imd lumhosacral \pinid cord

Munduriitn et al.. 197Y II21

Young Ct

ill ..

IYKI

Ccrehrllum

~1.3~

pnwmonia vt 3’ I

Ikltth;

niarkcd cognitive and

ccrehcllum, pans

Cooper

Outcome

(hrnlorrhagic)

Cl 5tic

“h~llliulglOhlil~tl~nli~” in Idt ccLr&AIuiii. Vil\Clllill’ lltillli~lnlilti~lll

hydrocephalus. lsft arm pitridysis, right foot drop. right sixth net-w palsy. left eye pwsis Hypotonin. brisk tendon

Death.. ciwdk

retlexcs , li.~ll limtanel Hydroccphulu\. hri&

inlirncj Surgical dccomprw.i,)n

illOIl)!

tcnd~~nrcllext‘\

mrningitk

at 35 da>\

1‘uilure in ot

cy\t at 0 WlXk\

IllCdiill cdpc Of the cyst; three wiullrr VilSCUliir malforniation~ Byard et id. . IYY I II-II

Bar-S,Y,, t’t al..

in ccrcl-wllo-

pontinc region Lcptonicningc~, choroid pkxu~

I~Cilttl~ c.u-disc ILlurc

tit 5

lllolltll\ IYY-!

I 151

Right middle crunial liwa

cutcnding into

po4tcrior part 01’the right cubit SUprilWllilr

Right eye prop1044

l’rcatnicnt H ith intcrfcron;Ilphil-Zti ctiu\cd “~gniticant reduction” in G/c‘()I’lhc k4ion 31 3

and

ciwrit

lllolltll\

CNS = Central ncrwus sy\tcm

with apparent autosomul dominant inheritance 1Ic)]. The Klippcl-Trenaunay-Wcber It

is II

syndrome is 01’wlt~a~~cc

congenital disorder wi:h ~nacular

WC

CLll~lllCOLIS

hCllli~ll~iOlllilS,

iltICt5OVt.!lltNtS

vascular l’iSllllik!,

Iwc.

nevi, VL’IlOlIS

The

use of IFN-alpha-,,3.1 in the

thrcalening or SupporL

“ikltmling”

In I989,

01’ ~)LIltllt)tlitt*y

Wbik

mwnicnt

ot’ Iilk-

bc~ll~tt~gio~~lus bits bccfl gaining et al. rcporlcd

hcnlatlfil)nlrrtoSis

4ll*ilmit(iC

rcgrcSSioti

in LI child trcatcd with

varicosiries, ;md skcletitl :uld/or soli tis,xuc hypcr(rophy.

alpha_IFN 1231. Also in Ic)XO.Orchard ct ill. pracntcd 2

Stephan et al. have rep~rred three patients with KIippcI-

CiISCS

Trenaunay-Weher

syndrome with

macroccphtily; three

with combined Klippel-Tlrnnunay-Weber the Sturge-Weber

anomaly with macrocephaly, syndac-

tyly. and polydactyly: klilllgiC!Ctilsiil

syndrome and

ilnd four with

cutis mi\rmortita

congenitrr, cutaneous ilnpiomata, and mac-

(OllC

with mul!iple

pCl’i~O~lL’ill

a

It seems likely that excess bFGF in our second case was

large t’;tciitl

hemangioma): both responded dramatically to trIphi]-IFN administration 1241. Ezekowitz

et al. ustxl ulphu-IFN in 20

patients with life- or vi~ion-~hrente~li~~~hemim~iOmiP+who had not responded to corticosleroids. In 18 01’ihe 20, the hemangiomas regressed by 50% or more ;&er

rocephaly [ 18 1.

wilh

Ilt?lllitll~it~~llit~

Kasabach-Merrilt syndrome. the other with

1111average

of 7.8 months of treatment. Side et’t’ects(fever. ncutropc-

important in the genesis of’the child’s progressive macro-

nia, skin necrosis) wen: minimal and transient 117). In our

cephaly, because bFGF

first patient, the addition of alpha-IFN was followed by

has been shown to increase sur-

vival of cells in culture, particularly of vascular cndothc-

complctc resolution

dial cells. and bFGF can at’l’ectthe development of’various

The

tissues for which it acts both ~1sa mitogen and a morpho-

resolution

of’the hepitlic and CNS homangiomas.

exact mechanism of action of alpha-IFN

in rhc

of hemangiomas is unknown. It may slow by inhibiting proliferation of endothelial

gen [20]. It may also have modulating effects on neurons,

qiogetwsis

glia, and blood vessels, in both the developing and the

cells, smooth muscle cells, or fibroblasts stitnulutcd by 0 collagen production, or by growth factors, by dccsrcasin,

mature CNS.

It has a role in neuronal survival.

and in

growth and dift’erentiation of neuritec: in vitro (211. The

increasing prostacyclin production and release by endo-

bFGF gene has been localized to chromosome 4~25 [ 221.

thelial cells [6,1. Thus, neuroimagin,$7in cases of diffuse hcmangionratosis is important because silent CNS lesions can bec~mc

Further

rrsearch

using

molecular

genetic techniques

should provide additional insight into the role of bF6F the pathogenesis of primary macrencephaly.

in

symptomatic later, causing morbidity and mortality. Fur-

Capin et al: CNS Hemanpi”mato~is in Childhood

369

ther, the discovery of such CNS lesions my influence the choice of treatment and affect prognosis. In @r first case, the use of IFN alpha-2a was followed by complete resolution of the hemangiomas. In the second case, the CNS lesions were accompanied by macrencephaly and a markedly elevated urinary assay of bFGF. The urinary bFGF assay helped to identify the brain lesions as hemangiomas, obviating the need for biopsy or surgical excision. Declining serial assays indicated that the hemangiomas were involuting. With bFGF’s known effects on growth and migration of neurons and glia, it seems likely that bFGF or other growth factors may play a role in the pathogenesis of macrencephaly in a variety of genetic and sporadic disorders.

[IO]

Burrnan D. Manscll PWA, Warin RP. Miliary hacmangiomata

in the newborn. Arch Dis Child 1967;42:193-7.

I1 11 Holden

KR. Alexander

[12]

Marandian

MH.

tions of infancy and childhood. Pcdiatr Clin North Am I993;40: I l77- I200.

Silverman RA. Hemangiomas and vascular malformations. Pe-

diatr Clin North Am I99 I ;.38:8 I I-34.

(“hcmnngiocndotheliornas”)

M. Cellular

hemangiomas

in infants: Light microscopic, immunohis-

tochemical. and ultrastructural observations. Am J Surg Pathol I99 I : I S: 760-78.

Pescual-Castroviejo I. The assoeiarion of cxtraeranial

and in-

tracranial vascular ~~~iIlfi)r~~~i~tions in children. Can J Ncurol Sci 1985;

I?:

139-48. 151

Folkman J. Tumor

angiogcncsis:

Thcrapcutic

implications.

pliqu&

cCr&rble:

d’icterc

obstructif et d’hcmorragie

Pediatric I979;34:827-3 1131

White CW.

‘I’rCi\tlllet~tof

intcrfcron alpha. Scmin Hcmatol 171

Tilkahtishi K. Mullikcn

I~O~~IIINI

&de

H.

com-

d’un eas.

I.

Young RSK, Zalneraitis

natal hemangiomatosis:

EL, Bauman ML. Disseminated neo-

Successful

hcpatic resection with subsequent

development of hydrocepha!us. J Pcdiatr Surg I98 I ; 16:7X!-3.

[14] infantile

Byard

RW,

Burrows

haemangiomatosis:

PE,

lzakawa

T,

Clinicopathological

Silver

MM.

Diffuse

features and manage-

ment problems in 5 fatal cases. Eur J Pcdiatr 199 I ; I50:224-7.

[lS]

Bar-Sever Z, Horcv G, Lubin E, Kornrcich L, Naor N. Ziv N.

Shimoui A, Grunebaum M. A rare coexistence of a multicentric hepatic with a large brain hemangioma

in a prcterm

hcmnngiolna(Osis with recombinant

1990:85:491-8.

117) Ezekowitz

RAB. Mulliken JB. Folkman J. Inlcrfcron alpha-2a hemangiomas

of infancy. N Engl J Med

1992;326: 1456-63. [IS]

Stcphsn MJ. Hall BD. Smith DW. Cohen MM. Macrocephaly

in association with unusual cutaneous angiomatosis. J Pcdiatr 1975:X7: 353-C). 1191

Zonanu J. Rimoin DL, Davis DC. Macrocephaly with multiple

lipomas and hemangiomas. J Pediatr l976:89:600-3. (201

Gospodarowicz

D. Biological

activities of fibroblast growth

JR, Ko/.akcwieh

[21]

Unsicker

K. Grothc C, Otto D. Wcstcrmann R. Basic fibroblast

growth factor in neurons and its putative funclions. Ann NY Acad Sci

1990:27: 15-22. HPW.

Rogers

RA,

J. F,/ckowitd RAB. Cellular markers that distinguish (he phases

of Ilcl~l~~l\gil~l~l;ttlrrrinp ilIfillIcy

of alarming hcmangiomas in infancy: A review of 25 eases. Pediatrics

factors. Ann NY Acad Sci 1991:638: l-8.

N Engl J Mcd 197 1:2X5: I 182-h. (61

A. Haghigat

ndonatlle disscmin&

therapy for life-threatening

Gonzalez-Crussi F. Rcycs-Mugica

141

Momenzade

1161 Enjolras 0. Riche MC, Merland JJ, Escande JP. Managcmcnt

Fbhmsn SJ, Mulliken JB. Hcmangiomas and vascular malforma-

[3]

M.

infant. Pcdiatr Radio1 1994;24: I4 I-2.

Wefkrcnces

121

Rakhchan

Lessani M, Youssefian H. Hemangiomatose

hemangioendothelioma

[I]

F. Diffuse neonatal hemangiomatosis.

Pediatrics 1970;46:4 I l-2 I.

ilId cl~iltll~ood. J CIII~

IIIVC~~ 1004;03:

101l:638:300-5.

(221

Fukushima Y. Bycrs MG, Fiddes Jc’. Shows TB. The human (FGI:B) is assigned IO chromosome 4~125.

fibr~~blast growth factor pwc Cyll~y~ncl Ccl1 Gcllcl

2.157~ b4.

IlOO;S4: I 59 - 60.

1231 White CW. Sondhcimcr I-IM, Crouch EC. Wilson H. Fan 1~1.. ‘I’l’Cillll~Cl~l 01’~lllllll~llil~y llL!lllilllgi~~llM~lhihwilh rcc0llll~illillll inlcrferon tk-?il. N l
Orchard

I’J, Smith C’M, Wood\

W(i.

I)ay Dl,.

Dchncr

1.1’.

Shilpilo R. ‘I’rCilllllCIll01’IlilClllilll~ilN!lldl~lllClionla4 will1 illldlil ililcrfwon.

I .i\llCCl I OHO~2:5~~5 . 7.

370

PEDIATRIC

NEUROLOGY

Vol. I7 No. 4