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DOI: 10.1542/pir.17-8-2651996;17;265Pediatrics in Review
Michael J. Rivkin and Joseph J. VolpeStrokes in Children
http://pedsinreview.aappublications.org/content/17/8/265the World Wide Web at:
The online version of this article, along with updated information and services, is located on
Print ISSN: 0191-9601.Village, Illinois, 60007. Copyright © 1996 by the American Academy of Pediatrics. All rights reserved.
trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Groveandpublication, it has been published continuously since 1979. Pediatrics in Review is owned, published,
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
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IM PO RTANT PO INTS
1 . S tro k e
occurs
at an an n u a l freq u en cy o f
2 .5 cases pe r 1 00 ,00 0 ch ild ren .
2 . S tro k e in ch ild ren is cau sed b y he art d ise ase, i nf ec ti on m et ab ol ic d is or
ders hemato log ic
d iso rde rs , an d vascu litic
d isord ers often d u e to a uto im
m u n e
processes.
3 . T h e th ree
processes
th at can cau se stro k e in ch ild ren a re
embol ism,
t hr om b o si s a n d h em o r rh a ge .
4 . A lth ou g h la teral ized f in d in gs m a y b e fo u n d o n n eu ro log ic ex am in ation in a
neo n ate w h o h as s uff er ed a s tr o ke focal se izu re m ay se rve as the sole
initial m an ifes ta tion of th is d iso rder in a n ew b orn .
5 .
M ag n etic reson an ce im a gin g p ro v id es n ot o n ly
bet ter
im a ge r es olu tio n
th a n com p u ted tom o grap h y b u t a lso is m u ch m ore
sensi t ive
t o s ub tl e
pa ren ch ym a l ch a n ges th at a cco m p a n y strok e
soo n afte r its occu rrence.
6 . A cu te la tera lized weakn es s in a ch ild does n o t a lw a ys in d icate th e occu r
ren ce of s trok e . C on d ition s tha t
produce
sym p to m s an d sign s s im ila r to
strok e in du d e T o d d p ostic ta l p ara lysis hemipare t ic se izures sub and
epidura l
he mo rrha ge , hyp og ly ce mia ,
a n d a lt er na ti ng
hemip leg ia
o f c h il dh o od .
*A ss ista n t P ro fessor o f N eu ro logy .
tB ronson C ro ther s P ro fes sor o f N euro lo gy ,
H arv ard M ed ica l Sc hoo l, B oston , M A .
P ed ia trics iv
i
Rev iew Vo l. /7 N o . 8 A ug ust 19 96
26 5
S tro k es in C h ild ren
M ichae l J . R ivk in M D and Joseph J . Vo lp e M D t
ART ICLE
S trok e den o te s the sudd en onse t o f a
foca l neu ro lo g ic de fic it an d m os t
o ften in clu des the ab ru p t appea ran ce
o f w eakness. In te rrup tio n o f b loo d
flow to a pa rt o f the cen tra l ne rv ous
system (CN S ) u sua lly un de rlie s th e
re su ltan t w eakn ess . B ecause m ost
strok es in ch ild ren are re la ted to foca l
ce reb ra l inv o lvem en t, th e m o st com -
m on c lin ica l m an ife sta tion is the
ab ru p t ap pearance o f hem ipa res is .
L ess frequen tly , th e cau se o f stro ke
invo lves th e b rain stem , ce rebe llum ,
o r sp ina l co rd . Th e fu nc tion al conse -
quences a lw ays ref lect the neuro -
ana tom ic featu re s o f the a ffec ted
CN S reg io n .
Ep idemio logy
Ch ildho od stro ke o ccurs w ith an
annu al inc iden ce of 2. 5 cases pe r
10 0 ,000 popu la tion an d has b een
rep orted in a ll rac ial and e thn ic
g rou ps. T he sequ e lae a re n o t tr iv ia l.
In add ition to la sting la tera lized
w eakn ess, cog n itive de ficits , d is tu r-
b an ces o f lan guage , v isua l d efic its ,
and se izu re s m ay pe rsis t long a fte r
the acu te even t h as co nc lud ed .
T he causes o f strok e in ch ild ren
d iffe r from tho se in adu lts . S trok e in
adu lts is as soc ia ted la rge ly w ith
h yp erten sion or a the ro sc lerosis an d
th e ir re spec tive hem o rrhag ic and
ischem ic co nsequ en ces. S troke in
ch ild ren m ore comm only is cau sed by
o r re lated to cong en ital h ea rt d isea se ,
in fec tion , m e tabo lic d iso rde rs , h em a-
to log ic d iath eses , an d vascu litic d is-
o rde rs , f req uen tly d ue to au to imm une
p rocesse s (T ab le 1 ) . N one the le ss ,
d esp ite the m o st th o ro ug h o f ev alu a-
tio ns, e tio log y escap es d etec tion in
app ro x im a te ly 3 0 o f th e ped ia tric
p atien ts in w hom s trok e occu rs .
Pa thogenes is
Is ch em ic in ju ry o f the b ra in o ccurs a s
a resu lt o f on e of th ree d ifferen t
m ech an ism s: em bo lism , th rom bosis ,
o r d im in ish ed system ic pe rfusio n .
Em bolic dam ag e to the b ra in o ccurs
w h en m a te ria l fo rm ed a t a s ite in the
vascu la r system prox im al to the b ra in
lodg es in a b loo d v essel, thu s b lock -
ing cereb ra l pe rfu sion . Em boli o rig i-
na te m ost com m on ly from the h ea rt,
ar is ing from a clo t o n ca rd iac cham -
be r w a lls o r from vege ta tions o n
va lve lea f lets . A rte ry -to -a rte ry em bo li
are com posed of a c lo t o r p la tele t
ag g reg ate s tha t o r ig ina te in vesse ls
p rox im al to the b rain b u t u ltim a te ly
com e to re st and to occ lude flow in
vesse ls c r itica l fo r cereb ral pe rfusio n .
Th rom bos is den o te s v ascu la r occ lu -
sion due to a localized process w ith in
a b lo od vesse l o r v essels . A lth ough
ath e roscle rosis u nde rlie s m ost th rom -
bo tic p ro cesses a ffec ting ad u lts , it is
no t a comm on cau se o f th rom bosis in
ch ild ren . L ocalized lum ena l c lo t fo r-
m a tion occu rs in po lycy th em ia o r in a
hyp e rcoagu lab le state . A lterna tive ly ,
an a tom ic abno rm alitie s m ay lead to
clo t fo rm a tion or m echan ical o bstruc -
tion , a s in f ib rom u scu la r dy sp la sia ,
ar te ritis , o r a r te r ial d issec tion .
If system ic p ressu re dec line s su ffi-
cien tly to com p rom ise ce reb ra l pe rfu -
s ion , the CN S m ay suffe r in ju ry d ue
to d im in ish ed system ic p e rfusion .
C ard iac pum p failu re (rela ted to co n-
g en ita l hea rt d isease and its su rg ical
repa ir) a s w e ll a s sy stem ic hy po ten -
sio n d ue to h ypovo lem ia a re com m on
causes o f hy po tens ive ce reb ra l
ischem ic in ju ry . O ften b ra in in ju ry is
m u ch m o re d iffuse in the con tex t o f
d im in ished ce reb ra l p erfu sion com -
p ared w ith the m ore focal in ju r ie s
cha rac te ris tic o f th rom bo tic and
em bo lic ce reb ra l ev en ts . C e reb ra l
ischem ia se rves a s th e fin al comm on
p athw ay lead ing to b ra in in ju ry irre -
spec tive o f w he the r an em bo lic ,
th rom bo tic , o r hy pop erfu sive m echa -
n ism h as caused th e s tro ke .
B o th th rom bo tic an d em bolic
strokes m ay be he ra ld ed b y th e o ccu r-
ren ce o f transien t isch em ic a ttacks
(T IA s) . T IA s a re b rief ep isodes o f
fo cal, non co nvu lsive neuro lo g ic
de ficit a ttrib u tab le to in te rrup tion of
cereb ral pe rfusio n . A s w ith stroke ,
the o nse t is ab ru p t, bu t a T IA ep iso de
lasts le ss th an 24 hou rs, and reco ve ry
is com p lete . A T IA freq uen tly p or-
tends th e subseq uen t o ccu rren ce o f a
stro ke and its re su ltan t fix ed de fic its .
H em orrh ag e o ccu rs w h en b lo od is
re leased in to the ex travascu la r
in trac ran ial o r in tra sp in al space. In
th is c ircum stan ce, foca l in ju ry o f
b ra in o r sp ina l tissu e occu rs a s a
re su lt o f bo th p re ssu re exe rted b y the
space-occupy ing m ass o f b loo d an d
hem orrh age -rela ted isch em ia . S uch
in ju ry m ay be exacerba ted b y the
dam ag ing e ffec ts on neural tissue o f
substances re lea sed in th e b lo od .
Ep id u ral and su bdu ra l h em orrh ag e
a re in trac ran ia l co llec tions o f b lo od
sep ara ted from brain pa ren chym a by
dura l o r arach no id m em bran es.
S u ba rachno id h em orrh ag e occurs
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T A B L E . Etiologies of Str ok e in C hildr en
26 6
Ped i a t r i c s
Review Vo l. 17 No. 8 Augu st 19 96
.
N U R O L O G Y
St rokos
Thrombosis
{ 1 4 9 }asc ular D ysplasias
-Moyamoya disease
-N eur ofibr om atosis type 1
-Fibromuscular dy splasia
-D issecting aneur ysm
-V asc ular m alform ations
#{149}asculopathy
-Sick le cell disease
-Radiation
-T ra u ma
Intraoral
Neck
#{149}asculitis
-Infec tion-mediated m ening itis
-V i ra l
and
postvir al causes
-Autoimmune-mediated
System ic lupus er ythem atosus
Polyarteritis
nodosum
Takay asu arte ritis
Henoch-S chOnlein purpura
Kaw asaki disease
#{149}asospasm
-M igra ine
I
-C ocaine use
-G lue sniff ing
-W asp/S corpion sting
#{149}ematologic
-H emoglobinopathies
Sick le cell disease
Sick le C disease
-Polycythemia
-Thrombocytosis
-Leukemia /Lymphoma
-Coagulopathy
P rotein S deficiency
Pr otein C deficiency
. A ntithr om bin I I I deficiency
L u pu s a nt icoa gu la nt
O ral contr aceptive use
w hen blood flow s out o f the intracra-
nial v ascular bed and onto the surface
o f the brain to adm ix w ith cere-
brospinal f luid in the subarachno id
space. Intracerebral hemorrhage
deno tes bleeding into the parenchyma
of the brain.
S tro k e in th e N e w b o rn
H Y P O X I C - I S C H E M I C
E N C E PH A L O PA T H Y (H I E )
B rain injury consequent to asphyx ia,
Pr egnancy and the
postpartum state
L-Asparaginase
D issem inat ed int ravascular
coagulation
{ 1 4 9 }etabolic
-Homocystinuria
-Fabry disease
-Sulf ite oxidase deficiency
-Pseudoxanthom a elasticum
-M ito chondrial diso rders
Embolus
{ 1 4 9 }ardiac D isease
-Congenital dis ease
A ortic stenos is
Mitral stenosis
V entricular septal de fec ts
Patent ductus ar ter iosus
Cyanotic congenital heart
disease
w it h r i gh t- to- lef t
shunt
-A cquir ed disease
Endocarditis
Cardiomyopathy
Atrial
myxoma
Arrhythmia
-Air embolus
-F at em bolus
Hemorrhage
#{149}ead T raum a
-Subdur al hem or rhage
-E pidur al hem or rhage
{ 1 4 9 }pontaneous Occurrence
-A rterio venous malformation
-R uptur ed aneur ysm
M y cotic aneur ysm
Saccular aneury sm
-Thrombocytopenia
-Hemophilia
-O ther bleeding diatheses
hypox ia, or ischem ia is an important
cause o f neonatal neuro log ic morbidi-
ty . Tissue oxygen defic iency is pre -
sum ed to underlie the neuro log ic
injury caused by hypox ic- ischem ic
insults . A sphyx ia denotes an impair-
m ent in g as ex change that results no t
only in a de fic it o f ox ygen in blo od
but also in an exces s o f carbon diox -
ide and, thereby , ac ido sis . Further,
sustained asphyx ia alm ost alw ays
results in hypotens ion and ischem ia,
consistent w ith the like ly predomi-
nant impo rtance of ischem ia as the
final common pathw ay to brain
injury.
Ev idenc e o f hy pox ic- isc he mic
injury to the neonatal nervous system
as a result o f asphyx ia is re flec ted by
a conste llatio n o f s igns that appear
early in the po stpartum period. This
conste llatio n constitute s the c linical
entity o f HIE. A lthough diffuse hypo -
tonia is the most frequently observed
mo tor de fic it found early in the
course o f neonatal HIE, patterns o f
w eakness may emerge by the end of
the first day of life that re f lec t the
distributio n of cerebral injury from a
generalized hypox ic - ischem ic insult.
Term infants may demonstrate a pat-
tern of parasag ittal cerebral injury
manife sted as quadriparesis w ith pre -
dom inant prox imal limb w eakness.
This pattern deriv es from ischemia in
the w atershed or parasag ittal reg ions
o f brain, w hich correspond to the bor-
der zones o f c irculation be tw een the
anterior and m iddle cerebral arterie s
and the m iddle and pos terior cerebral
arterie s . Pre term infants may mani-
fe st de ficits re flec ting periventricular
leukomalac ia. The resulting w eakness
occurs prim arily in the low er ex trem-
itie s due to perinatal ischem ic injury
of moto r fibers subserv ing the legs.
These fibers lie dorsal and lateral to
the ex ternal ang le s o f the lateral y en-
tric le s . In each o f these cases, c linical
features and cerebral neuropatho log ic
finding s sharing a bilateral distribu-
tion are found. How ev er, focal cere -
bral infarctio n-that s , stroke -does
occur in the new bo rn.
F O C A L C E R E BR A L I N F A R C T I O N I N
T H E T E R M N E O N A T E
Etiologies
The cause of cerebral infarc tion fre -
.
quently escapes detec tion among
infants w ho have not been subjected
to overt perinatal asphyx ia. Indeed, in
3 7 o f
5
1 reported cases o f neonatal
stroke (7 3%), a cause could not be
identif ied. Interes ting ly , a le ft hem i-
spheric lo catio n has been noted to be
most common; the reason for this
neuroanatom ic predilec tion has no t
been discovered. Embo lic or throm-
botic e tio lo g ie s have been recog -
nized. Emboli from the placenta may
lodge in cerebral vesse ls and cause
s troke . Further, it is possible that fea-
tures o f the no rmal new born’s heart,
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N EU R OLOGY
S trok.s
O n ce str oke is su spec ted , d ia gn o stic effo r ts sh ou ld
con cen tr a te on ... d iscover in g th e u n der lyin g ca u se .
CC T a n d M R I pr ovide r a p id eviden ce o f in fa r c tion o r
h emo r r h a g e .
P ed ia tr ics in R ev iew Vo l. 1 7 N o . 8 Aug us t /9 96 2 67
such as a patent f oramen ovale, per-
m i t the transm ission of embol i i nto
the system ic arter ial ci rculati on
through right- to-l ef t shunts. Once in
the system ic arter ial tree, the embol i
ul timatel y may ram i f y in the cere-
brovascular bed and cause f ocal
i nf arcti on. I n addi ti on, congeni tal
heart defects involv ing r ight-to- l ef t
shunts through septal def ects or a
patent ductus arteriosus serve as set-
ti ngs for embol i c stroke in neonates.
A nother eti ology of neonatal stroke
is thrombosis. Thromboti c infarcti on
probably i s most common in the new -
born as a consequence of bacter ial
meningi ti s. Polycy them ia and i ts
resul tant hyperv i scosi ty can cause
abnormal i ti es of blood f low and even
thrombosis. A pprox imatel y I .5 of
neonates are polycy them ic, w i th new -
borns w ho are smal l for gestati onal
age being af fected most f requentl y .
M ost cases of polycy them ia are idio-
pathi c or due to acqui red abnormal i -
ti es of oxygen del i very such as
maternal smok ing . N onetheless,
polycy them ias bearing autosomal
dom inant or recessive inheri tance
patterns have been described.
Cerebral venous thrombosis may
cause f ocal i nf arcti on in the new born.
Cerebral veins conduct deoxygenated
blood f rom the parenchyma to the
dural sinus system . These sinuses-
the sagi ttal , straight, transverse, cay-
ernous, and petrous-convey the
blood to the jugular veins for return
to cardiopulmonary ci rculati on.
Thromboti c occlusion of f l ow any-
w here in these venous condui ts leads
to i schem ia and sometimes inf arcti on,
usual l y hemorrhagic. I nf ecti on, dehy -
drati on, polycy them ia, congeni tal
heart di sease, and protein C def i cien-
cy al l have been impl i cated as causes
of cerebral venous thrombosis in
neonates; how ever, no def ini ti ve
cause need be found.
I ntracranial hemorrhage occurs in
neonates in one of f our neuroanatom-
i c di str i buti ons: subdural SD H , sub-
arachnoid SA H , intraparenchymal
I PH , or intraventri cular IV H . SD H
occurs more commonly in the term
inf ant; the other three types of hemor-
rhage are more common in preterm
inf ants. SD H in neonates appears to
resul t primari l y f rom mechanical
trauma. Cephalopelv i c di sproporti on,
ri gidi ty of the bony pelv i s, prolonged
duration of labor, unusual presenta-
ti ons, or the need f or prolonged
manipulati on or f orceps appl i cati on
may generate increased f orces on the
fetal head and predispose the inf ant to
SD H . Shear ing for ces may cr eate
tears in the vein of Galen or superf i -
cial cerebral veins. I f f orces are
ex treme, tears at the junction of fal x
and tentor ium can generate large sub-
dural blood col l ecti ons in the rela-
ti v ely smal l posterior fossa, culm inat-
i ng in brain stem compression and
cerebel l ar tonsi l l ar herniati on.
Smal ler tentor ial tears are relati v el y
common. W i th improved obstetr i c
practi ce, the incidence of SD H has
decl ined steadi ly .
B lood can occupy the subarachnoid
space in tw o w ays. Fi rst, i t may reach
the space af ter hemorrhage has
occurred in the cerebral parenchyma
or in the peri ventr i cular region.
Second, SA H may resul t f rom disrup-
ti on of the superf i cial l eptomeningeal
arter ies or of the f ragi l e vessels that
bridge the subarachnoid space; di s-
ruption of ei ther vascular structure
leads to di rect bleeding into the
space, so-cal l ed pr imary SA H . Prim -
ary SA H commonly occurs af ter
hypox ic-i schem ic brain insul ts and
af ter f etal head trauma. O f ten the
pathogenesis i s unclear.
I PH in the absence of I V H occurs
most commonly in term inf ants.
H emorrhage into the parenchyma of
the cerebral hem ispheres can be due
to head trauma, vascular mal forma-
ti on, coagulopathy , tumor, or inf arc-
ti on. Even though v i tam in K , a car-
boxy lati ng and acti vati ng agent f or
clotti ng f actors I I , V I I , I X , and X I , i s
adm inistered routinel y to new borns,
i ts def i ciency should be considered in
breastf eeding f ul l -term neonates w ho
present w i th intracranial hemorrhage.
In the absence of recognized coagula-
ti on or anatom ic abnormal i ti es, cere-
bral hem ispheri c I PH usual l y i s a
mani f estati on of hemorrhagic inf arc-
ti on. I n thi s ci rcumstance, embol i c
stroke precedes hemorrhage. W hen
the embol i c material occluding the
cerebral vessel eventual l y f ragments,
parti al or total perfusion through the
prev iously occluded vessel i s reestab-
l i shed. H emorrhage ensues as blood
escapes through the vascular w al l s,
w hich have been w eakened by the
embolus-induced ischem ia.
C linical F eatur es
Focal seizures have been identi f i ed as
the most common cl ini cal f eature
indicating the presence of stroke in
the ful l -term nonasphyx iated infant.
A l though lateral i zed f indings may be
found on neurologic exam ination,
they need not be present as hal lmarks
of cerebral i nfarcti on. Further, dim in-
i shed movement of ex trem i ti es on the
side of the focal sei zure may repre-
sent a T odd posti ctal paral ysi s rather
than paresis f rom upper motor neuron
injury due to cerebral i nfarcti on.
Recognizing focal sei zure as a mani -
f estati on of cerebral i nf arcti on i s
important because thi s may be the
only sign of the cerebrovascular
event; i ni ti al l y , other neurologic signs
may be absent.
C l i ni cal f eatures of SD H depend
on the location and size of the hemor-
rhage. T entor ial l acerati on can cause
stupor or even coma. Pupi l l ary and
ex traocular movement abnormal i ti es
are common. Retrocol l i s or opistho-
tonus is seen. Final l y , abnormal i ti es
of respi ratory pattern, such as
apneusti c or atax i c respi rati ons, are
ev ident and signi f y imm inent respi ra-
tory arrest. L ess severe SD H in the
poster ior fossa evolves more slow ly
and causes less severe brainstem dys-
function. Subdural col l ecti ons of
blood over the cerebral surfaces due
to tears of superf i cial cerebral veins
may be asymptomati c or accompa-
nied only by i rri tabi l i ty . I f the col l ec-
ti on i s suf f i cientl y large or accompa-
nied by cerebral contusion, seizures
can occur. G reater pressure, w i th
transtentorial herniati on, may di l ate
pupi l s uni l ateral l y and ablate pupi l -
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I n neonates focal seizures rather than lateralized
neurologic findings are the most common clinical
feature of a stroke
26 8
P e dia tric s in Review Vol 7 No 8 Aug ust 9 96
N U RO LOGY
S t ro k e s
l ary l i ght responses. H ow ever, SD H
may escape diagnosis in the f i rst few
w eeks of l i f e and appear later as a
chronic subdural ef f usion. Such an
occurrence is marked by a rapidl y
enlarging head ci rcum ference and
increased transi l l um ination of the
skul l . C l i ni cal l y , m i ld SA H occurs as
an occul t phenomenon w i th few , i f
any , mani f estati ons. G reater amounts
of blood col l ecti ng over the convex i -
ti es may resul t i n seizures.
Diagnosis
Once stroke is suspected, electroen-
cephalography EEG and neuro-
imaging are the most usef ul methods
of documenting its occur r ence. I f
f ocal sei zures herald f ocal cerebral
i nf arcti on, the EEG of ten is the f i rst
diagnosti c test ordered. Ev idence of
local i zed brain dysf unction on EEG
consists of focal , persi stent vol tage
reduction or marked focal slow ing
and sharp w ave acti v i ty . Per iodi c lat-
eral i zed epi l epti form discharges may
be present. I n some instances, there
may be electrographic ev idence of
cl i ni cal l y observed seizures. Each of
these f indings may ex ist w hi l e the
E E G r emains r elatively less affected
over other regions of the brain.
The areas of electri cal abnormal i ty
should correspond to the af fected
areas of brain revealed by neuroimag-
ing. Cranial computed tomography
C CT dem onstr ates a low-density
region that eventual l y evolves to atro-
phy . H ow ever, ear ly in the period f ol -
l ow ing infarcti on, the af f ected cere-
bral terri tory may not be w el l v i sual -
i zed w i th CCT . M agneti c resonance
imaging M RI perm its identi f icati on
of cerebral i nf arcti on earl y af ter i ts
occurrence. M RI w i l l demonstrate
low or i sointense signal i ntensi ty on
T l -w eighted images and high signal
i ntensi ty on T 2-w eighted images
because of increased w ater content in
the infarcted region. D i f f usion-
w eighted M RI i s most sensi ti ve in the
f i rst hours af ter the event. Final l y ,
i ntracranial bleeding can be identi f i ed
easi l y w i th ei ther CCT or M RI .
O ther laboratory tests should
include hematocr i t and hemoglobin
electrophoresi s i f pol ycy them ia is
suspected. Screening for inf ecti ous
and metabol i c di sorders as w el l as
coagulopathies that could ref l ect
thromboti c or embol ic stroke should
be perf or med. E chocardi ogr aphi c
exam ination of the heart, especial l y
employ ing bubble contrast, w i l l help
identi f y a structural def ect that may
have contri buted to a new ly identi f i ed
embol i c cerebral infarct.
Treatment
T reatment i s supporti v e and sympto-
mati c. A nti convulsants are given i f
sei zures have occurred. Phenobarbi tal
i s the pref erred drug and is adm inis-
tered as a loading dose of 20 mg/kg.
D oses of 3 to 4 mg/kg dai ly are suf f i -
cient f or maintenance therapy .
A ttention should be given to hydra-
ti on state, acid-base balance, and
hematocri t and any def i ci ts corrected.
U nderl y ing inf ecti ous or metabol i c
condi ti ons or coagulopathy must be
treated. I diopathi c cerebral venous
thrombosis does not appear to requi re
anti coagulati on. Infants w ho have
suf f ered intracranial hemorrhage
should be evaluated neurosurgi cal l y
to determ ine the need f or clot evacua-
ti on or vascular repai r .
Prognosis
I t i s di f f i cul t to estimate the develop-
mental outcome f ol l ow ing cerebral
i nf arcti on. The periods of f ol l ow -up
reported in ser ies of neonatal stroke
have been highly variable. A lthough
seizures f requentl y abate over time,
chronic motor def i ci ts of ten become
apparent. M RI ev idence of cerebral
i nf arcti on may be helpf ul i n deter-
m ining the prognosis. M ost infants
w ho have ev idence of marked w hi te
m atter dam age or cy sti c/m ul ti cysti c
encephalomalacia have proven to
have neurodevelopmental abnormal i -
ti es on short- term f ol l ow -up. I nf ants
w hose CCT studies are normal
demonstrate l i ttl e or no neurologic
def i ci t w hen studied in fol l ow -up.
T hose inf ants demonstrating marked
parenchymal hypodensi ty or hemor-
rhage rarel y have normal develop-
ment during fol l ow -up. L ong-term
f ol l ow -up of inf ants w ho had cerebral
i njury identi f i ed by M RI shortl y af ter
bi rth i s sti l l needed. I n the case of
idiopathi c cerebral venous thrombosis,
al though f ol l ow -up has been l im i ted,
neurologic prognosis appears good.
S t r o k e in h ild r e n O ld e r
Th a n I Ye a r
D espi te the inf requency of stroke
among chi l dren, a great variety of eti -
ologies ex ists. T hese may be grouped
according to w hether an embol i c,
thromboti c, or hemorrhagic event has
occurred Table 1 .
T H R O M B O S I S
V ascular D ysplasia
M oyamoya syndrome is observed
most commonly in chi l dren younger
than 15 years w ho typical l y present
w i th T IA s or f i x ed motor def i ci ts of
sudden onset. Progressive narrow ing
and occlusion of the intracranial supra-
cl i noid internal caroti d arter ies are
characteri sti c. Endothel i al prol i f era-
ti on, f i brosi s, and intimal thi ckening
consti tute the vascular pathology .
Resul tant prol i f erati on of col l ateral
vessels, pr incipal l y f rom the ex ternal
caroti d ci rculati on, creates an intr i -
cate latti cew ork of compensatory
blood f low . The character i sti c appear-
ance on angiography is a f ine vascular
netw ork in the region of the basal
gangl i a Fig. 1 . I t i s f rom this
appearance that Japanese physicians
coined the term “ moyamoya,” mean-
ing “ something hazy l i ke a puf f of
cigarette smoke dri f ti ng in the ai r .”
Chi l dren usual l y present w i th acute
hem iplegia due to uncompensated
occlusion of the internal caroti d
artery . B ecause the anatom ic abnor-
mal i ty i s of ten bi l ateral , bi l ateral
motor def i ci ts may be f ound. In addi -
ti on, f i ne motor f unction may be
observed. Chorea has been reported
in associati on w i th moyamoya syn-
drome. A l though the vascular abnor-
mal i ty may be congeni tal , moyamoya
syndrome can occur as a sequel to a
pr imary disorder causing internal
caroti d artery occlusion. I t has been
found in chi l dren w ho have sick le
cel l di sease, neu rof i br om at osi s,
tuberculous meningi ti s, and f ibro-
muscular dysplasia. Ev idence sug-
gesting a heredi tary etiology in some
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NEUROLOGY
Strokes
ic s tro ke .
T A B L E 2 . A u t o im m u n e D iso r d er s A ssoc ia t ed W it h
C e n t r a l
Nerv ou s
S yst em I n vo lv em en t
F
DISORDER
N S M N IF ES T TIO N S
System ic lu pus e ry them atosus
M igra ine headache , se izu re s,
F
strok e, ce rebe lla r d ysfunc tion ,
tran sve rse m ye lop ath y , a sep tic
men ing i t is
M ix ed con n ec t iv e t issu e d isease S e iz u r e s, s t r ok e, ce r eb e lla r d y s-
f u n c t i o n , t r igeminal n e u r o p a t h y
Po lya rte r itis nod osum M igrain e h ead ach e , s t r ok e , su b -
a rachn o id h em orrhag e, se izu re s
W e gen er gr an u lom a to sis M igrain e headache , su ba rachn o id
h em orrhage , s troke
Takay asu a rter itis
S eiz u re , s t r o k e
Heno ch -S ch { 246}n le in pu rp ura H eadache , s tro ke , s eizu re s, cho rea
270
Pediatr i cs i n Review Vol 17 No 8 August 1996
m otor lo ng trac ts co urse th rou gh the
b rain s tem , sym ptom s of gene ral s en -
so rim o to r im pa irm en t m ay b e found
as w e ll. V e rteb ra l a rte ry in ju ry in
ch ild ren has been reported in the set-
ting o f ath letic s (eg , ju do ), au tom o -
b ile accid en ts , o r ch iro p rac tic cerv i-
ca l sp ine m an ip u la tion . T he resu ltan t
v erteb robasila r s trok es a re d ue to
th rom bo sis o r to ve rteb ra l a rte ry d is-
s ec tion . A n ticoagu la tion w ith
an tip late le t agen ts has b een p ro posed
as the rapy . F ina lly , c ran ial rad ia tion
th erapy rece ived as p a rt o f can cer
the rapy m ay indu ce an o cc lus ive vas-
cu lopa th y lead in g to focal cereb ra l
isch em ia. B asa l gang lia frequen tly
are a ffec ted by th is v ascu lopa thy ,
re su ltin g in ex trapyram ida l m ov e-
m en t d ysfun ctio n , su ch as cho reo -
athetosis .
Vascu l i t i s
In fectio n is an im portan t and treat-
ab le cause o f stroke in ch ild ren .
C e reb ral vesse ls m ay becom e
in flam ed in the cou rse o f bac te ria l
m en ing itis . T h e sub arachno id a rte r ie s
becom e imm ersed in puru len t exu -
da te, and sm alle r v esse ls a re affec ted
as ex uda te m oves dow n V irchow -
R ob in spaces. The v es sel w a lls o f
ar te rie s and ve ins are a ffected by the
in flamm ato ry p rocess, and occ lusio n
of e ithe r can re su lt in s tro ke . A n ti-
b io tic s com bin ed w ith ste ro ids early
in th e course o f trea tm en t a re the co r-
ne rsto ne of the rap y . V ira l in fec tion
also m ay prom ote vascu la r in flam m a-
tion tha t m ay invo lve th e cereb ral
v es sels and cu lm ina te in strok e.
C e reb ral vascu litis and stroke h as
been d escribed in assoc iatio n w ith
hum an im m unode fic iency v iru s
H IV in fec t ion in ch ild ren .
Aneu ry sm s hav e been ob se rv ed in
asso cia tio n w ith the H I V -asso cia ted
v ascu litis . In add ition , he rp es zoste r
an d va rice lla v iruse s h ave b een asso -
cia ted w ith ang iitis o f the CN S ,
re su ltin g in acu te hem ip leg ia .
V ascu litis lead ing to a rter ia l occ lu -
s io n a lso has b een o bse rv ed in rub ella
and coxsack iev irus A 9 in fectio ns,
p ro bab ly as a po stv iral im m uno log ic
phenom enon . H ow eve r, v ascu litis
an d in fa rctio n have b een obse rved in
the po stv iral synd rom e o f acu te
n ec ro tiz ing h em orrh ag ic
leukoencephalopathy .
A u to imm une d iso rde rs o ften
inc lu de v ascu litis tha t m ay invo lve
th e CNS (T ab le 2 ). S ym ptom s o f
ab rup t onse t w ith accom pany ing
d efic its re fe rab le to the CN S lo ng
h av e been assoc ia ted w ith system ic
lup us ery th em ato sus (SLE ). A CN S
vascu litis had b een p re sum ed to
u nde rlie th e CN S m anife sta tions o f
S L E , b u t au t op sy st u d y o f p a t ien t s
su ffe rin g from SLE revea led a v ir tua l
absen ce o f ce reb rovascu la r in f lam m a-
tio n . R ath er , sm a ll a rea s o f in fa rc tion
re late to p ro life rativ e changes in ce re-
b ra l a r ter io le s , le ad ing to lum ena l
o cc lu sion . L arge a reas o f in fa rctio n
m ore like ly a re rela ted to lup us an ti-
coag u lan t-d e rived th rom bo em bo lism
o r to em bo lism from th e s ter ile car-
d iac v alv e lea fle t vege ta tion s assoc i-
a ted w ith SLE .
S trok e m ay occur in th e co urse o f
p o lya rter itis no dosa ; invo lvem en t o f
th e CN S is fo un d in 2 0 to 40 of
p atien ts . M ixed co nnec tive tissu e d is-
ea se (M CTD ), w h ich o ve rlaps clin i-
ca lly w ith po lym yo sitis , lu pu s, and
p ro gress ive sy stem ic sc le ro sis , can
in vo lv e the CN S. C ran ia l neu rop ath y ,
m ost comm only tr igem ina l ne rve
d ysfunc tio n , has been the d efic it cited
m ost freq uen tly . R ecen tly , how ev er ,
s trok e m an ife sting as sud den onset
h em ipa re sis an d aphasia has b een
reported in ch ild ren aff licted w ith
M C T D . T a k ay a su ar t e r it is , in v o lv in g
th e ao rta an d its p r inc ipa l b ranches,
h as been as soc ia ted w ith th rom bo tic
s trok e . In flamm atio n -in du ced lum e-
n al co nstr ictio n lead in g to th rom bosis
is th ough t to cause cereb ra l isch em ia
in these ch ild ren . A ng io g rap h ic
im p ro vem en t o f vessels in the ca ro tid
tree is o bse rved w ith imm uno sup -
p re ssiv e treatm en t. N ec ro tizin g arte ri-
tis w ith in f lam m ato ry in f iltra te h as
b een fo und in b o th m en in geal an d
ce reb ra l vesse ls o f ch ild ren su ffe rin g
from H eno ch -S ch { 246}n le in purpu ra .
B o th fixed and tran sien t de fic its
(T IA s) m ay occu r in th is d iso rde r.
T rea tm en t w ith ste ro ids o r o the r
im m unosuppres sive agen ts p rov e
m ost h e lp fu l. L ong-te rm an ticoagu la-
tio n h as no t been stu d ied . N euro lo g ic
com plica tions accom pany K aw asak i
d isease in I o f cases . H em ip leg ia
and se izu re s h av e been rep orted .
C hanges ind ica tive o f foca l ce reb ra l
in fa rc tio n h av e b een obse rved on c ra -
n ial C T stu d ie s . F in ally , th e CN S m ay
b e in vo lv ed in ch ild ren w ho h av e
h em oly tic -u rem ic synd rom e (H US );
en ceph a lo pa thy is fou nd in 20 .
S troke accom pan ied b y rad iog raph ic
ev idence of foca l CN S in ju ry h as
b een o bse rv ed in 5 o f ch ild ren w ho
h av e HU S . Focal in fa rc tion is foun d
p rim arily in the ce reb ra l h em isphe re
and basa l gang lia . E n do th elia l cell
dam age due to the Sh ig a tox in p ro -
duced by the cau sativ e
Eschericia
col i 0157: H7 organ ism is tho ugh t to
ac tiva te p late le ts an d coagu latio n cas-
cades, cu lm ina ting in th rom boem bol-
Vaso sp asm
S troke m ay occur in th e se tting of
m ig rain e headach e . T he occurrence
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NEUROLOGY
Stroke s
Acu te h em ip leg ia m a y fo llow a g en er a lized se izu r e
T odd pa r a lysis . T h ese a r e sh o r t-lived . P r ese r va tio n o f
con sc iou sn ess is n o t a fe a tu r e o f gen er a lized se izu r es .
Pediatrics
in R ev ie w
Vo l. 17 N o . 8 A ugu st 1 99 6
27 1
of f ocal motor def i ci ts during a
m igraine headache denotes compl i -
cated m igrai ne . A c ut e hem ipar esi s
has been w el l -documented during
these episodes and is bel i eved to
ref l ect the involvement of the cere-
bral ci rculati on deri ved f rom the
carotid artery . Symptoms such as
atax ia, corti cal bl i ndness, and cranial
nerve dysf unction correlate w i th
involvement of the vertebrobasi l ar
ci rculati on. Focal symptoms may be
f i xed or may occur as T IA s. Ini ti al l y ,
an associati on betw een m igrainous
stroke and discharged embol i f rom
m i tral val ve prolapse w as hypothe-
si zed, but recent studies have not sup-
ported thi s theory . A l though oral con-
tracepti ves are associated w i th hyper-
coagulabi l i ty , w hich i s thought to pre-
di spose to stroke, the postulated addi -
ti ve r i sk f or stroke in m igraine
headache among those tak ing oral
contracepti v es has been chal l enged.
A ngiographic studies in patients suf -
fer ing f ocal def i ci ts consistent w i th
stroke in the setti ng of m igraine
headache have documented vasocon-
stri cti on of vessels in ei ther the verte-
brobasi l ar or caroti d ci rculati ons. I n
these cases, the neuroanatom ic posi -
ti on of the constr i cted vessels corre-
lated w i th the location of the
observed def i ci ts. A s a resul t,
i schem ia provoked by vasoconstr i c-
ti on during prolonged m igraine has
been hypothesized as the mechanism
of stroke in these patients. Calcium
channel blockers have been used f or
treatment, but def ini ti ve studies of
thei r ef f i cacy are needed.
D rug abuse may promote throm-
boti c stroke. Cerebral i nf arcti on and
peripheral neuropathy have been
associated w i th glue sni f f i ng in chi l -
dren, and cerebral i nfarcti on and
SA H have been observed af ter
cocaine use. Cocaine blocks the reup-
take of catecholam ines at the synapti c
clef t. T he resul ti ng elevated synapti c
concentrati ons of epinephrine and
norepinephrine markedly enhance the
neural acti v i ty of adrenergi c systems.
Tachycardia, hypertension, and vaso-
constr i ction resul t. T he probabi l i ty of
SA H is higher among cocaine users
w ho have occul t i ntracranial aneur-
y sms or arteriovenous mal formations
than among those w ho have normal
cerebral vasculature. T he resul tant
sudden ri se in system ic blood pres-
sure i s thought to precipi tate SA H .
I schem ic lesions also have been
f ound in patients w ho have used
cocaine. Y et, the associati on of these
ischem ic strokes w i th cocaine use is
less clear. The appl i cati on of cocaine
di rectl y to the vasculature of animals
has caused m ark ed vasoconstri cti on,
w hich f avors vasoconstr i cti on as the
underl y ing etiology of i schem ic
stroke af ter cocaine use. N onetheless,
i ntracranial hemorrhage appears to
occur more commonly than ischem ic
inf arcti on among those using cocaine.
T reatm ent i s supporti ve.
H em atol ogi c Eti ol ogi es
Several di sorders of coagulati on can
lead to embol i c or thromboti c stroke.
A dverse consequences of antiphos-
phol i pid antibodies have been identi -
f l ed in al l age groups. H ow ever, chi l -
dren, adolescents, and young adul ts
mani fest the cerebrovascular conse-
quences of these antibodies most
of ten. A ntiphosphol ipid antibodies
are poly clonal antibodies f ound in
serum that can bind to both neutral
and negati vel y charged phospho-
l i pids. The best studied are the lupus
anti coagulant L AC and anti cardio-
l i pin antibodies aCL . T hese anti -
bodies f i rst w ere associated w i th
thromboti c or embol i c cerebrovascu-
lar events among patients w ho have
SL E. Subsequentl y , patients suf fer ing
stroke w ho had no ev idence of under-
l y ing immune-mediated i l l ness other
than the L A C or aCL antibody w ere
f ound. The antibody prolongs the par-
ti al thromboplasti n time PT T in
v i tro, but acts as a procoagulant in
v i v o. T he mechanism by w hich
thrombosis or embol i sm occurs i s
sti l l unclear, but the presence of these
antibodies in a patient w ho also
smokes cigarettes has a posi ti ve anti -
nuclear antibody test, or suf fers f rom
hyperl i pidem ia may impart a higher
r i sk for stroke than i f the patient car-
r i es the antibody alone. The anti -
body ’ s presence is indicated by a pro-
longed PTT and a f al se-posi ti ve
serum V D RL ; i t can be demonstrated
conclusi vel y both functional l y and
immunological l y . The most common
location f or arter ial thrombosis
among chi l dren w ho have antiphos-
phol i pid antibody is the cerebral ci r-
culati on. Cerebral i nf arcti on and
T IA s are neurologic mani f estati ons
observed most f requentl y . T herapy
for patients w ho have antiphospho-
l i pid antibodies and have suf fered
stroke has not been substantiated
ful l y by random ized prospecti v e
study , but low -dose anti coagulati on
has been adv ocated.
A n absence of speci f i c serum pro-
teins that act as inhibi tors of coagula-
ti on may lead to stroke in chi l dren.
D ef i ciencies of tw o of these proteins,
protein S and protein C, have been
associated w i th thromboti c or embol -
i c cerebrovascular di sease in the
young. Protein C and i ts cofactor pro-
tein S act as anti coagulants and syn-
ergi sti cal l y attenuate coagulati on by
deacti vati ng the acti v ated f orms of
f actors V and V I I I . A bsence of ei ther
of these proteins w i l l ti p the scale of
balanced coagulati on tow ard
increased spontaneous clotti ng, w hich
can resul t i n stroke. A nti thrombin-I II
opposes the action of the acti vated
f orms of f actors I I , IX , X , X I , and X I I
through the i rreversible formation of
inacti vati ng complexes w i th these
f actors. D ef i ciencies of proteins S or
C or of anti thrombin I I I may cause
arter ial thromboti c or embol i c stroke
or venous inf arcti on. A l though these
def i ciencies of ten are congeni tal , they
may be acqui red through l i ver di sease
or the nephroti c syndrome. Screening
tests, i ncluding PT , PiT , and speci f i c
immunologic and f unctional testi ng
f or the proteins suspected of being
def i cient, i s essential f or diagnosis.
M al ignancies and thei r treatment
may predispose chi l dren to cerebro-
vascular i schem ic events. Promyelo-
cy ti c leukem ia and i ts treatment can
provoke dissem inated intravascular
coagulati on, l eading to stroke.
L ymphoreti cular cancers more than
sol i d tumors have been l inked to
thromboti c and embol i c strokes. T IA s
fol l ow ing induction chemotherapy f or
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N E U R O t Y
.
a 9-yea r -o ld boy tr ea ted w ith L-a sp a r a g i-
na se fo r a cu te lymphocytic leukemia who
exper ienced new hea da che , se izu r es , a n d
le tha r gy. Br igh t sig na l in the supe r io r
sa g it ta l sinus la r ge a r r owhea d s a nd in
th e str a ig h t sinus sma ll a r r owhea ds
d eno tes L-a spa r a g ina se- ind uced cer ebr a l
venou s th r ombo sis.
Homocys t inur ia
Fabry d isease
S ick le ce ll d isease
Fibrom uscu lar dy sp lasia
Hemorrhage
Factor V if i d ef ic ien cy
Fac tor L X de f ic iency
Fac tor X I de f ic iency
Fam ilial in tracranial an eu ry sm s
S ick le ce ll d isease
Fam ilial cav ernou s angio m a
U n k n o w n
M echanism
27 2
Ped i a t r i c s in Review Vo l. 1 7 No. 8 Augu st 19 96
acu te ly m ph oblastic leu k em ia h av e
been repo rted . In addition , dural s inus
and cerebral v en ou s th ro m bo sis hav e
been fo und af ter th erapy w ith L -
asparag inase (Fig . 2 ).
O ral con tracep tiv es h av e been
assoc iated w ith stro k e in y ou ng
w om en. In so m e series, th e co m bin a-
tion o f m ig raine head ach e and co n-
curren t o ral co n tracep tiv e u se has
been cited as a risk fac tor f or strok e
(see earlier d iscussion). Pregnan cy
and the pos tp artum s tate hav e been
cons idered perio ds o f hy percoag ul-
ab ility . In add ition , v eno us stasis
increases. T hese tw o fac tors are
be liev ed to prom o te th e occu rrence o f
cerebral v en ous throm bosis an d resu l-
tan t cerebral v eno us in farctio n in
pregnant and im m ed iate ly p ostpartum
f em ales. Freq uently , the in itial m ani-
f estation is headache . S e iz ures , e ither
f ocal or g en eraliz ed , are com m on.
A cu te hem ip aresis is the m o st co m -
m o n f ocal f eature on n eu ro log ic
ex am in ation . Papilledem a can app ear
as in tracranial pressure rises d ue to
resu ltan t o bstruc tion o f cereb ral
v eno us outf low . T h e ap pearance o f
these sig ns or sy m p tom s in a g rav id
or p ostp artum ado lescen t sho uld raise
su sp ic ion abo ut the ex is ten ce o f
un derly ing cereb ral v en ous throm b o-
sis. I f se iz ures o ccur, an ticon v ulsan t
treatm ent sh ould b e in itiated . O nce
th e d iagno sis is con f irm ed , an tico ag -
u lan ts sh ould b e adm in istered .
Fin ally , insec t s tings hav e cau sed f ocal
cerebral in farctio n in ch ildren . W asp
and scorp ion v eno m activ ate p latele ts,
p ro m otin g th ro m bo genesis, w hich can
culm inate in fo cal in farctio n .
M etabo lic E tio lo gies
H om o cy stinu ria, a d isorder o f hom o-
cy ste ine m etabo lism , can cau se
throm botic strok e in ch ild ren
(T able 3 ). A bnorm al h om ocy ste ine
m etabolism resu lts f rom on e o f three
heritab le enz y m atic de f ec ts. T h e m ost
strik ing p henoty pe resu lts f ro m de f i-
c iency o f cy stath ion in e sy n the tase ,
the en z y m e th at cataly z es the catabo-
lism of hom ocy ste ine to cy stath ion-
m e . A ccum u latio n o f bo th ho m ocy s -
te ine and m eth ion in e resu lts .
C hild ren af f ec ted by th is au to som al
recessiv e d isorder m anif est m ar-
f an oid hab itus, g lob al d ev elo pm en tal
de lay , lens d islo cation , and th rom bo-
em bo lism . S erum hy p erho m ocy s -
tein em ia in ju res the v ascu lar endo the-
hum , w ith the d en uded v esse l w all
becom ing a site fo r throm bosis . T h e
resu ltin g thro m bu s m ay rem ain at its
site o f orig in or it m ay em bo liz e to a
dis tal locus. T heref ore , strok e m ay
hav e throm b otic or em b olic charac-
teristic s, and b oth arterial and v enou s
in f arc ts m ay resu lt. T reatm ent is
d ie tary an d aim ed at redu c ing lev e ls
o f ho m ocy s tein e in serum . Py rid ox in e
ad m in is tration and m eth ion in e
restrictio n are ef f ec tiv e as prop hy lac -
tic therap y f or th e de leterious seq ue-
lae in 3 0 to 40 of treated p atien ts
w h o h arbo r a d ef ect o f cy stath ion ine
syn thase .
S u lf ite o x idase de f ic iency , anoth er
au toso m al recess iv e d isord er o f su lfu r
am ino ac id m etab olism , resu lts in the
accum ulation o f serum sulf ite s. T he
assoc iated pheno ty pe m ay be du e to
de f iciency o f e ither th e enz y m e or its
assoc iated and essen tial p terin -co n-
tam ing m oly bdenu m co fac tor. M ental
re tard atio n , se iz ures, len s d isp lace -
m ent, and acute hem ip leg ia resu lt.
T he m ech anism of the strok e -lik e
ep iso des has not b een e luc id ated
fu lly . I t is po ssib le that isch em ic
m ech anism s are no t inv o lv ed an d that
d irec t m etab olic neuro to x ic ity
accou nts for th e sud den onse t o f
de f ic its resem bling those o f strok e.
S u lf ite s an d 5-su lf ocy ste in e accum u-
late in urine . D ie tary attem pts to
reduce su lf ite accum u latio n hav e
b ee n u nsu cc essf ul.
Fabry d isease, a lip id sto rage dis -
ease , is attribu tab le to ceram ide tri-
hex os idase de f ic iency . It resu lts in
accum u lation o f th e sph in golip id , tn -
hex os ide , in the k id ney , v ascu lar
en doth eliu m , and cornea. S y m ptom s
beco m e app aren t in ch ildh ood or ado-
lescence . A n giok eratom as and p ain fu l
paresthesias o f ten are the f irst sy m p -
tom s, f o llo w ed by renal f ailu re .
H ow ev er, the end othe lial accum ula-
tion o f sph ingo lip id in v esse l w alls
m ay cause cen eb nov ascu lar occ lusion
an d sub seq uent strok e. R ecurren t
stro k e is no t uncom m on in th is rare
X -link ed d isorder. S up portiv e care
an d treatm ent desig ned to im pro v e
renal f un ctio n and m in im iz e pain are
impor tan t .
M itochon drial d isorders m ay b e
m anif ested by recu rren t and som e-
tim es catastrop hic s trok e. T h e sy n -
drom e of M EL A S (m ito ch on drial
encephalom yop ath y , lac tic acid osis,
an d strok e ) presen ts in ch ildh oo d and
is due to a m utatio n o f m itochon drial
D N A . T h e m o st com m on b iochem ical
f ind ing is a de f ic iency o f co m plex I
o f the elec tro n tran spo rt chain . A n
e lev ated lev e l o f lactate in th e serum ,
or m o re co nsisten tly , in the C S F, sup -
T A BL E 3. C om m on
G enetic C auses of Str ok e
T hr om botic/E m bolic Str ok e
O rganic ac idem ia
M ito ch ond rial d isorders
Adapted from N atowicz M K el l ey
RT .
M en del i an eti ologies of str ok e
A nn N euro l.
22:1 98 7; 1 73
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F IG U RE 3. Axial cranial CTdemonstrat-
ing a hypodense region in the middle
cerebral artery territory of the left hemi-
sphere ar rowheads). This study was
obtained from a 4-month-old infant who
has tetralogy of F allot and presented with
focal seizur es.
Pediatr ics in Review Vol. 17 No. 8 August 1996
273
:NEUROLOGY
:
Stroke s
ports the d iagn osis . T h e d iagn osis can
b e con firm ed from m olecu la r b lood
ana lysis . A lth ough som e featu re s o f
M ELA S are sha red by o th er m ito -
chondrial syn drom es, hem ip are sis o f
ab rup t on se t, pa r ticu lar ly w ith hem i-
anop ia, is ch aracte r is tic o f th is sy n -
d rom e . A m ate rna l fam ily h isto ry o f
m ig ra ine is comm on . Exc ruc iatin g
headache th at resem ble s m ig ra ine
usua lly p recedes o r accom pan ie s th e
stro ke -lik e ep isod es . S e izu re s, sen -
so rin eu ra l h earing lo ss , dem en tia , an d
short s ta tu re u sua lly a re p resen t a t
som e po in t in the co urse o f illn es s .
B ecause the s trok es invo lve the po s-
ten o r ce reb rum , h em ian op ia o r m o re
com plex v isua l de fec ts a re cha rac te r-
is tic . N eu rop ath o log ic study of b ra in
from pa tien ts w ho have M ELA S has
sh ow n cystic cav itie s an d nec ro sis o f
th e co rtex , e spec ially the p oste rio r
ce reb rum , w ith rela tive spa rin g o f
w hite m atter .
O th er m etabo lic d iso rd e rs h av e
b een assoc ia ted w ith stro ke in ch ild -
ho od . U rea cyc le de fec ts , especia lly
o rn ith ine tran scarbam y lase de ficiency
tha t p re sen ts in hem izygous g ir ls , c an
cause stro ke . M etab o lic d iso rd ers
su ch as these ref lect som e of th e he ri-
tab le d iso rde rs th at a re as soc ia ted
w ith stroke (T ab le 3 ) .
EMBOLU S
Cong en ital h ea rt d isea se rem a in s a
ve ry com m on cau se o f stro ke in
ch ild hood . B o th the struc tu ral ca rd iac
de fec ts an d the com plica tio ns rela ted
to co rrec tive su rge ry co n tr ibu te sig -
n if ican tly to th e occurrence o f strok e.
C h ild ren w ho have cy an o tic con gen i-
ta l heart d isease face th e g rea te st r isk .
T he m o st comm on ce reb ro vascu la r
even t is em bo lic stro ke . C a rd iac
de fec ts in vo lv ing righ t-to - le ft sh un ts
a llow em boli o r ig ina ting in th e
pe riphe ral c ircu latio n to b yp ass the
standa rd filtra tion and rem ova l b y the
pu lm on ary v ascu lar b ed . T hu s,
em bo li en te rin g th e heart v ia venou s
retu rn m ay b e shun ted to th e pe rip h -
e ra l ar te ria l c ircu la tion , on ly to lo dge
in the ce reb rov ascu lar tree (F ig . 3 ) .
P a ten t fo ram en ova le (PFO ) co n-
tr ibu te s s ign if ican tly to th e occur-
ren ce o f stroke in ch ild ren and young
adu lts . E ch ocard io g rap h ic eva lua tion
of yo ung pa tien ts w ho h av e su ffered
stro ke reveal PFO or ev id en ce of
r igh t- to - lef t shu n ting in m o re th an
th ree tim es as m any p atien ts su ffe r ing
stro ke than con tro l pa tien ts . T rans -
eso phag ea l echo ca rd iog raph y con -
duc ted w ith V alsalv a bu bb le stu d ie s
fo r ev idence of d irec t r igh t- to - lef t
co ndu ctio n is the m o st u se fu l d iag -
n ostic te st.
C ongen ita l va lvu lar d efects such as
ao rtic steno sis an d m itra l s ten osis can
re su lt in stro ke . R h eum a tic va lvu lar
d isea se , on ce a comm on cau se o f
em bo lic stro ke , has b ecom e in fre -
quen t, b u t in fected v a lves foun d in
su bacu te bac te ria l en doca rd itis (SBE )
still po se con side rab le risk . In fectiv e
m itra l and aortic v alv u la r v eg eta tion s
m ay d islo dge , trave l d is tally , an d u lti-
m ate ly occ lude ce reb ra l a rte r ies . T he
m ost comm on organ ism s fou nd a re
strep tococc i an d staphy lococc i.
V eg e tatio n still m ay em bolize an d
cause stro ke , ev en a fte r h av ing b een
ste riliz ed . F ina lly , em bo li from
in fected va lvu la r vege tatio ns m ay
lead to o th er vascu la r le sion s. F o r
exam p le, em bo li m ay trav e l to the
ce reb ra l vascu la tu re and seed th e
adven titia o f the ce reb ra l v es sel. T h e
resu ltan t in fectio n an d in flam m ation
w eak en s th e vesse l, caus ing dev elo p -
m en t o f a m yco tic an eu rysm . Th ese
aneurysm s typ ically o ccu r in th e d is-
ta l ce reb ra l vascu la tu re . They m ay lie
do rm an t fo r som e tim e be fo re th eir
rup tu re leads to SAH or IPH and
resu ltan t neu ro lo g ic sig ns (F ig . 4 ).
R ecen tly , foca l ce reb ra l in ju ry
re la ted to co rrec tive su rge ry fo r con -
gen ita l ca rd iac de fec ts h as been id en -
tified , su ch as ce reb ra l v ascu lar acc i-
den ts d u ring the Fon tan correc tion . A
pa rado x ic d is soc iatio n o f in travascu -
la r and m itocho ndrial oxy gena tion
occu rs du rin g in traop era tive deep
hypo the rm ic card io pu lm ona ry byp ass
and circu la to ry a rre st, w h ich m ay
p rov ide a clu e to th e cau se o f such
ce reb ra l in ju ry . P oor ce llu la r ox y-
g en atio n , pa rticu lar ly at th e m ito -
ch ond ria l leve l, can be assoc ia ted
w ith ce reb ra l in ju ry .
F a t o r a ir em bo li can ram ify in the
ce reb ra l v esse ls . T h ese em bo li m ost
com m on ly a re fo rm ed fo llow ing trau -
m a in vo lv ing lon g bon e fractu re s .
H ow ev e r, b o th o f these ty pes o f
em bo li hav e been assoc ia ted w ith
no n traum a tic con d ition s. F a t em bo li
have been obse rved in assoc ia tion
w ith panc rea titis , s ick le ce ll d isea se ,
conn ec tiv e tissue d iseases, an d in tra-
veno us lip id adm in istra tion . B o th fa t
and a ir em bo li h av e been observed
afte r ca rd io pu lm on ary bypass
su rge ry . B ecause fa t o r a ir em bo li
occu r a s show ers, m u ltip le s ites w ith -
in the CN S m ay be invo lved . A s a
resu lt, im pa ired con scio usn es s, som e-
tim es accom pan ied b y de lir ium , m ay
be ob se rved . F o ca l o r late raliz ing
neuro log ic signs a re ap pa ren t in on ly
one th ird o f pa tien ts .
H EMORRHAGE
A lth ough som e coagu la tion d istu r-
bances m ay pred ispo se a pa tien t to
ischem ic stro ke , o th ers m ay prom o te
in trac ran ial b leed ing . B o th A and B
hem oph ilia s a re X -lin ked d iso rde rs
tha t m ay resu lt in in trac ran ial b leed -
ing (T ab le 3 ). B leed in g m ay occur in
eith e r in trapa ren ch ym a l o r sub arach -
no id lo catio ns. H em oph ilia A arise s
from fac to r V III de ficiency . A ffec ted
m ale s m ay expe rience in tracran ia l
b leed ing in as soc iatio n w ith head
traum a. U nfo rtu na tely , sp on taneou s
in trac ran ial b leed ing u nassoc ia ted
w ith h ead traum a a lso occurs . T he
risk o f sp on tan eo us b leed ing rise s as
the seve rity o f fac to r V III d efic ien cy
in creases . H em oph ilia B de rives from
a de fic iency of fac to r IX . In trac ran ia l
b leed ing is le ss freq uen t in these
pa tien ts than in th ose w ho have
h em oph ilia A . T he le ss frequen t
occu rrence o f hem oph ilia B com -
pa red w ith hem oph ilia A m ay acco un t
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F I GU RE 4. M ycotic cerebral aneurysm hemorrhage. A. Cranial CT reveals hvperdense region in left tempor al lobe arr owheads), repre-
seining intraparenchyinal hetnorrimage. B. Cerebral
angiography
in lateral view shows lobulated
vascular abnormality in the timiddle
cerebral artery tree ar rows). C’ . Anterior-posterior angiographic view confirms the location oft/ ic vascular abnor,nalitv in the middle
cerebral
artery
straight arrow), which is located lateral to the more medially located anterior cerebral artery curved arrow). These
neuroradiologic studies were performed on a boy who presented with acute onset of aphasia and rig/it hemipare.sis 2 weeks after the dis-
coven’ of low-grade fever and a cardiac m u rm u r
274
Pediatrics iii Review Vol. /7 No. 8 August 1996
N U R O L O Y
t r o k s
for the le ss frequent observation of
intracranial bleeding . Clinical symp-
tom s depend on the intracranial loca-
tion of the hemorrhag e. If the bleed-
ing occurs in the subarachno id space ,
severe headache , nuchal rig idity , and
mening ismus occur. M ental status
frequently is altered. If bleeding
occurs w ithin brain parenchyma,
focal c linical features, inc luding
hemiparesis , may be observ ed.
Sev ere thrombocytopenia leads to
cerebral hemorrhage in v ery few
patients . S ignificant risk of IPH
appears to occur only at platele t
counts o f 20 ,00 0 /mm3 or le ss . Small
pe techial hemorrhages into w hite
matter are more common than larg e
parenchymal hemorrhag es . Causes o f
thrombocytopenia include idiopathic
thrombocytopenic purpura, infec tion,
and malignancy . The features o f these
underly ing causes dom inate the c lini-
c al pi cture .
SAH occurs among children w ho
have s ickle ce ll disease , although the
frequency is les s than that o f infarc-
tion, occurring in few er than 2% of
patients . The ruptured cerebral
aneurysm that frequently is found in
adult sickle ce ll patients w ho hav e
SAH is absent in children. Clinical
f indings inc lude sev ere headache ,
vom iting , and altered mental s tate .
M eningeal signs and focal neuro lo g ic
de ficits m ay be found on examina-
tion. A ng io graphy usually should be
perfo rmed to detec t any surg ically
co rrectable vascular les ion underly -
ing the hemorrhage . Medical therapy
consisting of transfusio n therapy has
be en s ug ge ste d.
A rterio venous malfo rm ation
(A VM ) o f the brain is the mos t com -
mon cause o f intracranial hemorrhage
in preado lescent children and is more
common in males than females. This
deve lopmental anomaly presents w ith
hemorrhage more frequently in chil-
dren than in adults . The AVM con-
s ists o f dilated vascular channe ls ,
som e o f w hich exhibit the highly
muscularized w alls o f arterio le s .
Glio tic neural tissue resides in and
among the vascular branches o f the
malformation. The most frequently
observed ev ents assoc iated w ith AVM
in children are se izures and hemor-
rhag e. The vast majority o f A VMs are
lo cated in the cerebral hem ispheres ,
w ith 1 0% arising in the po sterior
fo ssa. The c linical feature of hemor-
rhag e due to A VM may be acute onse t
o f fo cal neuro log ic de ficit, according
to the area o f brain in w hich the hem-
orrhag e has o ccurred. Children who
have AVM complicated by hemor-
rhag e hav e a higher mortality rate
than adults . The risk o f hemorrhag e
from an unruptured AVM approx i-
m ates 3% per y ear.
Intracranial aneury sms are a com-
mon cause o f intracranial bleeding in
patients y ounger than 20 years o f ag e.
S accular aneurysm s are more fre -
quent among males than females.
U nlike aneurysm s in adults , the mo st
common s ite o f bleeding in children
is along the intracranial portion of the
internal carotid artery ; the vertebral
and basilar arteries are o ther common
sites . Intracranial aneury sms in chil-
dren tend to be larg er than tho se
found in adults . M ost aneury sms are
due to v ascular dev e lopmental anom-
alie s , but there are other causes.
D iso rders o f connectiv e tissue , such
as Ehler-D anlo s syndrome and
Marfan syndrom e, are as soc iated w ith
the formation of saccular cerebral
aneury sms. Intracranial aneurysms
are more common among patients
suffering from po lycystic renal dis-
ease and those w ho have ao rtic co arc -
tatio n. Patients should be observed
c lose ly for complicatio ns asso ciated
w ith subarachno id bleeding from
aneury sm rupture . Hydrocephalus
causing increased intracranial pres-
sure may o ccur subsequently .
A neury smal bleeding that results in
signif icant SAH can precipitate cere -
bral v asospasm , w hich in turn can
cause secondary cerebral infarc tion.
V asospasm occurs mos t commonly 7
to 1 0 day s after the hemorrhage .
D IAGNOSIS
Once stroke is suspec ted, diagnostic
effo rts concentrate on do cumenting
the o ccurrence and discovering the
underly ing cause . N euro radio log ic
and laborato ry evaluation are con-
duc ted simultaneously . A suggested
fo rmat fo r diagnostic ev aluatio n is
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R adiologic Evaluation
I . M RI
2. CCT
4’
L aboratory E val uation
4
I I
C N S I nf arcti on
r
Cardiac murmur found
o r P F O suspected
1 . CBC d i f f e r e n t i a l
2. Platelet count
3 . PT fPT
4 . E l e c t r o l y t e s
5.
To x i c ol o g y s c r e e n
6 . CS F e xa mi n a t i o n :
t o t a l p r o t e i n g l u c os e
c e l l c o u n t cu l t u r e s
l a c t a t e p y r u v a t e
7. Blood cultures
Subarachnoid o r
intraparenchymal
b l o o d f o u n d
Ad d i t i o n a l
def inition of
cerebral vasculature
n e e d e d
I
4
Echocardiography
Li
I M R A
2 . Percu taneous
a n g oi g r a m
I . A NA /RF
2.
Co a gu l a t i on p a ne l
including protein S. C ,
antithrombin I I I
assays
3. Antiphospholipid anti-
body
l u p u s a n t i -
coagulant assays
4. Serum amino acids
5. Lysosomal storage
e n z y m e s
Ped ia tric s in R eview Vol . /7 N o . 8 Au gu st 199 6
27 5
NEUROLOGY
-
‘S troke s
F IGU RE 5. D iag nos tic eva lua tio n o f stroke in ch ild ren : M R I = magne tic reson ance im ag itig ;
= cran ia l com pu ted tom og rap hy;
CB C
=
com ple te b lo od coun t; PT
= pro throm b in tim e: P iT = par tia l th rom bop las tin tim e: C SF =
cerebrosp ina l flu id ; A NA
=
an t i nu -
c lear an tib ody ; RF
=
rhe umato i d
fac to r ;
MRI4
= m agtze tic reso nance a ng iograph i
provided in Figure 5. CCI and M RI
provide rapid, topographic evidence
of infarction or intracranial hemor-
rhage. CCT images are acquired more
rapidly than M RI and provide clear
evidence of acute intracranial hemor-
rhage. M RI , which provides greater
resolution and structural detail than
does CCI , demonstrates smaller
infarctions. The emerging capability
of diffusion-weighted M RI permits
visualization of CNS infarction very
early in its course. This technique
focuses on the molecular motion of
water rather than on 11W , 12W , or
contrast-enhanced images. An
increase in intracellular water associ-
ated with a reduction in intracellular
transport functions occurs soon after
hypoxic-ischemic cerebral injury has
occurred, and di ff usi on- wei ghted
M RI can visualize the differences in
water flux between normal and dam-
aged cerebral tissue before changes
can be detected by conventional M RI .
M agnetic resonance angiography
(M RA ) yields reliable information
about blood flow in and structure of
large cervical and intracranial ves-
sels; small intracranial vessels are
visualized poorly. Invasive angiogra-
phy remains the neuroradiologic pro-
cedure of choice when detailed
knowledge of the cerebral vasculature
is requi red .
Initial laboratory tests should
screen for hematologic conditions
that predispose a child to stroke. In
addition, laboratory evidence of
inflammatory processes should be
sought. Serum electrolytes will pro-
vide initial evidence of a metabolic
acidosis that may accompany a mito-
chondrial disorder or an organic acid
disturbance. A toxicology screen
should be performed if drug-induced
stroke is suspected. A lumbar punc-
ture should be performed for cere-
brospinal f luid examination if CNS
infection, inflammation, or neoplastic
involvement is suspected. T he lumbar
puncture should no t be performed if
the physical examination findings or
neuroimaging indicate the presence
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NEURO L O G Y
ke s
M ultip le scle rosis
27 6
P ed ia tr ics in R e view Vol . 17 N o . 8 A ugu st 199 6
of a space-occupy ing abnorm ality
cau sing inc rea sed in trac ran ial p re s-
su re . P e rfo rm ing th is p roced ure in a
pa tien t w ho has such a u n ila te ra l
sup ra ten to r ia l o r cerebe llar le sion
cou ld p recip ita te tran sten to r ial o r
transm agna l he rn ia tion , re sp ec tive ly .
If a strok e h as been docum en ted
c lin ically an d rad io log ica lly , bu t th e
in itia l pane l o f lab o rato ry te sts has
y ie lded no rm a l re su lts , add itio na l te st-
ing is w arran ted (F ig . 5) . E vid en ce of
coagu lo pa thy , system ic in f lamm ation ,
and lu pus an ticoagu lan t sh ou ld b e
sou gh t. C SF lac tate and pyruva te 1 ev -
e ls sho u ld b e ob ta in ed , ev en if se rum
lev e ls a re norm a l, if a m itochondrial
d iso rd er is susp ec ted . If the clin ica l
da ta su ggest a lyso som al s to rag e d is-
ease o r su lfite o x idase d efic ien cy , th e
approp ria te u rine o r b loo d te sts sho u ld
be pe rfo rm ed . E ch ocard io g rap hy
sh ou ld be pe rfo rm ed if th e ch ild w ho
has susta ined a s trok e a lso h as a ca r-
d iac m urm ur. In deed , if the re is strong
c lin ical susp ic ion of a PFO , echo ca r-
d io g rap hy w ith bubb le con tra st sho u ld
be p erfo rm ed . C u rren tly , app rox im a te-
ly 30 of all ca se s o f stroke in ch il-
d ren app ea r to b e id iop ath ic.
T REATMENT
R eso lu tion of the d iso rde r u nde rly ing
a strok e in ch ild ren is the m o st effec -
tive long -te rm the rap y . C orrec ting
ca rd iac de fec ts th at con tribu te to
em bo lus fo rm atio n is c ruc ial.
T rea tm en t w ith an ticoagu lan ts m ay
be necessa ry fo r ch ild ren w ho have
chron ic va lvu lar abno rm a litie s o r in
tho se ex posed to righ t-to - le ft sh un ts
fo r long pe rio ds. T he e ff icacy of w ar-
farm as an an ticoagu lan t is w ell
e stab lished ; the d rug com m on ly is
em plo yed fo r th is pu rpo se in adu lts .
H ow eve r, it m u st be used jud icio usly
in ch ild ren becau se the re is a g rea te r
p rob ab ility o f traum a and d ru g-re la t-
e d b le ed in g.
P roph y lac tic th erapy rem a ins the
co rne rsto ne of th erapy fo r th rom bo tic
stro ke . Exchan ge tran sfusion
desig ned to d im in ish the frac tion of
b lo od com posed o f hem og lob in 5 -
con ta in in g red b lood ce lls (RBC s)
red uces the r isk o f recu rren t strokes
am ong ch ild ren w ho have sick le ce ll
anem ia . R ecen t c lin ica l tria ls have
show n th at hy dro xyu rea can inc rea se
the lev e l o f fe tal h em og lo b in -con ta in -
ing RBC s in th ose w ho h av e s ick le
ce ll d isea se . A lth ough th is use o f
h yd rox yurea rem ains in vestiga tion al,
it m ay redu ce the occurrence o f
s tro ke am ong tho se w ho have sick le
ce ll d isea se . S troke du e to coagu la -
tio n fac to rs , such as p ro te in 5 , p ro tein
C , o r an tith rom bin III, are trea ted
best w ith an ticoagu latio n . I t ha s no t
ye t been d ete rm ined w he the r w arfa rin
o r ste ro id the rapy is m o re effec tive
p roph y lactic the rapy fo r s trok e
am ong p atien ts w ho have sym ptom s
of the lu pus an ticoagu lan t (o r
an tipho sph o lip id an tibo dy); recen t
da ta favo r th e use o f w arfa rin .
C e reb ral in fa rc tion d ue to a ir o r fa t
em bo li is trea ted b est w ith system ic
stero ids.
In g ene ra l, th e re is no e ffec tive the r-
ap y fo r the m etab o lic d is ea se s tha t
m ay lead to recu rren t stro ke , an d they
have a p oor p ro gno sis . H ow eve r , the re
is pa llia tive treatm en t fo r h om ocy stin -
u ria th at in vo lv es th e red uc tion o f sys-
tem ic hom ocys tein e. S om e pa tien ts
re spo nd to 100 to 50 0 m g/d ay oral v it-
am in B 6 (py rido x ine ) the rapy . T hose
w ho do no t respon d sho u ld be p laced
on a low m eth io n ine d iet. S tric t m eta -
bo lic con tro l co rrela te s w ith redu ctio n
of stroke o ccu rren ce .
In itia lly , treatm en t o f vascu la r m a l-
fo rm a tio ns con sisted o f an ticon vu l-
san t th erapy fo r second ary seizu re s.
S u rge ry w as re se rved fo r th ose A VM s
tha t b led a t p re sen ta tion . M R I has
allow ed be tte r localiza tion of th ese
m alfo rm a tion s, and p e rcu taneou s
selec tive em bo liza tion o f pa rt o r o f
the en tire A VM has pe rm itted re sec-
tion in situ atio ns con side red prev i-
ous ly to be inop e rab le . A VM s in c riti-
ca l reg ion s o f th e CN S tha t a re no t
am en ab le to su rg ery h av e b een trea t-
ed w ith ste reo tac tic rad iosu rg ery w ith
p rom isin g resu lts . R ad ia tion dam age
to th e CN S has com plica ted the
recove ry of ap prox im ate ly 3 of
pa tien ts . M ed ica l trea tm en t o f rup -
tu red an eu rysm s fo cuses on m ain tain -
in g b lood pre ssu re th rou gh in trav as -
cu lar vo lum e exp an sion ; such trea t-
m en t can redu ce th e inc idence o f po st-
hem orrhag ic vaso spasm . E a rly en thu -
s iasm for treatm en t w ith ca lc ium
ch anne l b lo cke rs has b een dam pen ed
by fa ilu re s in p ro spec tive , ran dom -
ized clin ica l s tud ie s . Th e op tim a l
treatm en t o f m oyam oy a d isease has
n o t b een d ete rm ined . C a lc ium chan -
n d b lo ck ers have been repo rted to
in crease co llate ral vesse l d iam e te r,
im prove pe rfu sion , an d am e lio rate
n eu ro log ic sym ptom s. S eve ra l su rg i-
ca l p ro ced ure s designed to re-e stab -
lish e ffectiv e pe rfus io n of en dange red
brain have been pe rfo rm ed w ith
en co urag ing re su lts in sm a ll num bers
o f pa tien ts , b u t add itio na l stud y and
expe rien ce a re req u ired .
Cond ition s That M ay
M im ic S troke
Acute hem ip leg ia m ost frequen tly
ind ica tes stro ke , bu t a h isto ry and
physica l ex am ina tion con sisten t w ith
the occu rren ce o f s trok e a re cr itic al to
the d iag nosis . B ecause stro ke occurs
m ost o ften in ch ild ren as a co nse -
qu en ce o f an und erly in g process, c ir-
cum spect ev a lu a tion of the ch ild ’s
cond ition fo r such a pred isposin g
cond ition w ill inc rea se th e accu racy
of the d iagno sis .
N o t a ll in s tan ces o f acu te on set o f
hem ip leg ia o r o the r fo cal de fic its rep -
re sen t acu te ce reb rov ascu lar ev en ts
(T ab le 4 ). H em ipa re tic seizu re s th at
are cha rac te rized by acu te la te ra lized
w eakness an d pre se rved m en ta l s tate
m ay b e a fo rm of p artial ep ilepsy . In
ad d ition , se izu re s can be fo llow ed by
a postic ta l (T odd ) pa ra lysis tha t m ay
m im ic the m oto r d efic it o f stroke .
S eek in g a h isto ry o f p rev iou s seizu re s
is e ssen tia l. A po sticta l pa raly sis is
sho rt- lived and no t a sso cia ted w ith
neuro rad io log ic ch aracte r is tic s o f
recen t stroke . P re se rv atio n of con-
sc io usn es s, a fea tu re no t sh ared by
T A B L E 4 O ther
C ond i t i ons in
Chi ldhood
T hat M ay Mim i c Stroke
Pos ticta l T odd pa raly sis
H em ipa re tic s eizu re s
Subdura l/E p idu ra l h em orrh ag e
Hypog ly cem ia
An em ia
A lte rna ting h em ip leg ia o f
ch i ldhood
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:
NEUROLOGY
‘
‘Strokes
P e d i a t r i c s in
R ev iew Vo l. 17 N o . 8 A ug ust 19 96
27 7
general i zed seizures, may help di f f er-
entiate betw een epi lepsy and cere-
brovascular events. The diagnosis of
seizure remains cl i ni cal , but EEG
may help to establ i sh i ts occurrence.
Subdural and epidural i ntracranial
hemorrhages may m im ic stroke.
B ecause they are located adjacent to
the relati vel y nondistensible skul l , i f
they are suf f i cientl y large, they w i l l
exert pressure on the brain, causing
motor or sensory def i ci ts that cone-
spond to the af f ected cerebral area.
N euroimaging perm i ts def ini ti v e
diagnosis. I f no parenchymal injury
accompanies the hemorrhage, prompt
neurosurgi cal evacuation i s ef fecti ve.
M etabol i c di sturbances, such as
hypoglycem ia, may cause f ocal
motor def i ci ts resembl ing stroke.
Sim i larl y , transient hem iparesi s unas-
sociated w i th radiologic changes typ-
i cal of stroke have been observed in
chi l dren w ho have juveni l e diabetes
mel l i tus. T heref ore, survey ing for
condi ti ons that include these meta-
bol i c di sturbances is important v ia
serum electrol y te and glucose levels.
Sim i larl y , severe anem ia causing
reduced oxygen del i very to the brain
may resul t i n evanescent focal motor
def i ci ts; thus, evaluation of an hemat-
ocri t i s essential for any patient sus-
pected of hav ing suf f ered stroke.
A l ternating hem iplegia of chi l d-
hood A H C may simulate stroke in
chi l dren. This di sorder usual l y occurs
sporadical l y , but fam i l i al cases have
been described. The f i rst symptoms
of A H C appear before the age of 18
months. Repeated episodes of lateral -
i zed hem iplegia are most common,
but bi l ateral hem iplegia may occur.
H em iplegic attacks may last f or a f ew
m inutes to a few days. Ex tra-
pyram idal symptoms, oculomotor
dysfunction, and dysautonom ic f ea-
tures also may be present. Symptoms
disappear during sleep. Final l y ,
developmental delay or mental retar-
dation i s present in v i r tual l y al l cases.
Flunar i zine, a calcium channel block-
er, has show n some prom ise in i ts
apparent abi l i ty to reduce the f re-
quency and duration of hem iplegic
attacks, but experience is l im i ted.
Further study of potential therapies i s
necessary.
o n c l u s i o n
Focal cerebral i nfarcti on occurs
among chi l dren of al l ages. Thus, i t i s
important to recognize the signs of
stroke in neonates as w el l as in older
chi l dren. T he causes of stroke may be
thromboti c, embol i c, or hemorrhagic.
M ost commonly , pediatr i c stroke is
caused by structural abnormal i ti es of
cerebral vasculature, i nf l amm atory
condi ti ons that involve cerebral yes-
sels, or congeni tal heart di sease.
D iagnosis sti l l rel i es heav i l y on cl i ni -
cal recogni ti on of the cardinal signs
of focal cerebral i njury . Topographic
determ ination of the injured cerebral
area has been enhanced appreciably
by the advent of neuroradiologic
methods such as M RI . N onetheless,
several di sorders may m im ic presen-
tati on of f ocal cerebral i nfarcti on;
di f ferentiati ng them f rom stroke
depends heav i l y on an accurate
history and physical exam ination.
S UGG ES TED RE D ING
General
B utler I i . Cerebrovascul ar disorders of chi ld-
hood.
J C h ild N eum l.
1993;8: 197-200
Caplan L R .
S tr ok e: A C li nic alA pp ro ac h.
B utterw orth-H einemann: Stoneham, M ass;
1993:22-53
K err L , A nderson D M , Thompson JA , et al .
I schemi c stroke i n the young: evaluati on and
age comparison of patients six months to
thi rty nine years. J C h ild N euro l. 1993;
8:266-270
L anska M i , L anska D J, H orw i tz SJ, A ram D M .
Presentation, cl in ical course, and outcome
of chi ldhood stroke.
P ed ia tr N eu ro l .
1 9 9 1 ; 7 :3 3 3 3 4 1
N agaraja D , V erma A , Taly A B , et al . Cerebro-
v ascular disease in chi l dren.
Acta N eu ro l
S c a n d
1 99 4; 90 :2 5 1 25 5
Ri ela A , Roach ES. Et iol ogy of stroke in chi l -
dren. J C h il d Ne u ro l . 1993;8:201-220
Ri vk i n M , V olpe J. H ypox ic- i schem ic brain
injury i n the new born. S e mi n Ne u r o l
1 99 3; 1 3: 30
Schoenberg B S, M el l inger i F S ch oe nb er g D O.
C er eb ro va sc ul ar d is ea se i n i nf an ts a nd chil-
dren: a study of incidence, cl in ical f eatures,
an d su rv iv al .
Neuro l og ’
1978;28:763-768
V olpe JJ.
N eu ro lo gy o f th e
Newbo r n .
3rd ed.
Phi l adelphia, Penn: W B Saunders Company;
1995:299-310
W izni tzer M , M asaryk T . Cerebrovascular
abnormal i ti es in pediatri c stroke: assessm ent
using parenchymal and angiographic mag-
neti c resonance im aging.
An n N euro l.
1991 ; 2 9: 5 85 - 58 9
Spec if ic Causes of Stroke A mong
Children
Adams R M cK ie V. Nichols F et al. The use
of transcrani al ul t rasonography to predict
stroke i n sick le cel l disease. N E ng i J M ed .
1992;326:605 610
A l halabi M , M oore P. Seri al angiography in iso-
lated angi i ti s of th
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