Original article

Prognostic Value of Early MR Imaglng in Term Infants \,rrithSevere Perinatal Asphyxia

By Ch. Kuenzlel , O. Baenzigerl , .E. Msrtin2, L.Thun-Hohensteinl , M. Steinlinl , M. Goodl , S. Fanconi3,E. Boltshauser' and R. H. Largo"Dn'isiorrs of lNeurolog\r, 2X,lagrrctic Resonance, :lJnlensive (lare alcl a(lrouth ald Development, L)ep:utment of Ire atdcs,Zurich. S',r.itzerl:urd

191

Abstract

The prognostic signi.ficalce of magnerticresonance irnaging (NlIiI) in the neonatal period r'vas stu-died prospectivcl5, in 43 terrr-r infants u'ith perinatal asph5xia. NIRI u'as perlorned betu,een 1 ancl 14 days afterbirlh u'ith a liigh field system (2.35 'Ibsla). Neurodevelop-mental outcome t as assessed by a skmdardized neurologicalexamination and the Griffiths derelopmcntal test at a meanage of 18.9 months. The predictivc value ol the various N{RIpattelns s'as as follou,s: Severe diffuse lrrain injurr, (pattcrnAII+III; n = 7) and lesions of thalamus and basal g:urg[a(patterm C; n - 5) u.ere strong11, associated with pooroutcome and greatly reduc.ed head grouth. N1ikl dillusebrarn injur5, @attern AI; n = 7), parasagittal lesions (B; n- 7), perivuitricular h5perintensity (D; n = 2), focal brainnecrosis arcl hemorrhage (E; n = 3) and perir,entricularh5,pointense stripes (on T2 u'elghted i.mages; F; n = 3) 1cdin one third of the infants to minor neurological disturbances:rnd mi.lcl do'elopmental delay. Infants with normal NIRIfindings (G; n - 9) developed normally with the exception ofone infalt r,l.ho u'as mildly'dela1,ed at 18 months. Thc rcsultsindicate that l,{RI exami.nation clurinq thc lirst tu,o u,eeks of

Introduction

Acute perrinatal hlpoxicr i.schemic cerebral in-jury' in the term ner'r'born is a rnaior cause uf ncuroder.'elopnental abnormalities in childhood. Despitc maior aclvalces inperinatal mcdicirre, there has been little change in the incidenceof acutc perinatal asph5rria u,hich has been estimated to occurin approximatel5, I 4 per 1000 live tenn ner."'borns (I1, 16,'22,34). I-ongtenn neurologic sequelae such as cerebral pals5,,

mcntal retardation ald cpilepsy occur in 20-300/o of affectedinfants (11).

Early diagnosis alcl acc.uratc prediction ofoutcome of hypoxic ischemic cerebral injury is of itnpoftancein the context of management of Lhc intensive care measure-ments and for the evaluation ol therapeutic interuention. Anurnber oi methods have bccn proposed to provide al earlier

Receir.ed J:utuary 10, 1{)!)'1; rer.isecl, acccptcd Jute 21, 1994

Neuropcdialrics 25 ('l99.1) 191_200O Flippokrates Verlag Stuttg:ut

life is of prognostic significzurce in term infzurts sufferirigfrom perinatal asphlxia. Severe h5poxic-ischrmic brainlesions r.verc associatcd highly significantly with poor neurodevelopmental outr:ome, u'hereas infants with inconspicuous.\'ilRT develooed normall r:

Perinatal asph5xia - Term infants - NIagnetic. resonanc.e imaging - Neurodeveloprnental outcome

Abbreviations

CTDQHCMRINENOSSD

c.omputecl tomographydevelopmental quotienthead clrcumferencemagnetic. resonance imagin gneonatal enc.ephalopathyneurological optimality sc'.oreskndard derriation

and more ac.curate diagnosis of type and extent ol cerebrallesions (EEG ancl o'oked potentials 121, 28, 321), Dopplersonography (17), near infrared spectrosurpl,, (l3i)), positronemission tornographl, (33), P alcl II-rnagnetic resonalccspectroscop5, (2, 23, 27), ultrasound (3, 29) ald computecltomography (CT) (1, 9, 18, 19). High sensitirntv and specifity'ofMIII in detecting abnonnalities in asphlxiaterl inf:rnts ardyoung children has been demonstrated in several prospectivestudies (7 , 12, 13,20). NIRI has proved to be superior to cranialultrasonographl and CT in delineating multicystic encephalo-malacia (diffuse br:rin injury), basal g:urglia lesions ald ibcalparench5.mal hemorrhage (13). When compared with ultraso-nography and CT, MRI appears to be more sensitive in termner','boms (13, 20). Hourcvct thc experience with MRI in highrisk tcrm neonates is limited and little is knou'n aiout thepredictive value ol MI{ carried out in the first tu'o lveeks of lile.Thc purpose of this prospective study u'as to explore theprcdictive significance of early MRI in term neonates follou'ingperinatal asphl'xia for neurological and developmental outcomeat a mean age of 18.9 months.

192 Neuropediatrics 25 0994) Ch. Kuenzle et nl

Table 1 Signs of asphyxia as inclusion cri teria Table 2 Summarized cl inical data ln : 431

Neonates who fulf i l led at least one i tem in tvvo of the fol lowinethreecri teria groups were included in the study.

Signs of intrauterine asphyxia: bradycardia (heart rate < 80/min),l imited beat to beat variabi l i ty, late decelerat ions, or meconium-stained amniotic f luidSigns of perinatal asphyxiar Apgar score < 5 at 5 min or < 6 at 10 min,umbil ical cord artery pH < 7.1, and base defici t < 10 mmol/ lSigns of postpartum encephalopathy starting during the flrst 48 hours:seizures, lethargy, coma, e)densive hypo- or hypertonia or pathologicalspontaneous movements

Table 3 Detailed patient data.

Boys : girlscestational age (weeks)Bifthweight lgjBirth length (cmjHead circumference at birth {cmlMeconium stained amniotic f luidPathological cardiotocogramVaginal del iveryInstrumental deliveryCaesarean sectionIntubation and venti lat ionUmbil ical cord artery pH (n : 311Apgar at 1 min [n : 42JApgar at 5 min [n : 42]ConvulsionsNeonatal encephalopathy within the f irst 48 h

Number o rmean and range

2 3 : 2 039.43 1 7 049.634.416/423 3T 2

136.0-42.1)t18 1 0-43001t43.0-56.51t31.0-34.01t38 %lt77 %)l28vd123Y")149 Y")163Y" l16.59-7.35i{0 Bl12-el140%]167 %l

1 02 72 76.963.365.29I 729

MRI

Pattern

At birth

GAlweeksl

WeightISD]

N4RItdayl

HCtSD]

BLtSD]

BWtSD]

Follow-upAgelmonthsl

LengthtSD]

HC{SD]

123456789

1 01 11 21 3T 41 51 61 71 81 9202T

39.436.03 9 .139.437.938.738.438.037.940.340.136.739.941.039.33 9 .138.940.138.739.737.640.439.44 r . 039.041.038.940.0

36473736313

1 11 1I 4

17.019.521..020.030.018.519.018.018.020.025.022.018.06.0

24.02r .o18.016.018.018,021.077.O18.023.018.024.019.018.020.021..016.518.018.09.0

2r .018.019.020.o20.017.017.015.018.0

471 073

r0010085

100r00100901 01 61 093

10097

1001001001001003 685941 795

1001009798

10010010010010010010010010010010080

42.1.38.037.040.739.940.041.3? o /

40.04r .639.939.440.441.038.0

2 22 3242 5262 72829303 13 23 3343 5363 73839404 T4243

0.13 0 .901.55 - O.450.31 1 .350.44 0 .10

- 0.66 - r.6l1 .48 0 .19

- 1 .56 1 .360. r7 1 .380. r2 0 .772.11 0 .560.20 - 0.09

- 0.84 0.941.05 r .94

- 1 .31 - 1 .25- 0.61 0.69- 3 .72 - 2 .75

0.62 0.781.3 5 0 .101.03 0.29

- 0.18 - 0,950.51 0.48

- 7.34 - r.44- 0 .15 1 .06

0.71 . - O.121.00 - 0.730.15 - 0 .56

- 0 .3 i 0 .18- r .37 1 .33- 2 .86 1 .11- 2.22 2.30- 0.05 - 0.73

0.29 0.24- 0.29 0.82

0.22 0.96- 0.72 - 1..44

2.45 r.94- 1.01 2.90

1..1.2 0.780.20 0.38

- 0.40 r.29- 0.49 0.50

0.89 1.53

0.23 2.0r2.1.5 1.860.72 1.091.01 0 .50

- 1 .00 - 0 .110.88 0.953.59 4 .16

- 1 .55 - 1 .60- 2 .62 - 1 .85- 2 .67 2 .31- 2 F O - A a l

0.47 - 2.27- 3.54 - 2.OO- 1.99 - 2.08

0.91 0.92- 2.80 - 3.01

0.69 0.160.26 0.23

- 1 .76 - 7 .1 .20.21 - 0.26

- 0.99 0.010.87 0.692.98 5.63

- 1..62 - 3.08- 2.80 - 2.69

0.46 0.85- 1..49 - 1..27- 0.89 0.77

0.66 0.541.51 1 .72

- 0.48 - 0.520.70 r.731.38 0.04

- 0.58 - 0.090.45 - 0.7 40 .01 2 .2 r0.58 0.61

- 0.44 0.53- 1.48 - 0.06

0.20 - 0.77- 0.22 0.91

0.30 0.44

0.23 19.61.03 1.6.70.84 26.80.45 27.00.85 26.30.52 20.5

- 3 .52 27 .0- 1 .18 27 .0- 3.69 27.0

5.20 26.7- 4 .81 13 .8- 4.63 r7.0- 3 .92 11 .6- 1 .81 26 .1

1.09 26.3- 1..20 26.5

1.06 27.00.40 26.5

- 2.20 27.00.54 27.01.88 27.00.91 1.7 .5

- 4.49 24.54 .17 26 .1

- 3.73 17.6- 0 .79 27 .0

2.28 26.5- r .32 27 .0

0.1.7 26.72.36 26.2

- 0.33 26.8- 0.80 27.0

1.88 27.0- 1 .19 27 .0

1.08 27.00.92 27.0

- 1 .54 27 .00.67 27.0

- 1 .01 27 .00.00 27.o0.44 27.0

- 0.47 27.0

- 0.491.770.93r .64o.o21.401.23

+ 0.381 . 1 80.56

- 7 .270.450.691.581.99r .23

_ A A R

+ 1 .617 .7 6

- 0 . r20.341.320.000.337 . r 7

- 0.980.880.060. r40.41

- o.92- 0.42- 0 .14

2.42- 0.27

0.762.752.68

- 2.34- 0 ,14- 0.30

1.080.27

Bi l t DlB I FB IB IB t lB t lB l l

C Ic l i l AlC I I FC Ic l l

D IDl i l

EI FE l t lEI F

FFF

7T5335

1 521

1 1I 21 J

1 11 018

1 0423627177

1 298

AIA I I C IAilt cillA t lAIA I C I FA I I C IAIAIAIAIAlil cillA I I IA l t l

Gnn

GGnnr:

G

A-G: Predominant pattern of f i rst MRI {Table4J; l- l l l : Severity of lesions in MRI; l : mild, l l r moderate, l l l r severecA: cestat ional age, BW : Birthweight, BL: Birth length, HC : Head circumference,NOS : Neurological optimality score, DQ : Developmental quotient.

Prognostic Value of Early MR Imaging in Term Infnnts with Seaere Perinatal Asphyxia Neuropediatrics 25 0994) 193

Fig 1c

Fig. la-d Various patterns (a to el of postasphyxic brain lesions on axialT2-weighted images [a-c) and T1-weighted images [d, e]. The severity of thelesions is graded I to lll. ai Pattern A (lllJ at day 5. Diffuse hyperintensity ofboth hemispheres including the cortex with blurred border zonesbetween white and grey matter, indicative of severe cerebral edema.The cort ical r ibbon stands out hypointense on several locations due topetechial pial hemorrhage. Note that the lateral ventricles are notcompressed despite a severe cerebral edema due to the compliance of

Fig. lb

Fig. ld

the neonatal calvarium. bi Pattern B [lll] at day 7 Extended hyperintensityin the parietal, occipital and frontal periventr icular watershed zonesinvolving the cortex. c/ Pattern C [ l l l ) at day 7 Basal ganglia and thalamicnuclei are hyperintense and their structure somewhat blurred, Theposterior l imb of the internal capsule does not contain any myelin.di Pattern D [ l l l ] at day 5. Periventr icular leukomalacia and beginning cystformation.

Material and methods

Between October 19BO ald August 1991, 43term neonates suffering from perinatal asphlrria were effolledin this study. They had been referred for neonatal intensive careto the University Children's Hospital Zurich. They all fulfilledat least one item in two ol three groups of criteria of asphyxia(Tirble 1). Forty (9370) of the infants required artificial ventila-tion. Twenty-nine (67 7o) of the children showed signs of

neonatal encephalopathy (NE) with seizures, Iethargy, coma,h5,peftonia, pathological spontaneous movements conespond-mgto Sarnat stages 2-3 starting within the first 48 hours (28).Summarized clinical data of the neonatal period are given inThble 2; complete data of all 43 chitdren are presented inTl*le 3. Gestational age ranged from 36 to 42 weeks (meanage 39.4 weeks). All infants were bom at term except for oneborn at 36 weeks of gestation. Birthweight varied between 1810and 4300 g (mean birthweight 3170 g). Four infants were small1br date (birthweight below the 10th centile) according to Srviss

194 Neuropediatrics 25 0,994) Ch. Kuenzle et al

according to Swiss Grffiths standards (15). The infant'sweight, length and head circumference (HC) were plottedaccording lo Prader eL a1 (24).

The ilvestigators were pediatricians trained inneurological and developmental pediatrics and in the MRItechnique. They were not involved in the neonatal and post-natal care of the in-fants under investigation. They were blindedto clinical status and histories of the patients.

Means and standard deviations or medians andranges were calculated for all continuous variables. Standarddeviation scores of anthropometric measurements were esti-mated on the basis of Swiss growth standards (24). To deter-mine the association between the standard deviation scores ofthe anthropometric measurements, neurological optimalityscore and developmental quotient, Spearman correlation coef-ficients were ca,lculated. To determine whether there weresignificant differences across subgroups nonpararnetic WiI-coxon tesls were performed.

Table 4 MRI patterns in neonatal brain following perinatal asphyxia[T2-weighted images),

Pattern Severity of lesionsFig 1e Pattern E {ll) at day 8. Multiple hemorrhagic-ischemic lesions asa result of postasphyxic coagulopathy.

grorvth standards (14). Patients with dysmorphic syndromes,malformations, evidence of intrauterine or perinatal infections,and those who required surgical intervention in the neonatalperiod were excluded.

A11 43 children underwent MRI examinationon a2.35 Te'sla Bruker-Spectrospin-System within the first twoweeks of life: 16 infants on days 1-3, 13 on days 4-7 and 1,4infants on days 8-14 (mean 6.1 days; details see Table3).Clinically rurstable infants were transported to the MRI in anincubator which could be positioned inside the magnet, thusallowing extensive monitoring during the MRI examination (6).When necessary mechanical ventilation was conthued. Allexaminations were performed with the approval of the localethics committee and the in-formed consent of the parents. TheMRI findings were categorized according to pattem (A-F) aldseverity of lesions (I-III) (Table4, Fig. 1) (4,30,31). Eleveninfants displayed a combination of MRI pattems (Table 3).They were classified according to the predominant MRI pat-tern.

Neurological and developmental testing wasperformed in all 43 inJants between the ages of 6 and 30months (mean age 18.9 months). The results of the standard-ized neurological examination were expressed in a neurologicaloptimality score (NOS) according to Prechtl (25) (see Appen-dix, detailed information can be obtained from the first author).NOS consists of nine subgroups (spontaneous motility, posture,involuntary movements, muscle tone, tendon reflexes, primitiveresponses, Suality of motor behavior, vision and hearing) with atotal of 47 items. Each subgroup was scored according tonormal (3 points), moderately (2 points) and severely impaired(1 point). The optimal score reflecting complete neurologicalintegrity was 27 points, the lowest score indicating severeneurological impairment was 9 points. Development wasassessed by the Grffiths Scales (10); test results were analyzed

border zones be- border zones be- of structures totween cortex and tween cortex and a large degreesubcortical white subcortical whitematter matter

I

M i l d

ADiffuse hyperin-tensity of thecerebral hemi-spneres

B ln the frontalParasagittal andlor occlpitalhyperlntenslty of areas withoutwatershed blurred borderregions zones betvveen

coftex ano suo-cortical whltematter

C Single hyperln-Changes of basal tense leslon ofganglia and/or small sizethalamus

D ln one locationPerlventrlcularhyperintensity

E lsolated focalFocal parenchy- lesionmal ischemia orhemorrhage

FPeriventricularcentrifugal hy-n6intonqp ctr inoq

GNormal

Moderate

In the frontal In the frontal,and,/or occlpital parletal and oc-areas with cipital areasblurred border with blurredzones between border zonescortex and sub- between cortexcortical white and subcorticalmatter white matter

Hypo- andlor hy- Extended hypo-perintensity of andlor hyperin-the entire lenti- tensity of basalform or caudate ganglla and/ornucleus or the thalamusthalamus on oneor both sides

ln up to three lo- bdendedcations including lesions in thethe frontal and frontal, parletalocclpltal regions and occipltal

regions

Unilateral lesions Large unllateralor bilateral le-sions of variablesize

Prognostic Value of Early MR lmnging in Term lnfants with Seuere Perinatal Asphyxia Neuropediatrics 25 0994) 195

Results

The categorical distribution of the 43 infantsaccording to their predominant MRI pattern in the neonatalperiod and neurodevelopmental outcome at a mean age of 1f3.9months are presented in Ta,ble 5. Group Awas subdivided i.ntr-rtrvo subgroups (AI and AII + III) according to the extent andseverity of lesions and outcome. Detailed patient data are givenin Table 3.

Because of limited examination time rve ob-tained only 2 to 3 series, e.g. afal T1- and T2- and frequentlyfrontal T1-weighted images, and only occasionally frontal T2-weighted images. Six MRI pattems of lesions could be distin-guished and the severity of the leslons 'nl'as graded according toa three point scoring system. Mutuai agreement rvas satisfactoryto excellent for all pattems; diifuse (pattem A) ald parasagittal(pattem B) lesions were difficult to distinguish during the firstweek of life. Grading of the severity of lesions was possible in allgroups except Group F u.hich usually occ.urred in combinationu'ith other patterns.

Figure 1 demonstrates the neurological op-timality score (NOS) ranging liom 9 to 27 points at a me:rn ageof 18.9 months, grouped according to their predominzurt MRIpattem. NOS was strongl,l, related to the severity of clinicaldiagnoses. Nine chiidren shorved a NOS of less than 25 points.Six of them with NOS of less than 19 points displayed a severetetraspastic movement disorder, trvo infants with NOS of 19 to24 points were moderately disabled by a hemiparesis, rvhile onechild with 24.5 points shorved a mild form of tetraspasticcerebral movement disorder. Thirty four patients achieved aNOS score ol 26 to 27 points. T"l'enty-seven (63 0/o) of them u'ereneurologically unimpaired, 1 sufiered from mild spastic diplegia alrd six infants displayed a discrete as5rmmetry of musc.letone.

The MRI pattern and the severity of lesionswere strongly related tr,r neurological outcome (Figure 2, Th-ble 6). Only children from Groups A and C, and more precisely,those with moderate to severe MRI lesions (Grade II and III)

obtained low NOS scores ('lable 3). The mediar NOS of 16.7 insubgroup AII+III and ol 24.5 in Group C were significaltlylower than that ol Group G Q\II+III p<0.005, C p<0.01;thble 5). Nine of ten infarts in subgroups NI+III and CII+IIIhad a moderate to severe cerebral movement disorder. two ofthese died withln the first two years of life (Infants 12, 14Tirble 3). Five inlants in subgroup AIII and CIII and one insubgroup CII developed severe spastic tetraparesis. One childlrom subgroup CII had a moderate spastic tetraparesis and twochildren from subgroup AII, a hemiparesis. Al exception rvasPatient 4 u-ith an MRI pattem AII v'ho reached an optimalNOS of 27 points (Fig. 2). Most children from the Groups i\I, B,D, E, F and G rvere neurologically unimpaired. Six childrenwith minor neurological abnormalities shor.ved discrete asyrnmetry ol muscle tone (two children in Group AI, three childrenin Group B and one child in Group D) and one additional chilclin Group E u.as noted to have a mild diplegia. The tu'o infantsin subgroup CI u'ith small focal changes in the basal gangliaalso had a favorable neurological outc.ome. The median NOS ofGroups r\I, B, D, tr and F r'vere not significantly diflerent fromthose of Group G with normal MRI.

Visual impainnent such as loss ol visual con-tact, diminished visual pursuit or reduced field of view rvasobserved in seven of the nine moderately to severely handi-capped children belonging to Groups A and C. Epilepsy wasdiagnosed in fi.ve of 17 infalts rr,'ith neonatal seizures; fourchildren belonged to subgroups AII+III and CII+III, one tcrGroup B ('Ihbles 2, 6).

Developmental quotients (DQ) of the 43 chil'dren ranged betu'een 10 ard 100 (Fig. 3, Thble 3). Those nineof the ten children from Groups AII+1II and CII+III with NOSless thal 25 also were developmenhlly delayed (DQ <90), inparticulaq those 6 from subgroups AIII and CIII with a DQ ofIess than 40. The median DQs of 16 in subgroups AII+III and of85 ln Group C were significmt lor.ver than the medial value ofGroup G (AII+III p<0.0005, C p<0.01; Tirble 5). The childrenin Groups B, D, E and G showed an age appropriate develop

6zIoo

h

G

Eo

c.9o

l

z

252423

21201 91 81 71 6I E

1 4

1 3

1 2

1 lFtg 2 Neonatal MRI pattern and neurologicaloptimali ty score at 19 months [n : 43JSeverity of lesion, l : sl ight, l l : moderate, l l l : severeAge of N4Rl examination: 1: 1-3d, 2:4-7d,3 : B 1 4 d

1 8 20 22 24 26 2ACase number

Neonatal MRI Pattern

A B- - - - - - i l . - a a' r . 1 1 . l l 2 l l ii l2 t2 i l1

l1

c D E

l-u-ius I i i??

G

'h" l,

12 11 lr i;

a. i l 1lt2

t ,lt-|t2

ai l t3

Iilt:

1 .t3

ail3

a ailt1 l l3

3 .|||: 2r1 12 tl t2 t2 l3t3 t3

1 2 ' t 6

196 Neuroytediatrics 25 (7994) Ch" Kuenzle et al

GroupNOS

N4edian RangeDQlvledian

Table 5 Neurodevelopmental assessment at the aget n : 4 3 1 .

of 19 rnonths deliations (SD). An excreptrorl \\,as Inlurrlt 4li'om subgroup AIIu'ith NOS of 26.13, DQ of 73 :utd FIC of 0.84 SD (Tb}le 3). The

Range

me:rn values of IIC of 3.85 SD irr su}group AII+III zlrd of2.67 SD in Group C u,ere signilicantly loner than the mean

value of Group G (AII+III p < 0.0005, C p < 0.00 1 ; Ti:ible 7). Thethree infar-rts of Group B, D and E with HC betr,veen -2 ald-2.5 SD developed normally. 'fhe meran standard deviations oflveight ancl length of Group AII+III :urd C rvere also signific:intly lo11,gl than the mean values clf Group G.

In l'igure 5 the rncrease in IJC cluring the first19 months of life u'as cakrulated. Again, the 10 children ofGroup AII+III and CII+III displayed largely rliminishecl headgrouth r-rf at least 2.4 SD. In the other subgroups 5 inf:urts(numbers 15, 19, 20, 22 and 28) sltor'r'ed a reducecl headgro*th in the presence ol normal development (DQ > 90).

AIAl l+Al l lBcDEFG

77752339

26.8r6.726.524.526.526.727.027.0

100.016.0

i 00.085.095.098.0

100.0100.0

90 1001 0 7 393-1001 7 1 0 095 10097 1.00

1 0 080- 1 00

26.3-27.01L.6 26.826.3 27 .0r7 .5-27 .026.5-27 .026.2 27 .026.8-27.0

27.0

A-G : Predominant pattern of lVRl (Table 4l; l - l l l : Severiry of lesion in N4Rl;l : mild, l l : moderate, l l l : severeNOS : Neurological optimali ty score, DQ : Developmental quotient.

ment (DQ>90) exc.ept infant 43 ((iroup G), u'rth a DQ of 80.This in-fant and Infant 4 of subgroup AII u.ith a DQ of 73 u'erethe only inlants with a NOS above 26, but a DQ of less than 90.NOS and DQ s,ere highly coilelated rvith cach other(p<0 .001 ) .

'I'he distribution of head circuml'erence (I IC) instaldard deviations of the age-related mean arc prescnted inFigure 4. In all nine of the ten children fron'r suigroups AII+IIIand CII+III with NOS belou'25. HC rvas less th:rn 3.5 standard

Discussion

The clefinition of perinatal asphlxia valiesamong centcrs. lt includcs clinical signs of intrautcrinc ar-rdper-inatal asphyxia as u,ell as findings ol neonatal encephalopath5, (NE) also called hlpcrxic-ischcntic or postasph5,xialenccphalopatl4r (8, 16, 22). Although rnore rcliablc than signsof intrauterine ald perinatal asphlxia ('Ibbie 1) NII seems to be"

* . n t i l i r r - l r r r l n , ' l . n . , . i l i ' . , r i l - r i , ' n [ ' r , ' . n h r r y i " R i r l h

Ce reb ra I move me nt d tso rder-

J U V E T E L U L I d > p a ) L r L

- moderate tetraspastic- hemiplegic- dlplegic- minor motor abnormali t ies- normar

21 -

3 - - 14 2 1

61 -2 -16 2

2 7 5

C I2

AI7

t -- 1 1I l

3 32 31 . 2

77 -5

4

2 -

1

1 -

2 . 1 Y

Table 6 Neonatal lv lRl pat tern and c l in icald iagnosis at a mean age of 19 months (n : 431.

Fig. 3 Neonatal l \4Rl pattern and developmen-tal cluotient at 19 months (n : 431Severity of lesion: l : sl ight, l l r moderate, l l l : SevereAge of N4Rl examination: 1: 1 3d, 2: 4 7d,3: 8-i4 d

Developmental delay (DQ 1990]

Additional findingsVisual impairmentStrabismusEpilepsy

i +

90

oo g o

EF a 6

=o

6 b ucot r - ^a w0

o

30

16 18 20 22 24 26Case number

Neonatal MRI Pattern

A B c D E F G

'| 11 l2 l2t1 t1

al l

ail1

a|2

a|2

ilt3a

ilt2 ilt3 ilt3

. l1 lh l l2 lt312

t 1a12

ail3

at3

I

il:

oilt1

1il3I

t r , ll l 1 3 r J

2t1 t' 2 t1t2l1 t2t2 t3 t3

at3

1 2

Prognostic Value of Earltl MR Imaging in Term lnfnnts utith Seaere Perirtntnl Aspltyrin Neuropediatrics 25 (1994) I97

O=; 0OcOo

Fc=9 ^O

!NoI

Fig.4 Neonatal N4Rl pattern and head circum-ference ISD) at 19 months [n : 43]Severity of lesion: l : sl ight, l l : moderate, l l l : severeAge of N4Rl examination: 1: I 3d,2: 4-7d,3 : B 1 4 d

Fig. 5 Neonatal I\4Rl pattern and head growthfrom bir - th to the age of 19 months (n:431

Sever i ty of les ion: : s l ight , l l : moderate, l l l : SOVOTeAge o f N4R l exam ina t i on r 1 : 1 3d , 2 :4 l d ,3 : B 1 4 d

oo.a

c

EoE oo

oEIE- - 2c -o

s

Eoo!c - 4GO

I

1 2 f6 18 20 22 24 26

Case number

Table 7 Standard deviat ion score of weight, length and head circumference at 19 months ln : 431

Neonatal N4Rl Pattern

A B c o E F G

al 1

at2 a

l3

at2

ar 11 it 2 t l

l !

at 1

l 1 al 1

I

ailt3

l a1 t :

r , !t1 "

a

. 1 3o l 1 3l 1 t z

at2

at 2

a -|2 111 l12

ai l t1

at 1

ailt3

t z

ail1

n2 lI2

,,i. |J3.i l t :

oil3

a

WeightN4ea n

Length

MeanHead circumferencel\4ea n SD

AIAl l+Al l lBCDEFGN4ean A G

- 2 . r 5 1 . 0 1-3.59 - -0.47

2.80 - 0 692.98 0.871.49 0.46

*1 .51 0 .66-0.48 1.38-1.48 - 0.583.59 - 1 .38

1.86 2 .0 r-4 .31 1 .60-3 .01 - 0 .925.63 - 0.691.27 - 0.851 . 7 2 - 0 . 1 7o.52 1 .73o.77 2.21.

-5 .63 - 2 .21

-1.03 0.85-5 .20 - -1 .182.20 - r.094.49 0.91

-2.28 0.792.36 0 .17

-0.80 - 1.88-1 .54 1 .085.20 - 1.88

l7752339

-0.1 3-2 .58

0.901.50

-0.91-r.020.53

-0 .130.87

1.091 . 1 01.231.400.520.360.170.601..37

0.292.64

-0.7 4-2 . r4

1.060.700.420.20

-0.78

r . 7 71.031.302.280.2r0 7 80.960.901.68

0.193.850.422.61

-1..54_ 1 . 1 70.25

-0.271..1 7

0.66r .237.262.0r0.7 41.041 . 1 60.881.88

A-G: Predominant pat tern of MRI [Table 4i ; I l l l : Sever i ty of les ions in MRI; l : mi ld, l l r moderate, l l l : severe

198 Neuropediatrics 25 (L994) Ch. Kuenzle et al

asphl'xia sufficient to produce signs of NE may be difficult todistinguish from other events that unfold in the early minutesand hours after delivery such as inlections, intodcations,congenital defects and metabolic disorders (22). According toour inclusion criteria 29/43 (67 o/o) of the neonates shor,ved signsof NE, (Sarnaf stage 2-3) (28). All ten children with moderateto severe diffuse brain injury (pattem AII+III) or moderate tosevere lesions of basal ganglia and thalamus (pattem CII+III)suflered from NE. Nine of them had an adverse neurodevelop-mental outcome. Though our inclusion criteria may not be asstrict (33% u'ithout NE) as in other studies, the incidence ofmoderate to severe cerebral movement disorders of 210/o (9/43)comelates rvell u-ith the incidence of 18-28% of previousstudies (8, 16, 26).

Hou'early MRI can be done to be conclusiveand predictive? Serial MRI examinations rvhich delineate theevolution of brain lesions during the first weeks of life are notyet available. Howerer, recent studies and our results give somehints about the predictive value of early MRI. Asphyxia relatedbrain lesions have been described as up to 6 different pattemson MRI lr'rthin the first rveeks of life (4, 5, 13, 30, 31, 35). Weu'ere able to distinguish these patterns already during the iirst14 days ol life. Our MRI llndings seern to indicate thatexaminations peribrned during the second week of life weremore predictive than those performed i.n the first week. Onlytwo of ten infants with patterns AII+III, CII+III had the firstMRI examination early between days 1 to 3, in three infantsfrom days 4 to 7 and in five infants between days 8 to 14.Hor.vever, the timing and severity of the brain lesions were morelikely due to the fact that these infalts could not be examinedduring the first days of life because of great sickness. Thepredictive significa-nce of normal ald slightly a,bnr-rrnal MRIson days 7 to 7 for normerl neurodevelopmental outcomeprovides additional suppofi for the reliability of early MRI.During the first week of life distinction between diiTuse (patternA) and parasagittal (pattem B) lesions was diiTicult to establish:the distinction between focal ald more generalized lesions cannot be defi.ned explicitly. t\dditionally, edema in early MRI mayhave been judged too often as a pathological MRI pattem.Recent development in MRI technique will most likely allorvmore preclse differentiation between edema, gliosis and necrosisin luture studies.

Severe to moderate lesions ol patterns A and C(AII+III, CII+III) were strongly correlated with severe neurolo-gical abnormalities, general developmental delay zurd greatlyreduced head growth at a mqur age of 19 months. Neurodevelopmental outcome of subgroup AII+III and C differed signifi-

Appendix Neurological optimality score (NOS).

cantly from that of Group G. l'he deleterious outcome ofsubgroup AII+III might be explained by a diffuse brain injurywith selective neuronal necrosis ol the cortex (35). Pattem AIwith diffuse hyperintensity of cerebral hemispheres indicatesprobably tr:insient edema. This would explain the favclrableoutcome of Group AI r'vhich did not differ from that Group Gll'ith normal MRI. In Group C, the moderate to severe (CII+III)lesions may be related to a future status marmoratus of thebasal ganglia and thalamus, involving neuronal injury gliosisand hypermyelination in caudate, putamen, globus pallidus,zurd thalirmus (35). The neurodevelopmental outcome lbrGroups B, D, E and F was not signi.ficaltly different from thatof Group G. The seven iniants u'ith pattem B shou.ed nomalneurological lindings or only minor abnomalities in muscletone and all infants developed normally. lhvorable outcome insubgroup B might reflect the difficulty in differentiatingbetween edema ar-rd necrosis i.n the early MRI, u'atershedlesions were presumably overestimated in our series. This isdue to the fact that the differentiation between focal ald moregeneralized lesions is to some extent an arbitrary one. PattemD, the principal ischemic iesion of the premature infant, mayalso be observed in the term inlant subjected to ischemic insult(35). It is strikrng that the outcome of the tr.vo children u-ithpattern D rvas better than expected; they did not show any signsof spastic diplegia at follorv-up. Pattem E might be explainedby injury to all cellular elements in a vascular distribution (35).'fhe suisequent rnotor correlates consist of spastic hemip:uesisor spastic tetraparesis. They seem to depend greatly on thenumber, size, localizatlon, distribution and the type of lesions(hemorrhage or ischemia). Finally patterr F with centrifugalhlpointense stripes most probably results irom dilated periven-tricular vessels due to postasphyxial venous congestion. Thesignificance of this pattem is presumabiy low (4).

Our results indicate that MRI examinationduring the first 14 days of life is of prognostic significance lnterm neonates suffering from perinatal asphl'xia. Severe diffusebrain injury and severe lesions of the thalamus and basalganglia are strongly associated wi.th poor neurodevelopmentaloutcome, while infants u'ith normal and slightly abnormal earlyMRI develop normally or display only minor neurodevelop-mental disturbances.

This work is supported by the Sn'iss NationalScience For"rndation, grant no. 32-30176.90 and 32-30164.90.

Acknowledgement

The NOS consists of 9 subgr<-rups (spontaneous motility, posture, invohintary movements, muscie tone, rellexes, primitiveresponses, quality of motor behavior, vision, hearing) with a total of 47 items. Each item was separately scaled into normal (3points), moderately abnormal (2 points), or severely abnormal (1 point). The score of a subgroup was obtained by the mean of a-llindividual items. The maximal total score is 27 pciints, whereas the lowest total score is 9 points.

I2

12

Spontaneous motilityQuantrtySymmetry

PostureHeadTnmk

3 - normal, 2 = moderately deviant, 1 = severely denant3=s]'rnmetrical,2-occasionallyaslnnmetrical, 1=alin'aysasl.rnmetrical

3 - nonnal, 2 = moderately abnormal, 1 = severely abnomal3 = norrnal, 2 = moderately abnormal, 1 = severely abnormal

Prognostic Value of Early MR Imaging in Term lnfants with Settere Perinatal Asphyxia Neuropediatrics 25 0.994) 199

3 Hand 3-nonnal,2 =moderatelyabnormal, 1= severelyabnormal4 Arms 3 =normal,2 = moderatelyabnormal, 1= severelyabnormal5 Legs 3 =normal,2 -moderatelyabnomal, 1= severelyabnomal6 Extension of head, legs and tru-nk 3 = absent, 2 = in activity, 1 = always7 Pull- to-sit 3-nonnal,2=moderatelyabnormal, 1=severelyabnormal

Head controlThmh control

B Sitt ing 3 =normzrl,2=moderatelyabnomal, 1=severelyabnomalHead controlTiunk control

I Ventral suspension 3 = normal, 2 - moderately abnormal, 1 = severely abnormalPosture of the headPosture of the tnlrkPosture of the limbs

l0 Prone positionAsSrmmetry 3=slrnmetrical,2=occasionallyas5.nnmetrical, 1=alwaysasynmetricalPosture of the head 3 = normal, 2 - moderately abnormal, 1 = severely abnormalPosture of the llmbs 3 = nonnal, 2 - moderately abnormal, 1 = severely abnormal

Inaoluntary mooements1 T iemor 3 -absent ,2=modera te , 1=severe2 Choreat icmovements 3=zrbsent ,2=modera te , l -severe3 Athetoid-like movements ll = a]Jsent, 2 = moderate, 1 - severe

Muscle toneTnmk 3 = normal, 2 = moderately increased or decreased

1 active tone 1 = severely increased or decreased2 resistance against passrve tnovements

Upper limbs3 active tone4 resis*urce against passive movements

Lower limbs5 active tone6 resistance against passlve movements

Reflexes 3 = norma-I, 2 = moderately reduced or exaggerated, moderate as)mmetry1 AnJ<le jerk 1 = absent reflexes, severely exaggerated, severe asymmetry2 Knee jerk3 Biceps reflex4 Tiiceps reilex5 Brachioradial reflex6 Plantarresponse 3=zrbsent, l=present

Primitiae responses1 As5rmmetric tonic neck reflex 3 = norm:il, 2 - moderately abnormal, 1 = severely abnormal2 Palmar grasp reflex3 Plantar grasp reflex4 Moro response5 Protective reactions (parachute)

Quality of motor behaaior1 Rotation prone to side 3 = appropriate for age, 1 - not appropriate for age

prone lo supinesupine to prone

2 Pivoting, crau'ling3 Sitting u'ith help4 Sitting without help5 Sitting up u.'ith help6 Sitting up without help7 Standing with holdingB Standing up9 Walking along walls

10 Walking free

Vision1 Fixation2 Visual pursuit horizontal 3 = appropriate for age, 1 = not appropriate for age

vertical3 S t rab ismus 3-absent ,2=modera te , 1=severe4 Nystagmus 3=absent,2=directed, 1=spontaneous

Hearing1 Auditory localization 3 - nonnal, 2 = moderately reduced, 1 = severely reduced

200 Nettroptctlintrics 25 (1994) Ch. Kttenzle et al

Refcrences

)AL l se t t ,D .8 . ,C .R .F ' i t z ,A .H l l / ; I I . vpo : ; i c i sd re rn i ccc r c i r r a l i r i j u r l i n t hc

term nel-bom: corlel:ltion of O'l- findings uith nerrroloqical oLr{.ccinrt:. I)cr:I lcd. Chi ld Ncurol . 27 i1985) 115 1( i0

' Azzopnrdi, D., J. S. Wttntt, P. A. Hnmiltorr, E. B. Cadtt, D. T. Dtl1tt1, P.L. Hopt el:r1: l'hosphonrs rne|aboliLes anrl inl.rarr:llLtlar pl I itr lrrairrs ofnonlal rurd small for gestational age infants illvesligaled l)l nlagnet.icltsollulcc spectroscoplr l)ccLiatr. llcs. 25 (1981)) .11() 11.1

" Bnlrcock, D. 5., W. Bal1: I)ostasph.vxiul cru:ephulopathf il tirll-temrinfants: r r l l lasound diagnosis. RadioJogl ' 1 18 (1983) 411 123

I Batnzicer, O., E. Martirt, M. Steinlin, M. Gttod, R. Lnrgo, R. tsurgar tl:il: Earlv pattem rccognition in sevele perin:rtal asphlxia: :r prrispu't.ivt:.\lll l stu(.lr \curoladiologl' 35 (11)93) -l:17 7.1'2Bn r l . : r , t ' i , l t , A l , ( [ . l r t t u ' i t : I l r r i t r , l r r t r r r r q r ' J r , , t r r p , t i r ; r l : . ] ; . . l r l n x t r :io ln l lL ion ol l lR l int lu igs s i th gesLat ional :Lge. ,UNR I I (1990) 108710!)r ;

" Bocscli, C., E. Mnrtitt: Cornbirccl :rpplic:ation of rnagnetic reson:lrceinaging (IIRT) lnd spect.roscrip.v (\lRS) in nconates :urtl chiltlrcrr:installation lurd opelatiou of a 2.115

'Ii:sla svstem in a dinical set.t.ing.

I ladio logl ' 1(18 (1988).181 188't Bqrnc, t'., R. Welch, M. A. lohnsott, l. Darrnh, M. Pipe r: Srrial nagnclicr ' ( ,son: ln.e inraging in neon:r l : r l h lpoxic ischenr ic encrplra lopathl . . J .Ped ia t r 117 (11 ) ! ) 0 ) ( j 0 . 1 7 (X )

I Firrcr, N. N., C. M. Ro&crfsori, R. T. Richartls, L. E. Pinncll, K. L.Irclcrs: Tlvpoxic ischenric encephalr4r:rLh-r' in ternr neonalt's: pcrinatall:rctols :ull outcorrc. .J. I)ccLiatr. {)ii (1{)ll1) 712 117

"' Fltttlntnrk, O., L. E. Be ckcr, D. C. HuruLtod Nasli, P M. Fitzhnrtlingt, C.It. Fifz, S. H. Chuang: (lorrelation bets'een conrputed lornoqraplt.y atrdautopsl in plcnaturc ard lirll terrl rlconatcs that h:lvc sullered perinat:rlasphlx ia. l ladic i logl 137 (1980) 93 103

" 'Cr i f f i ths,R.:The' \b i l i t iesof l labies. I -ondon,I - ln ivers i tyolJ-ondonl)ress( 195 1 )

" Hill, A.: CLrrrt:rtl col<'r'pls ol hl'poxrc iscirrnric ierclrral irt.jurf in thc tcrmrteu l ront . Pet l i l rh Neut 'o l . 7 (191)1) 317 325

t t lo lutsort , M. A. , l .M. Pcnnot-k, G. M. Byddcr, L. M. S. DubLnoi tz, D. l .Tlnmos, 1. R. Yoang: Scli:rl \lR irnaging in rrtrnatal ccrcbral iujrrri, \ . r \ l l 8 (19s7) 83 1)2

):t Kteneq, S. E., E. W. Adcock, C. B. McArtllc:1'rospcctivc obscn.ations ofIOO l r iu l r l isk neonaLes l rv h igh l iek l (1.5 ' l i 's la)

rn:rgnt : t . ic r ( 'soral r (einraging of the centlrl ner\()us svster)I. II. I-esions associrted l'it.hllpoxic ischcuric cucephalcipalhl'. l1'cliallir:s fJ7 (1991) .131 ,131J

" Largo, R. H., R. Wiilli, C. Duc, A. Fancotti, A. Prader: Iivahratior ofpednatal grou'th. T{eh.. Pat'diat. r\c:t;r 3ir (1080).11{) ,130

tt' Lnrgrt, R. H., 5, Grnf, S. KunLiu, LL Huuziker, I-. Molinari: Prcclictingdclclcipnerttal out.rrrntt'at. scltool agt' fronr ilrlartt. [.rst.s cif norntal, at risk:rntl retarderl infants. I)er.. lled. (lhikl Neurol. ll2 (19!X)) 30 1o

t'\ Leiene, M. 1., H. Grindulis, C. SnnLis, I. R. Moore:Conparison of tloncthocls ol preclir:ting out.corlr irt perirtat.al asphl,'xia. Lanc:ct 8(l I (198i1)07 08

" Lez,ene, M. 1., A. C. Fcrttotr, D. H. Ez,Ltns, I N / Archer, D. B.Shortland, N. ,4. Cilrsol: Scverc birt.b aspliyxia :urd al.iuonnal ccrclrralblood flol'r,t'Jor:it1: l)er'. \lt 'r1. (lltild Neurril. ll l (1989) 127 ,13.1

1r LiplrZitahlen, A. E., T. Deonna, l. L. Micheli, A. CaLane, R.Chrznnttutski, E. Citrc: I)rognostic valuc of nconatal CT scans inasphl'xiatcd trrnt biJrit:s: lou' densitt' scofc conll)arrcd t,ith nt:onatalnerrnrlogic:rl signs. Neuropediatrics 10 (1085) 201) 217

"' Lippey, E. C., T. M. Vttorhies, G. Ross, R. C. Vnnnucci, P. A. M. Auld:IJarll' preclicLols of onc 1.c:lr outcorner lbr infnnls asphlxialed at birth. [)er:I{ed. Child Nr:urol. 28 (198i1) 303'309

tt' McArdle, C. ts., C. J. Richartlson, C. K. Horlden, D. A. Nichotns, E. G.Antparo:,\llnornaliljcs of nconal.al brain: I11l irnagiilg. Paft II. Htpoxic'ischcnic lrrairr injun. Iladiologv 1(i3 (l9ll7) 395 .103

21 Mut tit t, S. C., M. l. Tnylor, l. S. Koltny ashi, L. MacMiltnn, H. E. Whytc :Seri:rl visrral o'ohtxl poterttials arcl outcrrrle in tem birth asphtxia.I )cdiatr Neurol . 7 (1991) 8( l 90

" Ncisorr , K.8. , A. Lez, i tor t T lou'nruch ol neonatal enceplra lopathf is t lucto birlh :rsph.vxr.i'? ,\rlr. J. Dis. Child. 1.1ir (1991) 11l2ir-lill l l

'tt Ptden, C. J., F. M. Cowan, D. l. Brynnt, l. Sorgentoni, l. l. Cox, D. K.Mutott eL al: Prot.on \lR spect.rr-rscopv of the lrrain h influrt: L ( ( Input, \ss ist . Icrmogr 11(1090) 886 t t94

'' Pradr:r, 4., R. H. Lnrgo, L. Molinori, C. ls"-/cr: Phl,sical qrcirth of Suisschildren lront birlh tci 20 1'cals of :rgc. Fkrlr'. P:rediatr. Acta Suppl. 52(1989 ) 1 125'2t' Prechtl, H. F. R.:

'1-he optimalil.v {oncrpl. liarLl'l Iurn. Dor ,1 (1980) 201-

2Olttt\ Rolttrtsott, C. M., N. N. Finer:'Rrrn inf':utts sith hrpoxic ische.mic

elccphalopathv: outconle at ll.5 .t'ears. I)er'. \lecl. Child Nmroi. 27( r985 ) , 173 ' 184

2; Roth, S. C., A. D. Eduards, E, B. Cady, D. T. Dellty, l. S. Wyatt, D.Azzttpnrdi et al: Relat.itin lrt'tn'ct'n i:rrcblal oxidatir,c mctabolisrn lollov'-irrg birth asphrxia, and neurorlevelciprncnt:rl oulcornr urd irr:lin ero\\th atone \1'at I)t'v \lctl. Chllcl Ncurol. 3-1 (101)2) 285 21)lr

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Pntf. Dr. R. H. Lorgo

LLfr'crsity Children's HospitalSteinu'iessh 75CH-80112 ZurichSwitzeiliurtl