hypoxic-ischaemic encephalopathy: and magnetic …rutherford,pennock,schwieso,cowan,dubowitz table 1...

Archives ofDisease in Childhood 1996;75:F145-F151

ORIGINAL ARTICLES

Hypoxic-ischaemic encephalopathy: early and latemagnetic resonance imaging findings in relation tooutcome

Mary Rutherford, Jacqueline Pennock, Jane Schwieso, Frances Cowan, Lilly Dubowitz

AbstractSixteen infants with hypoxic-ischaemicencephalopathy (HIE) were studied usingserial magnetic resonance imaging (MRI)up to the age of 2 years. The infants hadregular neurological and developmentalassessments. An nuclear magnetic reso-nance (NMR) score was devised to quan-tify the early and late MRI findings and aneurological optimality score was used toquantify abnormal neurological signs atthe time ofthe final examination. The fol-low up MRI score was compared with theneonatal MRI score and the outcome ofthe child.There was a strong positive correlation

between the neonatal and foilow up MRIscores and between MRI scores andoptimality score. All infants with a normaloutcome had patchy white matter abnor-malities. All infants with an abnormaloutcome had extensive white matter ab-n6rmalities. The outcome was most severein those infants with additional basal gan-gli atrophy with or without cyst formation.

Infants with mild HIE who are develop-mentally normal at the age of 2 years donot have normal MRI scans and may be atrisk of minor neurological problems byschool age. Bilateral basal ganglia abnor-malities are associated with severe devel-opmental delay, but infants with mainlywhite matter and cortical abnormalitieshave less severe problems despite exten-sive tissue loss.

Department ofPaediatrics andNeonatal Medicine,HammersmithHospital,Du Cane Road,London W12 OHSM RutherfordF CowanL Dubowitz

Robert Steiner MRIUnit,HamnmersmithHospitalJacqueline PennockJane Schwieso

Correspondence to:Dr Mary Rutherford.

Accepted10 September 1996

Keywords: hypoxic-ischaemic encephalopathy, mag-netic resonance imaging, optimality score, signal intensity.

The neonatal magnetic resonance imaging(MRI) findings in infants with hypoxic-ischaemic encephalopathy (HIE) have beenwell documented.`'' Early neonatal findingsinclude brain swelling and abnormal signalintensity (SI) within the basal ganglia, theperiventricular white matter, the subcorticalwhite matter and the cortex.'0 Bilateral abnor-mal SI within the basal ganglia and thalamithat is also detected by ultrasonography isassociated with a poor outcome in neonateswith HIE.8 Cortical highlighting, diffuse loss ofgrey/white matter differentiation, and abnor-mal SI along the posterior limb of the internalcapsule are associated with structural changesin the brain at 3 months of age,'0 but this is too

early to assess clinical outcome. Magneticresonance images continue to change inappearance because of normal development,compensatory mechanisms, and secondarydegeneration as a result of the initial injury.There are few studies that document both neo-natal and late MRI findings in infants with HIEand detailed clinical outcomes are not given.'9The aim of this study was to document the

MRI findings in infants with HIE between 12and 24 months of age and relate these to: (i)magnetic resonance imaging in the neonatalperiod; and (ii) the clinical outcome at the timeof the final scan.

MethodsInfants were included in the study if they metall the following criteria: (i) term or post-term(37-43 weeks'gestation); (ii) evidence of fetaldistress; (iii) neurologically abnormal in thefirst 48 hours of life, with abnormalities of tonewith or without convulsions and alteredconsciousness. Fetal distress was diagnosed inthe presence of cardiotocographic abnormali-ties of bradycardia (<100/minute or late dece-larations (type II dips) with or withoutmeconium stained liquor and with low Apgarscores and the necessity for resuscitation.Hypoxic-ischaemic encephalopathy was classi-fied as mild, moderate, or severe (I, II, or III)according to Sarnat and Sarnat."

All infants had at least one MRI scanperformed within the first 4 weeks of life andone scan between 12 and 24 months of age.

MAGNETIC RESONANCE IMAGINGMagnetic resonance imaging was performedusing a Picker HPQ Vista system (Cleveland,Ohio) operating at 1.0 Tesla. T1 and T2weighted spin echo (T1WSE and T2WSE)sequences and age related inversion recovery(IR) sequences were used. In some infants afluid attenuated inversion recovery (FLAIR)sequence was also used.'2 The detailed scan-ning variables are given in table 1.The MRI studies were carried out with the

infant's head placed laterally in a specificallydesigned 24 cm split, clear receiver coil. Imageswere obtained in the transverse plane. Immobi-lisation was achieved by surrounding the headwith an air evacuated bag filled with polysty-rene balls. Neonates were examined unsedatedduring natural sleep. Older infants weresedated with chloral hydrate 60-100 mg /kgorally, or rectally as a suppository. All children

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Rutherford, Pennock, Schwieso, Cowan, Dubowitz

Table 1 Parameters for MRI sequences

Repetition time (ms) Echo time (ms) Inversion time (ms)

Inversion recovery 3600-3800 30 700-950FLAIR 6500 160 2100T, weighted spin echo 860 20T2 weighted spin echo 3400 120

were monitored with ECG and pulse oximetry.A paediatrician was present throughout theinvestigation.Abnormal SI within the basal ganglia and

thalami may predict outcome and a separatedetailed score for the basal ganglia and thalami(TBG) was used, as described before.8 Themaximum score was 18.The neonatal NMR score was obtained from

first week scans.'0 Points were given for thepresence of brain swelling and abnormal signalintensities within the cortex, subcortical andperiventricular white matter, basal ganglia andthalami (less detailed than in the TBG score)and from the posterior limb of the internalcapsule. The maximum score was 17.The follow up NMR score was adapted from

the neonatal scoring system '0 and includedpoints for atrophy and delayed myelination,but not for brain swelling as this was not seenafter the first week of life. The IR sequence andthe T2WSE sequence images were assessedvisually and a score reached by consensus. Acomparison was made with scans of neurologi-cally normal infants of equivalent age. Detailsof the follow up score are shown in table 2.The late MRI findings were compared with

the neonatal MRI findings and with the clinicaloutcome of the infant.

FOLLOW UP AND CLINICAL OUTCOMEInfants had a detailed neurological examin-ation 3 and a Griffiths developmental assess-ment at three monthly intervals over the firsttwo years of life. All infants were over 1 year ofage at their final assessment. Clinical outcomewas classified as normal or abnormal. Thoseinfants with an abnormal outcome were

divided into groups according to the severity oftheir developmental delay.Normal outcome-A normal neurological and

developmental assessment, although there may

have been transient disturbances of toneduring the first year of life.Abnormal outcome-These infants had per-

sistent neurological signs consistent with acentral motor deficit, with or without develop-mental delay.(a) No developmental delay(b) Moderate developmental delay(c) Severe developmental delay(d) Very severe developmental delay (no dis-

cernible development)The central motor deficit was classified as a

hemiplegia, spastic quadriplegia, athetoidquadriplegia or a mixed quadriplegia (spasticwith athetoid/dystonic movements).

OPTLIALITY SCOREA neurological optimality score was given toeach child at their last examination to give a

quantifiable assessment of their neurologicalfunction. This was adapted from a proformaused by Kuenzle.' The optimality score com-

bined both developmental and neurologicalfindings and was easy to complete even inseverely abnormal infants. The proformascored the following areas separately: tone,posture, spontaneous motility, elicited motility,interaction and reflexes. A mean score was

given in each area and a total mean score gave

the optimality score. The maximum optimalityscore and therefore a normal result was 21.

ResultsThe 16 infants had a total of95 follow up scans, 36after the age of6 months. All infants had at least onescan between 1 and 2 years of age. The abnormalimaging findings are given in table 3 and theMRI scores are given in table 4.

All sixteen infants had abnormalities in thewhite matter on follow up scans. In eight ofthese infants the changes were mild and patchyand limited to the periventricular white matter(fig 1). One of these eight infants had mildventricular dilatation, but in the remainingseven the scans were otherwise normal. Alleight infants had had signs of brain swelling ontheir first week scan, but only one had a

persistent area of abnormal SI in the whitematter (case7).

Table 2 Clinical neonatal details and optimality scores

Apgar score 1,5 OptimalityCase No Gestation Fetal distress minutes Delivery HIE grade Outcome score

1 40 ctg/msl 3,7 Ventouse II Normal 212 40 nil 4,4 nvd I Normal 20.73 41 ctg/tachy 4,4 nvd I/II Normal 20.54 40 ctg 2,7 nvd I Normal 215 41 NR 3,4 nvd I Normal 216 41 ctg/msl 2,6 Ventouse I Normal 20.97 43 NR 0,0 nvd II Hemisyndrome 20.38 39 ctg/msl 2,3 nvd II Hemiplegia 20.39 40 ctg 1,2 emcs II cmd/mdd 16.410 38 ctg 2,5 emcs II cmd/sdd 14.611 40 PA 2,6 emcs II cmd/sdd 11.912 41 ctg 0,0 Ventouse II cmd/sdd 11.713 42 ctg 0,0 Forceps II cmd/sdd 9.014 41 ctg/msl 1, Ventouse II cmd/sdd 8.815 41 ctg 2,5 emcs II cmd/vsdd 7.616 41 ctg/msl 0,4 emcs m cmd/vsdd 6.3

CTG = cardiotocograph; msl = meconium stained liquor; emcs = emergency caesarean section; NR = not recorded; PA =placental abruption; cmd = central motor deficit; mdd = moderate developmental delay; sdd = severe developmental delay; vsdd =very severe developmental delay.

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Table 3 Abnormal imagingfindings

No of No ofSite Abnormal neonatalfindings infants Follow up findings infants

Unilateral high SI on T2WSE 1~t Bilateral atrophy of lentiform and thalami 5

Basal gangla and thalami High and low SI on both IR and T2WSE 8 with low SI on IR and high SI on T2WSEsequences Severe atrophy of lentiform, caudate head 2

and thalami with both high and low SI onIR and T2WSE

Cortex Abnormal high SI on IR 6 - Low SI on T2WSE, only seen running 3along interhemispheric fissure

Subcortical white matter High SI on IR 7 - High SI on T2WSE, seen in "bats wing" 7(1) Corticospinal tracts pattern(2) Adjacent to Low SI on IR 6 - High SI on T2 on T2WSE 6

interhemispheric fissureFocal low SI on IR 1 Patchy high SI on T2WSE 8*

Areas of infarction seen as low SI on IR and high 3Periventricular white matter SI on T2WSE v Extensive high SI on T2WSE with 8

Streaky high and low SI on IR 5 generalised deficit in myelination

High SI in insula cortex on IR 7 v 8Insula Infarct involving insula 1 High SI on T2WSE and FLAIR

Cerebellum Nil Deficit in myelination but no atrophy 2Hippocampus High SI on IR 4 ' Atrophy of hippocampus with dilated 4

temporal horns of lateral ventricles

* All infants had signs of brain swelling on neonatal scan.

Table 4 MRI and optimality scores

Neonatal scan score Follow up scan scoreOptimality

Case No TBG (max=18) Total (max=17) TBG (max=18) Total (max=46) score

1 0 3 0 4 212 0 0 0 2 20.73 2 3 0 2 20.54 0 2 0 4 215 2 4 0 5 216 2 3 0 2 20.97 0 2 0 3 20.38 0 3 0 4 20.39 3 7* 2 16 16.410 12 14 10 31 14.611 12 11 10 28 11.912 15 11* 6 20 11.713 12 13 16 37 9.014 12 9* 14 28 8.115 18 12 18 46 7.616 18 13 18 45 6.3

* Minimum score.

Eight infants had more extensive abnormalSI in the periventricular white matter associ-ated with a deficit in myelination (fig 2). Theseeight infants also had abnormalities in the sub-cortical white matter, with increased T2 alongthe corticospinal tracts adjacent to the Rolan-dic fissure (fig 3C) and increased T2 runningparallel to the interhemispheric fissure (fig 4B).These abnormalities corresponded to in-creased SI in the corticospinal tracts (fig 3A)and decreased SI in the subcortical white mat-ter (fig 4A), respectively, on the neonatal inver-sion recovery sequence. Cerebral atrophy withventricular dilatation and/or widening of theinterhemispheric fissure was seen in these eightinfants. Focal widening ofthe interhemisphericfissure (fig 3B) developed in those infants withcortical highlighting and adjacent subcorticalbreakdown on neonatal scans. These infantshad additional changes within the basal gangliawhich varied in severity (figs 5 and 6). Bilateralatrophy of the brainstem was seen in twoinfants with severe basal ganglia changes andunilateral atrophy in one with a parietal infarct.

Figure 1 Boy with grade IHIE aged 1 year (case 5). T2weighted spin echo sequence (SE 3000/120). Minorbilateral SI is increased in posterior periventricular whitematter at 1 year of age (arrow).

Hippocampal atrophy was only seen in infantswith severe basal ganglia abnormalities.There was a positive correlation between the

neonatal and follow up TBG scores (Kendall'srank correlation, P=0.0005). There was a

Figures 2 A andB Boy with grade II HIE (case 12).Inversion recovery sequence (IR 3600130/800) (A) and T2weighted spin echo sequence (SE 3000/120) (B).Generalised mnyelination deficit is evident (A) withincreased T2 most evident in the region ofa parietal infarct(arrows) (B).

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Figures 3A andB Girl with grade II HIE (case 15). Inversion recovery sequence (IR 3800/30/950) (A), inversionrecovery sequence (IR 3600130/800) (B), and T2 weighted spin echo sequence (SE 34001120) (C). There is abnormalincreased signal intensity running along the corticospinal tracts in the centrum semiovale adjacent to the Rolandic fissure onthe three week scan (arrow) (A) and at 15 months increased T2. (arrow) (C). There is a generalised myelination deficitwith some widening of the interhemispheric fissure (B).

strong positive correlation between the neona-tal and follow up NMR scores (Kendall's rankcorrelation, P=0.0001).

NEONATAL AND FOLLOW UP MRI FINDINGS INRELATION TO CLINICAL OUTCOME

Normal outcome (n=6):Six children had a normal outcome (optimalityscores 20.5.-21).These children had patchywhite matter abnormalities on follow up scan(NMR score 1-2). Five infants had mild brainswelling on the neonatal scan, and two of thesealso had minor SI changes in the lentiformnuclei. The remaining infant had a subarach-noid haemorrhage.

Abnormal outcome (n=10):Eight infants had a central motor deficitinvolving all four limbs and two infants hadunilateral signs.

Normal development (n=2):Two infants had minor neurological signs andnormal development (optimality scores were20.3). One infant had a mild hemiplegia andone a mild hemisyndrome. The T2WSE followup scans showed patchy increased SI in theperiventricular white matter in both infants(NMR scores 2, 3). There were no focal lesionsor evidence of brainstem asymmetry.Both infants had brain swelling on the

neonatal scans and the infant with the

Figures 4A and B Girl with grade IIHIE (case 9).Inversion recovery sequence (IR 38001301950) (A) and T2weighted spin echo sequence (SE 30001120). There isbilateral highlighting of the cortex (short arrow), with lowsignal areas in the adjacent subcortical white matter (longarrow) at 3 weeks of age (A). At 15 months bilateral lowsignal is seen in the cortex running parallel to theinterhemispheric fissure (long arrow) There is bilateral highsignal in the subcortical white matter (short arrow) (B).

hemisyndrome also had persistent low signalon inversion recovery sequence in the rightposterior parietal white matter.

Moderate developmental delay (n=l):One infant had a central motor deficit withmoderate developmental delay (optimalityscore 16.4). The signs consisted of secondarymicrocephaly, extensor posturing and in-creased tone in lower limbs. In spite of this atthe age of 2 years she was able to cruise aroundthe furniture. She had a vocabulary of severalwords. Follow up scans showed pronounced

Figures SA, B, and C Boy with grade I HIE aged 1 year (case 12). Inversion recovery sequence (IR 3600/301800) (A),T2 weighted spin echo sequence (SE 30001 120) (B), and FLAIR (fluid attenuated IR 6500116012100) (C). There isatrophy of the lentiform nuclei with abnormal low signal intensity in the posteriorputamen (long arrow) and in the leftthalamus (short arrow) (A). These regions are high signal intensity (B). There is a deficit in myelination posteriorly (A).Abnormal increased SI around the lentiform nuclei and insula cortex is best seen in (C)

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Figure 6 Girl with grade II HIE, aged 15 months (case15). T2 weighted spin echo sequence SE 3000/120. There ispronounced bilateral atrophy of the lentiform nuclei,thalami, and head of the caudate nucleus with abnormallyhigh and low signal intensities (arrows).

white matter atrophy with increased T2 in thecentrum semiovale and periventricular whitematter. Decreased T2 was seen in the cortexadjacent to the interhemispheric fissure (NMRscore 9). The basal ganglia were of normalappearance. Her neonatal scan showed brainswelling and widespread cortical highlighting.

Severe developmental delay (n=5):Five infants had a central motor deficit, severedevelopmental delay, and secondary micro-cephaly. (The optimality scores ranged from8.1 -14.6.) All had secondary microcephaly.Three infants had a mixed quadriplegia with

athetoid or dystonic movements of the upperlimbs, hypotonia of the trunk, and increasedtone in the lower limbs (cases 12,13,14). Twoof these infants had no hand function, but thethird who had milder dystonic posturing wasable to transfer objects at 17 months of age(case 12). This infant had no abnormal facialappearances and showed good vocalisationwith a vocabulary of two words.A fourth infant had a generalised increase in

tone with dystonic posturing of the right hand(case 10). She was able to sit independentlyand spoke a few words. The sixth infant with acentral motor deficit and severe delay had gen-

erally decreased tone with severe visual prob-lems. He was able to sit with minimal supportand was able to transfer objects but had no finehand manipulation at 18 months (case 1 1).A follow up MRI scan showed severe basal

ganglia changes with atrophy and cyst forma-tion in the three infants with severe dystonicand athetoid movements. They also showed aloss ofwhite matter and an abnormal increase inSI around the primary corticospinal tracts on

T2WSE scans (NMR scores 16, 21, 31). Oneinfant had a posterior parietal infarct. These

infants had abnormal SI in the basal ganglia andthalami, the cortex, and in the subcortical andperiventricular white matter on neonatal scans.Two further infants (cases 10,11) with

severe developmental delay showed a differentpattern of abnormalities on MRI.

Follow up MRI showed- loss of tissuesecondary to infarction in both infants. Thebasal ganglia were affected in both infants,although these were asymmetrical in case 10.The images did not show any substantialincrease in SI on the T2WSE scan. Myelinationwas decreased in both infants but this decreasewas extreme in case 11 (NMR scores 20 and 28).

Their neonatal scans showed multiple areasof infarction involving the white matter andcortex and abnormal SI within the basalganglia and thalami.

Very severe developmental delay (n=2):Two infants made no discernible development.(Optimality scores were 7.6 and 6.3.) Both hadsecondary microcephaly, severe extensor pos-turing, ongoing convulsions, persistent feedingproblems necessitating nasogastric or gas-trotomy feeding.On follow up MRI both infants had

extensive atrophy of the basal ganglia, adecrease in white matter, and a substantialdecrease in myelination. On the T2WSEsequence images there was an increase in SIalong the primary corticospinal tracts (fig 3C)(NMR scores 39 and 40). Their neonatal scansshowed abnormal SI throughout the basal gan-glia and thalami with highlighting of thecortex, which was most severe around the cen-tral fissure and interhemispheric fissure.

Table 4 shows the details of the follow upoptimality score with the neonatal and followup TBG and total NMR scores. There was astrong positive correlation between the opti-mality score and the neonatal TBG(P=0.0004), the neonatal NMR (P=0.0034),the follow up TBG (P=0.0002) and the followup NMR score (P=0.00 12).

DiscussionIn neonates with HIE early MRI may showevidence of brain swelling. This clears duringthe first week of life as signs of permanentdamage become more obvious. Abnormalsignal intensities may be seen in the basal gan-glia and thalami, the internal capsule, theperiventricular and subcortical white matterand in the cortex.'" We have shown that in terminfants with HIE there may be late MRIabnormalities within the basal ganglia, the cor-tex, the white matter, the hippocampi, theinsulae and the brainstem. There were no nor-mal follow up scans and infants with a normaloutcome showed patchy abnormal SI withinthe periventricular white matter, which wasmost noticeable posteriorly. Persistent basalganglia abnormalities were always associatedwith an abnormal outcome, the severity andcharacter ofwhich were related to the degree ofabnormality seen. Infants with extensive whitematter abnormalities all had an abnormal out-come, but those without pronounced basalganglia abnormalities had less severe problems.There was a strong correlation between the

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neonatal and late NMR and TBG scores andthe outcome of the child, as measured by theoptimality score.

Infants with a normal outcome all showedpatchy white matter changes on their follow upscans. These changes were only deiectable onT2 weighted images and were difficult todistinguish from unmyelinated white matterbefore 1 year of age. It is not possible to saywhether these changes will persist with time orwhether they will be associated with moreminor neurological dysfunction at school age.Mild or grade I HIE is always considered to bea benign disorder, but to our knowledge therehave been no published studies that havelooked at the fine motor function in these chil-dren at 5 years plus.Byrne documented the development of

cerebral palsy in three children with normalscans at 3 months of age, but abnormal scans at8 months of age, with the development ofdelayed myelination and cortical atrophy.3 Wedid not see this type of deterioration in any ofour infants. Deterioration of a previouslynormal scan may imply that subtle butclinically important changes-that is, in thecortex or white matter-may have been diffi-cult to identify early on. This could be becausethe changes were time dependent or becausethe imaging sequences used were not optimal.We have shown that infants with patchy periv-entricular white matter changed on T2WSEscans at 1 year of age may have only had signsofbrain swelling on neonatal T,WSE sequencescans.'0 The signs of swelling were only visiblefor a few days. Alternatively, a child with anabnormal outcome but a normal early scanmay have an additional diagnosis, such as ametabolic problem, giving rise to ongoingdamage within the brain. Isolated delay inmyelination may be one of the earliest MRIchanges in children with a metabolic disor-der.'4 We have seen isolated deficit in myelina-tion in infants with neurological problems notdue to HIE, although they may have had fetaldistress and abnormal deliveries in addition totheir primary problem. In this study a deficit inmyelination was only seen in association withother structural changes within the brain.The basal ganglia are a common site for

abnormalities in the neonatal period, but onlythe more severe and persistent lesions seem tobe associated with a central motor deficit.Atrophy or cysts in the basal ganglia have beenreported in retrospective studies of childrenwith cerebral palsy and are felt to be good evi-dence in support of the occurrence of signifi-cant perinatal injury, as opposed to pre-existing prenatal abnormalities."' 6 The type ofmotor deficit may depend on the exact site andextent of basal ganglia injury and whetherthere is extension into the midbrain and dam-age in other parts of the brain. We have shownthat severe basal ganglia injury is associatedwith severe spastic quadriplegia with pro-nounced feeding difficulties and ongoing con-vulsions. The feeding difficulties are probablyrelated to involvement of the midbrain which ismore difficult to assess on MRI but isassociated with severe basal ganglia injury on

necropsy specimens."' In this study generalisedatrophy with or without cyst formation in thebasal ganglia was also associated with abnor-mal SI within the hippocampus, a pattern ofinjury that has been attributed to a period oftotal asphyxia using animal models.'8

Less severe damage with atrophy and cystformation within the lentiform nuclei was seenin three infants, all of whom had a mixedquadriplegia with athetoid and or dystonicmovements. A further infant with asymmetri-cal basal ganglia abnormalities had dystonicmovements in the contralateral arm only.Localised cysts in the posterior part of theputamen without generalised atrophy arestrongly associated with the development ofathetoid quadriplegia.'9 20 Interestingly, allthree infants in this study with a mixed quadri-plegia with athetoid movements had micro-cephaly and severe early feeding problems,with no suck and poor swallow. This contraststo our previous findings in three infants with apurer athetoid quadriplegia all of whom main-tained a normal head circumference and all ofwhom were bottle feeding by 2 weeks of age."White matter atrophy is a common finding

on the follow up scans of infants with HIE.Areas of white matter atrophy weredistinguished because of the lack of myelin andthe collapsing down of cortical gyri on IRsequences, but it was not possible to differenti-ate atrophy of the subcortical white matterfrom the periventicular white matter using the IRsequence alone. Abnormally increased T2 prob-ably representing secondary gliosis was, however,easily seen on the T2WSE sequences andpermitted a more accurate localisation of whitematter damage. A delay or deficiency in myelina-tion was easiest to identify on IR sequence scans,which was also the finding in Byrne's study.'Although NMR is the imaging method of choicefor assessing myelination, the patterns seen onlygrossly approximate the complex process of cen-tral nervous system development.Three changes on neonatal scans were asso-

ciated with the subsequent appearance ofwhitematter atrophy, areas of infarction, a streakyappearance in the white matter of the centrumsemiovale, and subcortical low signal on IRsequence. Infants with a streaky appearance inthe white matter during the first week of lifedid not develop cysts and the aetiology of theeventual white matter atrophy remains ob-scure. Low signal in the subcortical white mat-ter was associated with cortical highlighting.The cortical highlighting appeared in the firstweek of life but the adjacent areas of whitematter low signal did not appear for at leastanother seven days.'0 The timing of thesubcortical changes reflects either a primaryischaemic process in the tissue with cystformation appearing 10 to 14 days later, oralternatively, it may be secondary to thedamage within the cortex. The cortex and sub-cortical white matter around the central fissurein the region ofthe primary corticospinal tractswere most frequently involved and at follow updetected as increased T2. This region may bemore sensitive to asphyxial damage at termwhen it is actively myelinating.'

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The clinical relevance of the cortical high-lighting seen on neonatal IR scans is uncertain.The SI changes observed are in keeping with ahaemorrhagic lesion. The MRI appearance ofcortical highlighting may correspond to theincreased cortical echogenicity identified usingcranial ultrasonography in infants with HIE.This increased echogenicity corresponded toareas of cortical laminar necrosis on histologi-cal examination.2'On follow up MRI scans it was possible to

identify persistent low signal on T2WSEsequence within the cortex along the inter-hemispheric fissure. This would be consistentwith old haemorrhage. Cortical laminar abnor-malities, giving abnormal SI on T2 weightedimages have been described by other workerson late MRI scans in children with a history ofperinatal hypoxic-ischaemic brain injury andspastic quadripareses.22Only one of our infants had pronounced

cortical and subcortical white matter changeswith relatively preserved basal ganglia and shehas done remarkably well (case 9). The clinicalimportance of early and late cortical andsubcortical changes following HIE are poorlyunderstood and further insight may be gainedwith more sophisticated imaging combined withspecific electrophysiological studies in childrenwith no evidence of basal ganglia abnormalities.The dentate nuclei of the cerebellum are

sensitive to hypoxic-ischaemic damage inanimal models but there are few reports of cer-ebellar abnormalities following hypoxic-ischaemic injury in neonates.2324 The cerebel-lum may be damaged along with the thalamiand hippocampus as part of the injury followingsevere total asphyxia. In Eken's study of infantswith HIE, histological cerebellar lesions wereseen in 1 lof 20 infants,2' but it is not clear whatpattern of injury these infants had sustained.As all infants in our study survived, the

insults they sustained may have been insuffi-cient to cause major lesions within the cerebel-lum. The only abnormality seen in this studywas a deficit in myelination within the cerebel-lum, and this was associated with a generaliseddeficit of myelin throughout the brain. Al-though mild degrees of atrophy may have beenpresent but difficult to identify, the cerebellumseems to remain intact when the rest of thebrain is grossly damaged.MRI permits the detection of exact patterns

of early and late damage in infants with HIE.Some correlations with different patterns ofdamage can be made. In most cases, however,we are still not able to correlate accurately spe-cific areas of damage with specific clinicalsequelae. This is partly because in infants withHIE few areas are damaged in isolation. Theimaging techniques used did not measurefimction and while severe degrees of atrophyare identifiable, these could not be measuredand less severe atrophy may well have goneundetected. Further studies using a combina-tion of electrophysiological and MRI tech-niques will allow us to answer some of thequestions on the functional relevance ofspecific abnormalities.

Registration and subtraction of serial volu-metrically acquired images should help inmeasuring and detecting even mild degrees ofatrophy, and in detecting milder deficienciesand abnormalities in the progression andpatterns of myelination.25

Mary Rutherford was supported by Scope (formerly theSpastics Society). We are grateful to Professor Graeme Bydderfor his guidance and support.

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4 Keenay SE, Adcock EW, McArdle CB. Prospective observa-tions of 100 high-risk neonates by high-field (1.5 Tesla)magnetic resonance imaging of the central nervoussystem. U Lesions associated with hypoxic-ischaemicencephalopathy. Pediatrics 1991; 87: 431-8.

5 Roland EH, Hill A.MR and CT evaluation of profoundneonatal and infantile asphyxia. Am3'Neuroradiol 1992;13:973-5.

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