MR Imaging of Perinatal Brain Damage:Comparison of Clinical Outcome with Initial
and Follow-up MR Findings
Noriko Aida, Gen Nishimura, Yuriko Hachiya, Kiyoshi Matsui, Maho Takeuchi, and Yasufumi Itani
BACKGROUND AND PURPOSE: The purpose of our study was to determine whether MRstudies in the neonatal period are predictive of the neuroradiologic sequelae and clinicaloutcome in premature and term infants with perinatal brain injury.
METHODS: Thirty subjects (15 premature and 15 term infants) with abnormalities revealedby initial MR studies were reexamined approximately 1 year after birth with both MR imagingand a neurologic assessment. All initial MR studies were performed between 35 and 45 weekscorrected age in premature infants and within 28 days of life in term infants. The initial MRstudies were evaluated for deep gray matter involvement, hemispheric parenchymal change,intracranial hemorrhage, and periventricular signal and/or morphologic changes. These MRfindings were compared with the follow-up MR findings and with the neurologic outcome.
RESULTS: The development of cerebral palsy in premature infants was related to thefollowing initial MR findings: subependymal hemorrhage associated with parenchymal destruc-tion, periventricular signal alteration with irregularity of the ventricular wall, and widespreadcerebral infarction. These MR findings were predictive of the subtypes of cerebral palsy. In termasphyxiated infants, T2 signal alterations of the deep gray matter rather than T1 shorteningand diffuse involvement of the hemispheres were predictive of an unfavorable outcome. Both interm and premature infants, focal hemispheric parenchymal lesions alone (including infarctionand intracerebral, subdural, intraventricular, and subarachnoid hemorrhage) did not producepoor outcomes.
CONCLUSION: MR studies performed at or near term in either premature or term infantswith perinatal brain damage are effective in predicting both late neuroradiologic and clinicaloutcome.
The accurate prediction of clinical outcome after neo-natal brain damage, including intrapartum hypoxic-ischemic cerebral insult, is difficult because of theinability to determine the severity, timing, tempo, andduration of the insult. Early evaluation and diagnosisof neonatal brain injuries have been facilitated by theapplication of new imaging techniques, as suggestedin several reports on the usefulness of MR imaging(1–11). However, premature infants with perinatalbrain damage are often clinically unstable and diffi-
ed August 4, 1997; accepted after revision June 1, 1998.ted in part at the annual meeting of the American Societyradiology, Seattle, June 1996, and Toronto, May 1997.the Departments of Radiology (N.A., G.N., Y.H., M.T.)natology (K.M.), Kanagawa Children’s Medical Center,a, and the Department of Radiology, School of Medicine,
University (G.N.), Tochigi, Japan.ss reprint requests to Noriko Aida, MD, Department ofy, Kanagawa Children’s Medical Center, 2–138–4, Mut-inami-ku Yokohama, 232–0066 Japan.
ican Society of Neuroradiology
1909
cult to image with MR shortly after birth. Thus, fewreports discuss the results of early MR studies ob-tained in premature infants at or before 40 weekscorrected age (9–11). MR imaging is readily applica-ble for the assessment of term infants with perinatalbrain damage (5–8), but the accurate prediction ofclinical outcome is not an easy task even in this groupof affected infants. The relationship among MR find-ings in the neonatal period, MR findings on subse-quent follow-up studies, and the infants’ clinical out-come remain to be more thoroughly elucidated. Thepurpose of this study was to examine these relation-ships in both premature and term infants with peri-natal brain damage and to compare those findingswith the neurologic clinical evaluation obtained atleast 1 year after birth.
MethodsThirty neonates (15 premature and 15 term infants) met all
study criteria and were selected for detailed review. Entrycriteria included an initial clinical suspicion of perinatal hy-
1910 AIDA AJNR: 19, November 1998
TABLE 1: Clinical and Radiologic Findings of Premature Infants with Perinatal Brain Damage
poxic-ischemic injury in either premature or term infants, anearly MR study showing abnormalities, and both a delayed MRstudy and a neurologic evaluation as outlined below. The initialclinical diagnosis of perinatal asphyxia was based on low Apgarscores and clinical symptoms suggesting hypoxic-ischemic en-cephalopathy, such as convulsions, lethargy, agitation, and/orrespiratory problems. Infants with brain malformations, meta-bolic abnormalities, or perinatal infection were excluded.
Premature infants were defined as neonates less than 32weeks gestational age. They were examined with MR imagingat approximately 40 weeks corrected age and included in thestudy only if the initial MR study was performed at or before 45weeks corrected age. Detailed follow-up neurologic assessmentand MR studies were performed at least 1 year after birth.Term infants were included for evaluation if they were at least35 weeks gestational age and an initial MR study had beenobtained within 28 days of birth. Again, both a detailed fol-low-up neurologic assessment and MR study were performedapproximately 1 year later.
All initial MR examinations were performed with a 1.5-Tscanner. The studies consisted of 5-mm axial and coronal spin-echo (SE) T1-weighted images (400/15/2 [TE/TR/excitations])and axial SE T2-weighted images (3000/80–120/1). Follow-upMR studies included axial SE T1-weighted images (360–500/15/2) and T2-weighted images (3000/80–110/1), as well as coro-nal fast SE T2-weighted images (4000–5000/80–136; echo trainlength, 7–15) and/or SE T1-weighted images (450–500/15/2).Gradient-echo sequences were not performed. All MR studieswere reviewed retrospectively by one neuroradiologist withoutknowledge of the clinical outcome.
The following four MR findings were evaluated in bothpremature and term infants: deep gray matter involvement;hemispheric parenchymal change; intracranial hemorrhage, in-
cluding subependymal hemorrhage (SEH); and periventricularsignal alterations and/or morphologic changes. Because of thelength of time between birth and the initial MR study, SEH wasdefined as either focal periventricular hemosiderin depositsand/or hemosiderin accumulation along the ventricular wall asevidence of intraventricular hemorrhage (IVH). Although it iscontroversial how periventricular leukomalacia (PVL) shouldbe defined on MR studies, periventricular signal or morpho-logic alterations in premature infants have been generally pre-sumed to be sequelae of PVL. Therefore, for this study, wetentatively considered all patients with bilateral periventricularsignal alterations on the initial MR studies to have “radiologicPVL.” On follow-up MR studies, end-stage PVL was defined asT2 signal change and periventricular white matter volume loss.Periventricular T2 prolongation alone was considered to beperiventricular abnormal T2 prolongation.
A detailed neurologic assessment was performed by neurol-ogists at the time of a follow-up MR study. The assessmentincluded a description of the type of cerebral palsy, presence ofepilepsy, any EEG abnormality, and an estimate of develop-mental delay. Developmental delay was diagnosed when overtclinical delay in development was observed in the patientand/or when the developmental quotient score (examined bythe Mother-Child Counseling Test by Cattel [adapted for Jap-anese children] or the Tsumori-Inage Developmental Test,Tokyo, Japan) was under 70.
Results
Premature InfantsIn the 15 premature infants studied, the mean ges-
tational age was 28 weeks and the mean birth weight
AJNR: 19, November 1998 PERINATAL BRAIN DAMAGE 1911
TABLE 1: Continued
Initial MR Imaging (Continued)
Parenchymal Change Type of Hemorrhage
Radiologic PVL Follow-Up MR Imaging
Signal abnormality Irregularity of LVAge (mo) at Scan:
PCA (CA)Findings
. . . . . . Short T1, short T2 1 14 (18) End-stage PVL
. . . SEH Short T1 2 20 (23) SEH, end-stage PVL
. . . SEH, IVHventriculomegaly
Short T1, short T2 2 11 (14) SEH, PV long T2
R-frontal corticalinfarction
SEH Short T1, short T2 1, PV cyst 13 (16) End-stage PVL, old infarction
. . . SEH, IVH . . . 2 44 (47) Normal
. . . . . . Short T1, short T2 1, PV cyst 22 (25) End-stage PVL
. . . . . . Short T1, short T2 1, PV cyst 15 (18) End-stage PVL
. . . SEH, PV cyst, IVH,ventriculomegaly
Short T1, short T2 2 12 (15) SEH with PV cyst, end-stagePVL, ventriculomegaly
. . . . . . Short T1, short T2 1, PV cyst 21 (24) End-stage PVL
. . . . . . Short T1, short T2 2 26 (28) End-stage PVL
. . . . . . Short T1, short T2 1, PV cyst 11 (13) End-stage PVL, equivocalmyelination delay
. . . . . . Short T1, short T2 2 12 (14) PV long T2R-MCA hemorrhagic
infarctionSDH Short T1, short T2 1 14 (16) End-stage PVL, old infarction
. . . SEH, PV cyst, IVH, SAH,ventriculomegaly
. . . 2 31 (33) SEH with PV cyst
was 1221 g. The initial MR studies were performedbetween 35 and 45 weeks postconceptional age or 3 to18 weeks after birth. The average age at initial MRstudy was 39 weeks postconceptional age, or 10 weeksafter birth, and the follow-up MR examinations wereperformed between 11 and 44 months postconcep-tional age (average, 18 months).
The clinical and radiologic features of these infantsare summarized in Table 1. We did not note thepresence or absence of asphyxia but described clinicalsymptoms, because asphyxia is difficult to assess inpremature infants. We believe, however, that most ofthe infants had birth asphyxia. Indeed, 13 of 15 pa-tients were neurologically abnormal at the time offinal clinical assessment. Neurologic deficits includedcerebral palsy (n 5 12), developmental delay (n 5 4),and epilepsy or EEG abnormalities (n 5 5). Twopatients had all three abnormalities, three had bothcerebral palsy and epilepsy, and one had cerebralpalsy and developmental delay. Developmental delayalone was observed in only one patient.
Of the MR imaging features evaluated, we foundno evidence of deep gray matter involvement, diffusehemispheric parenchymal changes, or intracerebralhemorrhage on the initial MR studies. Thus, the MRfindings that were appreciated on the initial MR stud-ies were SEH or subdural hemorrhage (SDH),periventricular signal alterations and/or morphologicchanges (radiologic PVL), or cerebral infarctions rec-ognized as focal hemispheric parenchymal changes.On the basis of the initial MR findings, the 15 pre-
mature infants were divided into three groups: threewith SEH alone, seven with radiologic PVL alone,and three with both SEH and radiologic PVL. Twopatients had additional abnormalities of cerebral in-farction and/or SDH: one with radiologic PVL, in-farction, and SDH, and the other with SEH, radio-logic PVL, and cortical infarction of a middle cerebralartery (MCA) territory.
Follow-up MR examinations revealed only onehealthy patient and 14 patients with abnormal find-ings. The following abnormalities were documentedin the latter 14 patients: late sequelae of SEH withparenchymal destruction alone (n 5 1), periventricu-lar T2 prolongation alone (n 5 1), end-stage PVLalone (n 5 6), SEH and periventricular T2 prolonga-tion (n 5 1), SEH and end-stage PVL (n 5 1),parenchymal destruction from SEH and end-stagePVL (n 5 2), and end-stage PVL and cerebral infarc-tion (n 5 2). No patient had apparent delayed myeli-nation; only one follow-up MR study of the patientwith end-stage PVL revealed equivocal delayed my-elination. Below we outline each set of the imagingfindings on the basis of the initial MR studies, whichare related to the follow-up MR studies and clinicaloutcome.
Hemispheric Parenchymal Changes.—Initial diffusehemispheric parenchymal abnormalities were notidentified in any patient, but focal cerebral infarctionwas found in two patients with radiologic PVL on theinitial MR studies, one with disseminated intravascu-lar coagulation showing hemorrhagic infarction of the
1912 AIDA AJNR: 19, November 1998
FIG 1. Patient 10: 28-week-old 1355-g infant.Initial MR images, A and B (T2-weighted SE [3000/120/1]) and C and D (T1-weighted SE [400/15/2]), at 38 weeks corrected age show
large germinal matrix region hemosiderin deposit (arrowhead ) with adjacent multiple encephaloclastic cysts (arrows), diffuse hemosid-erin deposition along the lateral ventricle, ventriculomegaly, and absence of periventricular parenchymal signal change.
Follow-up MR images, E and F (T2-weighted SE [3000/100/1]), at 12 months corrected age reveal right periventricular hemosiderindeposition (arrowheads), ventriculomegaly, and parenchymal destruction involving the left deep gray matter. Also note the periven-tricular T2 prolongation (arrows) with white matter volume loss. The infant developed a spastic diplegia with hemiparesis.
right posterior MCA territory with deep white matterinvolvement, SDH, and radiologic PVL with subtleirregularity of the ventricular wall, and the other witha small cortical infarction of the right MCA territoryand radiologic PVL with periventricular cysts. On thefollow-up MR studies, both had radiologic evidenceof old infarction. The first patient was found to haveend-stage PVL on follow-up imaging, with spasticdiplegia associated with a mild hemiparesis and de-velopmental delay, while the second had end-stagePVL with only spastic diplegia and epilepsy.
Intracranial Hemorrhage.—On the initial MR stud-ies, no patient had primary intraparenchymal hemor-rhage or subarachnoid hemorrhage (SAH). One hadSDH, which disappeared on the follow-up MR study,accompanied by MCA infarction and radiologic PVL,as described above.
Seven had evidence of SEH, which was depicted asfocal periventricular hemosiderin alone in two pa-tients, and five had both hemosiderin deposits andIVH. Four of these five patients also had ventriculo-megaly. On follow-up MR studies, the hemosiderindeposits were absent in two and less conspicuous infive patients (Fig 1). Among the four patients whoinitially had ventriculomegaly, two showed consistentventriculomegaly. Associated adjoining encephalo-clastic cysts were revealed in three of the seven pa-tients with SEH on the initial MR studies, and allpatients sustained tissue loss (Fig 1) and a spastichemiparesis. However, four patients with hemosid-erin deposits alone on the initial MR studies did nothave spastic hemiparesis but had varied outcomes,depending on the accompanying abnormalities. Oneinfant had periventricular T2 prolongation on the
AJNR: 19, November 1998 PERINATAL BRAIN DAMAGE 1913
FIG 2. Patient 7: 28-week-old, 1100-g infant.Initial MR images, A (T2-weighted SE [3000/120/1]) and B–D (T1-weighted SE [400/15/2]), at 38 weeks corrected age show multiple
spots of periventricular T1 and T2 shortening (black arrows) with cyst formation (white arrows) and an irregular contour to the ventricularwall.
Follow-up MR images, E and F (T2-weighted SE [3000/100/1]), at 15 months postconceptional age reveal marked irregularity of theventricular wall, white matter loss, and periventricular T2 prolongation (arrows). The infant developed a spastic diplegia.
follow-up MR study and had a normal clinicaloutcome, one had end-stage PVL and spastic diple-gia, one had end-stage PVL with cortical infarctionand spastic diplegia with developmental delay, andone had normal MR findings and developmental de-lay without cerebral palsy.
Periventricular Abnormalities (Radiologic PVL).—Periventricular T1 and/or T2 shortening was shown in12 of 15 patients on the initial MR studies, meetingour radiologic criteria for suspected PVL (radiologicPVL) (Figs 2 and 3). T1 and/or T2 shortening alonewas shown in five patients (Fig 3), whereas seven wereassociated with bilateral irregularities of the ventric-ular wall (five with multiple periventricular cysts [Fig2] and two with irregularities of the ventricular wallalone). All 12 patients had periventricular T2 prolon-gation on the follow-up MR studies with or withoutwhite matter volume loss, and all seven with either
ventricular wall irregularity and/or cysts had end-stage PVL on the follow-up MR studies, with associ-ated spastic diplegia or quadriparesis (Fig 2). Amongthese patients, three had epilepsy, one had develop-mental delay, and two had both. The five patientswithout initial MR evidence of periventricular whitematter destruction had two outcomes: two hadperiventricular T2 prolongation on the follow-up MRstudies despite a normal neurologic outcome (Fig 3),while three had end-stage PVL on follow-up MRstudies and incurred a spastic diplegia.
A hybrid of SEH and end-stage PVL was evident inone exceptional patient, whose case we have not yetdiscussed. The initial MR study revealed only a prom-inent SEH and ventriculomegaly (Fig 1), without ev-idence of radiologic PVL. End-stage PVL was evidenton the follow-up MR study (Fig 1), and a spasticdiplegia with hemiparesis developed.
1914 AIDA AJNR: 19, November 1998
FIG 3. Patient 13: 31-week-old, 1735-ginfant.
Initial MR images, A (T2-weighted SE[3000/120/1]) and B and C (T1-weightedSE [400/15/2]), at 36 weeks corrected ageshow multiple spots of periventricular T1and T2 shortening (arrows) without abnor-malities of the ventricular wall.
Follow-up MR image, D (T2-weightedSE [3000/100/1]), at 12 months correctedage shows peritrigonal T2 prolongation(arrows) without loss of white matter. Theinfant was clinically normal.
Term InfantsIn the 15 term infants studied, the mean gestational
age was 39 weeks (range, 35 to 42 weeks), while themean birth weight was 2974 g (range, 1873 to 3575 g).The initial MR studies were performed an average of12 days after birth (range, 0 to 27 days), and thefollow-up clinical and MR examinations were per-formed between the ages of 11 months and 3 years(mean, 15 months).
The clinical and radiologic findings of these infantsare summarized in Table 2. In this group, the pres-ence of perinatal asphyxia was readily determined onthe basis of clinical criteria. Follow-up neurologicassessment was abnormal in only four of 15 patientsand included cerebral palsy (n 5 4), developmentaldelay (n 5 3), and epilepsy or EEG abnormalities(n 5 4). Three patients had all three abnormalities,and one had spastic hemiparesis and epilepsy.
On the basis of the initial MR findings, the 15patients can be divided into four overlapping groups:nine with deep gray matter abnormalities; seven withhemispheric parenchymal changes, both diffuse and
focal; four with intracranial hemorrhage; and threewith periventricular signal changes.
Follow-up MR examinations showed nothing ab-normal in four patients and revealed abnormalities in11. Persistent signal alterations and atrophy of thedeep gray matter were seen in three of nine patientswith initial deep gray matter changes, with delayedmyelination in two. Radiologic sequelae were notedin all seven patients with parenchymal injuries, butonly one infant with diffuse T1 and T2 prolongationon the initial MR study developed multicystic enceph-alomalacia. Two of three patients with initial intrace-rebral hemorrhage had atrophy or hemosiderin in theaffected area, and no radiologic sequelae were foundin patients with SDH, SAH, or IVH. The spotty T1and/or T2 shortening in the periventricular whitematter found in three infants later evolved into T2prolongation. Again, we detail each set of findings onthe basis of the initial MR studies and relate them tothe follow-up MR studies and clinical outcome.
Deep Gray Matter Involvement.—Deep gray matterinvolvement was identified in nine infants, with two
AJNR: 19, November 1998 PERINATAL BRAIN DAMAGE 1915
patterns of MR signal changes: six had T1 shorteningalone (Fig 4) and three had T1 shortening and T2signal changes, including both shortening and/or pro-longation (Figs 5 and 6). The three patients with T2signal alteration had more extensive T1 signalchanges than the remaining six. On the follow-up MRstudies, the group of six had normal T1 signal andnormal deep gray matter volume (Fig 4). The secondgroup of three showed persistent T1 and T2 signalabnormalities along with atrophy of the deep graymatter (Figs 5 and 6). Clinical evaluation indicatedthat the first group was neurologically normal,whereas the second group had cerebral palsy, devel-opmental delay, and epilepsy.
Hemispheric Parenchymal Change.—The seven in-fants with hemispheric parenchymal signal changeswere divided into two groups. First, four of sevenpatients with deep gray matter changes had hemi-spheric signal changes of the cortex and subcorticalwhite matter. One of these four patients with diffusehemispheric T1 and T2 prolongation on the initialMR studies developed multicystic encephalomalacia.In the remaining three patients, all of whom hadperirolandic involvement, neurologic outcome wasnot related to the hemispheric lesions but rather tothe associated deep gray matter signal changes. Anormal neurologic outcome ensued in one patientwith only basal ganglia T1 shortening, whereas cere-bral palsy, developmental delay, and epilepsy devel-oped in two patients with basal ganglia T2 signalchanges (Fig 6).
Evidence of MCA infarctions without additionalMR changes was found in the remaining three in-fants. The left MCA was affected in all, and the insultwas seen on the initial MR studies as T1 and T2prolongation with blurred border zones between thegray and white matter. Total involvement of the MCAterritory, including perforators, was shown in oneinfant, while two had lesions restricted to the tempo-ral region. Radiologic evidence of old infarction wasfound on the follow-up MR studies in all three, butthe only neurologic abnormality detected at clinicalexamination was a mild hemiparesis and epilepsy inthe patient with a total MCA infarction.
Intracranial Hemorrhage.—Evidence of both SDHand intracerebral hemorrhage in the temporal lobe,frontal lobe, or the cerebellum was detected in threeinfants, and one had SDH accompanied by left tem-poral infarction. These infants did not have deep graymatter signal abnormalities. The follow-up MR stud-ies showed subtle intraparenchymal hemosiderin de-posits with mild volume loss in two patients and noradiologic sequelae of hemorrhage in two; all patientswere clinically normal.
Periventricular Signal Alterations.—On the initialMR studies, three of 15 patients (two with T1 short-ening in the deep gray matter [Fig 4] and one withcerebellar hemorrhage) had spotty areas of T1 and/orT2 shortening in the periventricular white matteridentical to our initial radiologic criteria for PVL inpremature infants. These changes evolved into T2prolongation on follow-up MR studies, and all three
patients were clinically normal (Fig 4). The evolutionof these signal alterations was radiologically identicalto those of radiologic PVL in premature infants (Fig3), and no patient sustained white matter volume loss.
Discussion
The early recognition, prompt medical interven-tion, and accurate prognostic prediction of perinatalbrain damage are particularly important to decreasemorbidity and mortality in affected infants. Althoughthere have been a number of imaging studies thatemphasize the close relationship between late radio-logic sequelae and clinical outcome (9, 12–15), veryfew reports have focused on early MR findings andtheir relationship to the radiologic sequelae and clin-ical neurologic assessment (5, 8). In this study, weevaluated the relationship among early initial MRfindings, late follow-up MR findings, and neurologicoutcomes in both premature and term infants withperinatal brain injuries and found that several MRfindings closely correlated with the neurologic se-quelae, including deep gray matter involvement,hemispheric parenchymal changes, intracranial hem-orrhage, and PVL. We discuss each imaging findingand its clinical and radiologic implication.
Deep Gray Matter InvolvementThe deep gray matter has been thought to be vul-
nerable to selective neuronal necrosis as a result ofacute total asphyxia (16, 17). In our series, the deepgray injury was commonly found in term infants, ashas been reported in the recent literature (18, 19),whereas it was not seen at all in premature infants.This may represent a selection bias of this study,which excluded premature infants with profound totalasphyxia because of their early demise and severemorbidity, precluding the initial and/or late MR stud-ies (18, 19).
On the initial MR studies, deep gray matter in-volvement was depicted as T1 shortening in ninepatients and as T2 signal alterations in a subset ofthree. T1 shortening in the deep gray matter has beenattributed to acute and subacute hemorrhage. In con-trast, T2 signal alterations in the deep gray matter arereported to manifest as T2 shortening 6 to 10 daysafter hypoxic-ischemic injury, which argues againstthe signal change being caused by hemorrhage (18,19). However, the T2 signal alterations in our serieswere inconsistent with previous reports. Among ourthree patients, one underwent serial MR imaging thatrevealed T2 shortening 0 and 3 days after injury andsubsequent T2 prolongation by day 10. The remainingtwo patients underwent MR imaging on only oneoccasion, and T2 prolongation was revealed 16 and 27days, respectively, after injury. This T2 signal evolu-tion is consistent with microhemorrhage changingfrom deoxyhemoglobin to methemoglobin. Thus, theT2 signal alteration in these patients may be attrib-uted to microhemorrhage associated with hypoxic-
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TABLE 2: Clinical and Radiological Findings of Term Infants with Perinatal Brain Damage
Patient
Clinical information Outcome Initial MR Imaging
Gestational Age atBirth (wk)/Birth
Weight (g)
Apgar score(1/5)
Symptoms orDiagnosis
CP EPI DDAge atScan
(days)
Abnormalities of DeepGray Matter
16 35/1873 2/5 HIE grade II Quadriparesis 1 1 16 Short T1, short T2, long T2 inL and Th
17 36/2862 1/3 HIE grade I . . . 2 2 4, 20 Short T1 in L18 38/2800 8/? Asphyxia . . . 2 2 14 Short T1 in L
-ischemic injury of the deep gray matter, but thenumber of patients in our study is too small to defin-itively elucidate the precise cause. The conspicuity ofT1 shortening in the deep gray matter greater than T2shortening may simply be due to the relatively lowbackground intensity of neonatal gray matter. Ruth-erford et al (8) reported that the extent of T1 short-ening in the deep gray matter closely corresponded tothe severity of neurologic deficit at follow-up. In con-trast, our three patients with T2 signal change hadsevere clinical and radiologic sequelae, whereas thesix patients with only T1 shortening had a favorableneurologic outcome and normal findings on follow-upMR studies. We speculate that milder injuries can bedetected as T1 shortening, but that T2 signal changesare present with more severe injuries, causing a dev-astating neurologic outcome. In fact, all three caseswith T2 signal alteration had more extensive T1 signalchange than the remaining six patients. Thus, in in-fants with T1 shortening in the deep gray matter,meticulous MR imaging interpretation is required,and follow-up MR studies may be necessary to con-firm the development of T2 prolongation.
Hemispheric Parenchymal ChangesDiffuse hemispheric parenchymal changes have
been attributed to severe prolonged partial asphyxia(17, 20). In our series, no premature infant had suchdiffuse hemispheric changes. In the term infants withasphyxia, multicystic encephalomalacia ensued onlyin one patient, and typical parasagittal cerebral injurydid not manifest in any patients, although deep graymatter involvement was shown in most term infantswith asphyxia. These findings suggest a selection biasof this study, which included only infants in whomprotracted asphyxia was prevented by prompt perina-tal care.
Focal hemispheric change, or cerebral infarction,was found in both premature and term infants in ourseries. Infarction is considered to occur as a result ofarterial occlusive diseases, and the left MCA territoryis usually preferentially involved, as in our series ofterm infants (21). Cerebral infarction did not createsignificant neurologic deficits in either our prematureor term infants unless periventricular parenchymalinvolvement or total involvement of the MCA terri-tory was present. This observation implies that focal
AJNR: 19, November 1998 PERINATAL BRAIN DAMAGE 1917
TABLE 2: Continued
Initial MR Imaging (Continued)
Parenchymal Change Type of Hemorrhage PV Signal Abnormality
Follow-Up MR Imaging
Age atScan (mo)
Findings
Diffuse T1, T2 prolongation . . . . . . 28 Long T1, T2 and atrophy in Land Th multicysticencephalomalacia, delayedmyelination
. . . . . . Short T1, short T2 11 PV long T2Short T1 in the perirolandic region
and optic pathway. . . . . . 12 Long T2 in the optic pathway
. . . Cerebellar ICH, SDH,ventriculomegaly
Short T1 11 Old cerebellar hemorrhage,PV long T2
Short T1, short T2, long T2 in theperirolandic region
. . . . . . 36 Long T1, T2 and atrophy in Land Th long T1, T2 andatrophy in the periolandicregion
Entire Lt MCA infarction . . . . . . 12 Long T2 and atrophy in LtTh, old MCA infraction
injuries to the cerebral hemisphere tend to be func-tionally compensated for.
SEH and Other Intracranial HemorrhageSEH is one of the common sequelae in premature
infants (17, 22), and was readily depicted on the initialMR studies as periventricular hemosiderin depositsand/or evidence of IVH and as areas of hemosiderinin some cases on the follow-up MR studies. The rateof occurrence of SEH may be underestimated in ourseries because we did not use a gradient-echo se-quence, which is usually more sensitive to hemosid-erin than is SE imaging.
Parenchymal encephaloclastic cysts adjacent to he-mosiderin deposits as a result of SEH on the initialMR studies were considered to represent grade IVhemorrhage or hemorrhagic venous infarction (9, 22,23). Such lesions led to parenchymal destruction andvolume loss on follow-up MR studies. This combina-tion of findings was present in three of our patients,all of whom developed a component of spastic hemi-paresis, even if the affected area was small, suggestingthat either the injury was more extensive than thatimaged or the selective location of the injury affectedthe motor fibers and was easily detected clinically (22).
In our series, an unremarkable neurologic outcomewas evident in all term patients with intracerebralhemorrhage at follow-up evaluation. As in cerebral
infarction, focal parenchymal damage seems to befunctionally compensated for by the remaining brain.In both term and premature infants, SDH, SAH,IVH, or SEH without parenchymal destruction (he-mosiderin deposit alone) did not predict unfavorableoutcome.
Radiologic PVLT1 and T2 shortening in the periventricular white
matter in premature infants have been reported ex-tensively (2, 11). In our series, such MR signalchanges were frequently present on the initial MRstudies with or without cystic white matter injury oralteration in the contour of the ventricular wall, andwe tentatively called this radiologic PVL. The precisecauses of these signal changes on the initial MRstudies remain unknown but may share the samecauses of those in the deep gray matter. The signalchanges are easily recognizable because the T1 and/orT2 shortening occurs against a background of whitematter with much longer T1 and T2 values. The T1and/or T2 shortening developed into T2 prolongationon the follow-up MR studies, occasionally withoutwhite matter volume loss or appreciable neurologicdeficit. Periventricular T2 prolongation is regarded asa glial reaction, and very premature infants, especiallybefore the third trimester, have been reported to havea limited capacity to mount a glial reaction, but rather
1918 AIDA AJNR: 19, November 1998
FIG 4. Patient 28: 40-week-old, 3392-ginfant.
Initial MR images, A (T1-weighted SE[400/15/2]) and B (T2-weighted SE [3000/120/1]), at 6 days of age show bilateral T1shortening in the lenticular nuclei (arrows)and spotty areas of T1 and T2 shorteningin the periventricular white matter (arrow-heads).
Follow-up MR images, C (T1-weightedSE [500/15/2]) and D (T2-weighted SE[3000/100/1]), at 16 months show normal-appearing deep gray matter but withspotty areas of T2 prolongation (arrow-heads). The infant developed normally.
cavitate and destroy their white matter (17, 24). Inour series, however, all infants born at or before 28weeks gestation with radiologic PVL had someperiventricular T2 prolongation rather than paren-chymal destruction alone. The presence of bilateralperiventricular parenchymal destruction in prematureinfants on the initial MR studies signified the devel-opment of end-stage PVL and a significant neurologichandicap. However, end-stage PVL also developed ininfants with periventricular signal alterations alone,and even occurred in an infant who had SEH/IVHand ventriculomegaly on the initial MR study. Con-sequently, the initial MR findings provide significant,but limited, information in predicting the severity of aneurologic handicap associated with PVL. A draw-back to our study is that we were only able to observesubacute changes of PVL even on the initial MRstudies, and we may have missed early patterns ofsignal abnormalities that might be more predictive ofoutcome.
In our group of 15 term infants, three had spottysignal T1 and/or T2 shortening in the periventricularwhite matter on the initial MR studies, evolving into
T2 prolongation on the follow-up MR studies, typicalof the MR signal changes described for PVL in pre-mature infants. All three infants had a normal neu-rologic evaluation at follow-up and did not incurwhite matter volume loss. This spotty T1 and T2shortening in the periventricular white matter has notcome to light in previous studies on brain damage interm infants, although this finding may be identical to“patchy abnormal signal intensity within the periven-tricular white matter” in two asphyxiated infants withnormal developmental sequelae described by Ruther-ford et al (8). These periventricular white matterlesions may conceivably represent “periventricularleukomalacia in term infants” as postulated by Volpe(25, 26).
The Relationship between Each MR Finding andClinical Outcome
In the group of premature infants, four of the sevenpatients with SEH had evidence of PVL on the initialstudy, implying that SEH is often concurrent withPVL. The precise radiologic prevalence of SEH with
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FIG 5. Patient 20: 38-week-old, 3202-ginfant.
Initial MR images, A (T1-weighted SE[400/15/2]) and B (T2-weighted SE [3000/120/1]), at 3 days of age show T1 and T2shortening (arrows) in the posterior lentic-ular nuclei and ventral thalami.
Initial MR images, C (T1-weighted SE[400/15/2]) and D (T2-weighted SE [3000/120/1]), at 10 days of age show that thesignal alterations have evolved into T1shortening and T2 prolongation (arrows).
Follow-up MR image, E (T2-weightedSE [3000/100/1]), at 15 months of ageshows small areas of T2 prolongation (ar-rows) in the posterior putamen and ventralthalami, as well as mild brain atrophy anddelayed myelination. The infant had spas-tic quadriparesis, athetosis, epilepsy, anddevelopmental delay.
PVL is unknown to date, although the pathologicprevalence in severely affected infants has been re-ported in a few series (27).
In our series, poor neurologic outcome in prema-ture infants was related to SEH associated with adja-cent periventricular parenchymal destruction, PVLwith periventricular volume loss, and widespread ce-rebral infarction. The MR findings were predictive ofsubtypes of cerebral palsy. As previously reported,hemorrhagic venous infarction or grade IV hemor-rhage in severe cases of SEH and extensive cerebralinfarction both led to spastic hemiparesis, whereasMR evidence of PVL was often associated with spas-tic diplegia (22, 26, 28). In addition, the patients withend-stage PVL and periventricular parenchymal de-struction associated with SEH or cerebral infarctionhad the combination of spastic diplegia with hemipa-resis. To our knowledge, the combination of two typesof spastic cerebral palsy has not been well established.However, when considering the possible frequent co-existence of PVL and SEH, this combination is notsurprising.
No MR findings were predictive of developmentaldelay or epilepsy (or EEG abnormalities) in prema-ture infants. Patients with identical MR findings ofPVL and SEH had variable outcomes. Seizures anddevelopmental delay are thought to be caused bycortical injury (26), and although PVL and SEH pri-marily affect the deep white matter, small areas ofcortical injury may also occur.
In our group of asphyxiated term infants, T2 signalalterations in the deep gray matter, diffuse hemi-spheric parenchymal changes, and extensive cerebralinfarction predicted a poor neurologic outcome, in-cluding spastic quadriparesis and/or athetosis withepilepsy and developmental delay, and hemiparesiswith epilepsy.
Myelination delay is a well-known finding in bothterm and preterm infants with perinatal brain damage(24). As noted above, the rate of occurrence of de-layed myelination related to perinatal brain injury waslower than expected, particularly in premature in-fants.
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FIG 6. Patient 26: 40-week-old, 3260-g infant.Initial MR images, A and C (T1-weighted SE [400/15/2]) and B (T2-weighted SE [3000/80/1]), at 27 days of age show T1 shortening
(black arrows) and T2 prolongation (white arrows) in the posterior putamen and ventral thalami, with T1 shortening (black arrows) in theperirolandic cortices.
Follow-up MR images, D (T1-weighted SE [500/15/2]) and E and F (T2-weighted SE [3000/100/1]), at 3 years of age show that thesignal alterations have evolved into T1 and T2 prolongation (arrows). The child was developmentally delayed and had spasticquadriparesis, athetosis, and epilepsy.
ConclusionThe complex constellation of early radiologic ab-
normalities in premature infants with CNS insults is achallenge for accurate radiologic interpretation. Wefound that periventricular parenchymal destruction inSEH, PVL, and MCA infarction on initial MR studiesindicated not only the development of cerebral palsybut also its subtypes. Consequently, MR imaging atapproximately 40 weeks corrected age may play asignificant role in predicting neurologic outcomes.Some diagnostic limitations of the initial MR studiesremain, particularly the development of end-stagePVL, probably because only subacute and chronicbrain injuries were imaged, even with such early stud-ies. This observation reinforces the idea that muchearlier imaging may be well worth a clinical trial.
In term asphyxiated infants, T2 signal alterations ofthe deep gray matter, rather than T1 changes, werepredictive of an unfavorable outcome. Similarly, dif-fuse involvement of the hemispheres on the initialMR studies was predictive of an unfavorable progno-sis. The former finding is thought to represent selec-tive neuronal necrosis of the deep gray matter as aresult of total asphyxia, whereas the latter is the pre-cursor of multicystic encephalomalacia as a result ofsevere protracted partial asphyxia. Thus, MR imagingat or near term is useful for predicting neurologicoutcome in term infants with CNS injuries.
Acknowledgment
We thank K. J. Poskitt for his valuable comments.
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