Original Art ic les

Preservation of Single-flash Visual Evoked Potentials at Very Low Cerebral Oxygen

Delivery in Preterm Infants Oie Pryds , M D and G o r m Greisen, M D

Single-flash visual evoked potentials (VEPs) were re- corded in 32 preterm infants (mean gestational age: 29 weeks) during extreme physiologic conditions within the first day of life. The VEP configuration was normal in all patients at the onset of the investigation. Hypoxic episodes (Pao2 < 3 kPa) caused rapid and consistent attenuation of the VEP mostly with an instantaneous recovery after normalization of Pao2. In contrast, VEP amplitude and latency were unaffected during episodes with low cerebral blood flow (4.5 ml/100 gm/min) and correspondingly low oxygen delivery to the brain (1 ml/100 gm/min), severe hypocapnia (Paco2 1.6 kPa), and severe arterial hypotension (MABP 10 mm Hg), provided that the arterial oxygen tension was greater than 5 kPa. Absence of NI was observed soon after the development of severe intracranial hemorrhage; how- ever, this abnormality was short in duration. We con- clude that the neurons generating VEPs are supported sufficiently during extreme physiologic episodes, ex- cept during severe hypoxia. The recovery time may be proportional to the cerebral insult.

Pryds O, Greisen G. Preservation of single-flash visual evoked potentials at very low cerebral oxygen delivery in preterm infants. Pediatr Neurol 1990;6:151-8.

Introduction

The two major causes of neurologic handicap in the preterm newborn are periventricular leukomalacia (PVL) and hemorrhage [1 ]. During the last decade, several risk factors have been identified but the underlying pathophys- iologic mechanisms still remain to be understood [2,3]; therefore, the impact of isolated hypoxia or ischemia on the development of cerebral damage is unknown. Probably both factors are necessary for tissue destruction [4].

This study was designed to investigate cerebral function during episodes in which cerebral impairment may be pre-

sent. These episodes included hypoxia, hypotension, hypo- capnia, low cerebral blood flow (CBF), or recent devel- opment of brain lesions. The cerebral function was esti- mated by means of single-flash visual evoked potentials (VEPs). The visual tracts pass through the brain, close to the periventricular area where lesions are frequently found. Implicitly, VEPs reflect the functional state of the neurons responsible for the signal transmission from the eye to the visual cortex. In preterm infants, VEPs are easily evoked by single flashes without needing to average sev- eral responses [5]. Furthermore, VEPs are reproducible.

Recently, Pryds et al. published data on VEP latency and amplitude in stable preterm infants, investigated during the first day of life [6]. Over 2V2 years, we studied an addi- tional 32 preterm infants during abnormal physiologic conditions.

Methods

Thirty-two preterm infants with a mean gestational age of 29 weeks (range: 25-33 weeks) and a mean birth weight of 1,175 gm (range: 575-2,000 gm) were studied. Twenty-nine infants required mechanical ventilation because of respiratory distress and 3 were assisted by nasal CPAP or were breathing spontaneously. The mechanically ventilated infants were routinely sedated with phenobarbital (15 mg/kg) and dia- zepam (0.5-1.0 mg/kg) administered at intubation. Mean arterial blood pressure (MABP) was recorded directly from an umbilical artery cath- eter by means of a calibrated transducer (Deseret) in the mechanically ventilated infants, or by oscillometry (Dinamap ®, Critikon) in the non- ventilated infants. When an arterial line was present, blood gas analysis was performed from an arterial blood sample; when not present, cali- brated transcutaneous 02 and CO2 electrodes (TCM3 ®, Radiometer) supplemented with an arterial or capillary blood sample (ABL ®, Radio- meter) were used. The hemoglobin (Hb) concentration and oxygen saturation (Sao2) were also measured (OSM2 ®, Radiometer).

VEPs were recorded as previously described [6]. Two platinum electrodes were placed subcutaneously at Oz and C3 with a frontal ground. The raw electroencephalographic (EEG) signal was amplified by a cerebral function monitor (Critikon R, bandpass 0.3-50 Hz and amplification adjusted by a calibration signal) and transferred to an os- cilloscope and paper recorder (Siemens EM 34, bandpass 0-500 Hz, paper speed 100 mm/sec). The visual evoked responses were evoked by a flash unit (Nikon) placed about 10 cm from the infant's eyes. The

From the Department of Neonatology; State University Hospital; Copenhagen, Denmark.

Communications should be addressed to: Dr. Pryds; Department of Neonatology; Rigshospitalet, Blegdamsvej; 2100 Copenhagen ~, Denmark. Received December 18, 1989; accepted February 16, 1990.

Pryds and Greisen: Visual Evoked Potentials 151

T a b l e i . C l i n i c a l d a t a o f 3 2 p r e t e r m i n f a n t s

P t B i r t h VEP VEP

No. GA Weight CBF Pao2 Paco2 MABP La t A m p

1 30 1,370 NA 6.7 3.3 20 275 70

- NA 2.5 4.8 44 290 30

- 4.5 15.6 3.7 48 265 80

- - 4.6 7.2 2.5 46 260 611

- NA 4.6 2.3 42 ** **

2 29 1,100 NA 13.0 3.9 23 290 30(]

- - 4.9 7.8 3.9 47 295 297

- - 7.7 5.6 5.1 34 298 253

3 27 795 NA 25.0 1.9 22 282 98

- - 11.3 13.5 2.8 25 295 60

- - 28.5 8.2 5.7 33 295 40

- - 8.4 24 .0 3.3 26 300 40

4 32 1.560 7.1 1 1.0 3.9 40 285 25

- - 7.7 11.3 4.1 51 270 30

5 27 1,000 7.4 7.7 2.9 46 230 60

- - 10.6 7.1 3.9 43 230 92

- - NA 9.4 5.0 44 ** **

6 28 1,275 4.4 22.0 1.6 33 290 228

- - NA 2.9 3 . 3 3 5 3 1 0 15

- - 6.3 13.9 6.8 35 270 180

- - 8.1 18.9 3.1 39 265 150

- - NA 9.0 5.2 41 ** **

7 30 1,460 7.4 10.0 5. I 32 290 80

- - 6.6 9.1 3.1 39 280 73

- - 8.8 t0.4 3.2 38 270 45

8 33 1,700 5.6 14.4 5.9 34 270 130

- - 5.8 14.3 4.8 38 270 13(I

- - 5.7 13.8 4.7 42 270 130

- NA 8.2 5.2 46 270 130

9 30 1,345 9.9 8.1 4.8 40 250 6(I

- - 9.7 9.4 3.4 35 265 90

- - 10.0 9.2 2.9 37 260 90

10 29 1,185 6.5 8.3 5.6 30 290 40

- - 5.8 7. I 6.4 36 290 40

- 6.8 9.5 4.8 43 290 30

11 26 795 12.6 13.6 3.4 26 280 120

- 9.0 9.5 5.1 35 270 70

G r o u p Apgar* IJpH ( ) u t c o m e

2B 8 N A l)icd

I

2A

2A

I

2B 5 NA Died

2A

2A

2BC 8 NA Died

2B

2A

2A

2A 9 7.32 Normal

2A

2A 5 7.30 Died

2A

3

2AC 9 NA Died

1

2A

2A

3

2A 8 7.33 Normal

2A

2A

2A 9 7.22 Tetraplegia

2A

2A

3

2A 6 NA Tetraplegia

2A

2A

2A 7 7.40 Normal

2A

2A

2A 10 7.32 Died

2A

duration of the flash was 1.7 msec, the peak energy per flash was

155 cd (mean energy during flash period: 8.5 cd). The normal back-

ground illumination of 200 lux was reduced to 20 lux by covering the

incubator with a blue cloth.

The EEG was inspected on the oscilloscope; at the beginning of an

interburst interval, a flash stimulus was delivered. All VEP recordings

were performed with the infant's eyes closed. In each infant, 1 VEP

recording consisted of 3 flashes delivered at about 30 sec intervals. The

152 PEDIATRIC N E U R O L O G Y Vol. 6 No. 3

T a b l e 1. ( C o n t i n u e d )

P t B i r t h

N o . G A W e i g h t C B F P a o 2 P a c o 2

11 - - 14.3 10.8 4.4

12 31 1,735 6.0 15.0 2.7

- 12.9 10.2 4.4

13 32 2,000 9.1 8.2 4.2

- - 6.5 12.9 2.3

14 30 1,295 7.5 9.5 4.3

- 8.1 8.6 5.5

- - 13.1 12.8 4.8

15 3 0 1 , 5 6 5 5 . 4 1 4 . 6 2 . 6

- - 4.8 14.0 3.6

16 29 1,190 8.7 6.3 4.5

- - NA 2.4 9.2

17 29 1,230 NA 10.0 3.7

- - NA 2.4 4.0

18 26 585 6.5 9.1 1.9

- - 8 . 4 5 .1 2.7

19 27 690 14.5 4.3 4.4

- - 1 1 . 4 1 2 . 5 2.5

20 32 1,420 15.4 5.3 6.2

21 30 1,060 NA 6.8 2.0

22 27 975 NA 17.1 1.7

23 32 1,485 NA 13.0 1.6

24 25 1,065 7.2 21.8 2.0

25 26 820 NA 2.2 6.2

- - NA 8.4 5.7

26 28 1,580 NA 1.8 8.0

27 26 895 NA 1.7 5.4

28 26 821) NA 7.6 4.4

29 28 1,160 NA 8.1 5.2

30 30 1,080 NA 9.0 6.1

31 27 800 NA 10.2 5.3

32 27 680 NA 9.9 5.0

* Score at 5 min. ** Abolished VEE

Abbreviations: Amp = Amplitude (laY) BW = Birth weight

CBF = Cerebral blood flow (ml/100 grn/min) GA = Gestational age Lat = Latency (msec)

V E P V E P

M A B P L a t A m p G r o u p

34 270 70 2A

35 280 22 2A

49 295 40 2A

39 310 26 2A

42 330 20 2A

31 270 75 2A

32 275 75 2A

42 265 36 2A

43 250 75 2A

46 270 50 2A

27 310 50 2A

41 ** ** 1

23 295 156 2B

32 325 56 1

14 275 80 2ABC

10 275 80 2AB

15 360 22 2B

25 280 170 C

22 276 75 2B

32 273 95 2C

29 285 112 2C

32 245 32 2C

42 310 65 2AC

32 ** ** 1

35 290 125 3

49 ** ** 1

31 320 100 1

33 ** ** 3

37 ** ** 3

40 ** ** 3

39 270 175 3

37 280 40 3

MABP = Mean arterial blood pressure (mm Hg) NA = Not available UpH = Umbilical cord pH VEP = Visual evoked potential

A p g a r * U p H O u t c o m e

8 7.36 Normal

8 7.29 Normal

7 NA Normal

9 7.30 Normal

NA NA Died

9 7.33 Diplegia

9 NA Died

7 NA Hemiplegia

7 NA Died

7 7.28 Normal

8 7.33 Died

10 NA Normal

7 7.34 Normal

3 NA Died

10 7.33 Normal

9 7.36 Died

4 NA Died

5 7.28 Diplegia

9 7.36 Tetraplegia

9 NA Hemiplegia

9 7.36 Died

amplitude and latency of the first negative peak N1 were measured and the mean calculated for the VEPs in order to reduce the slight varia-

bility. During rapid 02 transitions, however, single-flash VEPs were recorded every 30 sec throughout the episode. While the infants were

tested in the incubator, care was taken to keep the core temperature at normal levels 36.5-37.5°C.

Most VEP recordings were performed longitudinally, beginning shortly after birth and continuing for about 12 hours because this

Pryds and Greisen: Visual Evoked Potentials 153

SD-score

2-

O,

-2-

-4,

-B

• •

! .

.i m

m

! . I

1 2A 2B 2C 3

GROUP

2-

SD-score o~

-2-

I I I

• ; o

• o o

• i

-4 t 2A 2B 2C 3

GROUP

I I

B

Figure 1. (A,B) VEP latency (upper) and amplitude (lower) in 32 preterm infants. The infants were grouped as follows: Group 1: hypoxia, Group 2A: low CBF, Group 2B: hypotension, Group 2C: hypocapnia, and Group 3: brain lesions. The data are presented as S.D. score from the predicted values (see text). • denotes extinction of the VEP.

period is the most critical (Table 1; groups 1,2). A series of VEPs was obtained at 15 min intervals and also when sudden deterioration occurred; therefore, serial VEPs were obtained to allow each infant to serve as his or her own control. All investigations were observat- ional in nature and performed without interfering with patient care procedures.

The effect of sedation on VEPs was studied in 5 infants. VEPs were recorded before and serially after the administration of sedatives for intubation. Intravenous diazepam (0.5-1.0 mg/kg) in combination with phenobarbital (15 mg/kg) attenuated the VEP amplitude significantly to a mean value of 31%, whereas the latency was unaffected. The VEP amplitude, however, recovered completely within the following 30 min implying that the VEP changes presented below are not confounded by drug effects.

CBF was determined by the intravenous 133Xe clearance technique, validated in preterm infants with respiratory distress [7]. In short, 0.5- 1.0 mCi/kg 133Xe was injected into a peripheral vein and the clearance

was recorded by scintillators placed over 1 frontoparietal region and the thorax. CBF infinity was calculated from the time when the activity in the tung had decreased to 15% of the peak activity using the Obrist 2-compartment analysis modified to adjust for increased recirculation of the tracer. CBF represents the weighted mean o f gray and white matter flow [8]. Because the head of the neonate is small and the scintillation geometry allows counting from a volume of 100-200 ml, CBF is believed to represent global CBF and is presented as mt/100 gm/min.

The oxygen delivery (OD) to the brain was calculated as follows: OD = (0.227 x Pao2 + 21.0 x Sao2 × Hb)/1000 × CBF (ml/t00 gm/min).

Ultrasonographic examination of the brain was conducted regularly (6 MHz, Briiel and Kjaer); hemorrhages were graded according to the method described by Papile et al. [9]. PVL was defined as periven- tricular echodensities evolving into cystic lesions.

The surviving infants were examined regularly for neurologic hand- icap (1-3 years).

154 PEDIATRIC NEUROLOGY Vol. 6 No. 3

Statistics. The hypothesis to be tested was as follows: Does a mark- edly reduced cerebral oxygen supply impair cerebral function and is it reflected by delayed VEP latency and attenuated VEP amplitude or ex-

tinction of VEPs? When studied longitudinally, the infant served as his or her own con-

trol; comparison of the VEP parameters was performed by use of ANOVA. The statistical program, SPSS (Chicago, IL), was used and the significance level was set at 0.05.

The VEP data adjusted for gestational age were also compared with the normal values [7] and are presented as S.D. scores: (observed -

expected )/S Dexpected. Our study received approval from the Ethics Committee of greater

Copenhagen and parental consent was obtained for each infant.

Results

Well-defined VEPs were obtained for all infants from the beginning of the investigation. VEPs consisted of an initial negative peak (N 1), a positive deflection, and a long negative peak.

VEP Amplitude and Latency During Hypoxia. Seven infants suffered from acute hypoxia due to apnea, pneumo- thorax, or persistent fetal circulation. The hypoxic episode was brief in 6 patients, lasting 2-10 min. Minimum values of Pao2 ranged between 1.7-2.9 kPa (Table 1; group 1). The VEP amplitude decreased and the latency increased rapidly and consistently in all patients immediately after the onset of severe hypoxia. Extinction occurred in 3 with Pao2 lower than 2.5 kPa (Figs 1,2). After Pao2 was nor- malized, VEPs recovered immediately in all but 2 patients. One infant had a recovery period of 3 hours, whereas the last infant died due to persistent hypoxia.

Patient 1 experienced a second episode of hypoxia 5 hours after the first; in this case extinction of VEPs occurred suddenly at Pao2 4.6 kPa (Paco2 2.3, MABP 42 mm Hg). Despite increasing values of Pao2 and accept- able levels of PaCO2 and MABP, VEPs did not return for 5 hours.

VEP Amplitude and Latency During Potentially Is- chemic' Conditions. In 18 infants, CBF values below the average of 10 ml/100 gm/min for mechanically ventilated neonates were measured shortly after birth (mean age: 6 hrs; range: 3-12 hrs). Serial CBF investigations, con- firming the low CBF level, were performed in 16 infants within a few hours (Table 1; group 2A). CBF above 10 ml/100 gm/min was also recorded earlier or later in 5 of these infants. The arterial oxygen tension was above 5.0 kPa during all measurements.

Despite low cerebral perfusion, VEP configuration, latency, and amplitude were normal except in 3 infants in whom the latency was delayed (p < 0.05; Fig 1).

The oxygen delivery to the brain averaged 1.80 ml/100 gm/min (range: 1.02-3.64 ml/100 gm/min). After adjusting for gestational age, the VEP latency and amplitude had no systematic relation to OD (Fig 3). Notably, not even the lowest OD was associated with VEP attenuation.

MABP decreased to low levels in 6 infants (range: 10- 23 mm Hg) without VEP attenuation. In 1 patient, CBF was low (Table 1: group 2B; Fig 1). Moreover, the VEP amplitude and latency remained stable compared to re-

Tc02 PA02 KPA

3.5 3.5

2,8

2.2

1,9

~ 1,0

1.8

"~ ~ 3,1

5.5

9.q

FLASH -50 ~IV ~ 100 MSEC

Figure 2. VEP during isolated hypoxia in Patient 26. VEPs are recorded at about 30 sec intervals. Calibrated transcutaneous 02 (To02) is presented.

cordings at higher MABPs before the episode and after treatment (mean MABP: 32 mm Hg; p = 0.37 for both amplitude and latency). Delayed VEP latency and low amplitude, however, were observed in another infant with an MABP of 15 mm Hg during an episode of low Pao2 (4.3 kPa). VEP parameters normalized in relation to the increase in Pao2.

Six infants were inadvertently hyperventilated to Paco2 between 1.6 to 2.0 kPa shortly after the initiation of me- chanical ventilation. In 3 of these infants (Patients 6,18, 24), CBF was low (Table 1; group 2C). All infants had normal VEPs (Fig 1), without any change after having increased the Paco2 tension to an average of 2.8 kPa within about 30 min (p = 0.54 and 0.83 for amplitude and latency, respectively).

VEP Amplitude and Latency in In/ants with lntra/peri- ventricular Hemorrhage. In 10 infants, VEPs were inves- tigated within a few hours after the development of severe intraventricular hemorrhage (IVH) and/or PVL and regularly thereafter (Table 1; group 3). Three infants had grade 3 IVH and 4 had grade 4 IVH with parenchymal extension around the body or the posterior horn of the

Pryds and Greisen: Visual Evoked Potentials 155

SD-score

-2-

-4-

° . .

I I I I

-6 0 1 2 3 4

Oxygen Delivery (ml/lO0 gin/rain)

4 -

SD-score

-2-

I I t I

. °

-4 0 1 2 3 4

Oxygen Delivery (ml/lO0 grn/min)

Figure 3. (A/B) VEP latency (upper) and amplitude (lower) versus oxygen delivery to the brain in 18 preterm infants investigated 1-3 times. The data are presented as S.D. score from the predicted values (see text).

lateral ventricle. Two other infants without IVH had in- creased echodensities evolving into large cysts near the body of the lateral ventricle, whereas the last infant was born with multiple subcorticaI cysts involving the occipital lobes•

In 2 infants with grade 3 IVH and 2 with grade 4 IVH, the VEP trace was abnormal with the absence of N1; however, this abnormality disappeared within a few days (Fig 4). No response could be evoked in the infant with multiple subcortical cysts. The remaining infants had nor- mal VEP parameters and configuration throughout the period (Fig 1).

VEP Amplitude and Latency Versus Outcome. Fourteen infants died in the neonatal period; 7 survived but de- veloped cerebral palsy (3 tetraplegia, 2 diptegia, and 2 hemiplegia). The remaining 11 infants appeared todevelop normally without neurologic sequelae. In general, all groups had a poor outcome which was especially pro- nounced in infants with hypoxia (group l), hypotension (group 2B), or severe ultrasonographic brain lesions (group 3). Table 1 summarizes the patient findings. Abnor- mal VEP recordings were obtained during hypoxia and transiently after the development of detectable brain le- sions; with the exception of these conditions, VEPs were

156 PEDIATRIC NEUROLOGY Vol. 6 No. 3

,• -50 uV j__

FLASH 100 MSEC

Figure 4. VEP obtained the day before (3 upper traces), shortly after development of severe periventricular hemorrhage (3 middle traces), and 2 days later (3 lower traces). The 3 VEPs are recorded at 30 sec intervals.

of no help in distinguishing the outcomes of the infants. Two of 3 patients with delayed VEP latency and low CBF survived without apparent neurologic sequelae.

Discussion

Reduced cerebral oxygen delivery may occur during various conditions; therefore, a decrease in the CBF (be- cause of vasoconstriction or a lowering of the perfusion pressure) or a decrease of the arterial blood oxygen content (due to anemia or hypoxia) both reduce the oxygen de- livery. In the normal brain, however, counteracting mech- anisms with vasodilation and increased oxygen extraction may conserve some of the supply.

In our study, isolated hypoxia with arterial blood oxygen tensions below 3 kPa was associated with consistent VEP changes in terms of delayed latency and decreased am- plitude. Extinction of the VEPs indicating electrical failure occurred at Pao2 levels below 2.5 k P a - - a critical level that was previously demonstrated in VEP and EEG studies of preterm neonates [10,11]. The lower Pao2 level, at

which electrical failure occurred, was slightly different between our infants, probably due to differences in cere- bral oxygen requirement and cerebral oxygen delivery with inter-subject variations of total Hb and Hb F con- centration, blood pH (Bohr effect), and ability to raise CBF during hypoxia. When hypoxia was only transient, VEPs recovered immediately in all but 1 patient who had a recovery period of several hours.

Variations in neuronal vulnerability may be another ex- planation as recently suggested [12] and observed in 1 infant experiencing repeated hypoxic episodes. The under- lying mechanisms for such a phenomenon are unknown but may be explained by a progressive membrane injury or a progressive depletion of the energy pool. Alternative- ly, irreversible brain injury may have been induced after the first hypoxic episode, though the adaptive mechanisms appeared appropriate [ 13].

Normal VEPs were recorded during episodes of very low CBF, low MABP, or severe hypocapnia, suggesting that the neuronal function was supported sufficiently; therefore, we were unable to identify acute cerebral is- chemia in infants with Pao2 levels above 5 kPa, indicating sufficient oxygen delivery and extraction. Normal VEPs were recorded in infants with ODs as low as 1 ml/100 gm/min. Assuming an Hb of 10 mM in the neonate, a P50 (Po2 with 50% Hb saturation) of 2.8 kPa [ 14] and a venous saturation (Svo2) of 0.3, maintenance of OD 1 ml/100 gm/min during hypoxia of 2.8 kPa would require a com- pensatory increase of CBF to about 25 ml/100 gm/min. Because higher CBF values of 30-35 ml/100 gm/min have been recorded during substrate deficiency (hypoglycemia) in the preterm infant [15] and lower Svo2 may occur at maximal oxygen extraction [16], the critical OD may be well below 1 ml/100 gm/min; however, this value is de- rived from the CBF which is the mean brain flow implying that the flow and OD to the gray matter may have been higher and thereby correspondingly lower to the white matter. Accordingly, it is difficult to compare the present CBF values with those obtained in adult human and animal studies where the neuronal transmission fails at a cortical flow below 15-20 ml/100 gm/min corresponding to an OD of about 2.5 ml/100 gm/min [17,18]. There is, however, evidence suggesting that the preterm brain requires very low oxygen [19]. This finding reflects the immaturity of the nervous system in preterm infants who have few synaptic connections and thereby low neurologic function and metabolism.

Because of the extreme conditions and the fact that some infants developed cerebral palsy, ischemia may be pre- sumed to have been present during the measurements. If so, present monitoring techniques are insufficient for re- cording such episodes. With regard to VEPs, critical reduc- tion of CBF and OD could lead to grossly inhomogeneous metabolic alterations, "sparing" the visual pathways which may have better perfusion than the watershed area. Alter- natively, cerebral function may be supported sufficiently, implying an extremely low ischemic threshold in preterm

Pryds and Greisen: Visual Evoked Potentials 157

itffants. Evidence supporting this theory comes from the demonstration of a normal outcome despite very low CBF (5 ml/100 gm/min) [20], very low oxygen consumption of the preterm brain [19], normal cerebral CMRO2 during extreme hypocapnia [21,22], and preservation of the central evoked response at severe hypotension [23].

Special electrophysiologic problems concerning local- ization and mechanism of VEP origin have not been con- sidered [24]. In preterm infants, we assume that the N1 is of cortical origin, as found in newborn kittens [25 ], but we do not have evidence for that; however, the VEP abnor- malities which accompanied the cerebral lesions may sup- port the assumption. In some infants, recent and severe intra- and peri-ventricular hemorrhage resulted in abnor- mal VEPs with absence of NI that only persisted for a few days. Because the lesions had no apparent relation to the visual tracts, other unknown factors may have caused the abnormality. Focal PVL did not affect VEPs, unless the lesion involved the visual tracts in the occipital re- gion [26].

We conclude that VEPs in preterm newborn infants is preserved during episodes of low CBF, hypocapnia, and hypotension provided that the arterial oxygen tension is greater than 5 kPa. During severe hypoxia, however, VEP attenuates when Pao2 values fall below 3 kPa. The re- covery time may be proportional to the cerebral insult.

The Dagmar Marshall and Gerda and Aage Haensch foundations pro- vided financial support.

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