close

Вход

Забыли?

вход по аккаунту

?

Cerebral metabolic effects of neonatal seizures measured with in vivo 31P NMR spectroscopy.

код для вставкиСкачать
Cerebral Metabolic Effects of
Neonatal Seizures Measured with In Vivo
'P NMR Spectroscopy
Donald P. Younkin, MD,*§ Maria Delivoria-Papadopoulos, MD,? John Maris, BS,$ Eileen Donlon, BS,4
Robert Clancy, MD," and Britton Chance, PhD4
In vivo phosphorus 31 nuclear magnetic resonance (31PNMR) spectroscopy was used to evaluate changes in cerebral
high-energy phosphate compounds in 8 infants with seizures. During the study 4 babies had seizures that caused a 50%
decrease in the phosphocreatine to inorganic phosphate (PCr/Pi)ratio. Focal seizures caused lateralized decreases in the
PCr/Pi ratio; generalized seizures caused bilateral decreases. Postictal spectra had increased PCr/Pi ratios, presumably
due to postictal inhibition. Interictal 31PNMR spectra were normal. One patient's seizures were successfully treated
with intravenously administered phenobarbital during NMR data acquisition, causing an immediate increase in the
PCr/Pi ratio from 0.7 to 1.2. These studies indicate that cerebral PCr concentration decreases by approximately 33%
and that oxidative metabolism increases by approximately 45% during neonatal seizures. Five babies had PCr/Pi ratios
of less than 0.8 during seizures and subsequently developed long-term neurological sequelae, which suggests that
neonatal seizures may cause or exacerbate cerebral injury by increasing cerebral metabolic demands above energy
supply.
Younkin DP, Delivoria-PapadopoulosM, Maris J, Donlon E, Clancy R, Chance B: Cerebral metabolic
effects of neonatal seizures measured with in vivo 31PNMR spectroscopy. Ann Neurol 20:513-519, 1986
Cerebral metabolic events during seizures and status
epilepticus have been investigated extensively in laboratory animals [27]. Cerebral blood flow (CBF), cerebral metabolic rates for oxygen (CMRo2) and glucose
(CMRGlc), and cerebral energy use increase several
times. Associated with these changes are decreased
phosphocreatine (PCr) levels and intracellular p H (pHJ.
Relatively few studies have examined the metabolic
effects of seizures in humans. CBF and C M R O ~increase during electroconvulsive seizures 131; regional
CMRGlc increases in seizure foci during the ictus and
decreases between seizures [18, 291; and CBF increases during neonatal seizures 1221. These studies
are important, but do not answer the fundamental
question of whether energy utilization exceeds energy
production in the human brain during seizures, a question that remains controversial in animal models of
seizures. This study examined this question by measuring changes in high-energy phosphate compounds
with phosphorus 31 nuclear magnetic resonance (31P
NMR) spectroscopy in infants with seizures:
Patients and Methods
Patient Population
From the Departments of *Neurology, tpediatrics, $Biochemistry,
and Biophysics, University of Pennsylvania School of Medicine, and
the $Division of Neurology, Children's Hospital of Philadelphia,
Philadelphia, PA 19104.
Received Oct 30, 1985, and in revised form Jan 14, 1986. Accepted
for publication Feb 19, 1986.
The study group consisted of 8 infants with seizures. Five
had had seizures after perinatal asphyxia (Table 1). The remaining 3 had had seizures starting in early infancy secondary to an inborn error of ammonia metabolism (1) or unknown cause (2) (Table 2). Despite seizure activity, the
babies were medically stable, did not require assisted ventilation or supplemental oxygen, and did not have indwelling
arterial catheters. Arterial blood gas values, serum glucose
and electrolyte levels, and other physiological parameters
were not measured during 31P NMR. No family refused
consent. The study was approved by the University of Pennsylvania Committee on Studies Involving Human Beings.
Electroencephalography(EEG)was performed in the standard manner using the international 10-20 system, modified
for neonates [ 2 8 ] . Since EEG wires interfere with the "P
NMR signal, EEG recording and "P NMR spectroscopy
were not performed simultaneously. Babies with seizures
during spectroscopy (Patients 2, 3 , 4 , 6 ;Table 3) had an EEG
within a few hours of the 31P NMR; babies with seizures
prior to the 31PNMR (Patients 1, 5 , 7, 8; Table 4 ) had an
EEG within 2 days of the 31PNMR.
D~ younkin, ~ i ~of ~i ~ i ~ ~
Address reprint requests
Children's Hospital of Philadelphia, 34th St and Civic Center Blvd,
Philadelphia, PA 19104.
513
~
~
Table I. Clinical Features of Patients with Seizures at Birth
Patient
No.
Intrauterine Data
Apgar Scores
Birth
Weight (gm)
Gestational
Age (wk)
1 min
5 rnin
10 min
1
Persistent decelerations; thick
meconium in
amniotic fluid
3,280
40
3
7
. ..
2
Moderate to severe variable
decelerations
4,200
40
1
6
. ..
3
Decreased fetal
movement; severe variable
decelerations
Preeclampsia;
late decelerations
3,130
40
2
6
,,
Maternal fever;
severe variable
decelerations
2,360
4
5
2,100
31
36
2
1
5
3
.
5
5
Resuscitation in
Delivery Room
Onset of
Seizures
Seizure Type
Outcome
Thick meconium below
vocal cords;
intubated
and manually
ventilated
Nuchal cord;
meconium
below vocal
cords; intubated and
manually
ventilated
Intubated and
manually
ventilated
30 min
Generalized
clonic; left
focal
clonic
1 year: normal
12 hr
Subtle
1 year: seizures,
spasticity, developmental delay
Generalized
clonic
9 months: develop-
Intubated,
manually
ventilated,
given medications
Nuchal cord;
intubated,
manually
ventilated,
given medications
12 hr
Subtle; multifocal
clonic
3 months: spastic
Subtle; tonic
extensions
6 months: developmental delay,
truncal spasticity
8 hr
16 hr
mental delay
quadriparesis
Table 2. Clinical Features of Patients with Seizures Starting after the Neonatal Period
Patient
No.
Diagnosis
Seizure Onset
Seizure Type
Seizure Frequency”
Outcome
6
Hyperammonemia,
hypoglycorrhachia
1 mo
Multifocal clonic
Daily
7b
Unknown cause
1 mo
Multifocal clonic
Flurry every 2 to 3
days
8b
Unknown cause
1 mo
Multifocal clonic
Flurry every 2 to 3
days
Moderate developmental
delay; nonfocal
neurological exam
Severe developmental
delay; nonfocal
neurological exam
Severe developmental
delay; nonfocal
neurological exam
“Seizure frequency when first studied.
’Twins.
3 1 P N M R Spectroscopy
Details of the in vivo 31PNMR spectroscopy technique in
neonates were reported previously E32). The babies were
transported to the NMR spectroscopy suite in a standard
manner, then stabilized in an infant spectroscopy isolette
(Phospho Energetics) with the temporoparietal region under
a 4-cm radiofrequency surface coil. NMR measurements in
newborn babies were made in a Phospho Energetics spectrometer, located in the intensive care nursery, with a clear
bore of 17.5 cm (‘H NMR frequency, 60.1 MHz; 31PNMR
frequency, 24.3 MHz); older children were studied in an
Oxford Research Systems TMR 32-200 spectrometer with a
clear bore of 29.6 cm (’H NMR frequency, 80.3 MHz; 31P
NMR frequency, 32.5 MHz). After placing the baby in the
magnet, the magnetic field was shimmed for a maximal proton spectral resolution of approximately 0.4 ppm. 31PNMR
514
Annals of Neurology
Vol 20 N o 4
October 1986
data were collected from each hemisphere for 10 to 16 minutes, using the following parameters: pulse delay, 4 seconds;
pulse width, 50 psec; sweep width, 3,000 Hz; and number of
data points, 1,024-in the Phospho Energetics spectrometer;
and pulse delay, 3 seconds; pulse width, 40 psec; sweep
width, 3,000 Hz; and number of data points, 2,048-in the
Oxford Research Systems specrrometer.
The surface coil samples from a roughly hemispherical
volume with a 2-cm radius El}. The neonatal scalp and skull
are thin and do not contain NMR “visible” phosphorus compounds, but part of the 31PNMR signal may be derived from
scalp muscles. In neonates these muscles are very thin, and in
vivo 31P NMR spectra obtained from a baby with a large
porencephalic cyst did not contain phosphorus signals; therefore, most of the 31PNMR spectrum comes from the brain,
primarily the cortex.
Table 3. Data on Babies with Seizures During 31P NMR
Patient
No.
2b
Age at
NMR
(days)
Right
Left Right EEG"
...
0.3
1.1
0.9
0.8
1.1
...
1.6
1.3
1.3
1.0
1.2
...
...
7.1
6.7
7.4
7.1
6.6
7.2
7.2
7.1
7.1
6.8
0.7
1.2
1.4
1.4
...
...
1.1
1.1
7.5
7.4
7.2
7.2
. ..
. ..
7.4
7.0
2'
2.5
3
4
5
0.5
1.4
1.3
0.9
0.9
0.7
...
0.5
0.8
0.6
7.2
6.9
7.1
7.0
7.0
7.1
...
7.0
7.2
7.2
9'
1.0
1.3
1.2
1.2
0.7
1.4
1.1
1.3
7.3
7.1
7.1
7.4
7.2
7.2
7.2
7.4
1
2'
14
60
1'
1
2
6
4d
bb
PHi
Left
6
9
3d
Pcr/P;
10
11
24
CT
Comments
Day 1: bilateral, multifocal seizures
Day 2: abundant left
seizures
Day 5: slow, abundant
sharp waves on left,
no seizures
Day 17: mild abnormal
due to left temporal
attenuation
Day 1: left occipital seizure with spread to
left rolandic area; left
centrotemporal slowing
Day 6: large hypodense
area with contrast enhancement of left
parietal area
Day 14: large left MCA
infarct; decrease in
density in right temporoparietal area
..
Day 3: possible S A H
Day 2: left temporal
seizures, right temporal attenuation, sharp
waves
Day 3: bilateral sharp
waves, no seizures,
right attenuation
Week 9: normal waking
record
Week 10: slight left
posterior slowing, bilateral, multifocal
sharp-slow waves
Week 24: mild, bioccipital slowing
Day 3: extensive
hemorrhage: IVH,
parenchymal, SAH;
edema, mass effect
on right
Day 1: before phenobarbital bolus
Day 1: immediately after IV bolus of
phenobarbital (10 mg/
kg)
Day 2: poorly controlled seizures
Day 2%: seizures controlled with more aggressive anticonvulsant therapy
Week 9: slight ventricular enlargement,
prominent frontal
white matter
Week 24: progressive
cortical atrophy
Week 9: multifocal seizures, left side more
than right during
NMR
Week 10: seizures controlled with anticonvulsants
Week 11: low protein
diet started
"EEG and NMR not done simultaneously.
bl.9-Tesla spectrometer with peak heights.
'Clinical seizure activity during NMR.
dl.5-Tesla spectrometer with curve fitting.
"P NMR = phosphorus 3 1 nuclear magnetic resonance;PCrlP, = phosphocreatineto inorganic phosphorus ratio; pH, = intracellular pH; EEG
= electroencephalogram;CT = computed tomography; MCA = middle cerebral artery; IVH = intraventricular hemorrhage; SAH =
subarachnoid hemorrhage.
Spectra were analyzed for the ratio of peak integrals
derived from a computer "curve fitting" program (Phospho
Energetics spectrometer) or for the ratio of peak heights
(Oxford Research Systems spectrometer) 1141. The pH; was
calculated from the chemical shift of Pi relative to PCr [24}.
The PCrlP, ratio was used in the analysis because it is related
to the phosphate potential and thus is a measure of
bioenergetic reserve 141.
Results
Figure 1 shows a normal 31PNMR spectrum from a
full-term infant. The PCr/Pi ratio is 0.9 and pHi is 7.2.
The normal PCr/Pi ratio for full-term infants in our
laboratory is 1.0 & 0.2 (mean & 1 SD) by curve fitting
in the 1.5-Tesla spectrometer, and 1.3 ? 0.2 by peak
heights in the 1.9-Tesla spectrometer; pH, is 7.2 ? 0.2
in both systems [19}.
Tables 3 and 4 list the NMR results obtained on the
children in this study. The PCr/Pi ratio was decreased
during seizures (initial study in Patients 2 , 3, 4, and 6)
and increased postictally (Patient 3-studies on days 1,
2, and 6; Patient 4-studies on days 2 % and 3). The
PCr/Pi ratio was normal interictally (Patient 6-studies
on week 10, 11, and 24; Patients 7 and 8-all studies).
Intracellular acidosis did not develop during neonatal
seizures (see Table 3).
Figure 2 shows the first 31PNMR spectra and EEG
from Patient 2. During spectral acquisition, a subtle
clinical seizure composed of slight lip smacking and
chewing movements was noted. The EEG taken
shortly after NMR spectroscopy showed abundant repetitive focal seizures in the left temporal region.
There are major interhemispheric differences. The
Younkin et al: 31P N M R in Neonatal Seizures
515
Table 4. Data on Babies with Seizures Prior t o 31PN M R
Patient
No.
lb
5'
7b
8b
Age at
MNR
3 da
4 da
7 da
3 da
4 da
6 da
10 da
12 da
18 da
24 da
8 wk
8Y2wk
16 wk
8 wk
8% wk
16 wk
Time between
Most Recent
Seizures and
NMRida)
2
3
6
2
3
5
9
11
17
23
1
1
1
1
1
1
PCrlPi
PHi
Left
Right
Left
Right
EEG"
CT
1.6
1.7
1.7
1.0
1.1
.. .
7.1
7.2
7.1
6.8
7.1
...
Day 1: right focal
seizures
Day 8: normal
0.5
0.5
...
0.6
0.5
0.5
0.5
...
0.5
0.4
0.7
0.5
0.9
0.8
7.1
7.3
.. .
7.2
7.2
7.4
7.3
...
7.1
7.1
7.2
7.4
7.2
7.4
1.7
1.9
1.7
1.8
1.4
1.6
1.3
...
7.1
7.0
7.0
.. .
1.6
1.6
1.7
7.1
7.1
7.1
7.2
...
7.1
Day 1: discontinuous,
no seizures
Day 4: discontinuous,
excess bilateral sharp
waves
Day 24: borderline abnormal with excess
frontal sharp waves
Week 8: seizures with
vertex origin and secondary generalization
Week 8: normal
Day 7: large hypodense
area with contrast
enhancement in right
posterior parietooccipital region
Day 14: diffuse hypodensity in white
matter
...
Normal
Normal
7.2
7.1
"EEG and NMR not simultaneous.
bl.9-Tesla spectrometer with peak heights.
'1.5-Tesla spectrometer with curve fitting.
3'P NMR = phosphorus 3 1 nuclear magnetic resonance; PCrlP,
= electroencephalogram; CT = computed tomography.
=
phosphocreatine to inorganic phosphate ratio; pH, = intracellular pH; EEG
PME
,
l
_____ Normal Hemisphere
ppm
~
.
-
.
&
A
~
~
f
l
k
~
-
~
-
~..%M+"M~\~"+w-Aww-~- L * v \ h v w w * ; -
"
w
+
+
.
-
PPm
F i g 1 . Characteristicphosphorus 31 nuclear magnetic resonance
(3'P NMRi spectrum from a full-term neonate, using the 1.5Tesla Phospho Energetics spectrometer. Spectral data were collected for 16 minutes using a 4-second pulse delay which causes
partial saturation of the phosphovylated monoester (PME) peak.
Individual peaks are PME; inorganicphosphate (Pi); phosphorylated diesten (PDE); phosphacreatine (PCr); and abha, beta,
and gamma adenosine triphosphate (ATP).
516 Annals of Neurology Vol 2 0 No 4
October 1986
dwM*+-
Fig 2. Initial spectra and electroencephalogram (EEG) of Patient
2. During the study he had subtle seizure activity. The spectrum
from the nonictal hemisphere (dotted line) is normal. The ictal
hemisphere (solid line) has major changes in PCr, P,, and P M E
levels. A T P concentration in the ictal hemisphere is approximately 40% of that of the nonictal hemisphere. IntracellularpH
is not significantly different between hemispheres 17.1 ictal; 7.2
nonictal). (Sameabbreviations as in Figure 1.)
-
~
*
f
30
20
10
-10
0
-20
-30
30
20
10
PQm
0
ppm
-10
-20
-30
24 weeks
9 weeks
Fig 3. Spectra from Patient 6 who had bilateral multifocalseizures. During the first study she had mild multifocal clonic activity (left more than right), causing bilateral decreases in the
phosphorreatinelinorganicphosphate (PCrIPJ ratio (lt$t, 1.O;
right, 0.7). lnterictal spectra obtained at 24 wee& were normal
(left, PCrIPi 1.2; right, 1.3).
1::
1
t
.Left Hemisphere
---a
Right Hemisphere
phenoborbttol
bolus
1
2
3
4
Age( Days)
5
6
Fig 4 . Changes in the phosphocreatine to inorganic phosphate
(PCrIP,) ratio in Patient 3. After the first spectrum, a bolus of
phenobarbital was given intravenously and the nuclear magnetic
resonance spectroscopy waJ repeated immediately.Postictal increases in the PCrIP, ratio are present i n the ldt hemisphere on
days 2 and 6 . The PCrIP, ratio in the right hemisphere was
normal.
nonictal hemisphere has a well-defined PCr peak, very
little Pi, a PCr/Pi ratio of 1.6, pH, of 7.2, and normal
concentrations of phosphorylated monoesters (PME),
phosphorylated diesters (PDE), and adenosine triphosphate (ATP). The ictal hemisphere has very little PCr
(just a shoulder on the PDE peak), a large Pi peak, a
PCr/Pi ratio of 0.3, a pHi of 7.1, only about 40% of the
nonictal hemisphere's ATP concentration, and an undetectable PME level.
Spectra from Patient 6 who had bilateral multifocal
seizures are illustrated in Figure 3. The baby had mild
left-sided clonic activity during the initial NMR. Multifocal clonic activity (left more than right) and unresponsive staring continued after the NMR. The spectra
demonstrate bilateral abnormalities, with a PCr/Pi ratio
in the right temporoparietal region of 0.7 and a left
PCr/Pi ratio of 1.0. Interictal spectra on this patient at
10, 11, and 24 weeks were normal.
Figure 4 illustrates the acute effects of phenobarbital
on the cerebral PCr/Pi ratios of Patient 3. This child
had perinatal asphyxia and partial seizures arising from
foci in the left hemisphere. On day 1, NMR spectra
were obtained only from the left hemisphere. The first
study revealed a PCr/Pi ratio of 0.7. With the baby still
in the magnet, a bolus of phenobarbital (10 mg/kg) was
given intravenously and the spectra repeated immediately. The PCr/Pi ratio improved to 1.2. Subsequent spectra on days 2 and 4 had persistently higher
PCr/Pi ratios in the left hemisphere.
Discussion
Infants with neonatal seizures often have a poor
neurological prognosis 12, IS}. However, the clinical
manifestations of neonatal seizures are usually mild
[30}, and it is not known whether seizures per se contribute to neuronal injury or are simply an innocent
clinical manifestation of severe cerebral injury.
Our results clearly demonstrate decreases in cerebral high-energy phosphate compounds during seizures in children. Focal seizures caused lateralized decreases in the PCr/Pi ratio, and generalized seizures
caused bilateral decreases. These changes in PCr concentration were probably caused by significant increases in cerebral energy utilization that tax energy
production during neonatal seizures. Decreases in
brain glucose concentration, despite normoglycemia
and uncoupling of CBF and metabolism, have been
reported during experimental neonatal seizures and
may contribute to the decrease in PCr concentration
during human neonatal seizures [9, 111. If seizures
continue, ATP concentration may decrease, with a
consequent loss of adenine nucleotides and decreased
possibility for recovery (Patient 2).
The PCr/Pi ratio decreased approximately 50% during seizures. Since every decrease in PCr concentration causes a nearly identical increase in the Pi level,
this represents an approximately 33% decrease in PCr
concentration during neonatal seizures. Despite the
obvious differences between spontaneously breathing
neonates and paralyzed, mechanically ventilated animals, the change in PCr concentration during human
neonatal seizures is comparable to that reported during
bicuculline- or pentylenetetrazole-induced seizures in
animals-PCr is approximately 33% less than in control animals {S, 10, 17, 311.
Younkin et al: '*P N M R in Neonatal Seizures
517
Changes in PCr/P, ratios can also be used to estimate
changes in the rate of oxidative metabolism (V). In
exercising muscle [ 5 ] , the PCr/P, ratio can be used to
estimate the ratio between V and the maximum rate
of oxidative metabolism (Vmax) with the equation:
VlVmax = 1/(1 [K,/(PJPCr)}). Although this formula is derived from muscle and may underestimate
actual cerebral changes, applying it to ictal and interictal spectral data (see Table 3 ) yields an approximately
45% increase in the cerebral V during neonatal seizures. This figure is in close agreement with animal
studies that report a 50 to 250% increase in C M R O ~
during status epilepticus [20, 23, 25, 31).
The effect of phenobarbital on the cerebral PCr/P,
ratio in Patient 3 demonstrates the effects of seizures
on the state and stability of oxidative metabolism. During seizures, his PCr/P, ratio of 0.7 was approximately
60% of Vmax, which placed him in an unstable region
of oxidative metabolism 121). After a bolus of
phenobarbital, the PCr/P, ratio increased to 1.2 (about
45% of Vmax) and he achieved a stable region of
cerebral oxidative metabolism. Despite seizure activity, this child‘s condition was very stable and he did not
require intubation, supplemental oxygen, or arterial
catheterization. Since we did not record physiological
parameters before and after phenobarbital administration, we cannot exclude the possibility that some of the
improvement was caused by increased blood pressure,
arterial oxygen content, or cerebral blood flow. However, we attribute the cerebral metabolic improvement
to decreased seizure activity and decreased metabolic
demand. This illustrates the dramatic effect of seizures
on cerebral oxidative metabolism.
Despite measuring major changes in the P W P ,
ratio, we were unable to demonstrate intracellular
acidosis during neonatal seizures. In hypoxic laboratory animals, lactate production increases and pH, decreases when the PCr/P, ratio drops below 1.0 { 1 4 ,
261. Therefore, we expect that local cerebral lactate
production is increased during seizures. Several factors
may explain the apparent paradox of increased lactate
production without intracellular acidosis: (1) increased
CBF during neonatal seizures may provide sufficient
oxygen to permit oxidation of lactate 1221; ( 2 ) the immature nervous system may have increased permeability to lactate, which combined with increased CBF prevents lactate accumulation 16, 7, 13); ( 3 ) lactate may
not be generated despite very low PCr/P, ratios; or ( 4 )
small changes in pH, may not be detected due to inadequate spectral resolution with current in vivo NMR
methods, relatively low magnetic field strength, and
short collection times. The introduction of in vivo hydrogen NMR spectroscopy that allows direct measurement of lactate levels may be very useful in answering
this paradox [21, 261.
Cerebral metabolite ratios improved interictally. In
-+
518
Annals of Neurology
Vol 20 No 4 October 1986
the postictal period, PCr/Pi ratios may be increased
due to increased perfusion and decreased CMR from
postictal inhibition.
In addition to changes in high-energy phosphate
compounds, Patient 2 had almost no PME in the ictal
hemisphere (see Fig 2). Alterations in the PME peak
were not seen in other babies with seizures, and the
peak returned in later spectra from this patient. The
PME peak, which usually dominates the newborn cerebral spectrum, is primarily phosphorylethanolamine
[12). Since this is a lipid precursor, we have hypothesized that it is present for later incorporation in
membrane phospholipids / 3 2 ) . Other compounds, like
the neurotransmitter phosphoinositol, may also contribute to the PME peak. In Patient 2, the complete
loss of this peak suggests that energy depletion from
seizure activity interrupted other important brain functions.
The rapid metabolic response to anticonvulsants in
Patients 3 , 4 , and 6 indicates that changes in cerebral
high-energy phosphate compounds were caused by
cortical seizure activity rather than structural damage.
Hope and colleagues 1161 have reported that PCr/Pi
ratios of less than 0.8 indicate a poor neurological
prognosis. Patients 2 , 3 , 4 , 5 , and 6 had at least one
measurement below this level; each patient has subsequently developed neurological sequelae, which supports the concept of a “critical” PCr/P, ratio. Patient 2
had an ictal PCr/Pi ratio of 0.3, and the ATP level in
the ictal hemisphere was only 40% of that in the nonictal hemisphere. Despite postictal improvement, he
developed a cerebral infarction, suggesting that seizures may actually contribute to neuronal injury by
increasing cerebral metabolic demands above energy
supply.
Supported by NIH-SBIR grant HDiHL 18540 and the Benjamin
Franklin Partnership Advanced Technology Center of Southeast
Pennsylvania. Dr Younkin is the recipient of Teacher-Investigator
Award NS 00774 from the National Institute of Neurological and
Communicative Disorders and Stroke.
Presented in part at the 95th Annual Meeting of the Society for
Pediatric Research, Washington, DC, May 1985, and at the 4th
Annual Meeting of the Society of Magnetic Resonance in Medicine,
London, August 1985.
We thank Drs Barry Lawson and Ronnie Guillet for medical assistance during NMR spectroscopy, and the nurses of the Hospital of
the University of Pennsylvania Intensive and Transitional Care
Nurseries for their support and assistance.
References
1. Ackermann JJH, Grove TH, Wong GG, et al: Mapping of
metabolites in whole animals by ”P NMR using surface coils.
Nature 283:167-170, 1980
2. Bergman I, Painter MJ, Hirsch RP, et al: Outcome in neonates
with convulsions treated in an intensive care unit. Ann Neurol
14:642-647, 1983
3. Brodersen P, Paulson OB, Bolwig TG, et al: Cerebral hyperemia in electrically induced epileptic seizures. Arch Neurol
28:334-338, 1973
4. Chance B: Applications of 31P NMR to clinical biochemistry.
Ann N Y Acad Sci 42:318-332, 1984
5. Chance B, Leigh JS, Hiller D , et al: 31P NMR quantitation of
muscle exercise performance (abstract). Med Sci Sports Exerc
17:257, 1985
6. Cremer JE, Braun LD, Olendorf WH: Changes during development in transport processes of the blood-brain barrier. Biochim
Biophys Acta 448:633-637, 1976
7. Cremer JE, Cunningham VJ, Partridge WM, et al: Kinetics of
blood-brain barrier transport of pyruvate, lactate and glucose in
suckling, weanling and adult rats. J Neurochem 33:439-445,
1979
8. Duffy TE, Howse DC,Plum F: Cerebral energy metabolism
during experimental status epilepticus. J Neurochem 24:925934, 1975
9. Dwyer BE, Wasterlain CG: Neonatal seizures in monkeys and
rabbits: brain glucose depletion in the face of normoglycemia,
prevention by glucose loads. Pediatr Res 19:992-995, 1985
10. Folbergrova J, Ingvar M, Siesjo BK: Metabolic changes in cerebral cortex, hippocampus and cerebellum during sustained
bicuculline-induced seizures. J Neurochem 37:1228-1238,
1981
11. Fugikawa DG, Dwyer BE, Wasterlain CG: Preferential blood
flow to brainstem during generalized seizures in newborn monkeys is not coupled to metabolic activation (abstract). Ann
Neurol 18:152, 1985
12. Gyulai L, Bolinger L, Leigh JS, et al: Phosphorylethanolaminethe major constituent of the phosphomonester peak observed
by "P NMR in developing dog brain. FEBS Lett 178:137-142,
1984
13. Hellman J, Vannucci RC, Nardis EE: Blood-brain barrier permeability to lactic acid in the newborn dog: lactate as a cerebral
metabolic fuel. Pediatr Res 16:40-44, 1982
14. Hilberman M, Subramanian VH, Haselgrove J, et al: In vivo
time-resolved brain phosphorus nuclear magnetic resonance. J
Cereb Blood Flow Metab 4:334-342, 1984
15. Holden KR, Mellits ED, Freeman JM: Neonatal seizures: I.
Correlation of prenatal and perinatal events with outcomes. Pediatrics 70: 165-176, 1982
16. Hope PL, Cady EB, Tofts PS, et al: Cerebral energy metabolism
studied with phosphorus NMR spectroscopy in normal and
birth-asphyxiated infants. Lancet 2:366-370, 1984
17. Howse DCN: Metabolic response to status epilepticus in the
rat, cat, and mouse. Can J Physiol Pharmacol57:205-212, 1979
18. Kuhl DE, Engel J Jr, Phelps ME, Selin C: Epileptic patterns of
local cerebral metabolism and perfusion in humans determined
by emission computed tomography of "FDG and I3NH3.Ann
Neurol8:348-360, 1980
19. Lawson B, Anday EK, Guillet R, et al: Effect of varying head
position on cerebral 31P nuclear magnetic resonance spectroscopy. Pediatr Res 19:350A, 1985
20. Meldrum BS, Nilsson B: Cerebral blood flow and metabolic
rate early and late in prolonged seizures induced in rats by
bicuculline. Brain 99:523-544, 1976
21. Nioka S, Chance B, Smith D, et al: Characteristics of energy
state, intracellular p H (pHJ, and lactic acidosis in steady state
hypoxia of animal model brain (abstract). Meeting of the Sociery
of Magnetic Resonance in Medicine, London, 1985
22. Perlman JM, Herscovitch P, Kreusser KL., et al: Positron emission tomography in the newborn: effect of seizure on regional
cerebral blood flow in an asphyxiated infant. Neurology
3 5:244-247, 1985
23. Petroff OAC, PrichardJW, Behar KL, et al: In vivo phosphorus
nuclear magnetic resonance spectroscopy in status epilepticus.
Ann Neurol 16:169-177, 1984
24. Petroff OAC, Prichard JW, Behar KL, et al: Cerebral intracellular p H by 31P nuclear magnetic resonance spectroscopy. Neurology 35:781-788, 1985
25. Plum F, Posner JB, Troy B: Cerebral metabolic and circulatory
responses to induced convulsions in animals. Arch Neurol
18:l-13, 1968
26. Schnall MD, Subramanian VH, Leigh JS, et al: A technique for
simultaneous 'H and 31P NMR at 2.2 Tesla in vivo. J Mag Res
Med 65:122-129, 1985
27. Siesjo BK: Brain Energy Metabolism. New York, Wiley, 1978,
pp 345-379
28. Tharp BR: Neonatal pediatric electroencephalography. In
Aminoff MJ (ed): Electrodiagnosis in Clinical Neurology. New
York, Churchill Livingstone, 1980, pp 67-117
29. Theodore WH, Brooks T, Margolin R, et al: Positron emission
tomography in generalized seizures. Neurology 35:684-690,
1985
30. Volpe J: Neonatal seizures. N Engl J Med 289:413-416, 1973
31. Wasterlain CG, Dwyer BE: Brain metabolism during prolonged
seizures in neonates. In Delgado-Escueta AV, Wasterlain CG,
Treiman DM, Porter RJ (eds): Status Epilepticus (Vol 34, Advances in Neurology). New York, Raven, 1983, pp 241-260
32. Younkin DP, Delivoria-Papadopoulos M, Leonard JC, et al:
Unique aspects of human newborn cerebral metabolism evaluated with phosphorus nuclear magnetic resonance spectroscopy.
Ann Neurol 16:581-586, 1984
Younkin et al: 31P NMR in Neonatal Seizures 519
Документ
Категория
Без категории
Просмотров
3
Размер файла
620 Кб
Теги
spectroscopy, effect, nmr, 31p, metabolico, seizure, measures, vivo, neonatal, cerebral
1/--страниц
Пожаловаться на содержимое документа