Prognostic Value of 1H-MRS in Neonatal
Encephalopathy
Luis Fernando Garcias da Silva, MD, PhD,* João Rubião Höefel Filho, MD†
Maurício Anés, BSc‡ and Magda Lahorgue Nunes, MD, PhD*
The aim of this study was to determine the prognostic
value of proton magnetic resonance spectroscopy in neonatal encephalopathy. Studies were carried out in 11
consecutive term newborns with encephalopathy probably caused by hypoxic-ischemic injury. The clinical evaluation included pregnancy data, labor conditions, encephalopathy grade, presence of seizures, and necessity of
antiepileptic drug therapy. Polygraphic recordings were
obtained in all cases. Interest areas evaluated by spectroscopy were the basal ganglia and thalami. Among the
cases, N-acetylaspartate/creatine, choline/creatine, and
lactate/creatine ratios were calculated and related to the
clinical variables, polygraphic recordings, and 6-month
neurodevelopmental outcome. Abnormal follow-up occurred in 5 of 11 patients (45.4%) and was clearly related
to an Apgar score <5 at 5 minutes (P ⴝ 0.003), encephalopathy grade (P ⴝ 0.02), early neonatal seizures (P ⴝ
0.02), and antiepileptic therapy (P ⴝ 0.01). No relationship was observed between spectroscopy results and
polygraphic recordings profile. The lowest mean N-acetylaspartate/creatine ratio was observed in four of five
patients with an adverse outcome and, although not
statistically significant, demonstrated a clear trend to
unfavorable follow-up (t test ⴝ 0.06). The choline/creatine
ratios could not be related to follow-up in our sample.
The most consistently observed abnormality on the spectra was the presence of the lactate peak in four of five
patients with unfavorable outcome, with a high relative
risk to determine evolution in the sample, relative risk 7.0
(␹2 ⴝ 0.01, 95% confidence interval ⴝ 1.1-42.9).
© 2006 by Elsevier Inc. All rights reserved.
Garcias da Silva LF, Filho JRH, Anés M, Nunes ML.
Prognostic value of 1H-MRS in neonatal encephalopathy.
Pediatr Neurol 2006;34:360-366.
From the *Division of Neurology and Clinical Neurophysiology
Laboratory, †Division of Radiology and Neuroradiology, and ‡Division
of Medical Physics, Hospital São Lucas, Pontifícia Universidade
Católica do Rio Grande do Sul School of Medicine, Porto Alegre,
Brazil.
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PEDIATRIC NEUROLOGY
Vol. 34 No. 5
Introduction
Neonatal encephalopathy is a clinically defined syndrome of disturbed neurologic function in the earliest
days of life in term newborns, manifested by difficulty
with initiating and maintaining respiration, depression
of tone and reflexes, subnormal level of consciousness,
and often by seizures [1]. Although perinatal asphyxia
persists as the major cause, other antenatal and intrapartum risk factors make this diagnosis heterogeneous.
Early identification of newborns with encephalopathy
secondary to perinatal asphyxia is crucial, so as to avoid
the cascade of biochemical events that eventually may
lead to irreversible brain injury [2].
A number of biochemical markers in the blood serum
and cerebrospinal fluid have been proposed as predictors of early and long-term neurodevelopmental outcome. However, the results are often delayed or inconstant [3,4]. Proton magnetic resonance spectroscopy
(1H-MRS) is a noninvasive method that can be used to
detect these alterations and measure the intracerebral
metabolites in vivo [5]. It has a definite use in accurate
prediction of adverse outcome in newborns with encephalopathy secondary to perinatal asphyxia, mainly
when performed near the “hypoxic-ischemic” event [6].
The optimal timing appears to be towards the end of the
first week after birth [7]. However, at this time most of
the newborns with perinatal asphyxia are still clinically
unstable because of cardiovascular or multisystemic
dysfunction and frequently mechanical ventilation that
does not permit magnetic resonance imaging evaluation. The objective of this study was to identify, through
encephalic proton magnetic resonance spectroscopy
performed after “optimal timing”, early predictors of
adverse neurologic outcome at 6 months of age.
Communications should be addressed to:
Dr. Nunes; Division of Neurology; Hospital São Lucas-PUCRS; Av.
Ipiranga 6690, Room 220; 90610-000 Porto Alegre, RS, Brazil.
E-mail: [email protected]
Received May 3, 2005; accepted October 17, 2005.
© 2006 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2005.10.011 ● 0887-8994/06/$—see front matter
Design and Methods
Patient Population and Study Design
Eleven term neonates born between March 2003 and March 2004 and
admitted to the Neonatal Intensive Care Unit of São Lucas Hospital, the
University Hospital from Pontifícia Universidade Católica do Rio Grande
do Sul, School of Medicine in Porto Alegre, Brazil, were consecutively
enrolled in the study and submitted to cerebral proton magnetic resonance spectroscopy. This unit is a referral center for the entire state of
Rio Grande do Sul and receives social security patients who are generally
from low socioeconomic classes. All newborns presented encephalopathy probably as a result of hypoxic-ischemic injury. The clinical data
were obtained from hospital charts and include information about
pregnancy, labor condition, Apgar scores at 5 minutes, and gestation. The
presence of seizures (diagnosis based on clinical observation and
classified according to Volpe’s scheme [8]), time of occurrence related to
birth date (classified as early if seizures began in the first 24 hours of life
and late between 48 hours and the 28th day of life), frequency, and
necessity of antiepileptic drug therapy were also evaluated. Neonatal
encephalopathy was categorized into three profiles by the pediatric
neurologist (L.F.G.S.), with the most severe grade within the first 72
hours of life assigned to each patient. Profile 1 was defined as an altered
level of consciousness that included somnolence or irritability, periods of
spontaneous eye opening, jitteriness, abnormal muscle tone, and abnormal reflexes. Profile 2 was defined as stupor with absence of spontaneous
but presence of stimulated eye opening, abnormal muscle tone, neonatal
seizures, and brainstem dysfunction. Profile 3 was defined as coma, with
no spontaneous or elicited eye opening, seizures, and brainstem dysfunction with abnormal cranial nerve or respiratory abnormalities [9]. The
probable hypoxic-ischemic etiology was diagnosed by one of the authors
(L.F.G.S.) if profiles 1, 2, or 3 were present, associated with Apgar score
at 5 minutes ⬍5, need of immediate resuscitation in the delivery room,
and, when information was available, cord blood acidosis [9]. Exclusion
criteria considered were progressive metabolic diseases, brain malformations, and congenital or acquired central nervous system infections.
Polysomnography Recordings
Polysomnographic recordings were obtained in all cases at the Clinical
Neurophysiology Laboratory. The registration process lasted at least 1
hour or a complete sleep cycle. Scalp electrodes were placed according
to the International 10-20 System modified for newborns [10]. The first
10-12 channels monitored electroencephalography, and five channels
monitored extracerebral parameters which were chin electromyogram,
electro-oculogram, electrocardiogram, nasal air flow, and thoracic-abdominal respiratory movements. The recording speed was 15 mm/s. The
recordings were all videotaped with a split screen to help recognition of
sleep stages. Some neonates underwent more than one polysomnography,
although only the first record was considered for statistical analysis. The
recordings were blind interpreted and classified into four profiles [10] by
a specialist in neonatal polysomnography (M.L.N.). Profile 1 was defined
as normal. Profile 2 was considered mildly abnormal, with background
less mature than expected for gestation (“dysmature”) or exhibiting
excessive spikes, sharp discharges, or slowing with normal amplitude.
Profile 3 was considered moderately abnormal, with low amplitude of
background (5-15 ␮V) and presence of discharges with or without ictal
correlation. Profile 4 was defined with low amplitude of background (⬍5
␮V), burst-suppression pattern, or electrographic evidence of status
epilepticus.
1
H-MRS Procedures
After obtaining informed consent from the parents and when medically
stable, patients were submitted to the magnetic resonance examination.
The patients were monitored by an anesthesiologist during the magnetic
resonance imaging and spectroscopy studies. Sedation with nitric oxide
plus oxygen was provided as needed.
All studies were performed using a circularly polarized head coil in a
conventional 1.5 Tesla whole-body imaging system (Magneton Vision
Plus; Siemens AG, Erlangen, Germany). The magnetic resonance imaging protocol included axial and coronal T2 sequences (repetition time
[TR] ⫽ 7100 milliseconds, echo time [TE] ⫽ 115 milliseconds, flip angle
⫽ 160°), fast fluid-attenuated inversion-recovery (TR ⫽ 9000 milliseconds, TE ⫽ 110 milliseconds, flip angle ⫽ 180°), and diffusion (TR ⫽
5700 milliseconds, TE ⫽ 139 milliseconds), followed by axial and
coronal T1 pulse sequences (TR ⫽ 9.7 milliseconds, TE ⫽ 4 milliseconds, flip angle ⫽ 12°). The spectroscopy was performed using the
point-resolved spectroscopy, bidimensional, multivoxel, and chemical
selective saturation, to suppressed signal from water (TR ⫽ 1500
milliseconds, TE ⫽ 135 milliseconds, field of view 240 ⫻ 240 mm, flip
angle 90°, and 16 ⫻ 16 phase encoding steps) [11]. The field of view
with a nominal voxel size of 7.5 ⫻ 7.5 ⫻ 15 mm was located in the basal
ganglia and thalami bilaterally, without bone or cerebrospinal fluid
contact, because these areas are most sensitive to the effects of perinatal
asphyxia and are known to reflect the global disturbances in hypoxicischemic encephalopathy [12]. Spectral postprocessing was analyzed
using the software Luise (Siemens AG, Erlangen, Germany), and
included k-space zero filling interpolation to 32 ⫻ 32 phase encoding
steps, and multiplication of corrected time domain signal by a Gaussian
function, Fourier transform to the frequency domain, and manual zero
order phase correction. The peak areas were integrated for the choline,
creatine, N-acetylaspartate, and lactate resonances, and peak area ratios
were calculated. The metabolite ratios of the right and left sides were
averaged for statistical analysis. Total creatine was selected as the
spectroscopy reference metabolite because of its relative stability after
hypoxia-ischemia and better reflection of deranged energy metabolism
[13]. All spectra were analyzed by a basic scientist (M.A.) with extensive
experience in spectroscopy, who was unaware of the patient’s clinical
picture. One experienced neuroradiologist (J.R.H.F.) blinded to the
newborn=s clinical condition scored the magnetic resonance imaging
examinations. One previously validated magnetic resonance imaging
score was used to define abnormalities present in the thalami and basal
ganglia only [14]. Newborns were classified as abnormal if the magnetic
resonance imaging score was greater than 0. The total time taken for
imaging and spectroscopy ranged between 50 and 60 minutes.
After discharge, all infants were reexamined clinically for their
neurodevelopmental progress. Clinical outcome was classified as normal,
abnormal (based on Denver II Neurodevelopment scale [15] and neurologic examination), or fatal. The first evaluation was performed at 30
days after discharge, and the next at 3 and 6 months, respectively.
The project was approved by the Ethics Committee of Pontificia
Universidade Católica do Rio Grande do Sul, and parents gave informed
consent to participate in the study.
Statistical Analysis
The statistical methods compared patients with neonatal encephalopathy,
abnormalities identified at proton magnetic resonance spectroscopy, and the
follow-up after the neonatal period. Because of insufficient patient number,
the neurodevelopmental outcome was divided into normal and abnormal for
the purpose of statistical analysis. Analysis between clinical and neurophysiologic variables with spectroscopy results was performed by means of the
chi-square test or Fisher’s Exact Test.
Metabolite ratios, N-acetylaspartate/total creatine, choline/total creatine, and lactate/total creatine of the groups with normal and abnormal
follow-up were compared by independent two-tailed t test. Differences in
the frequency of lactate detection in each group were examined by
chi-square test, and to identify prognostic indicators relative risks with
95% reliability interval were estimated. The adopted significance level
was 0.05. All the tests were performed using the Statistical Package for
Social Sciences, version 10.0 and Excel 97.
Garcias da Silva et al: 1H-MRS in Neonatal Encephalopathy 361
therapy to control seizures was necessary in 45.5% (n ⫽ 5)
of patients.
Results
Clinical Characteristics—Gestational, Perinatal, and
Neonatal Period
Polysomnography Results
Between March 2003 and March 2004, 575 newborns
were admitted to the neonatal intensive care unit of São
Lucas Hospital. From this data base, six males and five
females were diagnosed with neonatal encephalopathy and
included in this study. All of them were term neonates
with average 39 ⫾ 1.2 (S.D.) weeks of gestation, 81.8% (n
⫽ 9) appropriate for gestation, and 18.2% (n ⫽ 2) large for
gestation. Vaginal delivery occurred in 72.7% (n ⫽ 8) of
cases; the remaining 27.3% (n ⫽ 3) had cesarean section.
Immediately after birth, resuscitation was necessary in
72.7% (n ⫽ 8) of patients.
Adverse prenatal events took place in 27.3% (n ⫽ 3) of
pregnancies; urinary tract infection in two, and premature
membrane rupture in one. Adverse events took place in
36.4% (n ⫽ 4) of labors; difficult extraction in two and
tight nuchal cord in two. One patient included did not
manifest any prenatal or birth complication, but developed
a cardiac arrest 6 hours after birth and developed neonatal
encephalopathy.
With respect to encephalopathy grade, 27.3% (n ⫽ 3)
were diagnosed as grade 1, 45.4% (n ⫽ 5) as grade 2, and
27.3% (n ⫽ 3) as grade 3.
Neonatal seizures occurred in 63.6% (n ⫽ 7) of the total
sample; early seizures in relation to birth were observed in
four cases, all of them with neonatal encephalopathy grade
3. Seizures were classified in the sample as exclusively
subtle in 14.3% (n ⫽ 1), exclusively clonic in 14.3% (n ⫽
1), subtle plus clonic in 42.8% (n ⫽ 3), subtle plus clonic
plus tonic in 14.3% (n ⫽ 1), and clonic plus tonic in 14.3%
(n ⫽ 1) of cases. Maintenance of antiepileptic drug
Table 1.
All the patients were submitted to a polysomnographic
recording at an average 7.9 ⫾ 4.6 (S.D.) days of life. With
regard to polysomnography classification, we observed
9.1% (n ⫽ 1) normal examination and 90.9 % (n ⫽ 10)
abnormal examinations. Profile 2 corresponded to 72.7%
(n ⫽ 8), profile 3 to 9.1% (n ⫽ 1), and profile 4 to 9.1%
(n ⫽ 1) of cases. Burst-suppression pattern or neurophysiologic evidence of status epilepticus were not observed.
The only profile 4 case was diagnosed as having diffuse
low voltage. No relationship was observed between spectroscopy results and electroencephalographic recording
patterns. The fact of having presented clinical seizures also
did not relate to any specific electroencephalographic
recording profile. However, the polysomnography profile
2 cases (n ⫽ 8) were statistically related to clinical
neonatal encephalopathy profiles 1 and 2 (P ⫽ 0.05).
Spectroscopy Results and Outcome
The entire cohort was submitted to a brain magnetic
resonance imaging and spectroscopy examination at an
average 13.6 ⫾ 4.0 (S.D.) days after birth. A summary of
the clinical findings, magnetic resonance imaging scores,
spectroscopy results, and outcome at 6 months of age is
presented in detail in Table 1. Overall, thalamic abnormalities were observed in only 1 of 11 newborns with neonatal
encephalopathy (Fig 1).
No fatal outcome was detected, so all the patients
included were reexamined after discharge at the outpatient
Summary of the clinical characteristics, MRI scores, spectroscopy results, and follow-up
Patient No.
NE (grade)
MRI Score
NAA/Cr*
Col/Cr†
Lac/Cr†
Outcome at 6 Months
1
2
3
4
5
6
7
8
9
10
11
2
3
3
3
1
1
1
2
2
2
2
0
0
3
0
0
0
0
0
0
0
0
0.97
0.88
0.74
0.81
0.85
1.26
1.11
1.58
1.00
0.85
1.24
1.20
1.66
2.97
3.25
1.37
1.61
1.44
1.92
1.30
1.58
1.67
0.21
0.46
0.81
0.68
ND
ND
ND
ND
ND
ND
ND
Abnormal
Abnormal
Abnormal
Abnormal
Normal
Normal
Normal
Normal
Abnormal
Normal
Normal
Abbreviations:
Cr
⫽ Creatine
Col ⫽ Choline
Lac ⫽ Lactate
MRI ⫽ Magnetic resonance imaging
NAA ⫽ N-acetylaspartate
ND ⫽ Not detectable
NE ⫽ Neonatal encephalopathy
* Minimum peak-area ratios.
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PEDIATRIC NEUROLOGY
Vol. 34 No. 5
Figure 1. Proton magnetic resonance spectroscopy obtained from right thalamus 12 days after birth from Case 3 with abnormal neurodevelopmental
outcome at 6 months. The spectra clearly identified the characteristic lactate peak at 1.33 ppm.
clinic. The average follow-up time was 9.1 ⫾ 3.9 (S.D.)
months of life. Abnormal neurodevelopmental outcome
was confirmed by one pediatric neurologist (M.L.N.) in 5
of 11 patients (45.4%) and was clearly related to some
neonatal clinical aspects and spectroscopy results, as
summarized in Table 2.
The N-acetylaspartate/creatine, choline/creatine, and
lactate/creatine ratios were also calculated among the
groups with favorable and unfavorable outcomes. The
lowest mean N-acetylaspartate/creatine ratios were observed in four of five patients with an adverse outcome
and though not statistically significant, demonstrated a
clear trend to unfavorable follow-up. The choline/creatine
ratios could not be related to follow-up. The most consistently observed abnormality on the spectra was the presence of lactate peak in four of five patients with unfavorTable 2. The relationship between neonatal clinical variables and
identification of lactate peak on spectroscopy with outcome
Variables
Apgar ⬍ 5 at 5 minutes
Seizures
Early seizures
Antiepileptic drugs
NE grade 3
Lac ⴙ
AB Follow-up
4/4
4/7
4/4
4/5
3/3
4
5
4
5
3
Abbreviations:
AB ⫽ Abnormal
Lac ⫽ Lactate
NE ⫽ Neonatal encephalopathy
* Fisher’s Exact Test.
†
P ⬍ 0.05.
Significance*
P
P
P
P
P
⫽
⫽
⫽
⫽
⫽
0.003
0.19
0.02†
0.01†
0.02†
able outcome. In this group, the relative risk determined to
an unfavorable evolution was 7.0 (␹2 ⫽ 0.01, 95%
confidence interval ⫽ 1.1-42.9). The presence of this
metabolite was undetectable in those who later had a
normal evolution. Table 3 describes in detail these results
and the t test for independent samples.
Discussion
Clinical Characteristics: Gestational, Perinatal, and
Neonatal Period
The aim of this study was to identify, through magnetic
resonance spectroscopy obtained after the first week of
Table 3. Neonatal encephalopathy: Prediction of 6-month
neurodevelopmental outcome by 1H-MRS
Variable
Unfavorable
Outcome (n ⴝ 5)
Favorable
Outcome (n ⴝ 6)
t Test*
NAA/Cr‡
Col/Cr‡
Lac/Cr‡
0.90 (0.74–1.00)
1.70 (1.20–3.25)
0.57 (0.21–0.81)
1.17 (0.85–1.58)
1.60 (1.37–1.92)
0.00
P ⫽ 0.06
P ⫽ 0.17
*P ⫽ 0.01†
Abbreviations:
CI
⫽ Confidence interval
Col
⫽ Choline
Cr
⫽ Creatine
1
H-MRS ⫽ Proton magnetic resonance spectroscopy
Lac
⫽ Lactate
NAA
⫽ N-acetylaspartate
* Independent samples test.
†
P ⬍ 0.05 (95% CI).
‡
Values are given as medians and ranges.
Garcias da Silva et al: 1H-MRS in Neonatal Encephalopathy 363
life, prognostic indicators for neonatal encephalopathy.
The study group may be considered small to obtain any
significant results; however, as an etiologic factor, hypoxic-ischemic encephalopathy persists as a major cause,
with a prevalence of 1-2/1000 live births [8]. During the
study period, 575 newborns were admitted to the neonatal
intensive care unit of our institution, thus we consider our
sample appropriate.
It is difficult to determine the exact etiologic factor of
neonatal encephalopathy, and a clear history of asphyxia,
even during pregnancy or labor, could not be obtained in
many cases [1,16,17]. In the sample, adverse prenatal
events were present in three gestations and abnormal
neurodevelopmental outcome was identified in one of
them. However, the unfavorable outcome was attributed to
perinatal events and abnormalities identified in magnetic
resonance spectroscopy.
Vaginal delivery, at least in animal studies, could be
related to signs of brain hypoxia-ischemia. In humans this
relationship has not been confirmed, and conclusions are
based much more on biochemistry results than clinical
parameters [8]. In this group the adverse labor events took
place in four vaginal deliveries, with no correlation to
spectroscopic results or outcome. These findings are in
agreement with previous studies [18,19].
Although an Apgar score of less than 5 at 5 minutes of life
was not able to predict outcome, it was nevertheless useful to
determine the necessity of resuscitation maneuvers in the
delivery room. In premature infants, its reliability is even less
[20]. In the sample described herein, recently delivered
infants were included and—when analyzed in conjunction
with other clinical parameters, particularly neonatal encephalopathy grade, metabolic disorders, electroencephalographic
recordings, and neuroimaging studies—asphyxia was the
most probable etiologic factor.
Seizures are still the most important clinical manifestation of neurologic disorders in the neonatal period [21,22].
A close association between neonatal seizures and permanent deficits has been described in previous papers
[23,24]. In the present sample, seven patients were diagnosed as having seizures and four of them with early
presentation. With these patients, the identification of
lactate peak on spectroscopic examinations probably
meant a more severe neonatal encephalopathy, with an
additional tendency to an unfavorable outcome.
Despite the low efficacy reported, newborns with seizures are eventually administered antiepileptic drugs [25].
Antiepileptic drugs were prescribed for five neonates, four
of them with lactate peaks identified on spectroscopic
examination. The duration and need for a great amount of
these drugs are indicators of clinical severity and unfavorable prognosis [26,27] as occurred with this sample.
The neonatal encephalopathy grade appears associated
with severity of the neonate’s brain insult [8,22,24,27].
These observations are in agreement with the results of the
present study, where those neonates classified as grade 3
were also diagnosed as having lactate peaks on spectro-
364
PEDIATRIC NEUROLOGY
Vol. 34 No. 5
scopic examination and 6-month abnormal neurodevelopmental outcomes.
Polysomnography Recordings
Because of its noninvasive, easy-to-use nature, neonatal
polysomnography has become an important assessment
method for neurologically damaged infants. Polygraphic
evidence of status epilepticus, hypovoltage, and burstsuppression pattern has played an important role in predicting neurologic disabilities [28,29]. In the present
cohort, all the patients were submitted to an electroencephalographic recording during the first weeks of life and
no patient was diagnosed as having a polygraphic status
epilepticus or burst-suppression pattern. The low voltage
observed in only one patient is in agreement with literature
of unfavorable outcome [30]. Polygraphic abnormalities
when related to spectroscopy results were not significant.
Besides the small number of cases, both diagnostic tests
are sensitive and the majority of patients included had
alterations in both electroencephalographic and spectroscopic procedures.
1
H-MRS
The clinical utility of proton magnetic resonance spectroscopy rests upon two important properties. First, the
concentrations of brain chemicals identified are remarkably constant; and second, these neurochemicals are of
clinical relevance in healthy and diseased brains
[5,6,9,31]. Predicting outcome in neonatal encephalopathy
remains difficult, because not all abnormal magnetic
resonance imaging results are predictive of an unfavorable
outcome. The basal ganglia abnormalities appear extremely predictive of neurodevelopment follow-up and are
in close relationship to the severity of neonatal encephalopathy [4,6,14]. In the present cohort, only neonates with
clinical or laboratory results compatible with asphyxia
were included [32,33], and the necessity of clinical stabilization was crucial to our results. In only one case basal
ganglia alterations were demonstrated by magnetic resonance imaging. Lactate peaks were detected in four
spectroscopy examinations. Usually the increased lactate/
creatine ratio in the hours after hypoxic-ischemic insult is
an indirect evidence of impaired cerebral energy metabolism [34]. The detection of lactate/creatine ratios in the
sample could not be explained by this reason, because the
spectroscopy examinations were obtained during the second or third weeks of life. However, there are several
mechanisms that could be implicated in abnormal cerebral
energy metabolism in chronic phases after hypoxic-ischemic brain insult. Among them, impaired oxidative metabolism due to mitochondrial damage, reduction in the
activity of pyruvate dehydrogenase complex, and increased activity of microglia with infiltrating phagocytes
[35]. In the present sample, lactate could be detected even
later due to several mechanisms associated with hypoxia
and ischemia described earlier and possibly also due to
seizures [36]. Technical aspects of spectroscopy acquisitions also influenced the results. The long TE method has
been used preferably in neonates to produce better detection of lactate/creatine ratios even at a later date [37].
Patients studied 1-2 weeks after hypoxic-ischemic insult
and who developed neurologic deficits were more likely to
have reduced N-acetylaspartate/creatine metabolite ratios
compared with those who had good outcomes [12,15]. The
magnitude of change in the metabolite ratios correlates
with the severity of subsequent neurologic disability [38].
The findings reported here are in agreement with previous
descriptions once the lowest mean N-acetylaspartate/creatine ratios were observed in four of five patients with
unfavorable outcome.
In term infants with encephalopathy, the clinical characteristics are not sufficient to determine etiology and
prognosis, particularly when a clear history of asphyxia
could not be obtained [39]. The proton magnetic resonance
spectroscopy in these cases is a useful tool for determining
etiology and prognosis. Accurately predicting an adverse
outcome at 1 year with a specificity of 93% and positive
predictive value of 92% [40] can be done if the 1H-MRS
is performed soon after the cerebral hypoxic-ischemic
insult. In the patients in the present study, the presence of
a lactate peak on spectra in association with other metabolic disturbances and clinical alterations were important
issues related to etiology and outcome. The presence of
lactate peak was coincident with a high neonatal encephalopathy grade, low Apgar scores at 5 minutes, early
neonatal seizures, and necessity of antiepileptic drug
therapy. These clinical variables maintain a close relationship with the cases in our sample with unfavorable
outcomes and hypoxic-ischemia as the etiologic factor.
Although the number of patients in the present study was
relatively small, the data support that proton magnetic
resonance spectroscopy, performed after the first week of
life, can be used to identify neonates with encephalopathy
at risk of unfavorable outcomes, particularly when secondary to hypoxic-ischemic brain injury and with normal
magnetic resonance imaging.
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