Original Article

Long-Term Use of Oxcarbazepine Oral Suspension

in Childhood Epilepsy: Open-Label Study
Miguel Rufo-Campos, MD; Carlos Casas-Fernndez, MD; Antonio Martnez-Bermejo, MD

ABSTRACT

Studies designed specifically for the pediatric population are needed to assess the tolerability and safety of the new
antiepileptic drugs. The purpose of this study was to document the safety, ease of dosing, and acceptance of oxcarbazepine
oral suspension in pediatric patients in monotherapy and polytherapy. A prospective, multicenter, open-label study was
conducted at the neurology services of three pediatric university hospitals over 12 months. After obtaining signed informed
consent, we enrolled a series of 62 patients with epilepsy aged between 2 months and 14 years who began oxcarbazepine
treatment in monotherapy or in combination with other antiepileptic drugs to assess the seizure frequency, safety (adverse
events), and acceptance of the pharmaceutical form by the patients family. Fifty patients (80.6%) reduced seizures by at
least 50%, 44 (71%) saw a reduction in seizure frequency of over 75%, and 29 (46.8%) were seizure free at the end of the
study. The difference in the number of seizures before and after the study was statistically significant, both overall and by
type of pathology. Adverse events occurred in four patients (6.4%) and required withdrawal of the drug in two cases (skin
rash); three patients (4.8%) withdrew for inefficacy. Five patients (8.1%) withdrew from the treatment. We concluded that,
in this series of patients, oxcarbazepine in oral suspension form was seen to help reduce seizure frequency, to have few
side effects, and to be accepted by parents and patients. (J Child Neurol 2006;21:480485; DOI 10.2310/7010.2006.00120).

The characteristics of pharmacologic epilepsy treatment in the
pediatric population are different from those of adult epilepsy: the
pharmacodynamics and pharmacokinetics of drugs, like their tox-
icity, are not the same in the two population groups, and their
possible effects on intellectual ability, attention span, or behavior
are particularly important for schoolchildren.1
As with most drugs, experience with the use of antiepileptic
drugs has generally focused more on the adult population than on
pediatric patients. Moreover, the recommendations for use in chil-
dren are simply an extension of the results obtained in efficacy stud-
ies conducted in adults.1 Studies specifically designed for the
Received February 22, 2005. Received revised April 28, 2005 and June 21,
2005. Accepted for publication July 13, 2005.
From the Pediatric Neurology Service (Dr Rufo-Campos), Virgen del Roco
Childrens University Hospital, Seville, Spain; Pediatric Neurology Service
(Dr Casas-Fernndez), Virgen de la Arrixaca University Hospital, Murcia,
Spain; and Pediatric Neurology Service (Dr Martnez-Bermejo), La Paz
University Hospital, Madrid, Spain.
Address correspondence to Dr Miguel Rufo-Campos, Servicio de Neurologa
Infantil, Hospital Infantil Universitario Virgen del Roco, 41013 Sevilla, Spain.
Tel: +34 954611716; fax: +34 955912921; e-mail: miguel.rufo@telefonica.net.
pediatric population are therefore needed to assess the efficacy,
tolerability, and safety of the new antiepileptic drugs added over
recent years to existing epilepsy drugs, thereby complementing
reviews conducted on both pediatric and adult populations.2,3 With
these new specific studies and reviews, we can prepare guide-
lines for specific use in the pediatric population.
The new antiepileptic drugs include oxcarbazepine, which is
structurally related to carbamazepine (it is, in fact, a ketoderiva-
tive of carbamazepine) and which, according to the results of clin-
ical trials comparing the two, is equally effective and less toxic than
carbamazepine,4 is only slightly neurotoxic, and produces few
allergic reactions.5 Its effects on cognitive function following 4-week
treatment are minimal according to information obtained from
studies on adults with epilepsy.6 These data, along with the ease
of dosing and titration, support the use of oxcarbazepine as a first-
line drug for pediatric patients.
Given that the particular characteristics of the pediatric pop-
ulation can affect the pharmacokinetics of antiepileptic drugs and
given the importance of accurate dosing, it is particularly interesting
to provide these drugs in an oral suspension form, thereby obtain-
ing more accurate doses and easier administration. The purpose
of this study was to document the usefulness, safety, ease of dos-
ing, and acceptance of oxcarbazepine oral suspension in monother-
apy or polytherapy in a large pediatric population of patients (even
those of a very young age) with epilepsy.

480
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 Oxcarbazepine Oral Suspension in Childhood / Rufo-Campos et al
METHODS
This was a prospective, multicenter, open-label study conducted at the
neurology services of three pediatric university hospitals (Virgen del Roco
Childrens University Hospital, Seville; Virgen de la Arrixaca University
Hospital, Murcia; and La Paz Childrens University Hospital, Madrid) on a
series of epilepsy patients aged under 15 years with partial seizures with
or without secondary generalization.
Patients meeting the inclusion and exclusion criteria were regarded
as potential candidates for the study. Inclusion criteria were as follows:
Aged between 0 and 14 years
Partial seizures with or without secondary generalization
Likely to receive monotherapy or adjunctive therapy
Not previously treated with oxcarbazepine
Signed informed consent by the parents or legal guardians
Exclusion criteria were as follows:
History of toxic reactions to carbamazepine
Previous oxcarbazepine treatment
Any of the contraindications for oxcarbazepine administration listed in
the summary of product characteristics
The criteria for drug withdrawal were inefficacy, adverse reactions,
and the express wishes of participants or their legal guardians.
The study was designed to take place over 12 months, based on the
following schedule:
Start of the study after approval from independent review boards (ethics
committee) corresponding to the three participating hospitals and
enrollment of patients after obtaining the informed consent of the par-
ent or legal guardian; at this time, sociodemographic data were obtained,
as well as information related to the clinical features of epilepsy, includ-
ing diagnosis, seizure frequency, and electroencephalography (EEG); a
blood test was also done for baseline determination of complete blood
cell count, electrolytes, and plasma drug concentration to rule out inef-
ficacy owing to insufficient dosing of previous drug treatment.
Follow-up visits at 3, 6, and 9 months to assess treatment compliance,
seizure frequency, adverse events, and recording of data on a drug titra-
tion process
Final study visit at 12 months. Clinical summary recording seizure fre-
quency, maintenance dosage reached (maximum dosage reached after
drug dose titration), adverse events, and results from the Satisfaction
Assessment Questionnaire completed by patients and parents. This
questionnaire was designed ad hoc by our study team (where 0 = unsat-
isfactory and 5 = excellent) to record the overall satisfaction with the
drug administration following a long-term maintenance treatment
period. Blood samples were obtained twice for chemistries: the first sam-
ple was taken before completing 3 months of treatment and the second
at the end of the study.
The treatment was based on oxcarbazepine administration, either
as monotherapy or in combination with other antiepileptic drugs, dosed
as follows:
Low starting doses (on average 10 mg/kg/day)
Titration process adapted to individual needs
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481
Figure 1. Distribution of the frequency of participant ages, grouped.
For statistical analysis of the data, SPSS, version 10 (SPSS Inc, Chicago,
IL), was used and included descriptive and analytic statistics. Pearsons cor-
relation and Students t-test for comparison of means were applied for
variables following normal distribution.
The descriptive statistics indicated the distribution of the following
variables: age, type of epilepsy (symptomatic, idiopathic, or cryptogenic),
type of seizure (simple or complex), and number of seizures at the 3-month
follow-up visit and the end of the study, with the percentage of change in
seizure frequency, starting dose, final dose (maintenance dose), frequency
of drug increase (titration), length of follow-up, adverse events, and satis-
faction with treatment.
The analytic statistics indicated the outcome of the treatment by
comparing seizure frequency at the start and end of the study (within-
group comparison: Students t-test for paired samples, with a level of sig-
nificance of P .05) and overall sample, stratified by seizure type, epilepsy
type, monotherapy or polytherapy, or monotherapy alone. No correction was
applied for multiple comparisons.
Between-group comparison of the percentage of change (reduction)
in seizure frequency was also carried out for each class of seizure or
epilepsy. Drug usefulness was documented on the reduction in seizure fre-
quency, either in absolute numbers or expressed as a percentage.
RESULTS
Sixty-two patients participated in the study (26 girls and 36 boys)
aged between 2 months and 14 years (median age 3 years). Almost
half of the studied patients were children of 2 years of age or less
(Figure 1). The sample was composed of a majority of children suf-
fering from complex seizures and a symptomatic type of epilepsy
(Table 1); over one third of them (25 patients, 36.7%) were moder-
ately to severely mentally retarded at the time treatment was started.
All of them had been diagnosed with symptomatic partial epilepsy
owing, in most cases, to hypoxic-ischemic encephalopathy.
The overall data on age, starting dose and final dose, average
seizure frequency during the 3 months prior to starting treatment
and the 3 months prior to the final study visit, and degree of par-
ticipant satisfaction are indicated in Table 2. The results show
that satisfaction with the form of administration, oral suspension,
was very high on average.
482 Journal of Child Neurology / Volume 21, Number 6, June 2006

Table 1. Distribution of Participants by Seizure Type and Epilepsy Type

Type of Seizure Type of Epilepsy
Simple Complex Total Sample Symptomatic Idiopathic Cryptogenic Total Sample
Frequency 15 47 62 35 20 7 62
Percentage 24.2 75.8 100.0 56.5 32.3 11.3 100.0

Table 2. Overall Data on Age, Starting Dose and Final Dose, Seizure Frequency at the Start and End
of the Study, and Degree of Satisfaction*
Mean Seizure Mean Reduction
Frequency in Seizure
Dose Start/End 3 mo Before Frequency Follow-Up Satisfaction
Age (mo) (mg/kg/d) Start/3 mo Before End (%) (mo) Questionnaire
Median 36 10.29/30.41 26.69/7.92 78.19 8.08 3.87
SEM 4.87 0.31/0.95 7.22/3.76 3.76 0.28 0.04
SD 38.38 2.41/7.38 56.88/18.53 29.64 2.18 0.34
SEM = standard error of measurement.
*0 = unsatisfactory; 5 = excellent.

The drug was generally titrated on a weekly (46.8%), fort- Table 6 reveals the relationship between efficacy and fre-
nightly (27.4%), or half-weekly (25.8%) basis, depending on the quency in drug dose titration. The mean values of seizure reduc-
needs of each patient. Oxcarbazepine was first-line treatment in tion are similar, and the difference between them is not statistically
all but three patients (for whom oxcarbazepine was added to an significant. The relationship between maximum dose and efficacy
ongoing treatment because of poor crisis control). Obviously, no is indicated in Figure 3 (Pearsons correlation values and disper-
treatment was given to patients who had only one single seizure sion diagram). The diagram shows clustering of cases in the val-
episode and were not deemed candidates for drug treatment. ues, indicating a greater reduction (the more negative the
To answer the question, Did the frequency of seizures drop percentage, the greater the reduction in seizure frequency) and
significantly with the treatment? the within-group difference in the lower doses.
number of seizures was analyzed at the start and end of the study There was no difference in the amount of medication received
along with the percentage of overall change, stratified by seizure (means of maximum dose reached) in those who experienced
and epilepsy type (overall and stratified efficacy). The results of adverse events and those who did not. It is important to bear in mind
the overall analysis are illustrated in Figure 2. Fifty patients (80.6%) that few patients suffered adverse events, which occurred in four
reduced seizures by at least 50%, and 44 patients (71%) reduced of them (6.45%), two of whom required oxcarbazepine to be dis-
seizure frequency by over 75%. Moreover, 29 patients (46.8%) were continued. The frequency and description of adverse events,
seizure free at the end of the study.
The results of the stratified analysis of treatment helpfulness
by seizure and epilepsy type are illustrated in Table 3. The differ-
ence in the mean frequency of seizures at the start and end of the
study is statistically significant, both overall and for each type of
seizure or epilepsy, regardless of whether the treatment was given
as monotherapy or polytherapy. It must be said that although poly-
therapy in functional epilepsy is unusual, it was used on three
patients given the anxiety that the monotherapy option was caus-
ing their relatives.
To answer the question, In which type of seizure or epilepsy
is the treatment more effective? a comparative analysis (between-
group comparison) was carried out on the efficacy of the treatment
in the different types of seizure or epilepsy. This analysis is illus-
trated in Table 4. There were no statistically significant differ-
ences in the various types of pathology.
The comparison of the treatment as monotherapy or poly-
therapy is illustrated in Table 5, which compares the variables of
Figure 2. Percentage of change in frequency of seizures at the start
maximum dose in mg/kg/day and adverse events in patients treated and end of the study. Forty-seven percent of the sample became
with the drug as monotherapy or in polytherapy. seizure free (29 patients).

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 Oxcarbazepine Oral Suspension in Childhood / Rufo-Campos et al 483

Table 3. Within-Group Comparison of the Number of Seizures at the Start and End of the Study
by Seizure Type, Epilepsy Type, and Treatment Type
Difference in Number of Seizures
Start of Study End of Study
Mean SD SEM Mean SD SEM P
Total sample (N = 62)
Simple seizures (n = 15) 20.20 33.45 8.64 10.60 26.67 6.89 .001*
Complex seizures (n = 47) 28.77 62.70 9.15 7.06 15.36 2.24 .013*
Symptomatic epilepsy (n = 35) 37.34 72.63 12.28 10.03 19.34 3.27 .020*
Idiopathic epilepsy (n = 20) 9.50 5.92 1.32 1.55 3.14 0.70 .000**
Cryptogenic epilepsy (n = 7) 22.57 35.02 13.24 15.57 33.33 12.60 .002*
Overall 26.69 56.88 7.22 7.92 18.53 2.35 .050*

Monotherapy-only sample (n = 33)

Simple seizures (n = 10) 6.20 3.05 0.96 0.40 0.97 0.31 .001*
Complex seizures (n = 23) 8.70 6.23 1.30 1.39 3.14 0.66 .000**
Symptomatic epilepsy (n = 13) 8.46 6.77 1.88 2.15 3.93 1.09 .000**
Idiopathic epilepsy (n = 17) 8.29 4.82 1.17 0.47 1.18 0.29 .000**
Cryptogenic epilepsy (n = 3) 3.67 0.58 0.33 0.00 0.00 0.00 .008*
Overall 7.94 5.54 0.96 1.09 2.70 0.47 .000**

Polytherapy-only sample (n = 29)

Simple seizures (n = 5) 48.20 49.25 22.02 31.00 41.31 18.47 .027*
Complex seizures (n = 24) 48.00 83.89 17.12 12.50 19.98 4.08 .037*
Symptomatic epilepsy (n = 22) 54.41 87.70 18.70 14.68 23.15 4.94 .033*
Idiopathic epilepsy (n = 3) 16.33 8.08 4.67 7.67 4.04 2.33 .065
Cryptogenic epilepsy (n = 4) 36.75 42.75 21.38 27.25 42.39 21.20 .003*
Overall 48.03 78.28 14.54 15.69 24.95 4.63 .022*
SEM = standard error of measurement.
Statistical significance: *P .05; **P < .001.

Table 4. Between-Group Comparison of the Percentage of Seizure doses/kg/day, and reasons for discontinuing oxcarbazepine (five
Frequency Reduction by Seizure Type and Epilepsy Type With patients, 8.06%) are indicated in Table 7. The results of blood sam-
Statistical Significance (ANOVA) ples obtained twice (before completing 3 months of treatment and
% Reduction the second at the end of the study) showed that none of the patients
(Mean) n SD SEM P* had relevant hyponatremia or hematologic abnormalities.
Seizure type
Simple 80.67 15 34.74 8.97 .713 DISCUSSION
Complex 77.40 47 28.19 4.11

Epilepsy type It is well known that pediatric patients with a partial, idiopathic type
Symptomatic 74.31 35 29.90 5.05 .329 of epilepsy usually show a good response to treatment. In this
Idiopathic 86.38 20 26.47 5.92 series of heterogeneous patients, a better response to treatment was
Cryptogenic 74.17 7 36.26 13.70
also observed among those patients with this type of epileptic
Change (%) 78.19 62 29.64 3.76 event, almost all of whom received oxcarbazepine as monotherapy.
overall sample From the results obtained in this study, it can be concluded
ANOVA = analysis of variance; SEM = standard error of measurement. that oxcarbazepine was useful to reduce seizure frequency in this
P refers to the between-group comparison (simple vs complex; symptomatic vs series of patients, who, however heterogeneous they were, and even
idiopathic vs cryptogenic).
knowing that most of the patients with idiopathic partial epilepsy

Table 5. Comparison of Maximum Dose and Number of Adverse Events in Patients Treated With Monotherapy and Polytherapy
Polytherapy Monotherapy
Variable n Mean SD SEM n Mean SD SEM P
Maximum dose (mg/kg/d) 29 31.8 9.09 1.69 33 29.27 5.00 0.87 .171*
n Frequency % n Frequency %
Adverse events, n (%) 29 3 10.34 33 1 3.03 .332
SEM = standard error of measurement.
*t-test.

Chi-square, Fisher exact test.

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484 Journal of Child Neurology / Volume 21, Number 6, June 2006

Table 6. Comparison of Mean Percent Seizure Reduction Based on the Frequency of Drug Increases
Mean % Change in Seizure Frequency
Frequency of Dose Titration (wk) % Change (Mean) n SD SEM P
0.5 67.43 16 29.50 7.38 .171
1 84.75 29 24.01 4.46
2 77.13 17 36.45 8.84
SEM = standard error of measurement.

respond well to the first treatment, represent those admitted to three Table 7. Relationship Between Adverse Events
different pediatric hospitals for partial seizures and, as per crisis and Reasons for Withdrawal
description and/or EEG findings, needed antiepileptic treatment. Maximum Reason
Seventy-one percent of participants (44 patients) reduced seizure Adverse Dose for Oxcarbazepine
frequency by three quarters or more (reduction of over 76%), and Patient Event (mg/kg/day) Withdrawal
almost half of the patients were completely seizure free at the end 4 27.27 Ineffectiveness
of the study, possibly because their epilepsy was newly diagnosed. 17 26.25 Ineffectiveness
21 Strabismus* 26.96 Continued the study
Three patients (4.8%) withdrew owing to inefficacy, and four 36 Ataxia 40.40 Continued the study
patients (6.5%) had side effects that led to withdrawal in two cases, 37 Rash 40.00 Rash
but there were no aggravations of seizure frequency, nor did any 42 26.70 Ineffectiveness
50 Rash 13.30 Rash
patients develop infantile spasms after partial seizures.
If we compare seizure frequency at the beginning and end of *Unilateral strabismus in right eye lasting 40 to 60 minutes. Complete remission
following a 40% dose reduction.
the study in the full sample (within-group comparison), we see that
Ataxia in remission spontaneously after 1 week.
the mean frequency of seizures is lower at the end of the study and
that the difference is statistically significant, both overall and in the
stratified analysis of patients by seizure or epilepsy type. The results, it is important to note that they probably indicate more sat-
reduction in seizure frequency was less evident in the group receiv- isfactory results in patients requiring lower doses, that is, those with
ing polytherapy, probably because the pathology was more serious. less serious seizures and an improved clinical course. Therefore,
However, the between-group comparison to answer the ques- it would not be legitimate to conclude that monotherapy is supe-
tion in which type of seizure or epilepsy was the treatment more rior to polytherapy given that the seriousness of the disease or resis-
effective does not reveal statistically significant differences in tance to treatment is probably different in the two groups of
treatment efficacy in patients with different types of seizure or patients and logically greater in patients requiring polytherapy. As
epilepsy: the reduction in the number of seizures is similar for all expected, the better response with low doses was mainly observed
groups. in the group of patients with the partial, idiopathic type of epilepsy
A different result is obtained if we compare patients receiv- in which medication was titrated in such a way as to keep for as
ing monotherapy and polytherapy. Treatment appears to better long as possible the lower dose needed to maintain the patient free
reduce seizure frequency in the group of patients treated with of epileptic episodes and thus reduce the risk of drug adverse
monotherapy than those receiving polytherapy. This is fairly con- events.
cordant with Figure 3, which shows a tendency to group in the data According to animal studies, the mechanisms of action of
indicating better results and lower doses. When interpreting these oxcarbazepine are related to the blocking of neuronal sodium

Figure 3. Dispersion diagram of the vari-

ables of seizure frequency (percentage of
change) and maximum dose reached
(mg/kg/day).

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 Oxcarbazepine Oral Suspension in Childhood / Rufo-Campos et al 485

channels, particularly voltage-dependent channels, thereby stabi-
lizing the neuron membrane, inhibiting repeat neuronal firing, and
reducing the propagation of impulses through synapses.710 Some
studies indicate that oxcarbazepine also acts on high-voltage
activated calcium currents.11
The oral suspension form of oxcarbazepine is particularly
attractive in pediatric patients because it is easy to dose and admin-
ister, with a better absorption by a still immature bowel.
Although no oxcarbazepine blood levels were obtained in
this study, it is well known from pharmacokinetic studies that
oxcarbazepine is absorbed almost entirely when given orally (96%),
thereby obtaining a maximum blood concentration 1 hour after its
administration and regardless of the time of food ingestion. It
rapidly converts into its active metabolite, a monohydroxide deriv-
ative whose maximum blood concentration is reached 4 to 6 hours
after administration of the oxcarbazepine dose.12 Forty percent of
the monohydroxide derivative circulates bound to plasma pro-
teins and is excreted through the kidney.
In conclusion, treatment with oxcarbazepine oral suspension
in this series of patients was useful in simple and complex seizures
and in symptomatic, idiopathic, and cryptogenic epilepsies, with
few adverse events and good acceptance by parents and patients.
References
1. Gilman JT, Duchowny M, Campo AE: Pharmacokinetic consid-
erations in the treatment of childhood epilepsy. Pediatr Drugs
2003;5:267277.
2. French JA, Kanner AM, Bautista J, et al: Efficacy and tolerability
of the new antiepileptic drugs II: Treatment of refractory epilepsy:
Report of the Therapeutics and Technology Assessment Sub-
committee and Quality Standards Subcommittee of the American
Academy of Neurology and the American Epilepsy Society. Neu-
rology 2004;62:12611273.
3. French JA, Kanner AM, Bautista J, et al: Efficacy and tolerability
of the new antiepileptic drugs I: Treatment of new onset epilepsy:
Report of the Therapeutics and Technology Assessment Sub-
committee and Quality Standards Subcommittee of the American
Academy of Neurology and the American Epilepsy Society. Neu-
rology 2004;62:12521260
4. Serdaroglu G, Kurul S, Tutuncuoglu S, et al: Oxcarbazepine in the
treatment of childhood epilepsy. Pediatr Neurol 2003;28:3741.
5. Beydoun A: Monotherapy trials of new antiepileptic drugs. Epilep-
sia 1997;38(Suppl):2131.
6. Sabers A, Moller A, Dam M, et al: Cognitive function and anti-
convulsant therapy: Effect of monotherapy in epilepsy. Acta Neu-
rol Scand 1995;92:1927.
7. Bang LM, Karen LG: Oxcarbazepine: A review of its use in chil-
dren with epilepsy. Pediatr Drugs 2003;5:557573.
8. Tecoma ES: Oxcarbazepine. Epilepsia 1990;40(Suppl 5):S37S46.
9. Walmil AW, Schmutz M, Porte C, et al: Effects of oxcarbazepine
and 10-hydroxycarbamazepine on action potential firing and gen-
eralized seizures. Eur J Pharmacol 1994;271:301308.
10. Ichikawa K, Koyama N, Kiguchi S, et al: Inhibitory effect of oxcar-
bazepine on high-frequency firing in peripheral nerve fibres. Eur
J Pharmacol 2001;420:119192.
11. Stefani A, Pisan A, De Murtras M, et al: Action of GP 47779, the
active metabolite of oxcarbazepine on the corticostriatal system
II: Modulation of high-voltage-activated calcium currents. Epilep-
sia 1995;36:9971002.
12. Pariente-Khayat A, Tran A, Vauzelle-Kervuroedan F, et al: Phar-
macokinetic of oxcarbazepine as add-on therapy in epileptic chil-
dren, abstract. Epilepsia 1994;35(Suppl 8):119.

Original Article

Clinical and Imaging Study of Human

Immunodeficiency Virus-1Infected Youth Receiving
Highly Active Antiretroviral Therapy: Pilot Study
Using Magnetic Resonance Spectroscopy
Lidia Gabis, MD; Anita Belman, MD; Wei Huang, PhD; Maria Milazzo, RNP; Sharon Nachman, MD

ABSTRACT

The objective of this study was to correlate clinical and neuropsychologic findings with neuroimaging studies to assess
the value of magnetic resonance spectroscopy in detection and monitoring of central nervous system disease of children
vertically infected with human immunodeficiency virus (HIV)-1 and receiving highly active antiretroviral therapy. Eight

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