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1.
AJNR Am J Neuroradiol ; 30(9): 1799-803, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19556350

ABSTRACT

BACKGROUND AND PURPOSE: Previous studies of diffusion-weighted imaging (DWI) in fetuses are limited. Because of the need for normative data for comparison with young fetuses and preterm neonates with suspected brain abnormalities, we studied apparent diffusion coefficient (ADC) values in a population of singleton, nonsedated, healthy fetuses. MATERIALS AND METHODS: DWI was performed in 28 singleton nonsedated fetuses with normal or questionably abnormal results on sonography and normal fetal MR imaging results; 10 fetuses also had a second fetal MR imaging, which included DWI. ADC values in the periatrial white matter (WM), frontal WM, thalamus, basal ganglia, cerebellum, and pons were plotted against gestational age and analyzed with linear regression. We compared mean ADC in different regions using the Tukey Honestly Significant Difference test. We also compared rates of decline in ADC with increasing gestational age across different areas by using the t test with multiple comparisons correction. Neurodevelopmental outcome was assessed. RESULTS: Median gestational age was 24.28 weeks (range, 21-33.43 weeks). Results of all fetal MR imaging examinations were normal, including 1 fetus with a normal variant of a cavum velum interpositum. ADC values were highest in the frontal and periatrial WM and lowest in the thalamus and pons. ADC declined with increasing gestational age in periatrial WM (P = .0003), thalamus (P < .0001), basal ganglia (P = .0035), cerebellum (P < .0001), and pons (P = .024). Frontal WM ADC did not significantly change with gestational age. ADC declined fastest in the cerebellum, followed by the thalamus. CONCLUSIONS: Regional differences in nonsedated fetal ADC values and their evolution with gestational age likely reflect differences in brain maturation and are similar to published data in premature neonates.


Subject(s)
Brain/anatomy & histology , Brain/embryology , Diffusion Magnetic Resonance Imaging/methods , Pregnancy Trimester, Third , Brain/growth & development , Diffusion Magnetic Resonance Imaging/standards , Female , Humans , Male , Pregnancy , Reference Values , Reproducibility of Results , Sensitivity and Specificity , United States
2.
AJNR Am J Neuroradiol ; 30(6): 1142-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19246528

ABSTRACT

BACKGROUND AND PURPOSE: Patients with agenesis of the corpus callosum (AgCC) exhibit cognitive and behavioral impairments that are not replicated by surgical transection of the callosum, suggesting that other anatomic changes may contribute to the observed clinical findings. The purpose of this study was to determine whether the ventral cingulum bundle (VCB) is affected in patients with AgCC by using diffusion tensor imaging (DTI) and volumetry. MATERIALS AND METHODS: Twelve participants with AgCC (8 males and 4 females; mean age, 30 +/- 20) and 12 control subjects matched for age and sex (mean age, 37 +/- 19) underwent MR imaging and DTI at 3T. 3D fiber tracking of the VCB was generated from DTI and the average fractional anisotropy (FA) was computed for the tracked fibers. Additionally, the volume, cross-sectional area, and length of the VCB were measured by manually drawn regions of interest on thin-section coronal T1-weighted images. The Student t test was used to compare these results. RESULTS: Compared with controls, subjects with AgCC demonstrated significantly reduced FA in the right VCB (P = .0098) and reduced volume and cross-sectional areas of both the left and right VCB (P < .001 for all metrics). The length of the VCB was also significantly reduced in the complete AgCC subgroup compared with controls (P = .030 in the right and P = .046 in the left, respectively). CONCLUSIONS: Patients with AgCC have abnormal microstructure and reduced volume of the VCB, suggesting that abnormalities in intrahemispheric white matter tracts may be an important contributor to the clinical syndrome in patients with AgCC.


Subject(s)
Agenesis of Corpus Callosum , Corpus Callosum/pathology , Diffusion Magnetic Resonance Imaging/methods , Imaging, Three-Dimensional/methods , Adult , Female , Humans , Male , Organ Size , Reproducibility of Results , Sensitivity and Specificity
3.
AJNR Am J Neuroradiol ; 30(2): 282-9, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19001538

ABSTRACT

BACKGROUND AND PURPOSE: Little is known about the anatomic connectivity of callosal axons in individuals with partial agenesis of the corpus callosum (pAgCC). We used tractography based on both diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) to investigate interhemispheric white matter connectivity in pAgCC. MATERIALS AND METHODS: DTI and HARDI were performed at 3T on 6 individuals with pAgCC and 8 control subjects. For HARDI analysis, a Q-ball reconstruction method capable of visualizing multiple intravoxel fiber orientations was used. In both DTI and HARDI, whole-brain 3D fiber tractography was performed by using deterministic streamline algorithms. Callosal fibers were then segmented to identify separately connections between homologous cortical regions (homotopic fibers) and nonhomologous regions (heterotopic fibers) by using manually drawn regions of interest. RESULTS: In control individuals, we observed densely connected homotopic fibers. However, in individuals with pAgCC, we identified not only homotopic connections but also heterotopic connections in 4 of 6 subjects. Furthermore, the observed homotopic connections in pAgCC did not necessarily correlate with the position or size of the residual callosum. The nature of homotopic and heterotopic connectivity varied considerably among subjects with pAgCC, and HARDI recovered more callosal fibers than DTI. CONCLUSION: Individuals with pAgCC demonstrate a remarkable diversity of callosal connectivity, including a number of heterotopic tracts that are absent in healthy subjects. The patterns of their callosal connections cannot be predicted from the appearance of their callosal fragments on conventional MR imaging. More tracts and more extensive fibers within tracts are recovered with HARDI than with DTI.


Subject(s)
Acrocallosal Syndrome/pathology , Brain Diseases/pathology , Choristoma/pathology , Diffusion Magnetic Resonance Imaging/methods , Neural Pathways/pathology , Adolescent , Adult , Aged , Cerebral Cortex/pathology , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Models, Neurological , Nerve Fibers, Myelinated/pathology , Young Adult
4.
BMJ Case Rep ; 20092009.
Article in English | MEDLINE | ID: mdl-21731583

ABSTRACT

We identified a female patient with mental retardation and sensory hyperarousal. She has a de novo paracentric inversion of one X chromosome with completely skewed inactivation of the normal X chromosome. We aimed to identify whether a single gene or gene region caused her cognitive and behavioural impairment and that of others. Fluorescent in situ hybridisation (FISH) showed that the centromeric breakpoint disrupts a single gene: ARHGEF9 (CDC42 guanine nucleotide exchange factor (GEF) 9). We also found that the levels of the ARHGEF9 transcript from the patient are 10-fold less than those found in control samples. ARHGEF9 encodes a RhoGEF family protein: collybistin (hPEM), which is highly expressed in the brain. Collybistin can regulate actin cytoskeletal dynamics and may also modulate GABAergic and glycinergic neurotransmission through binding of a scaffolding protein, gephyrin, at the synapse. This potential dual role may explain both the mental retardation and hyperarousal observed in our patient.

5.
Neurology ; 71(21): 1676-82, 2008 Nov 18.
Article in English | MEDLINE | ID: mdl-18448871

ABSTRACT

OBJECTIVE: To determine if diffusion tensor imaging (DTI) metrics of the pyramidal tracts correlate with motor outcome in infants presenting with motor dysfunction. METHODS: DTI tractography of the pyramidal tracts was performed in 21 patients with clinical motor dysfunction who were less than 30 months of age and in 22 age-matched controls. We plotted tract-specific DTI metrics (fractional anisotropy, parallel diffusivity, transverse diffusivity, and mean diffusivity) against age for the controls and generated normative curves. For each patient, we calculated the deviation from the normative curves. Patients returned for a neurodevelopmental evaluation when they were over 36 months of age, and motor outcome measures were performed. We analyzed the association between normative deviation in DTI metrics and motor outcome measures using linear and logistic regression models. RESULTS: Normative deviation in fractional anisotropy and transverse diffusivity were significantly correlated with all measures of motor outcome. Lower fractional anisotropy and higher transverse diffusivity compared to controls were associated with worse motor outcome. Furthermore, children who were eventually diagnosed with permanent motor dysfunction had lower fractional anisotropy and higher transverse diffusivity compared with those whose motor dysfunction normalized. CONCLUSIONS: Diffusion tensor imaging metrics correlate with motor outcome in infants presenting with motor dysfunction. The identification of a quantitative imaging marker that can be applied to infants at the time of clinical presentation has implications for the evaluation of early motor dysfunction.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Movement Disorders/diagnosis , Pyramidal Tracts/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Image Processing, Computer-Assisted , Infant , Magnetic Resonance Imaging , Male , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Young Adult
6.
J Med Genet ; 45(2): 100-5, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17893116

ABSTRACT

INTRODUCTION: We identified a female patient with mental retardation and sensory hyperarousal. She has a de novo paracentric inversion of one X chromosome with completely skewed inactivation of the normal X chromosome. OBJECTIVE: We aimed to identify whether a single gene or gene region caused her cognitive and behavioural impairment and that of others. RESULTS: Fluorescent in situ hybridisation (FISH) showed that the centromeric breakpoint disrupts a single gene: ARHGEF9 (CDC42 guanine nucleotide exchange factor (GEF) 9). The telomeric break lies in a gene poor region. We also found that the levels of the ARHGEF9 transcript from the patient are 10-fold less than those found in control samples. Consequently, we sequenced the coding exons and intron/exon borders of the ARHGEF9 gene in 99 probands from families with X linked mental retardation (XLMR) and 477 mentally retarded males in whom a diagnosis of Fragile X syndrome had been excluded. We did not identify any pathogenic changes; however, we did identify intronic nucleotide changes that might alter splicing. CONCLUSION: ARHGEF9 encodes a RhoGEF family protein: collybistin (hPEM), which is highly expressed in the developing and adult brain. Collybistin can regulate actin cytoskeletal dynamics and may also modulate GABAergic and glycinergic neurotransmission through binding of a scaffolding protein, gephyrin, at the synapse. This potential dual role may explain both the mental retardation and hyperarousal observed in our patient. While ARHGEF9 appears to be an uncommon cause of mental retardation in males, it should be considered in patients with mental retardation and sensory hyperarousal.


Subject(s)
Arousal/genetics , Guanine Nucleotide Exchange Factors/genetics , Mental Retardation, X-Linked/genetics , Adolescent , Arousal/physiology , Chromosome Breakage , Chromosomes, Human, X/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Mental Retardation, X-Linked/psychology , Rho Guanine Nucleotide Exchange Factors
7.
AJNR Am J Neuroradiol ; 28(6): 1015-21, 2007.
Article in English | MEDLINE | ID: mdl-17569948

ABSTRACT

BACKGROUND AND PURPOSE: There is a lack of normative diffusion tensor imaging (DTI) and 3D MR spectroscopy (MRS) data in the early neonatal period. We report quantitative values from a cohort of healthy term neonates to serve as baseline data for studies assessing brain development and injury. MATERIALS AND METHODS: Sixteen healthy term neonates (median age, 7 days) were studied with spin-echo T1- and T2-weighted MR imaging, DTI, and 3D point-resolved spectroscopy sequence (PRESS) MRS without sedation on a 1.5 T scanner. Average diffusivity (D(av)), fractional anisotropy (FA), eigenvalues (EV), and metabolite ratios (N-acetylaspartate [NAA]/choline, lactate/choline) were calculated by automated processing in 7 brain regions. Neurodevelopment was assessed by blinded and validated neuromotor examinations and the Bayley II test at 3 and 14 months. RESULTS: Two neonates were excluded from the cohort: one had brain injury on T2-weighted imaging, and the other, who had normal MR imaging, showed mildly delayed cognition at 14 months. The mean DTI values of the remaining 14 neonates were between these ranges: D(av)=0.98-1.48 10(-3) mm(2)/s, FA=0.14-0.30, EV1=1.21-1.88, EV2=0.95-1.46, and EV3=0.77-1.24 (all x 10(-3) mm(2)/s). The NAA/choline ratio ranged between 0.58 and 0.73, and minimal lactate/choline (<0.15) could be detected in each neonate. All neonates exhibited clinically normal neuromotor status. CONCLUSIONS: Our study demonstrates the feasibility of obtaining high-quality quantifiable MR data in nonsedated healthy term neonates that can be used to study normal early brain development and as control data in studies of perinatal brain injury.


Subject(s)
Brain Chemistry , Brain/anatomy & histology , Brain/metabolism , Imaging, Three-Dimensional/methods , Infant, Newborn/growth & development , Magnetic Resonance Imaging/methods , Brain/growth & development , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Male , Reference Values , Sensitivity and Specificity
8.
Neurology ; 65(9): 1496-8, 2005 Nov 08.
Article in English | MEDLINE | ID: mdl-16275846

ABSTRACT

Absence of the corpus callosum is often associated with cognitive deficits, autism, and epilepsy. Using a genomic microarray, the authors analyzed DNA from 25 patients with radiographically confirmed callosal anomalies and identified three patients with de novo copy number changes in chromosome regions 2q37, 6qter, and 8p. Chromosomal deletions and duplications may be a relatively common cause of cerebral malformations.


Subject(s)
Agenesis of Corpus Callosum , DNA/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Nervous System Malformations/genetics , Child , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 2/genetics , Chromosomes, Human, Pair 6/genetics , Chromosomes, Human, Pair 8/genetics , Corpus Callosum/physiopathology , DNA/analysis , DNA Mutational Analysis , Female , Gene Dosage , Gene Duplication , Genetic Testing , Genomic Library , Humans , Male , Nervous System Malformations/complications , Oligonucleotide Array Sequence Analysis , Prospective Studies
9.
J Pediatr ; 139(4): 552-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11598603

ABSTRACT

OBJECTIVES: Opsoclonus-myoclonus-ataxia (OMA) syndrome affects 2% to 3% of patients with neuroblastoma. This study examined relationships between long-term neurobehavioral outcomes and potential biologic markers of OMA, including chronic changes on magnetic resonance imaging (MRI) brain scanning and prevalence of late antineuronal antibodies. STUDY DESIGN: Children with neuroblastoma and OMA were identified through medical record review of patients treated at the University of California at San Francisco Medical Center from 1979 to 1999. Eleven patients with a mean follow-up time of 7.6 years underwent standard neurologic, neurocognitive, developmental/behavioral, and academic assessments. Consenting patients underwent MRI brain scanning and a blood draw. Sera were analyzed for the presence of antineuronal immunoreactivity. RESULTS: Two (18%) patients had no observed neurologic abnormalities, 7 (64%) demonstrated mild deficits, and 2 (18%) had severe neurologic deficits. However, on neurocognitive, behavioral, and academic assessments, 6 (55%) children performed within the average range, 1 (9%) was moderately below average and 4 (36%) had severe cognitive and behavioral deficiencies. Brain MRI in 5 of 5 patients was notable for cerebellar atrophy without supratentorial involvement. Antineuronal activity was detected in sera of 0 of 10 children at follow-up. CONCLUSIONS: Certain patients with neuroblastoma associated OMA may achieve average-range neurobehavioral function in spite of residual neurologic abnormalities, with suggestion of continued improvement over time. Late cerebellar atrophy appears to be a common finding regardless of neurologic outcome, whereas antineuronal immune reactivity does not appear to be a long-term feature of OMA.


Subject(s)
Antibodies, Neoplasm/blood , Autoantibodies/blood , Brain Neoplasms/complications , Brain Neoplasms/pathology , Child Behavior Disorders/etiology , Child Behavior Disorders/pathology , Developmental Disabilities/etiology , Developmental Disabilities/pathology , Magnetic Resonance Imaging , Nervous System Diseases/etiology , Nervous System Diseases/pathology , Neuroblastoma/complications , Neuroblastoma/pathology , Paraneoplastic Syndromes, Nervous System/complications , Paraneoplastic Syndromes, Nervous System/pathology , Biomarkers/blood , Brain/immunology , Brain/pathology , Brain Neoplasms/blood , Child Behavior Disorders/blood , Child, Preschool , Developmental Disabilities/blood , Humans , Infant , Nervous System Diseases/blood , Neuroblastoma/blood , Paraneoplastic Syndromes, Nervous System/blood , Prognosis , Time Factors
12.
Child Dev ; 55(4): 1141-54, 1984 Aug.
Article in English | MEDLINE | ID: mdl-6488949

ABSTRACT

As part of a longitudinal study of offspring born to substance abusers, we videotaped 17 methadone-exposed and 23 comparison 4-month-old infants interacting with their mothers. Using a scale we developed, we rated communicative functioning in dyadic interaction and related mothers' interactive performance to their psychological and psychosocial resources and infants' interactive performance to their motor functioning as assessed on the Bayley Infant Behavior Record. We found, cutting across drug groups, that mothers who performed poorly on interaction were likely to have poor maternal resources and that infants showing poor communicative functioning were likely to show problematic motor functioning--namely, greater tension and poorer coordination relative to activity level; it was the opposite for mothers or infants who communicated well. Methadone was only one among several risk factors affecting interaction.


Subject(s)
Methadone/adverse effects , Mother-Child Relations , Prenatal Exposure Delayed Effects , Adolescent , Adult , Female , Humans , Infant , Longitudinal Studies , Maternal Behavior , Mothers/psychology , Motor Activity , Motor Skills , Pregnancy , Risk
13.
Am J Drug Alcohol Abuse ; 10(2): 161-93, 1984.
Article in English | MEDLINE | ID: mdl-6475886

ABSTRACT

As part of a longitudinal study of offspring born to substance abusers, we assessed 17 methadone-exposed and 23 comparison 4-month-old infants using the Bayley Scales, and videotaped their interaction with their mothers. In analyzing the Bayley Infant Behavior Record we found that the methadone-exposed group differed from the comparison group on motor functioning but not significantly on social or cognitive behaviors; methadone-exposed infants were more tense, active, and poorly coordinated than comparisons. Using a scale we developed, we rated communicative functioning in dyadic interactions, and related mothers' interactive performance to their psychological and psychosocial resources and infants' interactive performance to their behavioral functioning as assessed on the Bayley Infant Behavior Record. Applying a multidimensional technique, Guttman's Partial Order Scalogram Analysis by Coordinates (POSAC), we found an intriguing relationship that generalized across drug and comparison groups: greater tension than activity, with high tension especially, related to poorer functioning, but tension lower than activity related to better functioning. Specifically, infants who were tense and not active were also poorest on social functioning (low responsiveness to people and low cooperativeness) and showed short attention span and low persistence combined with high interest in sights and sounds. On the other hand, infants who showed low-to-moderate tension and moderate-to-high activity were highly responsive and cooperative; some also had long attention span and high persistence coupled with interest in sights and sounds. Infants who were both very tense and very active were poor on social functioning. Furthermore, most infants with tension higher than activity did poorly in communicating with their mothers, while infants with tension lower than activity interacted well. The POSAC technique has enabled us to identify meaningful subgroups of infants who were not merely quantitatively but qualitatively different in their behavioral functioning. Cutting across drug and comparison groups, we found that mothers who performed poorly on interaction were likely to have poor resources for maternal functioning. Methadone was only one among the risk factors affecting interaction.


Subject(s)
Child Development/drug effects , Heroin Dependence/rehabilitation , Methadone/adverse effects , Mother-Child Relations , Pregnancy Complications/rehabilitation , Child Behavior/drug effects , Cognition/drug effects , Communication , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Methadone/therapeutic use , Motor Activity/drug effects , Motor Skills/drug effects , Pregnancy , Psychological Tests , Social Adjustment
14.
Am J Drug Alcohol Abuse ; 10(2): 195-207, 1984.
Article in English | MEDLINE | ID: mdl-6475887

ABSTRACT

Infants exposed to methadone in utero were compared to infants of drug-free women at 4, 8, and 12 months on two aspects of their behavior: motor coordination and attention. The purpose of this paper is to discuss how differences between the methadone and comparison infants were affected by other family and medical risk factors. No matter what the level of other risk factors, methadone infants showed poorer motor coordination at 4 months and poorer attention at 12 months as a group than comparison infants. Family risk factors, however, did modulate the strength and direction of differences between methadone and comparison infants. After 4 months, methadone infants continued to show poorer motor coordination than comparison infants only in families with poorer resources (such as low SES, maternal psychopathology and low intelligence, absence of father). Poorer early medical resources (pre- and perinatal complications) heightened the differences between methadone and comparison infants at early ages, but by the end of the first year no longer played a role in modulating the drug effect. The authors tentatively conclude that methadone exposure in utero has very limited teratological effects per se on the long-term development of infants, and that the pathology seen in some individual children is probably due to an interaction with other factors.


Subject(s)
Child Development/drug effects , Heroin Dependence/rehabilitation , Methadone/adverse effects , Pregnancy Complications/rehabilitation , Attention/drug effects , Child Behavior/drug effects , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Methadone/therapeutic use , Motor Skills/drug effects , Pregnancy , Risk , Social Environment
15.
Neurobehav Toxicol Teratol ; 4(4): 459-62, 1982.
Article in English | MEDLINE | ID: mdl-7121697

ABSTRACT

Motor and state functioning of 20 infants born to methadone-maintained women and 25 born to controls was assessed at 1 day and 1 month of age using Brazelton Neonatal Behavioral Assessment Scale with Kansas Supplements (NBAS-K). The infants were of mothers who were Black, of low SES, between the ages of 18 and 35 years, and who had good prenatal care. Motor behaviors were scored on NBAS-K items: General Tonus, Motor Maturity, and Tremulousness. State behaviors were scored on 2 items: Alertness and General Irritability. Guttman's Multidimensional Scalogram Analysis (MSA) of individual profiles revealed an orthogonal relationship between motor and state functioning, with motor functioning being a much clearer discriminator between methadone and non-methadone infants than state functioning. With age, both groups generally improved, but non-methadone infants maintained some of their advantage in motor functioning. Both groups showed a variety of behavior patterns during the neonatal period. The results suggest that methadone acts differentially on CNS functioning, with strong effects on neuro-motor functioning.


Subject(s)
Child Development/drug effects , Methadone/adverse effects , Motor Skills/drug effects , Adolescent , Adult , Female , Follow-Up Studies , Heroin Dependence/rehabilitation , Humans , Infant , Infant, Newborn , Longitudinal Studies , Methadone/therapeutic use , Motor Activity/drug effects , Nervous System Diseases/chemically induced , Pregnancy , Psychological Tests , Substance Withdrawal Syndrome/diagnosis
16.
Neurobehav Toxicol Teratol ; 4(4): 473-6, 1982.
Article in English | MEDLINE | ID: mdl-7121699

ABSTRACT

Motor functioning of 38 infants, 15 exposed in utero to methadone, was assessed on Brazelton Neonatal Behavioral Assessment Scale with Kansas Supplements (NBAS-K) (Items: General Tonus, Motor Maturity, Activity, and Tremulousness) at 1 day, and at 4 months on Bayley Infant Behavior Record (IBR) (Items: Tension, Activity, Interest in Body Motion, Gross Coordination, and Fine Coordination). At 4 months, methadone infants generally showed a profile of poorer motor coordination, greater tenseness and interest in body motion, and higher activity level than did non-methadone infants. Guttman's Multidimensional Scalogram Analysis (MSA) of the 5 IBR motor-item profiles showed that a line can be drawn that almost perfectly discriminates the methadone and non-methadone infants by their joint performance on these 5 variables. A scatterplot of each infant's sum scores of the Brazelton versus IBR motor items revealed a significant correlation between 1-day and 4-month motor functioning. Methadone infants showed poorer motor functioning at both ages. This analysis of behavioral continuity again revealed an almost perfect discrimination between the two groups.


Subject(s)
Methadone/adverse effects , Motor Activity/drug effects , Motor Skills/drug effects , Female , Heroin Dependence/rehabilitation , Humans , Infant , Infant, Newborn , Male , Methadone/therapeutic use , Muscle Tonus/drug effects , Pregnancy , Psychological Tests , Tremor/chemically induced
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