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Biomedical subjects

A James Barkovich

Publications and source records attributed to A James Barkovich.

At least 19 recordsLinked to original sources
PubMed2006

Postnatal onset cortical dysplasia associated with infarction of white matter.

On MRI at 35 weeks of a boy born at 25 weeks, focal disorganization of the cortex was observed near a frontal venous infarct developed in the first week. Disruption of the final steps of cell migration, injury to the subplate and/or disruption of corticospinal axons are possible mechanisms behind it. Preterms with white matter lesions at or below 25 weeks postconceptional age should be scrutinized for cortical dysplasia.

Cerebral Cortex↗
PubMed2006

Candidate gene polymorphisms do not differ between newborns with stroke and normal controls.

BACKGROUND AND PURPOSE: Neonatal stroke is increasingly recognized with an estimated incidence of one in 4000 live births per year. Pathways involved in the pathophysiology of neonatal stroke are diverse and may include thrombosis and thrombolysis, vascular reactivity, and inflammation. METHODS: We compared frequencies of polymorphisms in genes regulating thrombosis and thrombolysis, nitric oxide, cytokines, vascular tone, and cell adhesion in a hospital-based cohort of 59 newborns with stroke relative to a random sample of 437 California newborns. RESULTS: Of the 31 polymorphisms evaluated, no variant allele was significantly more common than the reference allele in newborns with stroke than in the general population. CONCLUSIONS: Using a series of polymorphisms in pathways implicated in the etiology of stroke, newborns with stroke were not distinguished from a normal control group. Further studies are needed to determine the interaction of genetic polymorphisms with environmental risk factors in the pathogenesis of neonatal stroke.

Adolescent↗
PubMed2006

Central roles of the roof plate in telencephalic development and holoprosencephaly.

The roof plate is a well known signaling center in CNS development, but its roles in the developing telencephalon and the common holoprosencephaly (HPE) malformation have been uncertain. Using cellular ablations in mice, we show that roof plate cell loss causes failed midline induction and HPE in the dorsal telencephalon. This morphologic phenotype is accompanied by selective deficits in midline gene expression and a reduced activity gradient for bone morphogenetic proteins (Bmps), the major signals produced by the roof plate. In dissociated cells and mutant explants, exogenous Bmp4 is sufficient to mimic roof plate selectivity in midline gene regulation and to rescue roof plate-dependent midline patterning. Previously unrecognized neuroanatomical defects predicted by the mouse model are then confirmed in human HPE patients. These findings establish selective roles for roof plate-dependent Bmp signaling in dorsal telencephalic patterning and HPE and define novel candidate genes for the human disorder.

Animals↗
PubMed2006

An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation.

Cerebral palsy (CP) is defined as any nonprogressive motor deficits resulting from cerebral abnormalities that occur in the prenatal or perinatal period. Symptoms become apparent during the first year of life. Genetic forms of CP account for about 2% in European populations but are thought to cause a substantial proportion in consanguineous families. We have identified a large consanguineous family from Oman with spastic diplegia, microcephaly, and mental retardation. Additional manifestations include hyperreflexia, clumsiness, unstable gait, drooling, and dysarthria. There was phenotypic variability among different individuals, but spastic diplegia, microcephaly, and mental retardation were three constant traits present in all affected individuals.

Adolescent↗
PubMed2006

Factor analysis of neuroanatomical and clinical characteristics of holoprosencephaly.

The objective of this study is to better understand the relationship between neuroradiologic and clinical characteristics in holoprosencephaly (HPE) using the multivariate analysis called factor analysis. HPE is a brain malformation characterized by incomplete cleavage of the cerebral hemispheres and deep gray structures. We performed evaluations on 89 children with HPE that included their history, developmental assessment, and physical examination. Ten clinical variables included in factor analysis were the grade of spasticity, dystonia, choreoathetosis, hypotonia, mobility, upper extremity/hand function, expressive language, feeding/swallowing difficulty, endocrinopathies, and temperature dysregulation. Five neuroimaging variables graded by pediatric neuroradiologists were the grade of HPE (from least to most severe: lobar, semilobar, and alobar) and the degree of non-separation of caudate, lentiform, thalamic, and hypothalamic nuclei. Factor analysis using principle component extraction and varimax rotation was utilized. Four significant factors were identified: (1) neuroimaging/developmental factor, (2) motor factor, (3) hypothalamic/oromotor factor, and (4) hypotonia factor. These four factors accounted for 65.2% of the variance. In this factor analysis of HPE patients, we were able to reduce the large number of clinical and radiological variables into four factors. These factors and the constructs underlying them provide structure to the data and provide key parameters for future studies involving neurodevelopmental outcomes in HPE.

Brain↗
PubMed2006

Balloon atrial septostomy is associated with preoperative stroke in neonates with transposition of the great arteries.

BACKGROUND: Preoperative brain injury is common in neonates with transposition of the great arteries (TGA). The objective of this study is to determine risk factors for preoperative brain injury in neonates with TGA. METHODS AND RESULTS: Twenty-nine term neonates with TGA were studied with MRI before cardiac surgery in a prospective cohort study. Twelve patients (41%) had brain injury on preoperative MRI, and all injuries were focal or multifocal. None of the patients had birth asphyxia. Nineteen patients (66%) required preoperative balloon atrial septostomy (BAS). All patients with brain injury had BAS (12 of 19; risk difference, 63%; 95% confidence interval, 41 to 85; P=0.001). As expected on the basis of the need for BAS, these neonates had lower systemic arterial hemoglobin saturation (Sao2) (P=0.05). The risk of injury was not modified by the cannulation site for septostomy (umbilical versus femoral, P=0.8) or by the presence of a central venous catheter (P=0.4). CONCLUSIONS: BAS is a major identifiable risk factor for preoperative focal brain injury in neonates with TGA. Imaging characteristics of identified brain injuries were consistent with embolism; however, the mechanism is more complex than site of vascular access for BAS or exposure to central venous catheters. These findings have implications for the indications for BAS, timing of surgical repair, and use of anticoagulation in TGA.

Catheterization↗
PubMed2006

Pyramidal tract maturation after brain injury in newborns with heart disease.

OBJECTIVE: Our objective was to quantify white matter tract development in term newborns with congenital heart disease, a population at high risk for perioperative brain injury, using magnetic resonance imaging diffusion tensor tractography (DTT). METHODS: Twenty-five newborns with congenital heart disease were imaged before and after surgery, with a median of 2 weeks between serial magnetic resonance imaging examinations. DTT was performed to segment bilateral pyramidal tracts using semiautomated fiber tracking software, and manual region of interest measurements were taken for comparison. RESULTS: Significant maturational rates of increasing fractional anisotropy (median, 4.4% per week) and decreasing mean diffusivity (D(av)) (median, -2.0% per week) in the pyramidal tract were measured in infants without brain injury. Fractional anisotropy maturation rates were highest in newborns with normal scans, intermediate (median, 2.4% per week) in those with postoperative injury, and lowest (median, 0.9% per week) in those with preoperative injury, indicating a significant trend across brain injury groups (p = 0.015). D(av) maturation rates did not differ across injury groups (p = 0.15). Manual region of interest measures showed greater variability in serial measurements, and no significant differences were identified between injury groups, suggesting that DTT may provide more sensitive measures. INTERPRETATION: DTT is feasible in term newborns and may help to characterize abnormal white matter tract development following acquired brain injury.

Brain Injuries↗
PubMed2006

Neuroimaging abnormalities in infants with congenital hemiparesis.

Clinical and neuroimaging characteristics of congenital hemiparesis were examined in a retrospective cohort study nested within 199,176 births within the Kaiser Permanente Medical Care Program, 1997-2002. Infants with a physician diagnosis of paresis or cerebral palsy were electronically identified, and charts were reviewed to confirm congenital hemiparesis. A neuroradiologist reviewed available head MRI and CT scans. Of 96 infants with congenital hemiparesis (population prevalence 4.8 per 10,000), 81% received either a head magnetic resonance imaging (n = 55) or head computed tomography only (n = 23). Perinatal arterial infarction was the most common (30%) neuroimaging finding in term infants. Infants with right-sided hemiparesis (relative risk 4.6, 95% confidence interval 1.4-14.4) or moderate to severe weakness (relative risk 4.4, 95% confidence interval 1.1-17.7) were more likely to have had a perinatal arterial infarction. Periventricular white matter lesions predominated in preterm infants (71%). Brain malformations observed in 14 (18%) patients included polymicrogyria, heterotopia, and schizencephaly. The 14 infants (18%) with a normal head imaging study were more likely to outgrow all signs of hemiparesis by age 3 than were infants with an abnormal brain image (29% vs 0%, P < 0.001). Neuroimaging studies provide useful diagnostic and prognostic information in infants with congenital hemiparesis.

Brain↗
PubMed2006

Prolonged indomethacin exposure is associated with decreased white matter injury detected with magnetic resonance imaging in premature newborns at 24 to 28 weeks' gestation at birth.

OBJECTIVES: Newborns delivered before 28 weeks' gestation commonly have white matter lesions on MRI that are associated with adverse neurodevelopmental outcomes. Our objective was to determine the risk factors for MRI-detectable white matter injury in infants delivered before 28 weeks' gestation who were treated with prophylactic indomethacin. METHODS: This was a prospective cohort study conducted at the intensive care nursery at University of California San Francisco Children's Hospital. Patients included 57 premature newborns between 24 and 27 (+6 days) weeks' gestation at birth (October 1998 to October 2004). We identified perinatal and neonatal risk factors associated with moderate-severe "white matter injuries" (T1 signal abnormalities >2 mm or >3 areas of T1 abnormality) and moderate-severe "brain abnormality" (moderate-severe white matter injuries, any degree of ventriculomegaly, or severe intraventricular hemorrhage) on MRI. Infants were studied with MRI at 31.1 weeks' postmenstrual age (median). RESULTS: Moderate-severe white matter injuries were detected in 12 (21%) of 53 preterm newborns, and 20 (35%) of 57 had moderate-severe brain abnormality. Prolonged indomethacin exposure was the only risk factor independently associated with a lower risk of white matter injury or brain abnormality, even when adjusting for the presence of a hemodynamically significant PDA, gestational age at birth, prenatal betamethasone, systemic infection, and days of mechanical ventilation. CONCLUSIONS: In this observational study, a longer duration of indomethacin exposure was associated with less white matter injury in infants delivered before 28 weeks' gestation. A randomized trial of prolonged indomethacin treatment is needed to determine whether indomethacin can decrease white matter injury and neurodevelopmental abnormalities.

Brain↗
PubMed2006

Anomalies of the corpus callosum: an MR analysis of the phenotypic spectrum of associated malformations.

OBJECTIVE: We sought to categorize the structural brain anomalies associated with abnormalities of the corpus callosum and anterior and hippocampal commissures in a large cohort. MATERIALS AND METHODS: Brain MR images of adult and pediatric patients from our institution and from a national support organization (the ACC Network) were retrospectively evaluated for the type and severity of commissural anomalies and the presence and type of other structural abnormalities. RESULTS: Of 142 cases that were reviewed, 82 patients had agenesis of the corpus callosum (ACC), while 60 had hypogenesis of the corpus callosum (HCC). Of the overall cohort, almost all had reduced white matter volume outside the commissures, the majority had malformations of cortical development (most commonly heterotopia or abnormal sulcation), many had noncallosal midline anomalies (including abnormal anterior or hippocampal commissures and interhemispheric cysts and lipomas), and several patients had abnormalities of the cerebellum or brainstem. Sixty-six patients had Probst bundles, which were more common in patients with ACC than in those with HCC. Probst bundles were present in all four patients who had ACC or HCC but no other midline, cortical, or posterior fossa anomalies. CONCLUSION: Isolated commissural anomalies were rare in the populations of patients examined. Most cases of ACC and HCC were associated with complex telencephalic, diencephalic, or rhombencephalic malformations. Reduced cerebral hemispheric white matter volume and malformations of cortical development were seen in more than half of the patients, suggesting that many commissural anomalies are part of an overall cerebral dysgenesis. ACC and HCC appear to lie along a dysgenetic spectrum, as opposed to representing distinct disorders.

Adolescent↗
PubMed2005

Quantitative diffusion tensor MRI fiber tractography of sensorimotor white matter development in premature infants.

Diffusion tensor MRI (DTI) fiber tracking is the first non-invasive and in vivo technique for the delineation and quantitation of specific white matter pathways. In this study, quantitative fiber tracking was used to assess the structural development of the motor tract and somatosensory radiation in premature human newborns. These pathways are unmyelinated in the youngest premature infants and begin to myelinate during late preterm maturation. Previous studies have only been able to delineate parts of these pathways that could be manually outlined in 2D based on anatomical landmarks. Furthermore, these previous studies could not separate motor and sensory regions. A high-sensitivity neonatal head coil was employed in conjunction with an MR-compatible incubator to perform high-resolution imaging of the premature infant brain. The motor and somatosensory tracts were successfully delineated with 3D DTI fiber tracking in 37 exams of preterm newborns between 28 and 43 weeks gestational age. Both streamline deterministic and probabilistic methods were employed to perform quantitative fiber tractography. Tract-specific measurements of diffusion parameters including fractional anisotropy, directionally averaged diffusivity, and eigenvalues were obtained from the motor and sensory pathways. Using both deterministic and probabilistic fiber tracking, all tract-specific diffusion parameters were found to be significantly correlated with age and the motor tracts were found to have higher anisotropy and lower diffusivity than the sensory pathway. By segmenting the 3D fiber tracks by slice, measurements from different axial levels of the brain were found to vary with region and age. In summary, deterministic and probabilistic DTI fiber tracking methods were used to quantify the developmental changes of motor and somatosensory pathways in premature infants.

Adult↗
PubMed2005

Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes.

Human cerebral cortical polymicrogyria is a heterogeneous disorder, with only one known gene (GPR56) associated with an apparently distinctive phenotype, termed bilateral frontoparietal polymicrogyria (BFPP). To define the range of abnormalities that could be caused by human GPR56 mutations and to establish diagnostic criteria for BFPP, we analyzed the GPR56 gene in a cohort of 29 patients with typical BFPP. We identified homozygous GPR56 mutations in all 29 patients with typical BFPP. The total of 11 GPR56 mutations found represented a variety of distinct founder mutations in various populations throughout the world. In addition, we analyzed five patients with BFPP who did not show GPR56 mutation and found that they define a clinically, radiographically, and genetically distinct syndrome that we termed BFPP2. Finally, we studied seven patients with a variety of other polymicrogyria syndromes including bilateral frontal polymicrogyria, bilateral perisylvian polymicrogyria, and bilateral generalized polymicrogyria. No GPR56 mutation was found in these patients. This study provides a molecular confirmation of the BFPP phenotype and provides the wherewithal for diagnostic screening.

Adolescent↗
PubMed2005

Tractography-based quantitation of diffusion tensor imaging parameters in white matter tracts of preterm newborns.

PURPOSE: To evaluate the feasibility of performing diffusion tensor tractography (DTT) to map and quantify the pyramidal white matter tracts of premature newborns. MATERIALS AND METHODS: Fourteen diffusion tensor MRI (DTI) examinations of nine premature newborns were evaluated. DTT was performed to segment bilateral pyramidal tracts, using a fiber-tracking algorithm originating in the cerebral peduncle (CP) and filtering through the posterior limb of the internal capsule (PLIC) and precentral gyrus (PCG). Voxels containing the resulting tracts were then used for quantitation of DTI parameters along the tract. The DTT-based tract measurements were compared with standard manually placed region-of-interest (ROI) measurements at four locations along the pyramidal tract, and the reproducibility of each technique was evaluated. RESULTS: DTT demonstrated improved reproducibility over manual ROI measurement for pyramidal tract quantitation and was less subject to intra-operator variability (P < 0.0001, Fisher test for equal variance). In general, the anatomic locations and measurements obtained with the two techniques were in good agreement, although some systematic differences were identified in the PLIC and CP. CONCLUSION: Fiber DTT is feasible in premature newborns, provides more reproducible tract measurements than manual ROI methods, and allows quantitation along the entire tract for more detailed DTI assessment of white matter maturation.

Diffusion Magnetic Resonance Imaging↗
PubMed2005

Patterns of brain injury in term neonatal encephalopathy.

OBJECTIVES: To determine whether the pattern of brain injury in term neonatal encephalopathy is associated with distinct prenatal and perinatal factors and to determine whether the pattern of injury is associated with 30-month neurodevelopmental outcome. STUDY DESIGN: A total of 173 term newborns with neonatal encephalopathy from 2 centers underwent magnetic resonance imaging (MRI) at a median of 6 days of age (range, 1-24 days). Patterns of injury on MRI were defined on the basis of the predominant site of injury: watershed predominant, basal ganglia/thalamus predominant, and normal. RESULTS: The watershed pattern of injury was seen in 78 newborns (45%), the basal ganglia/thalamus pattern was seen in 44 newborns (25%), and normal MRI studies were seen in 51 newborns (30%). Antenatal conditions such as maternal substance use, gestational diabetes, premature rupture of membranes, pre-eclampsia, and intra-uterine growth restriction did not differ across patterns. The basal ganglia/thalamus pattern was associated with more severe neonatal signs, including more intensive resuscitation at birth ( P = .001), more severe encephalopathy ( P = .0001), and more severe seizures ( P = .0001). The basal ganglia/thalamus pattern was associated with the most impaired motor and cognitive outcome at 30 months. CONCLUSION: The patterns of brain injury in term neonatal encephalopathy are associated with different clinical presentations and neurodevelopmental outcomes. Measured prenatal risk factors did not predict the pattern of brain injury.

Brain Diseases↗
PubMed2005

Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome.

OBJECTIVE: To determine the neurodevelopmental outcome of prematurely born newborns with magnetic resonance imaging (MRI) abnormalities. STUDY DESIGN: A total of 89 prematurely born newborns (median age 28 weeks postgestation) were studied with MRI when stable for transport to MRI (median age, 32 weeks postgestation); 50 newborns were studied again near term age (median age, 37 weeks). Neurodevelopmental outcome was determined at 18 months adjusted age (median) using the Mental Development Index (Bayley Scales Infant Development II) and a standardized neurologic exam. RESULTS: Of 86 neonatal survivors, outcome was normal in 51 (59%), borderline in 22 (26%), and abnormal in 13 (15%). Moderate/severe MRI abnormalities were common on the first (37%) and second (32%) scans. Abnormal outcome was associated with increasing severity of white matter injury, ventriculomegaly, and intraventricular hemorrhage on MRI, as well as moderate/severe abnormalities on the first (relative risk [RR] = 5.6; P = .002) and second MRI studies (RR = 5.3; P = .03). Neuromotor abnormalities on neurologic examination near term age (RR = 6.5; P = .04) and postnatal infection (RR = 4.0; P = .01) also increased the risk for abnormal neurodevelopmental outcome. CONCLUSIONS: In premature newborns, brain abnormalities are common on MRI early in life and are associated with adverse neurodevelopmental outcome.

Brain Injuries↗
PubMed2005

Comparing microstructural and macrostructural development of the cerebral cortex in premature newborns: diffusion tensor imaging versus cortical gyration.

This study assessed microstructural development in four regions of the human cerebral cortex during preterm maturation using diffusion tensor imaging (DTI), compared to the macrostructural development of cortical gyration evaluated using three-dimensional volumetric T1-weighted MR imaging. Thirty-seven premature infants of estimated gestational age (EGA) ranging from 25 to 38 weeks were prospectively enrolled and imaged in an MR-compatible neonatal incubator with a high-sensitivity neonatal head coil. Cortical gyration was measured quantitatively as the ratio of gyral height to width on the volumetric MR images in four regions bilaterally (superior frontal, superior occipital, precentral, and postcentral gyri). Mean diffusivity (D(av)), fractional anisotropy (FA-the fraction of D(av) that is anisotropic), and the three DTI eigenvalues (components of diffusivity radial and tangential to the pial surface of cortex) were measured in the same cortical regions. Cortical gyration scores, FA, and radial diffusivity were all significantly correlated with EGA (P < 0.0001). However, in multivariate analysis, no significant relationship (P > 0.05) was found between DTI parameters and cortical gyration beyond their common association with estimated gestational age. Pre- and postcentral gyri had significantly lower anisotropy than the superior occipital and superior frontal gyri (P < 0.05), indicating that DTI is sensitive to regional heterogeneity in cortical development. Maturational changes in the DTI eigenvalues of cortical gray matter were found to differ from those that have previously been described in developing white matter, with a significant age-related decline in the radial diffusivity (P < 0.0001) but not in the tangential diffusivities (P > 0.05).

Algorithms↗