Biomedical subjects

Steven P Miller

Publications and source records attributed to Steven P Miller.

At least 19 recordsLinked to original sources

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

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

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↗

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

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

Cerebral oxygen balance is impaired during repair of aortic coarctation in infants and children.

OBJECTIVE: During repair of aortic coarctation through a left thoracotomy without cardiopulmonary bypass, clamping the proximal transverse aortic arch occludes antegrade flow to the left carotid and vertebral arteries. It is assumed that flow through the right carotid and vertebral arteries is adequate for cerebral perfusion. The study objective is to determine whether aortic occlusion impairs left hemispheric cerebral oxygen balance measured by near-infrared spectroscopy. METHODS: In 18 children having repair of aortic coarctation, we measured the maximum change and integral for hemoglobin D (difference of oxyhemoglobin and deoxyhemoglobin), total oxygenation index, and the redox state of cytochrome aa3. Thirteen subjects had recordings from the left hemisphere to test the hypothesis that aortic occlusion impairs left hemispheric oxygen balance. Five subjects had recordings from the right hemisphere for comparison. RESULTS: After aortic clamping, a significant decrease in hemoglobin D was observed in recordings from the left hemisphere compared with those from the right hemisphere (P = .03, maximum change in hemoglobin D). Total oxygenation index and cytochrome aa3 were generally preserved. There was an inverse linear relationship for the change in hemoglobin D during clamp application and after removal (Spearman rho = -0.74), with increased hemoglobin D after clamp removal in those subjects with the greatest decrease of hemoglobin D during arch occlusion. Linear regression analysis identified nitroprusside administration as significantly associated with a decrease in hemoglobin D (P < .001). CONCLUSIONS: Significant impairment in left hemispheric cerebral oxygen balance was identified during arch clamping. The neurodevelopmental significance of impaired cerebral oxygen balance detected by near-infrared spectroscopy during aortic coarctation repair remains to be elucidated.

Aorta, Thoracic↗

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↗

PubMed2005

Infant botulism, type F, presenting at 54 hours of life.

We report a case of botulism in a 54-hour-old infant with rapidly progressive fulminant paralysis and rapid spontaneous recovery atypical for infant botulism. Clostridium baratii and type F botulinum neurotoxin were isolated from the patient's stool. This unique presentation with rapid recovery is consistent with pharmacokinetics of type F botulinum neurotoxin. Interestingly, a muscle biopsy also revealed pathologic changes early in the disease course. This article reports the youngest known case of infant botulism and only the third reported case of this disease caused by type F neurotoxin. Botulism should be considered in patients of any age with subacute or acute neuromuscular weakness.

Acute Disease↗

PubMed2005

Type I spinal muscular atrophy can mimic sensory-motor axonal neuropathy.

Spinal muscular atrophy is a group of allelic autosomal recessive disorders characterized by progressive motoneuron loss, symmetric weakness, and skeletal muscle atrophy. It is traditionally considered a pure lower motoneuron disorder, for which a current definitive diagnosis is now possible by molecular genetic testing. We report two newborns with a clinical phenotype consistent with that of spinal muscular atrophy type I and nerve conduction studies and electromyography suggesting more extensive sensory involvement than classically described with spinal muscular atrophy. Molecular testing confirmed spinal muscular atrophy in patient 1 but not in patient 2. Thus, in the setting of a suspected congenital axonal neuropathy, molecular testing might be necessary to distinguish spinal muscular atrophy type I from infantile polyneuropathy.

Diagnosis, Differential↗

PubMed2004

Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome.

In term neonatal encephalopathy, little is known about the relationship between early inflammatory markers, neonatal brain injury, and long-term neurodevelopmental outcome. Our goal was to determine whether neonatal serum cytokine levels are associated with cerebral metabolism assessed by proton magnetic resonance spectroscopy (MRS), with magnetic resonance imaging (MRI) abnormalities, and with neurodevelopmental outcome at 30 mo of age. Levels of seven cytokines [IL-1 beta, IL-6, IL-8, IL-9, IL-12, IL-13, and tumor necrosis factor (TNF)-alpha] were measured in dried neonatal blood by immunoaffinity chromatography in a prospective cohort of 62 term newborns at risk of neonatal encephalopathy. MR images (n = 61) were scored and lactate/choline and N-acetyl-aspartate (NAA)/choline were measured by MRS (n = 42) on median day of life 6 in the deep gray nuclei (DGN) and in the watershed/cortical zone (WS). Neurodevelopmental outcome (n = 54) was considered abnormal if the infant died or if cognitive delay and/or functional motor deficit were detected at 30 mo. IL-1 beta, IL-6, IL-8 and TNF-alpha were significantly associated with lactate/choline in the DGN (p = 0.03, 0.02, 0.03, and 0.01 respectively), but not in the WS (all p > 0.1). Cytokines were not associated with NAA/choline in any region or with MRI scores. Children with abnormal neurodevelopmental outcome had higher neonatal levels of IL-1 beta, IL-6, IL-8, and lower levels of IL-12 (p = 0.04, 0.03, 0.01, 0.03 respectively). Elevated inflammatory cytokines were associated with impaired cerebral oxidative metabolism, but not with detectable MRI changes in the neonatal period. Understanding the link between elevated cytokines and outcome would inform novel strategies of cerebral protection.

Biomarkers↗

PubMed2004

Catalytic asymmetric carbohydroxylation of alkenes by a tandem diboration/Suzuki cross-coupling/oxidation reaction.

[reaction: see text] Chiral nonsymmetric 1,2-diboron adducts are generated by catalytic enantioselective diboration. Oxidation of these adducts provides 1,2-diols in good yield. Alternatively, 1,2-diboron compounds may be reacted, in situ, with aryl halides wherein the less hindered C-B bond participates in cross-coupling. The remaining C-B bond is then oxidized in the reaction workup thereby allowing for net asymmetric carbohydroxylation of alkenes in a tandem one-pot diboration/Suzuki coupling/oxidation sequence.

Alkenes↗

PubMed2004

Preoperative brain injury in newborns with transposition of the great arteries.

BACKGROUND: The objective was to determine the timing and mechanism of brain injury using preoperative and postoperative magnetic resonance imaging (MRI) and three-dimensional MR spectroscopic imaging (MRSI) in newborns with transposition of the great arteries (TGA) repaired with full-flow cardiopulmonary bypass. METHODS: Ten term newborns with TGA undergoing an arterial switch operation were studied with MRI, MRSI, and neurologic examination preoperatively and postoperatively at a median of 5 days (2 to 9 days) and 19 days (14 to 26 days) of age, respectively. Five term historical controls were studied at a median of 4 days (3 to 9 days). Lactate/choline (marker of cerebral oxidative metabolism) and N-acetylaspartate (NAA)/choline (marker of cerebral metabolism and density) were measured bilaterally from the basal ganglia, thalamus, and corticospinal tracts. RESULTS: Four TGA newborns had brain injury on the preoperative MRI. The only new lesion detected on the postoperative study was a focal white matter lesion in one newborn with a normal preoperative MRI. The MRSI of age-adjusted lactate/choline was quantitatively higher in newborns with TGA compared with those without heart disease (p < 0.0001), even in newborns without MRI evidence of preoperative brain injury. Lactate/choline decreased after surgery but remained elevated compared with controls. In newborns with TGA, those with preoperative brain injury on MRI had lower NAA/choline globally (p = 0.04) than those with normal preoperative MRI. Five newborns had a decline in NAA/choline from the preoperative to postoperative studies. CONCLUSIONS: Abnormal brain metabolism and injury was observed preoperatively in newborns with TGA. Brain injury is not solely related to the operative course.

Brain Injuries↗

PubMed2004

Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia.

OBJECTIVES: To determine if the incidence of sonographically detected cystic periventricular leukomalacia (PVL) and periventricular hemorrhagic infarction (PVHI) have changed over the past decade and to determine if a decline in cystic PVL was associated with a change in neurodevelopmental outcome. STUDY DESIGN: Premature newborn infants admitted to our intensive care nursery from 1992 to 2002 were identified in a comprehensive nursery database. Premature newborn infants had routine neurosonography by means of a standardized protocol. Infants weighing < or =1500 g at birth surviving to nursery discharge were enrolled in a nursery follow-up clinic. RESULTS: Adjusting for gestational age, there was a significant decrease in cystic PVL from 1992 to 2002 (P=.003) without a concurrent decrease in PVHI (P=0.5). Cystic PVL and PVHI accounted for only 9 of the 28 cases of cerebral palsy and 12 of 90 cases of abnormal Developmental Scores in infants weighing <1500 g at birth. The decline in cystic PVL was not associated with improved developmental outcome from 1992 to 2002. CONCLUSIONS: The incidence of cystic PVL declined significantly from 1992 to 2002 at our center. Cystic PVL was detected by ultrasound in a minority of infants with abnormal neurodevelopmental outcome, indicating that other forms of cerebral injury account for the majority of abnormal neurodevelopmental outcomes in premature newborn infants.

Brain↗

PubMed2004

Single-shot fast spin-echo diffusion tensor imaging of the brain and spine with head and phased array coils at 1.5 T and 3.0 T.

In this study, we investigated the use of a single-shot fast spin-echo-based sequence to perform diffusion tensor imaging (DTI) with improved anatomic fidelity through the entire brain and the cervical spine. Traditionally, diffusion tensor images have been acquired by single-shot echo-planar imaging (EPI) methods in which large distortions result from magnetic susceptibility effects, especially near air-tissue interfaces. These distortions can be problematic, especially in anterior and inferior portions of the brain, and they also can severely limit applications in the spine. At higher magnetic fields these magnetic susceptibility artifacts are increased. The single-shot fast spin-echo (SSFSE) method used in this study utilizes radiofrequency rephasing in the transverse plane and thus provides diffusion images with negligible distortion even at 3 Tesla. In addition, the SSFSE sequence does not require multiple fast-receivers, which are not available on many magnetic resonance (MR) systems. Phased array coils were used to increase the signal-to-noise ratio of the images, offering a major inherent advantage in diffusion tensor imaging of the spine and brain. The mean diffusion measurements obtained with the SSFSE acquisition were not statistically different (p > 0.05) from EPI-based acquisitions. Compared to routine T(2)-weighted MR images, the DTI-EPI sequence showed up to 20% in elongation of the brain in the anterior-posterior direction on a sagittal image due to magnetic susceptibility distortions, whereas in the DTI-SSFSE, the image distortions were negligible. The diffusion tensor SSFSE method was also able to assess diffusion abnormalities in a brain stem hemorrhage, unaffected by the spatial distortions that limited conventional EPI acquisition.

Adult↗

PubMed2004

Early laminar organization of the human cerebrum demonstrated with diffusion tensor imaging in extremely premature infants.

Diffusion tensor imaging (DTI) was used to delineate early laminar organization of the cerebrum in two extremely premature infants imaged postnatally at estimated ages of 25 and 27 menstrual weeks. The diffusivity and anisotropy of the cortical plate, subplate zone, intermediate zone, subventricular and periventricular zones, and germinal matrix are examined. Automated segmentation of diffusion tensor images to reveal the laminar architecture of the developing human cerebrum is also demonstrated.

Aging↗