Aberrant Structural Brain Connectivity in Adolescents with Attentional Problems Who Were Born Prematurely.

BACKGROUND AND PURPOSE: Differences in structural brain connectivity that underlie inattention have been previously investigated in adolescents with attention deficit/hyperactivity disorder, but not in the context of premature birth, which is often associated with attentional problems. The purpose of this study was to identify the neural correlates of attentional problems in adolescents born prematurely and determine neonatal predictors of those neural correlates and attention problems. MATERIALS AND METHODS: The study included 24 adolescents (12.5 ± 1.8 years of age; 12 girls, 12 boys) who were born prematurely and underwent MR imaging of the brain and cognitive assessment, both shortly after birth and as adolescents. Structural connectivity was assessed at adolescence using diffusion tensor imaging and tractography. RESULTS: Of the 24 subjects, 12 had attention deficits. A set of axonal pathways connecting the frontal, parietal, temporal, and occipital lobes had significantly lower fractional anisotropy in subjects with attentional problems. The temporoparietal connection between the left precuneus and left middle temporal gyrus was the most significantly underconnected interlobar axonal pathway. Low birth weight and ventriculomegaly, but not white matter injury or intraventricular hemorrhage on neonatal MR imaging, predicted temporoparietal hypoconnectivity in adolescence. However, neither birth weight nor other neonatal characteristics were associated with attention deficits directly. CONCLUSIONS: We identified an aberrant structural brain connectivity pattern, involving temporoparietal hypoconnectivity, in prematurely born adolescents with attentional problems. We also identified birth weight as a potential neonatal predictor of the temporoparietal hypoconnectivity. These findings add to our understanding of the neural basis and etiology of inattention in adolescents after premature birth.

Cooling in neonatal hypoxic-ischemic encephalopathy: practices and opinions on minimum standards in the state of California.

OBJECTIVE: Although hospitals increasingly offer therapeutic hypothermia (TH), there is variable implementation of related services. We assessed current practices and opinions regarding what services should be required of centers providing TH in California. STUDY DESIGN: We surveyed neonatal intensive care unit physicians statewide regarding practices and opinions about services related to TH. RESULTS: Of the 50 participating centers (47% response rate), 66% offer TH. Most TH centers reported using: an evidence-based protocol (92%), neurology consultation (92%), amplitude-integrated electroencephalography (aEEG) or EEG (88%), magnetic resonance imagings (MRIs) interpreted by pediatric neuroradiologists (71%) and developmental follow-up (93%). TH centers reported treating a median of 11 patients annually (interquartile range (IQR) 4 to 24). Respondents considered it 'critical' that TH centers offer: aEEG monitoring (70%), MRI (69%), occupational and physical therapy (67%) and developmental follow-up (94%). Over 70% thought TH centers should treat a minimum volume annually (median=10, IQR 5 to 12). CONCLUSION: Physicians across practice settings in California endorsed minimum standards for TH centers to promote quality of care.

Continuous Video Electroencephalographic (EEG) Monitoring for Electrographic Seizure Diagnosis in Neonates: A Single-Center Study.

The objective of this study was to determine the diagnostic yield of continuous video electroencephalographic (EEG) monitoring in critically ill neonates in the setting of a novel, university-based Neonatal Neurocritical Care Service. Patient demographic characteristics, indication for seizure monitoring, and presence of electrographic seizures were obtained by chart review. Among 595 patients cared for by the Neonatal Neurocritical Care Service, 400 (67%) received continuous video EEG. The median duration of continuous video EEG monitoring was 49 (interquartile range = 22-87) hours. Electrographic seizures were captured in 105 of 400 (26% of monitored patients) and of those, 25 of 105 (24%) had no clinical correlate. In addition, 52 of 400 subjects (13%) were monitored due to paroxysmal events concerning for seizures, but never had electrographic seizures. Continuous video EEG monitoring helped confirm or rule out ongoing seizures in more than one-third of the cases. This finding helps to support the use of continuous video EEG in critically ill neonates.

Therapeutic hypothermia for neonatal encephalopathy results in improved microstructure and metabolism in the deep gray nuclei.

BACKGROUND AND PURPOSE: Therapeutic hypothermia has reduced morbidity and mortality and is associated with a lower burden of lesions on conventional imaging in NE. However, its effects on brain microstructure and metabolism have not been fully characterized. We hypothesized that therapeutic hypothermia improves measures of brain microstructure and metabolism. MATERIALS AND METHODS: Forty-one neonates with moderate/severe NE (29 treated with hypothermia, 12 nontreated) and 12 healthy neonates underwent MR imaging, DTI, and (1)H-MR spectroscopy. MR imaging scans were scored by the predominant pattern of brain injury: normal, watershed, and BG/thalamus. ADC, FA, Lac:NAA, and NAA:Cho values from bilateral BG and thalamus ROIs were averaged. T test and linear regression analysis were used to determine the association between hypothermia and MR imaging quantitative measures. RESULTS: Conventional MR imaging findings were normal in 41% of treated neonates; all nontreated neonates had brain injury. Values of MR imaging metrics were closer to normal in treated neonates compared with nontreated neonates: ADC was 63% higher in the BG and 116% higher in the thalamus (both P < .05), and Lac:NAA was 76% lower (P = .04) in the BG. Treated neonates with normal MR imaging findings had normal (1)H-MR spectroscopy metabolites, and ADC was higher by 35% in the thalamus (P = .03) compared with healthy neonates. CONCLUSIONS: Therapeutic hypothermia may reduce disturbances of brain metabolism and preserve its microstructure in the setting of NE, possibly by minimizing cytotoxic edema and cell death. Long-term follow-up studies are required to determine whether early post-treatment DTI and (1)H-MR spectroscopy will be useful biomarkers of treatment response.

Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

BACKGROUND: Therapeutic hypothermia (TH) is becoming standard of care in newborns with hypoxic-ischemic encephalopathy (HIE). The prognostic value of the EEG and the incidence of seizures during TH are uncertain. OBJECTIVE: To describe evolution of EEG background and incidence of seizures during TH, and to identify EEG patterns predictive for MRI brain injury. METHODS: A total of 41 newborns with HIE underwent TH. Continuous video-EEG was performed during hypothermia and rewarming. EEG background and seizures were reported in a standardized manner. Newborns underwent MRI after rewarming. Sensitivity and specificity of EEG background for moderate to severe MRI brain injury was assessed at 6-hour intervals during TH and rewarming. RESULTS: EEG background improved in 49%, remained the same in 38%, and worsened in 13%. A normal EEG had a specificity of 100% upon initiation of monitoring and 93% at later time points. Burst suppression and extremely low voltage patterns held the greatest prognostic value only after 24 hours of monitoring, with a specificity of 81% at the beginning of cooling and 100% at later time points. A discontinuous pattern was not associated with adverse outcome in most patients (73%). Electrographic seizures occurred in 34% (14/41), and 10% (4/41) developed status epilepticus. Seizures had a clinical correlate in 57% (8/14) and were subclinical in 43% (6/14). CONCLUSIONS: Continuous video-EEG monitoring in newborns with HIE undergoing TH provides prognostic information about early MRI outcome and accurately identifies electrographic seizures, nearly half of which are subclinical.

Quantitative fiber tracking of the optic radiation is correlated with visual-evoked potential amplitude in preterm infants.

BACKGROUND AND PURPOSE: Children born preterm are at risk for adverse outcome, including visual impairment. We examined the relationship between neonatal DTI and sVEP in children born preterm to determine whether visual outcomes are related to early measurements of brain microstructure. MATERIALS AND METHODS: Subjects were born at <34 weeks gestation and imaged before term-equivalent age. DTI fiber tracking was used to delineate the optic radiations and measure tract-specific average FA, D(av), and parallel and transverse diffusivity. Visual-evoked response amplitudes were measured as a function of spatial frequency, contrast, and vernier offset size with sVEP at 6-20 months after birth. The association between DTI and sVEP was assessed by using the Spearman correlation coefficient and linear regression for repeated measures. RESULTS: Nine children with 15 scans were included. The peak response amplitudes for spatial frequency sweeps were associated with increasing FA and decreasing D(av) and transverse diffusivity (P ≤ .006) but not with parallel diffusivity (P = 1). There was only modest association with the swept contrast condition and no detectable association with the vernier offset sweeps. CONCLUSIONS: Microstructure of the optic radiations measured shortly after birth is associated with quantitatively measured responses elicited by moderate-to-high contrast spatiotemporal gratings in infancy. These findings are in keeping with studies showing a relationship between brain microstructure and function. While the clinical impact is not known, quantitative neuroimaging of white matter may ultimately be important for predicting outcome in preterm neonates.

Normative apparent diffusion coefficient values in the developing fetal brain.

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.

Quantitative fiber tracking analysis of the optic radiation correlated with visual performance in premature newborns.

BACKGROUND AND PURPOSE: Many prematurely born neonates have abnormalities of vision or visual processing. This study tests the hypothesis that a correlation exists between the microstructure of the optic radiation and visual performance in premature neonates. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed on 36 premature neonates ranging in age from 29 to 41 weeks of gestational age (GA) at time of MR imaging. DTI fiber tracking methods were developed to delineate the optic radiations and segment the tract into anterior, middle, and posterior regions. Structural development and spatial heterogeneity in the delineated optic radiations were quantitatively assessed with diffusion tensor parameters including fractional anisotropy (FA), directionally averaged diffusivity (D(av)), parallel diffusivity (lambda(1)), and transverse diffusivity (lambda( perpendicular)). Visual maturity of the preterm neonates at the time of MR imaging was assessed with a visual fixation task. Regression analysis was used to examine the relationship between neonatal visual performance and the microstructure of the optic radiation. RESULTS: Fractional anisotropy within the optic radiation was observed to increase with GA (P < .0001). D(av), parallel diffusivity, and transverse diffusivity within the optic radiation each decreased with GA (P < .0003, P < .02, and P < .0001, respectively). The anterior segment of the optic radiation exhibited higher FA and lower D(av), parallel diffusivity, and transverse diffusivity (P < .005 each) than within the middle and posterior segments. Optic radiation fractional anisotropy correlated significantly with scores from the visual fixation tracking assessment, independent of GA (P < .006). CONCLUSIONS: This study detected a significant link between the tissue architecture of the optic radiation and visual function in premature neonates.

A study on the nature of genetic metabolic practice at a major paediatric referral centre.

A retrospective chart review of new paediatric patients seen during the calendar year 1998 by specialists of the Division of Clinical and Metabolic Genetics of the Hospital for Sick Children in Toronto, the largest such referral centre in the country, showed that 81% of specific genetic metabolic diagnoses were made within one month of being seen in consultation by one of the consultants of the programme. In 5% of cases, a specific diagnosis was not reached 4 years after initial consultation. We concluded from this study that the specific diagnosis of inborn errors of metabolism at a major medical genetic referral centre tended to be made quickly, or never. Some of the causes of delays in diagnosis include (1) the lack of ready access to existing diagnostic laboratory testing; (2) technical barriers to the identification of specific metabolic or genetic defects; and (3) incomplete knowledge of genetic defects causing inherited metabolic diseases.