PEDIATRICS Vol. 122 No. 3 September 2008, pp. 507-512 (doi:10.1542/peds.2007-2002)
ARTICLE |
Occipital Lobe Injury and Cortical Visual Outcomes After Neonatal Hypoglycemia
Department of Pediatrics, Divisions of a Neurology
d Neonatology
b Department of Diagnostic Imaging, Division of Neuroradiology, Hospital for Sick Children, Toronto, Ontario, Canada
c Department of Pediatrics, Division of Neonatology, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry, England
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONADDENDUMREFERENCES |
|---|
OBJECTIVES. Hypoglycemia is a significant problem in neonates, and a pattern of parietooccipital diffusion restriction on MRI scans has been reported. The purpose of this study was to determine whether hypoglycemic injury, as indicated by diffusion restriction in the occipital lobes, correlated with visual evoked potentials and long-term cortical visual dysfunction.
METHODS. A cohort of 45 neonates from 2000–2005 with diffusion-weighted MRI studies after hypoglycemia was studied retrospectively. Perinatal history and follow-up data were analyzed, and results were correlated with diffusion-weighted imaging findings.The presence of occipital diffusion restriction was assessed qualitatively, and the mean apparent diffusion coefficients of mesial occipital lobes were calculated.
RESULTS. Among 25 patients who underwent diffusion-weighted imaging within 6 days after the onset of hypoglycemia, restricted diffusion in the occipital lobes was found in 8 (50%) of 16 term infants but not in preterm infants. For the remaining 20 patients, who had diffusion-weighted imaging performed >6 days after the initial onset of hypoglycemia, occipital diffusion restriction was not seen, even if hypoglycemia was ongoing. Restricted diffusion was associated with abnormal visual evoked potentials detected within 1 week after birth. Cortical visual deficits were seen in a significant proportion of patients with recurrent hypoglycemia and were correlated significantly with low mesial occipital apparent diffusion coefficient values.
CONCLUSIONS. Diffusion-weighted imaging studies performed within 6 days after initial hypoglycemia were sensitive in term but not preterm neonates. Diffusion restriction, with low apparent diffusion coefficient values, in the mesial occipital poles may indicate the prognosis for visual outcomes in acute settings after neonatal hypoglycemia.
Key Words: hypoglycemia • MRI • visual impairment
Abbreviations: DWI—diffusion-weighted imaging • ADC—apparent diffusion coefficient • VEP—visual evoked potential
Hypoglycemia is a frequent occurrence in neonates, and significant neonatal hypoglycemia may result in both short- and long-term neurologic effects. Short-term effects include neonatal seizures and neurophysiologic abnormalities. Abnormal evoked potentials are found immediately after the onset of hypoglycemia but resolve with reversal to normoglycemia.1 A limited number of studies have reported neurodevelopmental deficits in children with prolonged neonatal hypoglycemia, mostly defining hypoglycemia as blood levels of <2.6 mmol/L.2–4 Little evidence exists with regard to significant thresholds for treatment or prognostic factors.5
Neuroradiologic changes with severe and recurrent neonatal hypoglycemia have been described. Since the first case report in 1994,6 other studies have confirmed the findings of parietooccipital white matter abnormalities, as well as abnormal signals in the deep gray matter structures of the thalamus and basal ganglia, after symptomatic neonatal hypoglycemia in term neonates.7–10 More-recent series studying diffusion-weighted imaging (DWI) reported diffusion restriction in the parietooccipital areas, underlying white matter, and corpus callosum.11,12 In this study, findings for a cohort of neonates with documented hypoglycemia and DWI studies were reviewed to determine the conditions associated with occipital diffusion restriction. Because there is occipital predominance of these changes, specific attention was paid to cortical visual deficits. We hypothesized that acute injury to the occipital lobes secondary to neonatal hypoglycemia, as detected with DWI, would be predictive of long-term cortical visual dysfunction.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONADDENDUMREFERENCES |
|---|
Study Group
A detailed, systematic, hospital database search was conducted to identify all neonates with hypoglycemia who were admitted to our hospital between 2000 and 2005 and underwent MRI. Our hospital is a tertiary and quaternary care pediatric hospital that services a catchment area with an estimated 65000 births per year; it is a referral center with no in-born infants. The NICU electronic database was queried to identify patients with documented blood glucose levels of <2.6 mmol/L. The radiology electronic database was queried to obtain a list of neonates who underwent MRI during the hospital admission. All neonates who met those criteria were included in the study cohort, with no exclusions for concomitant diagnoses. The subjects were classified as term if they were born at gestational age of
37 weeks. Infants were classified as small, appropriate, or large for gestational age, with small for gestational age being defined as a birth weight of <3rd percentile and large for gestational age as >97th percentile for gestational age. This study was approved by our institutional research ethics board.
Clinical and Radiologic Data Collection
The hospital health records of this cohort were reviewed for demographic data, perinatal history, concomitant diagnoses, and in-hospital investigations. Demographic data included gestational age at birth, birth weight, and gender. Perinatal history included fetal distress, initial blood glucose level, and other perinatal diagnoses. Diagnosis of hypoxic-ischemic encephalopathy was made by using the American College of Obstetricians and Gynecologists criteria.13,14 The frequency and recurrence of low blood glucose levels and the need for intravenous glucose infusions or other medications were recorded.
MRI findings were reviewed independently by 2 pediatric neuroradiologists who were blinded to patient history. DWI scans and corresponding apparent diffusion coefficient (ADC) maps were visually inspected for the presence of diffusion restriction in the occipital lobes. MRI findings were categorized as positive or negative for occipital lobe diffusion restriction. For the measurement of average ADC values, an elliptical region of interest of 100 mm2 was drawn in the area of the mesial occipital lobes bilaterally, including the calcarine cortex. To obtain surrogate control subjects for mesial occipital ADC values, 25 neonates without neonatal hypoglycemia were chosen; they were matched with the study cohort with respect to postmenstrual age at the time of MRI. These surrogate control subjects were all reported to have normal DWI findings, despite being studied because of clinical suspicion of hypoxic-ischemic encephalopathy.
Short-term outcome data included neonatal seizures and death. Seizure activity included lip-smacking and cycling movements or tonic-clonic activity. Antiepileptic medication (phenobarbital) was used in all cases of seizures. Results of electroencephalography and visual evoked potential (VEP) studies were documented. The presence of neonatal seizures was defined by clinical presentation and supported by electroencephalographic findings. VEP results were classified as abnormal if cortical responses were poor or absent. For patients who died during neonatal admission, available pathology reports were reviewed. Patients were reassessed in the clinic every 4 months for the first year and again at postmenstrual ages of 18 and 24 months. All patients were referred to a pediatric ophthalmologist for assessment at corrected ages of 4 to 8 months. Long-term ophthalmologic outcomes were reviewed, especially for cortical blindness.
Statistical Analyses
Associations between occipital diffusion restriction and gestational age, neonatal seizures, VEPs, and long-term visual outcomes were assessed by using Fisher's exact test. Differences between term and preterm neonates with respect to the lowest blood glucose levels and the number of days with measured hypoglycemia were determined by using Student's t test. The Wilcoxon signed-rank test was used to compare the mean ADC values in the mesial occipital lobes of neonates with or without visual loss and gestational age-matched control subjects. Statistical significance was set at a P value of .05.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONADDENDUMREFERENCES |
|---|
Subjects for Analysis
Between 2000 and 2005, 45 neonates with documented hypoglycemia were admitted and underwent MRI. Twenty infants underwent MRI >6 days after the first documentation of hypoglycemia. For those 20 patients, no diffusion restriction was seen in the occipital regions. These cases were excluded from further analysis, because normalization of diffusion restriction might have occurred in the time since the onset of hypoglycemia. Additional analysis was thus restricted to the 25 subjects who underwent MRI within 6 days after the initial documentation of hypoglycemia.
Demographic Characteristics
Of the 25 neonates, 16 were male and 9 were female. Sixteen patients were born term and 9 preterm. Additional patient demographic data are shown in Table 1. With regard to the cause of hypoglycemia, 6 patients had early transitional-adaptive hypoglycemia (including infants of mothers with diabetes mellitus), 13 had secondary hypoglycemia (associated with other illnesses, including asphyxia, intracranial hemorrhage, sepsis, and congenital heart disease), 3 had classic transient neonatal hypoglycemia (associated with intrauterine growth restriction), and 3 had severe recurrent hypoglycemia (associated with endocrine and hereditary metabolic defects).15
|
Although hypoglycemia was defined as a blood glucose level of <2.6 mmol/L, all neonates in the final cohort had documented blood glucose levels of
2.1 mmol/L. All subjects required intervention for normalization of their glucose levels and initially were treated with intravenous dextrose administration. Most patients did not require additional therapy; however, 7 required the use of glucagon and 1 required diazoxide. One neonate diagnosed as having growth hormone deficiency was treated with human growth hormone. All patients achieved good blood glucose control within 8 days after the initiation of therapy. Concomitant diagnoses were varied, with the most common being outlined in Fig 1. Other diagnoses (for 1 subject each) included CHARGE syndrome, congenital neuroblastoma, growth hormone deficiency, and maternal drug abuse. Three patients had dysmorphic facies and ambiguous genitalia, likely representing undiagnosed genetic syndromes. Subjects also had findings consistent with other comorbidities, including hypoxic-ischemic encephalopathy (44%), periventricular leukomalacia (12%), subependymal hemorrhage (4%), parenchymal hemorrhage (8%), and subdural hemorrhage (16%).
|
DWI Findings
General Findings
Diffusion restriction, with hyperintensity on the trace map and hypointensity on the ADC map, was identified in the occipital lobes of 8 of 25 subjects (Fig 2). Bilateral occipital hyperintensity on the trace map without corresponding hypointensity on the ADC maps was seen for 4 subjects. The presence or absence of occipital lobe diffusion restriction was compared with gestational age, neonatal seizures, VEP abnormalities, and cortical visual deficits in follow-up evaluations (Table 2).
|
|
Gestational Age
There was no significant difference in the lowest blood glucose levels or days with measured hypoglycemia between term and preterm neonates (P > .05). In a comparison of occipital diffusion restriction between term and preterm neonates, 8 of 16 term neonates showed diffusion restriction (P = .01). In contrast, none of the 9 preterm neonates showed occipital diffusion restriction. Of the 8 term neonates without occipital diffusion restriction, 3 were born at the gestational age of exactly 37 weeks.
Neonatal Seizures
Thirteen of the 25 subjects were documented to have experienced seizures. Seizures were consistently observed in close temporal relationship with the initial documentation of hypoglycemia. There was no difference in the severity of hypoglycemia for infants with and without seizures. Infants with occipital diffusion restriction were more likely to have experienced neonatal seizures, but this finding did not reach statistical significance (P = .07).
VEP Results
VEP studies were performed within 1 week after the onset of hypoglycemia for 20 of the 25 neonates in the study cohort. Eleven (55%) of the 20 neonates showed poor or absent cortical responses in VEP testing. Significant association between VEP results and occipital diffusion restriction was found (P = .05).
Visual Outcomes
Of 25 neonates, 4 patients died and 3 patients were lost to follow-up monitoring. Eighteen of the 25 subjects had follow-up visits, at 6 months to 7 years. Formal ophthalmologic evaluation by a pediatric ophthalmologist (and, if necessary, a pediatric neuroophthalmologist) was performed at a corrected age of 4 to 8 months, with follow-up care as clinically indicated. One child was noted to have macular hypoplasia associated with a presumed genetic abnormality, 1 had cortical blindness, and 1 had homonymous hemianopsia. The cohort included 10 neonates with hypoglycemia measured on 2 days, including both children with cortical visual deficits (20%). None of the 8 neonates with hypoglycemia measured on only 1 day had cortical visual problems in long-term monitoring. Subjects with occipital diffusion restriction were more likely to have cortical visual deficits in follow-up evaluations, but this did not reach statistical significance.
Quantitative analysis of ADC values in the mesial occipital lobes, including the calcarine cortex, showed significantly lower ADC values for subjects with cortical visual loss, compared with gestational age-matched control subjects (P < .01) (Table 3). The ADC values for subjects without cortical visual loss were not significantly different from those for gestational age-matched control subjects (P > .05).
|
Of the original cohort of 45 subjects with neonatal hypoglycemia who underwent MRI in the neonatal period, 11 died and 28 survived with long-term follow-up monitoring. Although interpretable DWI findings were not available for the total cohort because of delayed MRI, cortical visual loss was documented for 6 (33%) of 18 infants with hypoglycemia measured on
2 days. No infants with hypoglycemia documented on a single day showed long-term visual loss.
Neuropathologic Findings
Of the 4 subjects who died during the neonatal period, 2 underwent postmortem pathologic investigations. Both exhibited occipital diffusion restriction on MRI scans and died after >1 week of life. Histologic evaluation of the occipital lobes showed neuronal eosinophilic degeneration comparable to that in other cortical regions and in keeping with global hypoxia-ischemia.
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONADDENDUMREFERENCES |
|---|
This study systematically reviewed a relatively large cohort of neonates with hypoglycemia and DWI studies. Restricted diffusion in the occipital poles bilaterally was found in neonates who underwent DWI within 6 days after hypoglycemia onset. These changes were found only for term neonates and correlated with early abnormal VEPs and late cortical visual deficits.
The period during which occipital diffusion restriction was found in neonatal hypoglycemia was in keeping with previous studies of hypoxic-ischemic encephalopathy and neonatal stroke, after which time imaging changes disappear in a phenomenon known as pseudonormalization.16,17 DWI changes were seen only within 6 days after the initial brain insult. These changes did not persist beyond 6 days after the initial onset of hypoglycemia even if there was continued hypoglycemia at the time of imaging. These findings are important clinically, because they imply that any DWI studies performed >1 week after the initial onset of hypoglycemia would not result in the expected diffusion restriction and therefore could not confirm injury resulting from neonatal hypoglycemia during a subacute period. Later conventional MRI to look for subtle signs of occipital gliosis would be necessary to assess such injury.
The subjects in this study had a number of other comorbid diagnoses, which might have confounded the findings. Although multiple imaging features were observed, only the more-specific occipital changes were considered for this study. Although the occipital lobes can be involved in multiple brain injury mechanisms, the pattern of bilateral occipital cortical injury is quite specific for neonatal hypoglycemia.11,12 The pathophysiologic aspects of neonatal hypoglycemia also include combined effects with other disorders, such as ischemia and hypoxemia. These insults in combination may cause more-significant injury than a single mode of insult alone.18 Hypoglycemia often occurs not in isolation but in combination with other disorders affecting brain metabolism.19 As a result, it is important to study not only neonates with isolated hypoglycemia but also those with multiple concomitant diagnoses.
Within 1 week after the initial documentation of hypoglycemia, DWI did not detect changes in neonates born at gestational ages of <37 weeks, an observation not reported previously. Gestational age-dependent susceptibility suggests developmental changes placing term neonates at greater risk for occipital lobe injury. The mechanism of occipital diffusion restriction in hypoglycemia is not fully understood, although it may be attributable to regional and developmental differences in glucose utilization between brain regions.20,21 The differences between term and preterm neonates suggest developmental changes with gestational age, including variable regional glucose utilization, blood flow, and vascular permeability.22,23
Another possible explanation for the gestational age differences may originate in the principles of DWI. DWI is a MRI technique that detects the random diffusion of water molecules, which is restricted in normal tissue structures. Increased diffusion restriction can be seen in cytotoxic edema and myelin edema. In contrast to hypoglycemia, diffusion restriction can be seen in hypoxic-ischemic encephalopathy and neonatal stroke in preterm neonates. If changes seen in ischemia result from cytotoxic edema, then changes seen in hypoglycemia may indicate myelin edema. It may be postulated that preterm neonates did not show diffusion restriction either because of a lesser degree of myelination in preterm neonates or because of variable metabolic activity of differentiating glial cells in term neonates, particularly in the occipital white matter. To support this theory, the term neonates who did not show diffusion restriction in this study had concurrent disorders, including growth hormone deficiency and other endocrine imbalances (manifesting as ambiguous genitalia), which might affect brain and myelin development. Pathologic studies were not helpful in clarifying this hypothesis, because the subjects who died did so >1 week after neonatal hypoglycemia, beyond the period of expected DWI changes.
Although the study cohort included infants with a range of gestational ages at birth, the youngest subject who underwent MRI within 6 days was born at a gestational age of 35 weeks. The cohort thus consisted of term and near-term infants and did not include more-premature infants. This limitation might stem from the fact that the medical teams avoided MRI because of clinical instability of the more-premature infants.
Although a trend was observed, diffusion restriction was not found to be significantly associated with neonatal seizures. Neonatal seizures are known to be common manifestations of symptomatic hypoglycemia. In addition, seizures are associated with greater energy use, secondary to increased neuronal activity, and thus may increase the risk of brain injury. This may be of long-term importance, because the occurrence of neonatal seizures with neonatal hypoglycemia was associated with poorer long-term neurologic outcomes.24,25 Only neonatal seizures were considered in this study and, although other investigators described a correlation between symptomatic hypoglycemia and occipital lobe epilepsy,26 longer-term follow-up monitoring is required to correlate the occurrence of persistent seizures with imaging findings.
Quantitative ADC measurements were performed in the region of the calcarine cortex, and results were compared between study subjects and control subjects matched with respect to postmenstrual age. Serial studies with preterm neonates showed decreased ADC values with increasing postmenstrual age.27 Therefore, we specifically selected surrogate control subjects of comparable age, to account for developmental differences. Although we included neonates with suspected hypoxic-ischemic injury as surrogate control subjects, those neonates had normal MRI findings, including no visible changes on ADC maps. Moreover, the mean ADC values for our control subjects were comparable to values reported previously for the corresponding postmenstrual age range.27
The neonates exhibited a spectrum of occipital abnormalities after hypoglycemia. Of the neonates who showed occipital hyperintensity in DWI studies, only some had true diffusion restriction, according to a review of the corresponding ADC maps. In a review of the distribution of injury, only some of those with occipital diffusion restriction showed changes specifically in the calcarine cortex, resulting in abnormally low ADC values in that area. These findings indicate that neonatal hypoglycemia results in different degrees and distributions of occipital lobe injury.
Because it is recognized that there can be occipital injury after neonatal hypoglycemia, it was postulated that there would be a correlation with abnormal early VEPs and later visual function. Previous reports found optic nerve hypoplasia associated with neonatal hypoglycemia.28 Although there was no significant association between overall parietooccipital lobe diffusion restriction and cortical visual deficits, subset analysis of subjects with diffusion restriction specifically involving the calcarine cortex demonstrated significant correlation with visual deficits in follow-up evaluations. The location of injury is in keeping with the neuroanatomic location of the calcarine cortex for primary vision. The ADC values in the calcarine cortex that correlated with long-term cortical visual loss were comparable to values reported previously for poor outcomes after perinatal asphyxia.16
These results suggest that neonates with hypoglycemia, especially those with hypoglycemia detected on 2 days, should be evaluated with DWI within 6 days after onset. If mesial occipital diffusion restriction is found, then counseling regarding the potential risk of later cortical visual deficits should be initiated. In the remainder of cases of occipital lobe diffusion restriction, more-detailed studies of visuospatial processing need to be performed at an older age, for assessment of subtler, late-appearing deficits.
Parameters for neonatal hypoglycemia in relation to long-term outcomes have been poorly understood to date. This study provided evidence that hypoglycemia to a blood glucose level of <2.1 mmol/L in the neonatal period and diffusion restriction in the calcarine cortex in DWI studies performed up to 6 days after the onset of hypoglycemia correlated with significant, long-term, cortical visual deficits. Continued follow-up monitoring to investigate the relationships with occipital lobe epilepsy and subtle visuospatial deficits will be important for further characterization of the sequelae of severe, recurrent, neonatal hypoglycemia.
|
ADDENDUM |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONADDENDUMREFERENCES |
|---|
We read the recent publication of Burns et al29 on the subject of this paper with interest. We suggest that the apparent differences in the two studies can be related primarily to the timing and type of neuroimaging. Our study concentrated on the early MRI diffusion weighted imaging (DWI) findings, within 6 days of a hypoglycemic episode, in contrast to Burns’ study which included neuroimaging within the first 6 weeks of life. We showed a significantly higher incidence of occipital lobe findings; however Burns’ et al report T1- and T2-weighted MRI images, but not DWI. We also confirmed the known limited time window for DWI, as the bilateral occipital lobe diffusion restriction normalized and was not apparent on imaging 6 days post-hypoglycemia, similar to the pseudo-normalization of DWI seen following HIE or neonatal stroke.
|
ACKNOWLEDGMENTS |
|---|
We thank Shafagh Fallah, PhD, for her guidance with respect to statistical analyses.
|
FOOTNOTES |
|---|
Accepted Dec 20, 2007.
Address correspondence to Aideen M. Moore, MD, FRCP(C), MHSc, Department of Pediatrics, Division of Neonatology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. E-mail: aideen.moore{at}sickkids.ca
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject Short- and long-term neurologic effects, including optic nerve hypoplasia and visual deficits, after significant neonatal hypoglycemia have been reported. Recent neuroradiologic studies have shown occipitally predominant diffusion restriction associated with neonatal hypoglycemia.
|
| What This Study Adds This study of neonates with hypoglycemia and early neuroimaging findings characterizes the conditions resulting in occipital diffusion restriction. Follow-up evaluations with visual evoked potential studies and ophthalmologic assessments show the value of early diffusion-weighted imaging in predicting long-term visual outcomes.
|
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONADDENDUMREFERENCES |
|---|
- Koh TH, Aynsley-Green A, Tarbit M, Eyre JA. Neural dysfunction during hypoglycaemia.
Arch Dis Child. 1988;63
(11):1353
–1358
[Abstract/Free Full Text] - Lucas A, Morley R, Cole TH. Adverse neurodevelopmental outcome of moderate neonatal hypoglycemia.
BMJ. 1988;297
(6659):1304
–1308
[Abstract/Free Full Text] - Duvanel CB, Fawer C-L, Cotting J, Hohlfeld P, Matthieu JM. Long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in small-for-gestational age preterm infants. J Pediatr. 1999;134 (4):492 –498[CrossRef][Web of Science][Medline]
- Moore AM, Perlman M. Symptomatic hypoglycemia in otherwise healthy, breast-fed term newborns.
Pediatrics. 1999;103
(4):837
–839
[Abstract/Free Full Text] - Cornblath M, Hawdon JM, Williams AF, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds.
Pediatrics. 2000;105
(5):1141
–1145
[Abstract/Free Full Text] - Spar HA, Lewine JD, Orrison WW. Neonatal hypoglycemia: CT and MR findings. AJNR Am J Neuroradiol. 1994;15 (8):1477 –1478[Abstract]
- Barkovich AJ, Al Ali F, Rowley HA, Bass N. Imaging patterns of neonatal hypoglycemia. AJNR Am J Neuroradiol. 1998;19 (3):523 –528[Abstract]
- Traill Z, Squier M, Anslow P. Brain imaging in neonatal hypoglycemia.
Arch Dis Child Fetal Neonatal Ed. 1998;79
(2):F145
–F147
[Abstract/Free Full Text] - Alkalay AL, Flores-Sarnat L, Sarnat HB, Moser FG, Simmons CF. Brain imaging findings in neonatal hypoglycemia: case report and review of 23 cases.
Clin Pediatr (Phila). 2005;44
(9):783
–790
[Abstract/Free Full Text] - Kinnala A, Rikalainen H, Lapinleinu H, et al. Cerebral magnetic resonance imaging and ultrasonography findings after neonatal hypoglycemia.
Pediatrics. 1999;103
(4):724
–729
[Abstract/Free Full Text] - Kim SY, Goo HW, Lim KH, Kim ST, Kim KS. Neonatal hypoglycaemic encephalopathy: diffusion-weighted imaging and proton MR spectroscopy. Pediatr Radiol. 2006;36 (2):144 –148[CrossRef][Web of Science][Medline]
- Filan PM, Inder TE, Cameron FJ, Kean MJ, Hunt RW. Neonatal hypglycaemia and occipital cerebral injury. J Pediatr. 2006;148 (4):552 –555[CrossRef][Web of Science][Medline]
- Hankins GDV, Speer M. Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy. Obstet Gynecol. 2003;102 (3):628 –636[CrossRef][Web of Science][Medline]
- American College of Obstetricians and Gynecologists. Neonatal encephalopathy and cerebral palsy: executive summary. Obstet Gynecol. 2004;103 (4):780 –781[Web of Science][Medline]
- Volpe JJ. Hypoglycemia and brain injury. In: Volpe JJ, ed. Neurology of the Newborn. 4th ed. Philadelphia, PA: Saunders;2001 :497 –520
- Boichot C, Walker PM, Durand C, et al. Term neonate prognoses after perinatal asphyxia: contributions of MR imaging, MR spectroscopy, relaxation times, and apparent diffusion coefficients.
Radiology. 2006;239
(3):839
–848
[Abstract/Free Full Text] - Küker W, Möhrle S, Mader I, Schöning M, Nägele T. MRI for the management of neonatal cerebral infarctions: importance of timing. Childs Nerv Syst. 2004;20 (10):742 –748[Web of Science][Medline]
- Salhab WA, Wyckoff MH, Laptook AR, Perlman JM. Initial hypoglycemia and neonatal brain injury in term infants with severe fetal acidemia.
Pediatrics. 2004;114
(2):361
–366
[Abstract/Free Full Text] - Miralles RE, Lodha A, Perlman M, Moore AM. Experience with intravenous glucagon infusions as a treatment for resistant neonatal hypoglycemia.
Arch Pediatr Adolesc Med. 2002;156
(10):999
–1004
[Abstract/Free Full Text] - Powers WJ, Rosenbaum JL, Dence CS, Markham J, Videen TO. Cerebral glucose transport and metabolism in preterm human infants. J Cereb Blood Flow Metab. 1998;18 (6):632 –638[CrossRef][Web of Science][Medline]
- Chugani HT, Phelps ME. Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography.
Science. 1986;231
(4740):840
–843
[Abstract/Free Full Text] - Chugani HT. Positron emission tomography study of human brain functional development. Ann Neurol. 1987;22 (4):487 –497[CrossRef][Web of Science][Medline]
- Skov L, Pryds O. Capillary recruitment for preservation of cerebral glucose influx in hypoglycemic, preterm newborns: evidence for a glucose sensor?
Pediatrics. 1992;90
(2):193
–195
[Abstract/Free Full Text] - Koivisto M, Blanco SM, Krause U. Neonatal symptomatic and asymptomatic hypoglycemia: a follow-up study of 151 children. Dev Med Child Neurol. 1972;14 (5):603 –614[Web of Science][Medline]
- Pildes RS, Cornblath M, Warren I. A prospective controlled study of neonatal hypoglycemia.
Pediatrics. 1974;54
(1):5
–14
[Abstract/Free Full Text] - Caraballo RH, Sakr D, Mozzi M, et al. Symptomatic occipital lobe epilepsy following neonatal hypoglycemia. Pediatr Neurol. 2004;31 (1):24 –29[CrossRef][Web of Science][Medline]
- Miller SP, Vigneron DB, Henry RG, et al. Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury. J Magn Reson Imaging. 2002;16 (6):621 –632[CrossRef][Web of Science][Medline]
- Fahnehjelm KT, Jacobson L, Hellstrom A, Lewensohn-Fuchs I, Ygge J. Visually impaired children with posterior ocular malformations: pre- and neonatal data and visual functions. Acta Ophthalmol Scand. 2003;81 (4):361 –372[CrossRef][Web of Science][Medline]
- Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia.
Pediatrics 2008;122
(1):65
–74
[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
