An In Vivo Assessment of Regional Brain Temperature during Whole-Body Cooling for Neonatal Encephalopathy.

OBJECTIVE: To assess differences in regional brain temperatures during whole-body hypothermia and test the hypothesis that brain temperature profile is nonhomogenous in infants with hypoxic-ischemic encephalopathy. STUDY DESIGN: Infants with hypoxic-ischemic encephalopathy were enrolled prospectively in this observational study. Magnetic resonance (MR) spectra of basal ganglia, thalamus, cortical gray matter, and white matter (WM) were acquired during therapeutic hypothermia. Regional brain tissue temperatures were calculated from the chemical shift difference between water signal and metabolites in the MR spectra after performing calibration measurements. Overall difference in regional temperature was analyzed by mixed-effects model; temperature among different patterns and severity of injury on MR imaging also was analyzed. Correlation between temperature and depth of brain structure was analyzed using repeated-measures correlation. RESULTS: In total, 53 infants were enrolled (31 girls, mean gestational age: 38.6 ± 2 weeks; mean birth weight: 3243 ± 613 g). MR spectroscopy was acquired at mean age of 2.2 ± 0.6 days. A total of 201 MR spectra were included in the analysis. The thalamus, the deepest structure (36.4 ± 2.3 mm from skull surface), was lowest in temperature (33.2 ± 0.8°C, compared with basal ganglia: 33.5 ± 0.9°C; gray matter: 33.6 ± 0.7°C; WM: 33.8 ± 0.9°C, all P < .001). Temperatures in more superficial gray matter and WM regions (depth: 21.9 ± 2.4 and 21.5 ± 2.2 mm) were greater than the rectal temperatures (33.4 ± 0.4°C, P < .03). There was a negative correlation between temperature and depth of brain structure (rrm = -0.36, P < .001). CONCLUSIONS: Whole-body hypothermia was effective in cooling deep brain structures, whereas superficial structures were warmer, with temperatures significantly greater than rectal temperatures.

Cerebral Lactate Concentration in Neonatal Hypoxic-Ischemic Encephalopathy: In Relation to Time, Characteristic of Injury, and Serum Lactate Concentration.

BACKGROUND: Cerebral lactate concentration can remain detectable in neonatal hypoxic-ischemic encephalopathy (HIE) after hemodynamic stability. The temporal resolution of regional cerebral lactate concentration in relation to the severity or area of injury is unclear. Furthermore, the interplay between serum and cerebral lactate in neonatal HIE has not been well defined. The study aims to describe cerebral lactate concentration in neonatal HIE in relation to time, injury, and serum lactate. DESIGN/METHODS: Fifty-two newborns with HIE undergoing therapeutic hypothermia (TH) were enrolled. Magnetic resonance imaging and spectroscopy (MRI + MR spectroscopy) were performed during and after TH at 54.6 ± 15.0 and 156 ± 57.6 h of life, respectively. Severity and predominant pattern of injury was scored radiographically. Single-voxel 1H MR spectra were acquired using short-echo (35 ms) PRESS sequence localized to the basal ganglia (BG), thalamus (Thal), gray matter (GM), and white matter. Cerebral lactate concentration was quantified by LCModel software. Serum and cerebral lactate concentrations were plotted based on age at time of measurement. Multiple comparisons of regional cerebral lactate concentration based on severity and predominant pattern of injury were performed. Spearman's Rho was computed to determine correlation between serum lactate and cerebral lactate concentration at the respective regions of interest. RESULTS: Overall, serum lactate concentration decreased over time. Cerebral lactate concentration remained low for less severe injury and decreased over time for more severe injury. Cerebral lactate remained detectable even after TH. During TH, there was a significant higher concentration of cerebral lactate at the areas of injury and also when injury was more severe. However, these differences were no longer observed after TH. There was a weak correlation between serum lactate and cerebral lactate concentration at the BG (rs = 0.3, p = 0.04) and Thal (rs = 0.35, p = 0.02). However, in infants with moderate-severe brain injury, a very strong correlation exists between serum lactate and cerebral lactate concentration at the BG (rs = 0.7, p = 0.03), Thal (rs = 0.9 p = 0.001), and GM (rs = 0.6, p = 0.04) regions. CONCLUSION: Cerebral lactate is most significantly different between regions and severity of injury during TH. There is a moderate correlation between serum and cerebral lactate concentration measured in the deep gray nuclei during TH. Differences in injury and altered regional cerebral metabolism may account for these differences.

The Impact of Venoarterial and Venovenous Extracorporeal Membrane Oxygenation on Cerebral Metabolism in the Newborn Brain.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an effective therapy for supporting infants with reversible cardiopulmonary failure. Still, survivors are at risk for long-term neurodevelopmental impairments, the cause of which is not fully understood. OBJECTIVE: To elucidate the effects of ECMO on the newborn brain. We hypothesized that the cerebral metabolic profile of neonates who received ECMO would differ from neonates who did not receive ECMO. To address this, we used magnetic resonance spectroscopy (1H-MRS) to investigate the effects of venoarterial and venovenous ECMO on cerebral metabolism. METHODS: 41 neonates treated with ECMO were contrasted to 38 age-matched neonates. RESULTS: All 1H-MRS data were acquired from standardized grey matter and white matter regions of interest using a short-echo (TE = 35 milliseconds), point-resolved spectroscopy sequence (PRESS) and quantitated using LCModel. Metabolite concentrations (mmol/kg) were compared across groups using multivariate analysis of covariance. Elevated creatine (p = 0.002) and choline (p = 0.005) concentrations were observed in the grey matter among neonates treated with ECMO relative to the reference group. Likewise, choline concentrations were elevated in the white matter (p = 0.003) while glutamate was reduced (p = 0.03). Contrasts between ECMO groups revealed lower osmolite concentrations (e.g. myoinositol) among the venovenous ECMO group. CONCLUSION: Neonates who underwent ECMO were found to have an abnormal cerebral metabolic profile, with the pattern of abnormalities suggestive of an underlying inflammatory process. Additionally, neonates who underwent venovenous ECMO had low cerebral osmolite concentrations as seen in vasogenic edema.

The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study.

Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy ((1)H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand.

Early Cardiac Iron Overload in a Child on Treatment of Acute Lymphoblastic Leukemia.

An 11-year-old boy with Down syndrome and acute lymphoblastic leukemia developed hepatic dysfunction after only 10 months of treatment. MRI revealed severe iron deposition in the liver, pancreas, and heart. In stark contrast to what is seen in hemoglobinopathies, pancreatic and cardiac iron overload occurred with relatively low transfusion exposure and in a very short time period in this patient. Although extensive experience managing iron overload in hemoglobinopathies informs our approach in other diseases, it is clear that factors not present in hemoglobinopathies may be operative in patients with malignancy undergoing intense chemotherapy that lead to high levels of free iron and rapid loading of the heart and endocrine organs.

Serial procalcitonin levels to detect bacteremia in febrile neutropenia.

BACKGROUND: Our objective was to evaluate serial procalcitonin (PCT) levels compared with an initial PCT level at admission in predicting bacteremia in pediatric febrile neutropenic oncology patients. PROCEDURE: Serum PCT levels were measured at admission (t0) and within 24 hours of admission (t1) in pediatric oncology patients presenting with fever and neutropenia. A blood culture was collected at t0 and monitored for 5 days for bacterial growth. PCT value of 0.5 ng/mL at either t0 or t1 was considered predictive for bacteremia. RESULTS: PCT levels were significantly higher in children with positive blood cultures than with negative blood cultures. Serial PCT values mirrored t1 values. Serial PCT showed 76% specificity and negative predictive value of 93% in ruling out bacteremia. CONCLUSION: Elevated PCT levels are predictive of bacteremia. Using serial PCT levels within 24 hours allowed a better prediction of bacteremia than the PCT level at t0.

Outcomes of a two-drug chemotherapy regimen for intraocular retinoblastoma.

BACKGROUND: Retinoblastoma is the most common intraocular tumor of childhood. Vision salvage rates in advanced cases are less than ideal, and the optimal treatment for intraocular retinoblastoma has not been established. We report the results of an institutional retinoblastoma treatment trial to determine the vision salvage rates and toxicity of a regimen combining carboplatin and etoposide with focal retinal therapy. PROCEDURE: Twenty-nine patients diagnosed with retinoblastoma in 48 eyes were treated between 1992 and 2004 with at least six cycles of carboplatin and etoposide combined with focal retinal therapy. RESULTS: The response rate of eyes after six cycles of chemotherapy was 85.4%. Twenty-two eyes were enucleated, but only seven eyes received EBRT. The vision salvage rate without EBRT was 82.6% for eyes with Reese-Ellsworth (R-E) groups I-IV tumors and 20% for eyes with R-E group V tumors. The vision salvage rate without EBRT for eyes with Murphree groups A and B tumors was 77.3% but was only 26.9% for eyes with groups C and D tumors. Acute side effects were minimal. CONCLUSIONS: The combination of carboplatin and etoposide with focal therapy is a well-tolerated regimen that has acceptable vision salvage rates for R-E groups I-IV and Murphree groups A and B retinoblastoma. This combination avoids the use of EBRT and the toxicity of additional chemotherapy agents. However, patients with R-E group V and Murphree groups C and D retinoblastoma have poorer outcomes and require more intensive therapy.

Endoscopic third ventriculostomy in children: early and late complications and their avoidance.

INTRODUCTION: Endoscopic third ventriculostomy (ETV) is considered by many authors the initial surgical procedure of choice for the treatment of non-communicant hydrocephalus. However, this procedure has early and late complications that neurosurgeons must be aware of when performing it. MATERIALS AND RESULTS: A retrospective study of infants and children treated with ETV at Children's Memorial Hospital (Chicago, IL) between 1993 and 2004 is presented. A total of 136 ETVs in 122 patients were performed with 8.8% early complication rate (hemorrhage, CSF leak, infection, diabetes insipidus, and seizures). There were no fatalities but one patient had severe neurological disturbances due to intracranial hemorrhage at the second ETV. We identified several significant factors that influence the late ETV failure rate: age under 12 months (p=0.012), cases performed early in our experience (p=0.009), patients with hydrocephalus without expansive lesions (p=0.026), patients that had an external ventricular drain (EVD) after ETV (p<0.005), and patients who developed early complications (p=0.035). CONCLUSION: A careful patient selection and preoperative planning lead to better results of ETV. A higher early and late complication rate in children younger than 1-year-old were noted in our series. There is definitely a learning curve for this technique, and several technical considerations are helpful to avoid adverse events. Most of the early complications are transient, while potential devastating injuries can occur. Long-term follow-up is needed to identify delayed closure of the fenestration. Ventricular access devise is helpful for diagnostic and therapeutic purposes during the follow-up.

Craniopharyngioma and Cushing disease: case report.

Craniopharyngioma is a common sellar region tumor occurring in children. It usually manifests as endocrinological deficits such as short stature, delayed puberty, and obesity. Patients with craniopharyngioma commonly present with visual deficits and hydrocephalus. The authors present the case of a child who presented with short stature and clinical evidence of Cushing disease (CD) associated with a suprasellar tumor. The patient underwent insertion of an Ommaya reservoir into the tumor's cystic portion. High adrenocorticotropic hormone (ACTH) levels were demonstrated within the cyst's fluid and in the serum. After adequate decompression of the tumor, the patient underwent total resection. The tumor pathology was compatible with an adamantinomatous craniopharyngioma and immunohistochemical studies failed to show staining for ACTH. Panhypopituitarism developed postoperatively in the patient and he received hormone substitution therapy with final adequate height and normal-high weight. The neurosurgical implications of CD along with a possible mechanism for this patient's presentation are discussed in detail on the basis of the pertinent literature.

Astroblastoma in childhood: pathological and clinical analysis.

OBJECT: The object was to describe the clinical, radiologic, and pathologic features of astroblastomas in an unselected group of children who were treated in a single institution during an 11-year period. METHODS: Eight children with astroblastomas of the brain were examined. Diagnosis was based on cell morphology, vascular attachment of the cell main process, lack of an epithelial-free surface differentiation, and poor intercellular cohesiveness. In addition to sections, tumor smears and electron microscopy were required for demonstrating or confirming such features. CONCLUSIONS: Clinical findings seem to confirm an apparent predilection of astroblastomas for younger children (median age of onset, 5 years) and the existence of two prognostically different types of tumor-well differentiated (low grade) and anaplastic (high grade). Microscopic findings suggest a closer resemblance of tumor cells to astroblasts rather than to "tanycytes" or ependymal cells. It seems, however, that anaplastic astroblasts have a tendency to evolve toward, or be associated with, less differentiated cells, either neuroepithelial or sarcomatous.

Post-shunt ascites in infants with optic chiasmal hypothalamic astrocytoma: role of ventricular gallbladder shunt.

INTRODUCTION: We report a series of infants with optic chiasmal hypothalamic astrocytomas (OCHAs) who developed abdominal ascites following ventriculo-peritoneal (VP) shunting. The mechanism of ascites development among these patients with OCHA remains speculative and unclear. METHODS: We treated four infants with hypothalamic tumors who were shunted for hydrocephalus using standard VP shunts and who subsequently experienced symptomatic ascites. RESULTS: In three patients the gallbladder proved an effective alternative site for shunting prior to conversion to other sites, and in one patient the gallbladder shunt remains functional and revision-free. CONCLUSIONS: Several aspects of the gallbladder as a reservoir for CSF make this approach appealing. Ventricular gallbladder shunting provided an effective (at least temporarily) receptacle for CSF in these patients.