Munhyang Lee

Neurodevelopmental Outcomes in Preterm Infants: Comparison of Infants with and without Diffuse Excessive High Signal Intensity on MR Images at Near–term-equivalent Age

PURPOSE To compare the neurodevelopmental outcomes between preterm infants with diffuse excessive high signal intensity (DEHSI) and those without DEHSI on magnetic resonance (MR) images, in association with other white matter lesions. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and requirement to obtain informed consent was waived. High-risk preterm infants (n = 126) who underwent screening brain MR imaging at near-term-equivalent age were classified into two groups according to the presence of DEHSI. Bayley Scales of Infant Development-II, presence of cerebral palsy, and neurosensory impairment between 18 and 24 months of age were compared between the two groups. The associations of MR findings of other white matter lesions (cystic encephalomalacia, punctate lesions, loss of volume, ventricular dilatation, and delayed myelination) and subsequent outcomes were also analyzed. Outcome data were evaluated by using exact logistic regression analyses and Fisher exact test. RESULTS DEHSI was present in 75% (95 of 126) of infants. Subsequent neurodevelopmental outcomes did not differ significantly between the two groups. Severe motor delay and cerebral palsy were more common in infants with both DEHSI and other white matter lesions as compared with infants with normal white matter (P = .001 and P < .001, respectively). Among other white matter lesions, cystic encephalomalacia (odds ratio, 19.6; 95% confidence interval: 1.3, 333.3) and punctate lesions (odds ratio, 90.9; 95% confidence interval: 6.4, 1000) were significant predictors of cerebral palsy. CONCLUSION Although the incidence of DEHSI was high (75%) in preterm infants at near-term-equivalent age MR imaging, DEHSI was not predictive of following adverse outcomes. Cystic encephalomalacia and punctate lesions were more significant predictors of cerebral palsy.

The role of ketogenic diet in the treatment of refractory status epilepticus

Ketogenic diet (KD) is known to be effective in intractable epilepsy. However, the role of KD in refractory status epilepticus (RSE) has not been well described. The aim of this study is to explore the role of KD in patients with RSE. We retrospectively reviewed the medical records of four children and one adult with RSE between October 2006 and August 2010. All presented with status epilepticus (SE) that was presumed to be associated with viral encephalitis. After we failed to control the seizures with standard measures for SE, we tried KD. The overall seizure frequency decreased to <50% of baseline in median eight (1–19) days. At one month of KD, two patients were seizure‐free, one patient showed >90% seizure reduction, and the others had >75% decrease without generalized seizures. With improvement in the RSE, we were able to taper the antiepileptic drugs (AEDs) and wean patients from prolonged mechanical ventilation. The adverse events of KD in RSE included aspiration pneumonia, gastroesophageal reflux, constipation, and hypertriglyceridemia. Those results demonstrate that KD can be a valuable therapeutic option for patients with RSE.

Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after acute transient global hypoxia-ischemia in the newborn piglet.

This study was done to determine the effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after hypoxia-ischemia (HI). Forty-five newborn piglets were divided randomly into four experimental groups: normoxia control (NC, n=9); HI/reoxygenation-reperfusion (RR) control (HC, n=11); HI/RR hyperglycemia (HE, n=12); and HI/RR hypoglycemia (HO, n=13) group. Animals were subjected to transient HI for 30 min followed by 2 h of RR. Cerebral HI was induced by temporary but complete occlusion of bilateral common carotid arteries with surgical clips and simultaneous breathing with 8% oxygen. Glucose was unregulated in HC group, and controlled by modified glucose clamp technique immediately after HI in HE (350 mg/dl) and HO (50 mg/dl) groups. During HI, heart rate, base deficit, glucose and lactate level in the blood and cerebrospinal fluid increased, and arterial pH, oxygen saturation and blood pressure decreased significantly in HC, HE and HO groups. During RR, these abnormalities returned to normal values, but lactic acidosis persisted especially in HO group. Cerebral Na(+),K(+)-ATPase activity decreased, and lipid peroxidation products increased significantly in HC group than in NC group, and these abnormalities were significantly aggravated in HE, but not in HO, group. Brain ATP and phosphocreatine levels in HE group were significantly reduced compared to the corresponding values in NC, HC and HO groups. In summary, hyperglycemia, but not hypoglycemia immediately after HI interfered with the recovery of brain cell membrane function and energy metabolism. These findings suggest that post-hypoxic-ischemic hyperglycemia is not beneficial and might even be harmful in neonatal hypoxic-ischemic encephalopathy.

Acute necrotizing encephalopathy in Korean infants and children: imaging findings and diverse clinical outcome.

Objective The purpose of our study was to describe acute necrotizing encephalopathy in Korean infants and children, and we sought to evaluate the prognostic factors. Materials and Methods Acute necrotizing encephalopathy was diagnosed in 14 Korean infants and children. We retrospectively analyzed the neuroimaging findings including the follow-up changes. The clinical course of the disease was graded, and we evaluated prognostic factors including age, serum level of the aminotransferase, hemorrhage, and localized atrophy of the brain. Results This encephalopathy predominantly affected the bilateral thalami (n=14), pons (n=12), and midbrain (n=10) in a symmetrical pattern. Hemorrhage was observed in eight patients (57%). On the follow-up images (n=12), the brain lesions were reduced in extent for all patients, and generalized atrophy was seen in six patients. Localized tissue loss was observed in five patients and a complete resolution occurred for one patient. All the patients survived and two recovered completely; mild (n=6) to severe (n=6) neurological deficits persisted in the remaining 12 patients. The significant prognostic factors identified in this study were the presence of hemorrhage (p = 0.009) and localized atrophy (p = 0.015). Conclusion Acute necrotizing encephalopathy in Korean patients showed the characteristic patterns of the post-infectious encephalopathy as described in the literature. The high survival rate and the relatively favorable clinical course observed for the present study suggest a more diverse spectrum of disease severity than was previously described. The presence of hemorrhage and localized tissue loss on MR images may suggest a poor prognosis.

Effect of hyperglycemia on brain cell membrane function and energy metabolism during hypoxia–ischemia in newborn piglets

The purpose of this study was to test the hypothesis that hyperglycemia ameliorates changes in brain cell membrane function and preserves cerebral high energy phosphates during hypoxia–ischemia in newborn piglets. A total of 42 ventilated piglets were divided into 4 groups, normoglycemic/normoxic(group 1, n=9), hyperglycemic/normoxic(group 2, n=8), normoglycemic/hypoxic–ischemic(group 3, n=13) and hyperglycemic/hypoxic–ischemic(group 4, n=12) group. Cerebral hypoxia–ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. Hyperglycemia (blood glucose 350–400 mg/dl) was maintained for 90 min before and throughout hypoxia–ischemia using modified glucose clamp technique. Changes in cytochrome aa3 were continuously monitored using near infrared spectroscopy. Blood and CSF glucose and lactate were monitored. Na+, K+-ATPase activity, lipid peroxidation products (conjugated dienes), tissue high energy phosphates (ATP and phosphocreatine) levels and brain glucose and lactate levels were determined biochemically in the cerebral cortex. During hypoxia–ischemia, glucose levels in blood and CSF were significantly elevated in hyperglycemic/hypoxic–ischemic group compared with normoglycemic/hypoxic–ischemic group, but lactate levels in blood and CSF were not different between two groups. At the end of hypoxia–ischemia of group 3 and 4, ▵ Cyt aa3, Na+, K+-ATPase activity, ATP and phosphocreatine values in brain were significantly decreased compared with normoxic groups 1 and 2, but were not different between groups 3 and 4. Levels of conjugated dienes and brain lactate were significantly increased in groups 3 and 4 compared with groups 1 and 2, and were significantly elevated in group 4 than in group 3 (0.30±0.11 vs. 0.09±0.02 μmol g−1 protein, 26.4±7.6 vs. 13.1±2.6 mmol kg−1, p<0.05). These findings suggest that hyperglycemia does not reduce the changes in brain cell membrane function and does not preserve cerebral high energy phosphates during hypoxia–ischemia in newborn piglets. We speculate that hyperglycemia may be harmful during hypoxia–ischemia due to increased levels of lipid peroxidation in newborn piglet.

Dysembryoplastic neuroepithelial tumors in pediatric patients

OBJECTIVE Dysembryoplastic neuroepithelial tumors (DNTs) are benign cortical tumors that are frequently associated with the medically intractable focal epilepsy. In this study, the authors delineate the clinical characteristics of DNTs in children and evaluate the role of cortical dysplasia (CD) in the epileptogenicity to find out the optimum surgical strategy. METHODS A retrospective analysis was performed for clinical data of children with DNT, who underwent surgery between 1996 and 2006. The adopted surgical methods were uniform according to the tumor location and included intraoperative electrocorticography (ECoG)-guided resection. The prognostic factors were evaluated for the two prognostic group categorized by the seizure outcome at one year after surgery. RESULTS Of 22 patients, the overall seizure free rate was 90.9% and the other two patients belonged to Engel class II during the mean follow-up period of 44.1 months. There was no worsening of the seizure after one year of surgery. Associated CD was found in 18 cases (81.8%) and in the 80% (8 of 10 cases) of the additionally resected areas according to the electrophysiologic studies. CONCLUSIONS The CD associated with DNT appears to have its own epileptogenicity. Therefore, complete removal of the CD with tumor itself is important for patient outcome. A thorough surgical approach can be accomplished by comprehensive presurgical evaluations and extensive surgery with the aid of the intraoperative ECoG or intracranial recording.

Resection extent versus postoperative outcomes of seizure and memory in mesial temporal lobe epilepsy

OBJECTIVES To investigate the effects of the resection of hippocampus and temporal neocortex on postsurgical seizure and memory outcomes in mesial temporal lobe epilepsy (mTLE) patients. METHODS Sixty-eight mTLE patients underwent pre- and postsurgical brain magnetic resonance imaging (MRI). The patients were divided into seizure-free group (SF, N=54) and non-seizure-free group (NSF, N=14). The resection length of hippocampus was determined by the difference between presurgical and postsurgical hippocampus lengths in MRIs. The lengths of resected temporal gyri were measured on three-dimensional MRI reconstruction. Among SF group, 37 patients performed pre- and postsurgical neuropsychological tests. The postsurgical memory decline (PMD) was calculated by subtracting postsurgical memory score from presurgical one in verbal and visual memory tests. RESULTS The resection length of hippocampus in SF was significantly longer than in NSF (32.7 +/- 7.7 mm versus 25.1 +/- 7.3 mm, t-test, p=0.002), regardless of intersubject difference in the extent of hippocampal sclerosis (logistic regression, p=0.003) while the resection lengths of the lateral temporal gyri were not different between SF and NSF. Overall postsurgical change of verbal or visual memory was not significant. However, regression analysis showed a significant correlation between the resection length of inferior or basal temporal gyrus and verbal PMD (p<0.001) in left TLE patients with seizure-free outcome. CONCLUSION More resection of hippocampus may predict a better postsurgical seizure-free outcome. The larger resection of inferior or basal temporal gyrus seems to be related to a postsurgical verbal memory decline in left TLE patients.

Near infrared spectroscopic monitoring of secondary cerebral energy failure after transient global hypoxia-ischemia in the newborn piglet.

The present study was done to establish whether the secondary cerebral energy failure could be reproduced in the newborn piglet subjected to transient global hypoxia-ischemia, and whether the evolution of secondary cerebral energy failure could be monitored by measuring the changes of Cyt aa3 using NIRS. Fifteen anesthetized, ventilated newborn piglets (< 3 day) were divided into 2 groups. Eight of hypoxia-ischemia (HI) group were induced transient HI by breathing 8% oxygen and complete occlusion of bilateral common carotid arteries for 30 min followed by release of occluders and reoxygenation and maintained for up to 48 h. Seven were given sham operation and maintained for 48 h also. Monitoring of cerebral Hb, HbO, HbT and Cyt aa3 were continued throughout the experiment using near infrared spectroscopy. Na+, K(+)-ATPase activity, lipid peroxidation products (conjugated dienes), tissue high energy phosphates (ATP and phosphocreatine) levels and brain glucose and lactate levels were determined biochemically in the cerebral cortex harvested at the termination of experiment. HbT as an index of a cerebral blood volume increased at 2 h after resuscitation significantly in HI group. During hypoxia-ischemia Cyt aa3 fell to -2.0 +/- 0.5 mu l-1 (p < 0.01), returned to baseline on resuscitation, but decreased again progressively from 33 h, and finally fell to -2.2 +/- 0.9 mumol l-1 (p < 0.01) at 48 h in spite of normal physiologic values. There were no changes in control animals. Cerebral level of ATP and PCr in HI group decreased significantly compared to control and ATP concentrations were correlated with the final levels of Cyt aa3. In HI group, cerebral Na+, K(+)-ATPase activity decreased, but the cerebral level of conjugated dienes, glucose, lactate was not different compared to controls. These findings suggest that secondary cerebral energy failure was successfully reproduced in the newborn piglets after transient hypoxia-ischemia and the continuous in vivo NIRS monitoring can be used as a useful tool for the monitoring of delayed cerebral injury.

Effect of induced hyperglycemia on brain cell membrane function and energy metabolism during the early phase of experimental meningitis in newborn piglets

This study was done to elucidate the mechanism of hypoglycorrhachia and elevated lactate concentrations leading to neuronal dysfunction in neonatal meningitis, and to determine the effects of induced hyperglycemia on these disturbances. Thirty-eight newborn piglets were divided into three groups: 12 in the control group (CG), 12 in the normoglycemic meningitis group (NG), and 14 in the hyperglycemic meningitis group (HG). Meningitis was induced by intracisternal injection of 108 cfu of Escherichia coli. Hyperglycemia (blood glucose 300-400 mg dl-1) was induced and maintained for 60 min before induction of meningitis and throughout the experiment using modified glucose clamp technique. CSF-to-blood glucose ratio decreased significantly in NG. In HG, baseline CSF-to-blood glucose ratio was lower than two other groups, but increased at 1 h after induction of meningitis. CSF lactate concentration was increased progressively in both meningitis groups, and positively correlated with CSF leukocyte numbers (r=0.41, p<0.001) and TNF-alpha level (r=0.43, p<0.001). Brain glucose concentration was significantly increased in HG and showed inverse correlation with CSF leukocyte numbers (r=-0.59, p<0.01). Brain lactate concentration was not significantly different among three groups and positively correlated with the CSF TNF-alpha level (r=0.51, p<0.05). Lipid peroxidation products were increased in NG. Na+,K+-ATPase activity, ATP/PCr concentrations were not different among three groups. Increased intracranial pressure, CSF pleocytosis (214+/-59 vs. 437+/-214/mm3, p<0.02) and increased lipid peroxidation products observed in NG were reduced in HG. These results suggest that hypoglycorrhachia and elevated lactate concentration in the CSF during meningitis originates primarily from the increased anaerobic glycolysis in the subarachnoid space, induced by TNF-alpha and leukocytes. Induced hyperglycemia attenuates the inflammatory responses of meningitis and might be beneficial by providing an increased glucose delivery to meet its increased demand in meningitis.

Genetic Analysis of Dystrophin Gene for Affected Male and Female Carriers with Duchenne/Becker Muscular Dystrophy in Korea

Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessive disorders caused by mutation in dystrophin gene. We analyzed the results of a genetic test in 29 DMD/BMD patients, their six female relatives, and two myopathic female patients in Korea. As the methods developed, we applied different procedures for dystrophin gene analysis; initially, multiplex polymerase chain reaction was used, followed by multiplex ligation-dependent probe amplification (MLPA). Additionally, we used direct DNA sequencing for some patients who had negative results using the above methods. The overall mutation detection rate was 72.4% (21/29) in DMD/BMD patients, identifying deletions in 58.6% (17/29). Most of the deletions were confined to the central hot spot region between exons 44 and 55 (52.9%, 7/19). The percentage of deletions and duplications revealed by MLPA was 45.5% (5/11) and 27.2% (3/11), respectively. Using the MLPA method, we detected mutations confirming their carrier status in all female relatives and symptomatic female patients. In one patient in whom MLPA revealed a single exon deletion of the dystrophin gene, subsequent DNA sequencing analysis identified a novel nonsense mutation (c.4558G > T; Gln1520X). The MLPA assay is a useful quantitative method for detecting mutation in asymptomatic or symptomatic carriers as well as DMD/BMD patients.