Value of Repeat Brain MRI in Children with Focal Epilepsy and Negative Findings on Initial MRI.

OBJECTIVE: To evaluate the value of repeat brain magnetic resonance imaging (MRI) in identifying potential epileptogenic lesions in children with initial MRI-negative focal epilepsy. MATERIALS AND METHODS: Our Institutional Review Board approved this retrospective study and waived the requirement for informed consent. During a 15-year period, 257 children (148 boys and 109 girls) with initial MRI-negative focal epilepsy were included. After re-evaluating both initial and repeat MRIs, positive results at repeat MRI were classified into potential epileptogenic lesions (malformation of cortical development and hippocampal sclerosis) and other abnormalities. Contributing factors for improved lesion conspicuity of the initially overlooked potential epileptogenic lesions were analyzed and classified into lesion factors and imaging factors. RESULTS: Repeat MRI was positive in 21% (55/257) and negative in 79% cases (202/257). Of the positive results, potential epileptogenic lesions comprised 49% (27/55) and other abnormalities comprised 11% of the cases (28/257). Potential epileptogenic lesions included focal cortical dysplasia (n = 11), hippocampal sclerosis (n = 10), polymicrogyria (n = 2), heterotopic gray matter (n = 2), microlissencephaly (n = 1), and cortical tumor (n = 1). Of these, seven patients underwent surgical resection. Contributing factors for new diagnoses were classified as imaging factors alone (n = 6), lesion factors alone (n = 2), both (n = 18), and neither (n = 1). CONCLUSION: Repeat MRI revealed positive results in 21% of the children with initial MRI-negative focal epilepsy, with 50% of the positive results considered as potential epileptogenic lesions. Enhanced MRI techniques or considering the chronological changes of lesions on MRI may improve the diagnostic yield for identification of potential epileptogenic lesions on repeat MRI.

Prognostic factors of infantile spasms: role of treatment options including a ketogenic diet.

OBJECTIVES: The aim of this study was to provide additional evidences on prognostic factors for infantile spasms and the possible role of a ketogenic diet. METHODS: A retrospective analysis was performed for patients with infantile spasms who had been followed up for more than 6months between January 2000 and July 2012 at Samsung Medical Center (Seoul, Republic of Korea). We analyzed the association between possible prognostic factors and seizure/developmental outcomes. RESULTS: Sixty-nine patients were included in this study and their mean follow-up duration was 52.5 (9-147) months. In the patients who had been followed up for more than 2years, 53.6% (n=30/57) remained seizure-free at the last visit. Sixty patients (86.9%) showed developmental delay at last follow-up. Forty-two patients (60.9%) became spasm-free with one or two antiepileptic drugs, one patient with epilepsy surgery for a tumor, and seven patients with a ketogenic diet after the failure of two or more antiepileptic drugs. The etiology and age of seizure onset were the significant prognostic factors. CONCLUSIONS: In this study, about 60% of the patients became spasm-free with vigabatrin and topiramate. Ketogenic diet increased the rate by 10% in the remaining antiepileptic drug resistant patients. However, 86.9% of the patients showed developmental delay, mostly a severe degree. Early diagnosis and prompt application of treatment options such as antiepileptic drugs, a ketogenic diet or epilepsy surgery can improve outcomes in patients with infantile spasms.

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.

Clinical and genetic analysis of Korean patients with congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease characterized by anhidrosis, insensitivity to noxious stimuli, and mental retardation. Mutations in the NTRK1 gene are associated with the pathogenesis of CIPA. In this study, we performed a clinical and genetic analysis on the NTRK1 gene in four Korean patients with CIPA. All patients had typical clinical manifestations of CIPA, including anhidrosis, recurrent fever, absent pain perception, and developmental delay. Sequencing analysis revealed one predominant mutation, c.851-33T>A, in four affected alleles and three novel mutations, including c.287+2dupT, c.2155G>A (p.Glu719Lys), and c.1218delC (p.Pro407ArgfsX), in each affected allele. For one patient, who was heterozygous for c.851-33T>A, another mutation could not be identified, suggesting that a possible hidden intronic or large genomic mutation may have been present. This study extends the spectrum of mutations in the NTRK1 gene and confirms that Korean patients with CIPA have the same genetic background as other ethnicities.

A novel ATP7A gross deletion mutation in a Korean patient with Menkes disease.

Menkes disease (MD, MIM 309400) is a fatal X-linked recessive disorder that is caused by mutations in the gene encoding ATP7A, a copper-transporting, P-type ATPase. Patients with MD are characterized by progressive hypotonia, seizures, failure to thrive, and death in early childhood. Two Korean patients were diagnosed with Menkes disease by clinical and biochemical findings. We found one missense mutation and one gross deletion in the ATP7A gene in the patients. The missense mutation in Patient 1, c.3943G>A (p.G1315R) in exon 20, was identified in a previous report. Patient 2 had a gross deletion of c.1544-?_2916+?, which was a novel mutation. The patients' mothers were shown to be carriers of the respective mutations. Prenatal DNA diagnosis in the family of Patient 2 was successfully performed, showing a male fetus with the wild-type genotype. The gross deletion is the first mutation to be identified in the ATP7A gene in Korean MD patients. We expect that our findings will be helpful in understanding the wide range of genetic variation in ATP7A in Korean MD patients.

Atypical basal ganglia germinoma presenting as cerebral hemiatrophy: diagnosis and follow-up with 11C-methionine positron emission tomography.

OBJECTS: Some basal ganglia germinomas are difficult to diagnose in early stage of disease due to vague initial presentation without discernable mass lesion on brain imaging. We performed this study to determine the usefulness of 11C-methionine positron emission tomography (MET PET) for the diagnosis and monitoring of disease activity. MATERIALS AND METHODS: MET PET was performed in three consecutive patients; they presented with cerebral hemiatrophy without definite mass lesions on brain image. The maximum standard tracer uptake values (max SUVs) were calculated and used for the quantitative evaluation of the abnormal MET uptake. A pathological diagnosis was made after stereotactic biopsy using MET PET/computed tomography. The max SUVs significantly decreased after treatment. CONCLUSION: Basal ganglia germinoma should be considered in the differential diagnosis of patients with progressive hemiparesis and hemiatrophy on magnetic resonance imaging. The MET PET was useful for diagnosis, and it can be valuable in evaluation of treatment effects and monitoring for tumor recurrence.

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.

Frequent association of cortical dysplasia in dysembryoplastic neuroepithelial tumor treated by epilepsy surgery.

BACKGROUND: We report on our experience with epilepsy surgery in the treatment of localization-related epilepsy caused by dysembryoplastic neuroepithelial tumor (DNT) aimed at achieving the best seizure control. METHODS: A retrospective analysis was performed on the pathological reports as well as on clinical data of 24 case patients with medically intractable epilepsy with DNT treated surgically between 1995 and 2000 at the Samsung Medical Center. Resective surgery was performed using subdural electrodes or intraoperative electrocorticography in all patients. RESULTS: The mean follow-up period was 57.2 months. Two patients had rare seizures transiently after surgery but remained free from seizures after 6 months. Others remained completely free from seizures. There was a strong tendency of temporal lobe involvement (19 cases; 79.2%). Size of tumors located at medial temporal regions was significantly smaller than those at lateral temporal or frontal lobes (P < .05). A rather radical resection (tumor plus surrounding tissue showing active epileptogenicity) was performed in all but one case where only focal lesionectomy was done. In 20 of the 24 cases (83.3%), association of cortical dysplasia (CD) was found on pathological examination. CONCLUSIONS: We conclude that DNT is frequently associated with CD, with a wide area of epileptogenic activity that might be related to the presence of CD around the DNT. Comprehensive preoperative investigations for accurate localization of epileptogenic activity, meticulous brain mapping, and a rather radical resection of pathological areas might be essential for the achievement of excellent seizure control in DNT-associated epilepsy.

Postoperative alteration of cerebral glucose metabolism in mesial temporal lobe epilepsy.

To investigate postoperative changes in the cerebral glucose metabolism of patients with mesial temporal lobe epilepsy (MTLE), statistical parametric mapping (SPM) analysis was performed on pre- and postoperative (18)F-fluorodeoxyglucose PET (FDG-PET) images. We included 28 patients with MTLE who had undergone surgery and had been seizure-free postoperatively (16 had left MTLE and 12 right MTLE). All patients showed hippocampal sclerosis by pathology or brain MRI. FDG-PET images of the 12 right temporal lobe epilepsy patients were reversed to lateralize the epileptogenic zone to the left side in all patients. Application of the paired t-test in SPM to pre- and postoperative FDG-PETs showed that postoperative glucose metabolism decreased in the caudate nucleus, the pulvinar of the thalamus, fusiform gyrus, lingual gyrus and the posterior region of the insular cortex in the hemisphere ipsilateral to resection, whereas postoperative glucose metabolism increased in the anterior region of the insular cortex, temporal stem white matter, midbrain, inferior precentral gyrus, anterior cingulate gyrus and supramarginal gyrus in the hemisphere ipsilateral to resection. No significant postsurgical changes in cerebral glucose metabolism occurred in the contralateral hemisphere. Subtraction between pre- and postoperative FDG-PET images in individual patients produced similar findings to the SPM results, and additionally showed that postoperative glucose metabolism increased in the anterior thalamus in 12/28 patients (42.8%). SISCOM (subtraction ictal-interictal SPECT co-registered to MRI) performed in 17 patients showed ictal hyperperfusion in the ipsilateral temporal lobe, including the temporal stem white matter, midbrain, insular cortex and cingulate gyrus, bilateral basal ganglia and thalami, and multiple small regions in the frontoparietal lobes during seizures. This study suggests that brain regions showing a postoperative increase in glucose metabolism appear to represent the propagation pathways of ictal and interictal epileptic discharges in MTLE, whereas the postoperative decrease in glucose metabolism may be related to a permanent loss of afferents from resected anterior-mesial temporal structures.

In vitro and in vivo efficacy of new blue light emitting diode phototherapy compared to conventional halogen quartz phototherapy for neonatal jaundice.

High intensity light emitting diodes (LEDs) are being studied as possible light sources for the phototherapy of neonatal jaundice, as they can emit high intensity light of narrow wavelength band in the blue region of the visible light spectrum corresponding to the spectrum of maximal bilirubin absorption. We developed a prototype blue gallium nitride LED phototherapy unit with high intensity, and compared its efficacy to commercially used halogen quartz phototherapy device by measuring both in vitro and in vivo bilirubin photodegradation. The prototype device with two focused arrays, each with 500 blue LEDs, generated greater irradiance than the conventional device tested. The LED device showed a significantly higher efficacy of bilirubin photodegradation than the conventional phototherapy in both in vitro experiment using microhematocrit tubes (44+/-7% vs. 35+/-2%) and in vivo experiment using Gunn rats (30+/-9% vs. 16+/-8%). We conclude that high intensity blue LED device was much more effective than conventional phototherapy of both in vitro and in vivo bilirubin photodegradation. Further studies will be necessary to prove its clinical efficacy.

Effects of alpha-phenyl-N-tert-butyl nitrone (PBN)on brain cell membrane function and energy metabolism during transient global cerebral hypoxia-ischemia and reoxygenation-reperfusion in newborn piglets.

We sought to know whether a free radical spin trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN) influences brain cell membrane function and energy metabolism during and after transient global hypoxia-ischemia (HI) in the newborn piglets. Cerebral HI was induced by temporary complete occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min, followed by release of carotid occlusion and normoxic ventilation for 1 hr (reoxygenation-reperfusion,RR). PBN (100 mg/kg) or vehicle was administered intravenously just before the induction of HI or RR. Brain cortex was harvested for the biochemical analyses at the end of HI or RR. The level of conjugated dienes significantly increased and the activity of Na+, K+ -ATPase significantly decreased during HI,and they did not recover during RR. The levels of ATP and phosphocreatine (PCr)significantly decreased during HI, and recovered during RR. PBN significantly decreased the level of conjugated dienes both during HI and RR, but did not influence the activity of Na+, K+ -ATPase and the levels of ATP and PCr. We demonstrated that PBN effectively reduced brain cell membrane lipid peroxidation, but did not reverse ongoing brain cell membrane dysfunction nor did restore brain cellular energy depletion, in our piglet model of global hypoxic-ischemic brain injury.

Effect of 7-nitroindazole on bilirubin-induced changes in brain cell membrane function and energy metabolism in newborn piglets.

We evaluated the effects of 7-nitroindazole, a selective neuronal nitric oxide synthetase (nNOS) inhibitor, on bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglets. The decreased cerebral cortical cell membrane Na(+),K(+)-ATPase activity and increased lipid peroxidation products, indicative of bilirubin-induced brain damage, were significantly attenuated by 7-nitroindazole treatment. 7-Nitroindazole also significantly improved the bilirubin-induced reduction in both brain ATP and phosphocreatine levels, decreased blood-to-brain glucose ratio and increased brain lactate level. In summary, 7-nitroindazole significantly attenuated the bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglet. These findings suggest that nitric oxide produced by nNOS is involved in mediating or facilitating bilirubin-induced cerebral dysfunction.