Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats.

BACKGROUND: Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. METHODS: We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7) rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. RESULTS: Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. CONCLUSION: These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

Heart rate variability in patients with frontal lobe epilepsy.

OBJECTIVE: To identify autonomic dysregulation in frontal lobe epilepsy (FLE). METHODS: We studied 14 male and 11 female subjects with FLE and an equal number of matched healthy control subjects. Lead I electrocardiograms were obtained for 5 min in the interictal state during daytime. Frequency-domain analysis of heart rate variability was performed and the data subsequently converted to heart rate interval and high frequency (HF; 0.15-0.45 Hz) power which representing vagal or parasympathetic regulation, as well as low frequency (LF; 0.04-0.15 Hz) power and LF/(HF+LF) expressed in normalized units (LF%) (considered to mirror sympathetic regulation). Differences in data between groups were compared using t-test. RESULTS: The epilepsy group had a lower mean heart rate interval and a lower high frequency power. CONCLUSIONS: Patients with FLE have interictally faster heart rates, attributed to lower parasympathetic drive, which may contribute to the higher incidence of sudden death that is seen in this group of patients. This suggests that the mechanism of decreased HRV in patients with FLE is probably different from that in patients with temporal lobe epilepsy.

Heart rate variability in children with refractory generalized epilepsy.

OBJECTIVE: Repetitive seizures can alter the regulation of cardiac activity by the autonomic nervous system (ANS), and ANS dysregulation is thought to be associated with higher morbidity and mortality in epileptic patients, especially from sudden unexpected death. Few studies of interictal dysregulation of cardiac activity in children with epilepsy have been performed. In this study we characterize heart rate variability (HRV) in children with refractory generalized epilepsy. METHODS: Fifteen male and 15 female children, average age = 10.9+/-0.6 years, all with refractory generalized epilepsy were enrolled into the study group. A control group consisted of 15 males and 15 females with average age = 10.6+/-0.6 years. A lead I ECG was recorded for 5 min in the interictal period during daylight hours from each subject while awake. Frequency-domain analysis of HRV was performed using a non-parametric method of fast Fourier transformation. Changes of HRV were categorized into high frequency power (HF; 0.15-0.45 Hz), which represented vagal regulation, and low frequency power (LF; 0.04-0.15 Hz). LF/(HF+LF) expressed in normalized units (LF%) was considered to mirror sympathetic regulation. RESULTS: There were significant reductions in RR, LF, and HF in the study group when compared to controls. There was no significant difference in LF% between the two groups. CONCLUSIONS: We postulate that the lower HRV in our patients results from parasympathetic or vagal reduction. This suggests that decreased HRV in epileptic children occurs by a different mechanism than in adults with epilepsy.

Matched unrelated bone marrow transplantation without splenectomy for a child with Gaucher disease caused by homozygosity of the L444P mutation, who also suffered from schizencephaly.

Splenectomy followed by bone marrow transplantation (BMT) has been applied successfully in the treatment of neuronopathic Gaucher disease (GD). GD in combination with schizencephaly has not previously been reported. We describe a girl who presented with hemiparesis and oculomotor apraxia since infancy, and thereafter developed progressive anemia, thrombocytopenia, hepatosplenomegaly, psychomotor retardation, and skeletal abnormalities. GD caused by homozygosity of the L444P mutation was diagnosed, in combination with schizencephaly. The child received enzyme replacement therapy for 3 years, followed by successful matched unrelated BMT without splenectomy. The strategy of BMT without splenectomy after a period of enzyme replacement may be feasible in neuronopathic GD.

Effect of multiple subpial transection on patients with uncontrolled atypical infantile spasms.

We report a favorable outcome of multiple sub-pial transaction (MST) in two patients who had intractable atypical infantile spasms preceded by partial seizures, without any lateralized magnetic resonance imaging (MRI) abnormalities.

ACTH therapy for Taiwanese children with West syndrome -- efficacy and impact on long-term prognosis.

To study the efficacy of adrenocorticotrophic hormone (ACTH) in treating Taiwanese children with West syndrome (WS) and the impact on long-term prognosis, 66 patients with WS (54 symptomatic and 12 cryptogenic) were collected from 1987 to 1998 in a medical center in Taiwan. A total of 53 patients were enrolled in this study and treated with ACTH at the dosage of 2.5IU/kg daily for 2 weeks with gradual tapering in subsequent 6 weeks. Immediate responses, side effects of ACTH and long-term outcomes of the patients including seizure and developmental status were evaluated during the average follow-up period of 35.6 months. The spasm-free percentage after one or two courses of ACTH treatment was 77.4%. Nine (17%) patients encountered severe side effects such as major infections, which prompted us to stop ACTH. At the end of follow-up, 22 (41.5%) patients had intractable seizures but 25 (47.2%) patients remained seizure free with or without anticonvulsants. The ACTH-responders had a better chance of remaining seizure free (P<0.05). Regarding the long-term developmental outcome, 12 (22.6%) patients had normal or borderline development; two thirds of them belonged to the crytpogenic group. Six (11.3%) patients expired and 24 (45.3%) were severely retarded; all but one of them belonged to the symptomatic group. The prognosis of WS heavily relies on whether a patient is cryptogenic or symptomatic (P<0.001). Good response to therapy or short treatment lag did not favorably affect the developmental outcomes of the symptomatic cases. We conclude that the long-term outcomes of WS in Taiwan were generally poor despite of treatment. Only cryptogenic patients had favorable prognosis. For symptomatic patients, ACTH therapy may be used to control the spasms and decrease the incidence of subsequent epilepsy, but it will not improve developmental outcome. Considering a high percentage of severe side effects in our study, a lower dosage of ACTH with adequate therapeutic efficacy but less side effects should be considered for treating Taiwanese children with WS.

Electroclinical characteristics of seizures-comparing Prader--Willi syndrome with Angelman syndrome.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurobehavioral syndromes that are caused by deficiency of gene expression from paternally or maternally derived homologues on chromosome 15q11-q13, respectively. Clinical and genetic heterogeneities are common in both syndromes and they are now regarded as 'sister genetic imprinting syndromes'. This study aimed to describe and compare the electroclinical characteristics of seizures between PWS and AS, and to try to explore the possible mechanisms of epileptogenesis in these two syndromes. Fifty patients with genetically documented PWS and 18 patients with a putative diagnosis of AS were included in this study. These patients were diagnosed on the basis of characteristic physical findings and their neurobehavioral phenotype, as well as cytogenetic and molecular studies. Epileptic seizures were present in 16 of 18 patients with AS, but in only eight of 50 patients with PWS. Using electroencephalography (EEG), the most characteristic findings for AS were rhythmic 2-3 Hz delta waves of high-amplitude that were maximal over the frontal regions, and 3-4 Hz spikes and sharp wave runs posteriorly. These were never seen in PWS. Patients with AS had a much higher incidence of seizures with characteristic EEG findings, similar to those seen in mice that are deficient in a single gene (UBE3A) that displays regional brain-specific imprinting in humans and mice. In this series, cases with no detectable cytogenetic or molecular defect at the AS locus displayed similar AS phenotype, seizure severity and EEG abnormalities compared to those with such a defect. Thus, the UBE3A gene is presumed to be potentially involved in the epileptogenesis of AS. It is also possible that UBE3A and another gene located nearby, gamma-aminobutyric receptorbeta3 subunit, may interact in some way, and result in the severe epilepsy seen with AS. Some patients with PWS and AS share the common EEG features of persistent high-amplitude 4-6 Hz activity in recordings during sleep, and while awake. The significance of such EEG findings needs further experience to clarity.

Congenital adrenal hyperplasia with 11 beta-hydroxylase deficiency.

A rare form of congenital adrenal hyperplasia (CAH), 11 beta-hydroxylase deficiency, may be misdiagnosed as 21-hydroxylase deficiency, the most common form of CAH, because of similar clinical presentations at times and elevated level of 17-hydroxyprogesterone in both conditions. We report a case of 11 beta-hydroxylase deficiency that was originally misdiagnosed as 21-hydroxylase deficiency. Hypertension and hypokalemia complicated with seizures and arrhythmia developed in this 9-year-old girl after abrupt withdrawal of oral dexamethasone but maintenance of fludrocortisone. Suspicion of 11 beta-hydroxylase deficiency led to DNA mutation analysis, which revealed a novel point mutation (CTG 461 CCG) in the CYP11B1 gene converting leucine to proline. Her condition stabilized rapidly after withdrawal of fludrocortisone and administration of hydrocortisone. Regular measurement of blood pressure should be performed in all patients with CAH and test of serum 11-deoxycortisol or deoxycorticosterone level should be performed in those patients with elevated blood pressure to avoid misdiagnosis of 11 beta-hydroxylase deficiency.

Human herpesvirus 8-related childhood mononucleosis: a series of three cases.

Human herpesvirus 8 has been implicated in the pathogenesis of a limited subset of lymphoproliferative disorders in adults, but its role in children is unclear. A prospective evaluation of children with atypical lymphocytosis residing in the Hualien area, where the incidence of adult Kaposi sarcoma is high, revealed 3 cases caused by human herpesvirus 8.

Estimation of prevalence and incidence of infantile spasms in Taiwan using capture-recapture method.

PURPOSE: To estimate the prevalence, incidence, and case-fatality of infantile spasms (IS) in Taiwan. METHODS: A retrospective cohort of patients with IS was obtained from one medical center to identify 69 IS cases from 1985 to 1997. This cohort, in conjunction with the claimed data from the National Health Insurance, was used to estimate the prevalence and incidence of IS by capture-recapture design, taking the case-fatality of IS into account. RESULTS: The prevalence rate of IS for aged 0-9 years was 0.046 per thousand. The incidence rate was estimated as 6 over 100,000 per year in Taiwan. Of the 69 IS cases, 8 deaths were ascertained. The case-fatality rate was 11.6%. The leading cause of death was status epilepticus. CONCLUSIONS: We have demonstrated an efficient method to estimate the incidence and prevalence rates of IS in Taiwan. Our results help to make a clear understanding of the disease burden of IS in this society.

Adrenoleukodystrophy: clinical analysis of 9 Taiwanese children.

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder and identified in many races without apparent predilection for any race. This study was designed to investigate the clinical and therapeutic aspects of X-ALD in Taiwanese children with this disorder. We retrospectively reviewed all children admitted to NTUH from Nov. 1993 to Aug. 2002 with the diagnosis of ALD, defined by increased very long chain fatty acid (VLCFA). The mean age at diagnosis of the patients was 7.4 years (range, 2.8 to 13 years). Seven out of 9 patients had abnormal brain magnetic resonance image (MRI) studies. Three patients received bone marrow transplantation. Of these, two died of severe graft-versus-host disease and the other remained stable. Of the remaining 6 patients, two patients were in vegetative status and the other two patients were neurologically normal. X-ALD in Taiwanese children had similar clinical manifestations as reviewed in western countries. Symmetrical demyelination in parieto-occipital region and the accumulation of contrast material at the edge of the lesion are the typical MRI findings. Proton MR spectroscopy (MRS) can be used to evaluate either the asymptomatic patient or patient with normal brain image. Performance of T-cell depletion bone marrow transplantation or cord blood transplantation is suggested for X-ALD with early cerebral involvement.

Maple syrup urine disease presenting with neonatal status epilepticus: report of one case.

Maple syrup urine disease (MSUD) is a rare inborn error of the branched chain amino acid metabolism, which can be classified as classical, intermediate, intermittent, and thiamine responsive types. We report a 16-day-old boy who suffered from difficult feeding, persistent metabolic acidosis, and tricycling movement of the lower legs. Status epilepticus was the initial impression, but classical type MSUD was later diagnosed. Under the diagnosis, dietary therapy effectively prevented further neurological deterioration. However, amino acid deficiency manifested as acrodermatitis enteropathica-like skin rash occurred once. Early parenteral glucose supplementation and periodic plasma amino acid monitoring are very important in the management of metabolic diseases, including MSUD.

Lumbosacral agenesis in a premature infant of a diabetic mother.

We report a non-familial case of lumbosacral agenesis born to a type 1 diabetic mother who had hyperglycemia during pregnancy despite regular insulin therapy. The male baby was noted to have atrophy of pelvis, flattening of the buttocks, and deformity of the lower limbs at birth. Spinal X-ray film revealed total agenesis of lumbar, sacral, and caudal spines. Magnetic resonance image disclosed interruption of the spinal cord at the level of T12 and adhesion between the two malrotated kidneys. Peripheral blood cytogenetic study revealed a normal male karyotype. Recurrent episodes of respiratory distress and urinary tract infection had bothered the patient subsequently. It is suggested that lumbosacral agenesis, a severe congenital defect, might be one of the anomalies of diabetic embryopathy.

Auditory brainstem evoked potentials in early-treated congenital hypothyroidism.

To evaluate the effect of early treatment of congenital hypothyroidism on central nervous system development, auditory brainstem evoked potentials were determined in 32 patients with hyperthyrotropinemia diagnosed during neonatal screening. The patients included 27 with congenital hypothyroidism and 5 with transient hypothyroidism. Abnormal auditory brainstem evoked potential tracings were found in 8 patients (congenital hypothyroidism in 7 and transient hypothyroidism in 1). Four of these patients had increased peripheral conduction time (wave I prolongation), and the other 4 had increased central conduction time (wave III or V prolongation). The patients with abnormal auditory brainstem evoked potentials did not show increased initial manifestations, yet 6 of them had lower initial thyroxine levels. Specific auditory brainstem evoked potential abnormalities were found in 25% of early-treated patients with congenital hypothyroidism. The possible causal relationship between deviant auditory brainstem evoked potential patterns and later neurodevelopment demands further clarification. This study suggests the usefulness of auditory brainstem evoked potential assessment to provide information about electrophysiologic deviation of the auditory pathway in patients with early-treated congenital hypothyroidism.