Inn-Chi Lee

Seizure precipitants in children with intractable epilepsy

PURPOSE To investigate the seizure precipitants in children with intractable epilepsy, and to determine any distinctive clinical features contributing to seizures in these patients. METHODS A questionnaire and seizure diary prepared by the parents of the patients. Demographic and seizure data were reviewed. RESULTS Of 120 patients with intractable epilepsy, 74 (62%) had one (n=43), two (n=23), or three seizure precipitants (n=8). The three most common precipitants were illness or fever (32%), sleep deprivation (13%), and menstruation (10%). Of these precipitants, inducing factors (endogenous origin) were more common than triggering factors (exogenous origin): 73% versus 27%, respectively. Three distinctive clinical features - neurological abnormalities (P=0.01), status epilepticus (P=0.017), and abnormal neuroimaging (P=0.007) - were significantly more common in patients with than in patients without precipitants. CONCLUSIONS Prompt recognition and management of seizure precipitants has practical implications for treating patients with refractory epilepsy. Such patients can be counseled to avoid specific precipitants.

SURF1-Associated Leigh Syndrome: A Case Series and Novel Mutations

Leigh syndrome (LS) is a mitochondrial disease that typically presents in infancy with subacute neurodegenerative encephalopathy. It is genetically heterogeneous, but mutations in the complex IV assembly genes, particularly SURF1, are an important cause. In this study, SURF1 gene was sequenced in 590 patients with clinical suspicion of LS, complex IV deficiency, or clinical features of mitochondrial disorders. We identified 21 patients with clinical features of LS who are either homozygous or compound heterozygous for SURF1 mutations. Twenty‐two different mutations were identified, including 13 novel mutations. Of the 42 mutant alleles, 36 (86%) are null mutations (frameshift, splicing, or nonsense) and 6 (14%) are missense. We have also reviewed the previously reported SURF1 mutations and observed a clustering of mutation in exon 8 of SURF1, suggesting a vital function for this region. Although mutations in SURF1 have been mainly associated with typical LS, five of the patients in this report had an atypical course of LS. There is no definite genotype–phenotype correlation; however, frameshift mutations resulting in protein truncation closer to the C‐terminus may carry a better prognosis. Hum Mutat 33:1192–1200, 2012.

Efficacy of intermediate-dose oral erythromycin on very low birth weight infants with feeding intolerance.

BACKGROUND Erythromycin is generally used as a prokinetic agent for the treatment of feeding intolerance in preterm infants; however, results from previous studies significantly vary due to different medication dosages, routes of administration, and therapy durations. The effectiveness and safety of intermediate-dose oral erythromycin in very low birth weight (VLBW) infants with feeding intolerance was examined in this study. METHODS Between November 2007 and August 2009, 45 VLBW infants with feeding intolerance, who were all at least 14 days old, were randomly allocated to a treatment group and administered 5mg/kg oral erythromycin every 6hours for 14 days (n=19). Another set of randomly selected infants was allocated to the control group, which was not administered erythromycin (n=26). RESULTS The number of days required to achieve full enteral feeding (36.5±7.4 vs. 54.7±23.3 days, respectively; p=0.01), the duration of parenteral nutrition (p<0.05), and the time required to achieve a body weight ≥2500g (p<0.05) were significantly shorter in the erythromycin group compared with the control group. The incidence of parenteral nutrition-associated cholestasis (PNAC) and necrotizing enterocolitis (NEC) ≥ stage II after 14 days of treatment were significantly lower (p<0.05) in the erythromycin group. No significant differences were observed in terms of the incidences of sepsis, bronchopulmonary dysplasia, or retinopathy of prematurity. No adverse effects were associated with erythromycin treatment. CONCLUSIONS Intermediate-dose oral erythromycin is effective and safe for the treatment of feeding intolerance in VLBW infants. The incidences of PNAC and ≥ stage II NEC were significant lower in the erythromycin group.

Common Etiologies of Neonatal Pleural Effusion

BACKGROUND Pleural effusion is rare and includes several disease entities in the neonatal period. The aim of this study was to investigate the etiology, management, and outcome of neonatal pleural effusions. METHODS We retrospectively collected all neonates who were admitted to the neonatal intensive care unit of Chung Shan Medical University Hospital, Taichung, Taiwan, with discharge diagnosis of pleural effusion, chylothorax, hydrothorax, hemothorax, and empyema, from January 1999 to December 2009. The characteristics, etiology, management, and outcome were analyzed. RESULTS There were 21 patients identified, 16 males (76%) and 5 females (24%). Eight patients (38%) had primary and 13 patients (62%) had secondary etiologies. The etiologies included four parapneumonic effusions or empyema (19%); nine chylothorax (42.8%) with four congenital and five iatrogenic after thoracic surgery; three percutaneously inserted central venous catheter extravasation (14%); one umbilical venous catheter extravasation (4.7%); three hydrops fetalis (14%); and one congestive heart failure (4.7%). Fifteen patients (71%) needed chest tube placement. Conservative management with complete cessation of enteral feedings and use of total parenteral nutrition followed with infant formula containing medium-chain triglyceride was successful in six of the patients (67%) with chylothorax. There were two patients (22%) with chylothorax who received somatostatin administration; one was successful and the other one failed. Thoracic duct ligation was performed uneventfully in two patients with acquired chylothorax. There were three mortalities (14.3%) in this study, which were related to causes other than pleural effusion. CONCLUSIONS Pleural effusions in the neonatal stage may result from chylothorax, hydrops fetalis, extravasation of percutaneously inserted central venous catheter, parapneumonic effusion, congestive heart failure, or other less frequently occurring conditions. Diagnostic chest tap is required for subsequent management. Good outcome is the rule except in hydrops fetalis, which carries high mortality rate.

Posthemorrhagic hydrocephalus in newborns: clinical characteristics and role of ventriculoperitoneal shunts.

BACKGROUND The incidence of neonatal intraventricular hemorrhage (IVH) does not decrease even after using a surfactant and advanced intensive care. Posthemorrhagic hydrocephalus (PHH) is major complication after IVH. The roles of the ventricuLoperitoneal (VP) shunt and the prognostic factors of neurodevelopmental outcomes in infants with PHH remain controversial. We compared the neurodevelopmental outcomes in newborns with and without VP shunts to delineate the clinical characteristics of patients with PHH and to determine the useful prognostic factors of short-term outcomes and neurodevelopmental results at a corrected age of more than 1 year old. METHODS We retrospectively reviewed the records of 83 cases of neonatal IVH, grades 2-4. Thirty (36%) of the cases were complicated with PHH. We classified survivors into four groups by outcome-normal, mildly abnormal, moderately abnormal, and severely abnormal-to compare prognoses. RESULTS Among the 30 PHH cases, 10 patients died during their first admission (early deaths), and four died after their first discharge (late deaths). We found no statistically significant differences in gestational age, birth weight, gender, the maximum number of red blood cells in cerebral ventricular fluid, the lowest glucose levels, or total protein. Patients with grade 3 IVH were more likely to have shunts than were patients with grade 2 IVH. Patients with shunts had more late deaths and fewer normal neurodevelopmental outcomes than those without shunts. CONCLUSION Patients who were shunt-dependent had worse neurodevelopmental outcomes and greater mortality than those without shunts. The results appeared to depend on how far the hydrocephalus had progressed and on the degree of IVH, but the necessity of VP shunts requires reevaluation before they are implanted.

Interstitial deletion of chromosome 14q in a taiwanese infant with microcephaly

Deletion (14)(q11.2q13.1) is a rare cytogenetic abnormality associated with severe neurological deficit, microcephaly and psychomotor retardation. We report a case of de novo interstitial deletion of chromosome (14)(q11.2q13.1) in an 8-month-old girl, who presented with marked microcephaly, a nearly closed anterior fontanelle, dysmorphic facies, severe neurological deficits, and delayed developmental milestones. Three-dimensional computed tomography of the brain showed premature closure of the coronal suture and magnetic resonance imaging of the brain showed frontal atrophy and hypoplastic corpus callosum.

Benign familial neonatal convulsions: novel mutation in a newborn.

Benign familial neonatal convulsions are a rare, autosomal-dominant form of neonatal epileptic syndrome. It can occur 1 week after birth, and usually involves frequent episodes, but with a benign course. The diagnosis depends on family history and clinical features. The mutant gene locates at 20q13, a voltage-gated potassium-channel gene (KCNQ2). Our patient exhibited an uneventful delivery course and onset of seizures at age 2 days. The general tonic seizures were unique and asymmetric, with frequencies of >20 per day. Results of examinations were within normal limits, including biochemistry and brain magnetic resonance imaging. Abnormalities included a small ventricular septum defect on cardiac sonography unrelated to the seizures, and nonspecific, multiple, high-voltage sharp waves and spike waves occurring infrequently in the central region on electroencephalogram. After phenobarbital and phenytoin use, the seizures persisted. On day 12, another antiepileptic drug, vigabatrin (unavailable in the United States), was used, and seizures decreased. A novel mutation of KCNQ2 was identified from a blood sample. The baby had occasional seizures with drug treatment at age 3 months. Benign familial neonatal convulsion should be considered in a baby with a unique seizure pattern and positive family history. Genetic counseling and diagnosis are mandatory.

Mitochondrial Depletion Causes Neonatal-Onset Leigh Syndrome, Myopathy, and Renal Tubulopathy

The authors describe a newborn with postnatal myopathy who subsequently developed feeding difficulties, ophthalmoplegia, ptosis, encephalopathy, and seizures. She became ventilator dependent after sudden apnea. The myopathy was without ragged red fibers in the muscle biopsy. An electron transport chain study showed a markedly generalized low level of enzyme activity, particularly in complexes I, I + III, and IV. An initial electroencephalogram finding was normal; subsequent electroencephalograms showed suppression bursts. The mitochondrial copy number in skeletal muscle was 2% of normal.

Nine genes that may contribute to partial trisomy (6)(p22→pter) and unique presentation of persistent hyperplastic primary vitreous with retinal detachment.

We report on a newborn girl with facial anomalies, a congenital heart defect, severe pre‐ and postnatal growth retardation, feeding problems, and persistent hyperplastic primary vitreous. Cytogenetic analysis by high resolution GTG banding showed extra chromosomal material on the short arm of one chromosome 1 of the patient, but neither parent. SKY and CGH analysis demonstrated that the patient had a de novo 46,XX, der(1)t(1;6)(p36.3; p22). Compared with previously reported cases of partial trisomy 6p22 syndrome, this patient exhibited a unique condition for this syndrome: persistent hyperplastic primary vitreous (PHPV) with retinal detachment. The human genome database was searched for candidate genes and we propose the following nine genes located in the 6p22→6pter region for their potential contribution to the phenotype of partial trisomy 6p22→pter and persistent hyperplastic primary vitreous (PHPV) with retinal detachment: Forkhead box Q1 (FOXQ1), FOXF2, FOXC1, NRN1, EDN1, ATXN1, DEK oncogene, E2F3, and NRNS1.

Unusual spinal tuberculosis with cord compression in an infant.

Spinal abscess is rare in children, especially in young infants. The most common etiology is bacteria, Staphylococcus aureus in particular. Mycobacterium tuberculosis is another cause. We report an unusual cervical spinal abscess with spinal cord compression in a 13-month-old child. The presenting symptoms were weakness in the right arm and, predominantly, the right leg for 1 month. Magnetic resonance imaging showed an abscess of the cervical spine, extension with bony destruction, and spinal cord compression. The patient underwent an emergency neurosurgical decompression and laminectomy. Pathology and culture results confirmed Mycobacterium tuberculosis. After 12 months of antituberculosis treatment, the child could walk with a walker. At 37 months, he was able to walk without assistance. We conclude that spinal tuberculosis should be considered in cases of children with spinal cord-compression symptoms and an image showing an extraspinal abscess. Early diagnosis and prompt treatment are critical for maximizing a functional recovery.