Familial chylomicronemia syndrome: case reports of siblings with deletions of the GPIHBP1 gene.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare monogenic form of severe hypertriglyceridemia, caused by mutations in genes involved in triglyceride metabolism. Herein, we report the case of a Korean family with familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). CASE PRESENTATION: A 4-year-old boy was referred for the evaluation of severe hypertriglyceridemia (3734 mg/dL) that was incidentally detected 4 months prior. His elder brother also demonstrated an elevated triglyceride level of 2133 mg/dL at the age of 9. Lipoprotein electrophoresis revealed the presence of chylomicrons, an increase in the proportion of pre-beta lipoproteins, and low serum lipoprotein lipase levels. The patient's parents and first elder brother had stable lipid profiles. For suspected FCS, genetic testing was performed using the next-generation sequencing-based analysis of 31 lipid metabolism-associated genes, which revealed no pathogenic variants. However, copy number variant screening using sequencing depth information suggested large heterozygous deletion encompassing all the coding exons of GPIHBP1. A real-time quantitative polymerase chain reaction was performed to validate the deletion site. The results showed that the siblings had two heterozygous copy number variants consisting of the whole gene and an exon 4 deletion, each inherited from their parents. During the follow-up period of 17 months, the patient did not develop pancreatitis, following dietary intervention. CONCLUSION: These siblings' case of familial chylomicronemia syndrome caused by rare GPIHBP1 deletions highlight the implementation of copy number variants-beyond next-generation sequencing-as an important consideration in diagnosis. Accurate genetic diagnosis is necessary to establish the etiology of severe hypertriglyceridemia, which increases the risk of pancreatitis.

Impact of nusinersen on the health-related quality of life and caregiver burden of patients with spinal muscular atrophy with symptom onset after age 6 months.

INTRODUCTION/AIMS: Novel disease-modifying approaches for spinal muscular atrophy (SMA) have highlighted the patient's perspective on functional changes over time. In this study, we evaluated the impact of nusinersen on the health-related quality of life (HRQoL) of patients with later-onset SMA and the caregiver burden. METHODS: We assessed the changes in HRQoL using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL GCS) and the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM) during 26 months of treatment. Caregiver burden was assessed using the Assessment of Caregiver Experience with Neuromuscular Disease. We also assessed motor function using the Hammersmith Functional Motor Scale-Expanded (HFMSE) and the Revised Upper Limb Module score. RESULTS: Twenty-four patients and their caregivers were included. The median age of patients at treatment onset was 148.8 (6.8 to 269.4) months. A significant improvement was observed in psychosocial health in proxy-reported PedsQL (P = .023). However, the physical health scores of the PedsQL GCS and About my neuromuscular disorder subscores of the PedsQL NMM did not change, although there was a significant increase in HFMSE scores. Regarding the caregiver burden, the financial burden was reduced, whereas time burden increased. A higher HFMSE score was associated with better self-reported PedsQL GCS total scores (P < .001). DISCUSSION: Our results provide insights into the multifaceted implications of disease-modifying therapies for SMA through patient-reported outcome measures (PROMs). PROMs should be taken into consideration to assess the clinical significance of the functional changes identified by clinician-reported scales.

Relationship Between the Serum FGF21 Level and Growth in Children of Short Stature.

BACKGROUND: This study investigated the relationship between fibroblast growth factor 21 (FGF21) levels and growth in children with growth hormone deficiency (GHD) and idiopathic short stature (ISS), and the effects of the FGF21 level on response to growth hormone (GH) treatment. METHODS: We included 171 pre-pubertal children with a GHD (n = 54), ISS (n = 46), and normal height (n = 71). Fasting FGF21 levels were measured at baseline and every 6 months during GH treatment. Factors associated with growth velocity (GV) after GH therapy were investigated. RESULTS: The FGF21 level was higher in short children than in the controls without significant difference between the GHD and ISS groups. In the GHD group, the FGF21 level was inversely associated with the free fatty acid (FFA) level at baseline (r = -0.28, P = 0.039), however, was positively correlated with the FFA level at 12 months (r = 0.62, P = 0.016). The GV over 12 months of GH therapy was positively associated with the delta insulin-like growth factor 1 level (ß = 0.003, P = 0.020). The baseline log-transformed FGF21 level was inversely associated with GV with marginal significance (ß = -0.64, P = 0.070). CONCLUSION: The FGF21 level was higher in children of short stature, both those with GHD and the ISS, than in children with normal growth. The pretreatment FGF21 level negatively affected the GV of children with GH-treated GHD. These results suggest the existence of a GH/FFA/FGF21 axis in children.

Investigating factors influencing post-operative growth in pre-pubertal children after adenotonsillectomy.

PURPOSE: To check the change in growth-for-age after adenotonsillectomy in pre-pubertal children and investigate the affecting factors. METHODS: Two hundred and six pediatric patients who underwent adenotonsillectomy by a single surgeon between January 2011 and December 2014 were included for the retrospective cohort study. The z-scores of height-, weight-, and body mass index (BMI)-for-age were measured before adenotonsillectomy and 1 year after the operation. The Korean version of the obstructive sleep apnea-18 questionnaire (OSA-18), symptom questionnaire, physical examinations, demographic data, and pre-operative z-scores were used to analyze the factors affecting z-score change. RESULTS: Among 206 pediatric patients, 167 patients were normal growth; 19 were undergrowth; and 20 were obese. After the operation, height, weight, and BMI z-scores all increased both in 167 normal-growth patients and 19 undergrowth patients (p value < 0.05). However, in 20 obese patients, only height z-score significantly increased (p value = 0.028). The multiple regression test showed that the sleep disturbance domain of OSA-18 was positively correlated with height z-score change (p value = 0.041), and age was negatively correlated with weight z-score change (p value = 0.016). Pre-operative BMI z-score was negatively correlated (p value = 0.019) and adenoid grade was positively correlated (p value = 0.023) with BMI z-score change. CONCLUSIONS: These findings suggest that adenotonsillectomy may positively affect growth in pre-pubertal children, without undesirable weight gain. Additionally, the sleep disturbance domain of OSA-18 may play a role in predicting post-operative height increase in pre-pubertal children.

Long-term Outcomes of Ophthalmic and Retinal Artery Occlusion After Cosmetic Facial Filler Injection.

BACKGROUND: Ophthalmic artery occlusion (OAO) and retinal artery occlusion (RAO) after facial filler injection have become increasingly significant due to the growth in cosmetic injection procedures for aesthetic purposes. OBJECTIVES: The aim of this study was to analyze the long-term visual outcomes and complications of cosmetic facial filler-related OAO and RAO. METHODS: This single-center, retrospective case series included 17 eyes of 16 filler-related OAO or RAO patients with a follow-up period of 1 year or longer. Main outcome measures were best-corrected visual acuity (BCVA) and long-term complications. RESULTS: The mean [standard deviation] age at diagnosis was 31.7 [9.7] years; all the patients were female. The mean follow-up period was 5.4 [2.4] years. The mean BCVA was 2.34 and 2.41 logMAR at the initial and final visits, respectively, which indicates sustained long-term visual impairment. Ocular complications included retinal atrophy and degeneration (100.0%), optic atrophy and blindess (no light perception) (82.4%), strabismus (80.0%), retinal fibrous membrane (68.8%), posterior synechiae (35.3%), neovascularization (29.4%), iris atrophy and cataract (23.5%), corneal opacity and phthisis bulbi (17.6%), visual field defect and iris defect (11.8%), ophthalmoplegia (7.7%), and pupillary block (5.9%). Extraocular complications of brain infarction and depression were found in 25.0%, whereas skin necrosis was found in 13.3% of patients. CONCLUSIONS: Facial filler-related OAO or RAO resulted in long-term poor visual outcome, and most of the patients experienced irreversible visual impairment with no light perception despite various treatments. Various long-term ocular and extraocular complications were observed, which should be monitored for a long-term follow-up period. Our findings suggest that prevention should be emphasized more than treatment.

Thyroid nodules in childhood-onset Hashimoto's thyroiditis: Frequency, risk factors, follow-up course and genetic alterations of thyroid cancer.

OBJECTIVE: We evaluated the frequency, risk factors and the follow-up outcomes of thyroid nodules, and genetic alterations in thyroid cancer, in youth with childhood-onset Hashimoto thyroiditis (HT) residing in an iodine-sufficient country. DESIGN: A retrospective cohort study. PATIENTS AND MEASUREMENTS: A total of 213 patients (194 females, mean age 10.6 years at the time of HT diagnosis) were ultrasonographically evaluated. Thyroid nodules were categorized using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TI-RADS). RESULTS: Thyroid nodules were detected in 40 (18.8%) patients over a median follow-up period of 3.4 years, usually after the onset of puberty. A family history of thyroid disease (hazard ratio 2.1, p = .031) was predictive of thyroid nodule detection. Papillary thyroid carcinoma (PTC) was diagnosed in 9 (4.2% of all and 22.5% of nodule-positive patients). The malignant nodules had a higher K-TIRADS or ACR-TI-RADS risk level compared with benign nodules (p < .01 for both). Genetic alterations were revealed in 7 (BRAFV600E in 6 and RET-ERC1 fusion in 1) of the eight available tumour tissue samples. None showed evidence of disease over a median follow-up period of 3.4 years. CONCLUSIONS: The nodule detection rate was 18.8%, with a 22.5% risk of malignancy among the detected nodules in childhood-onset HT patients, showing increased risk in those with a family history. Additional large-scale studies are required to evaluate the usefulness of K-TIRADS or ACR-TI-RADS risk level for the differentiation of paediatric thyroid nodules.

Outcomes of Adjunctive Drug-Coated Versus Uncoated Balloon after Atherectomy in Femoropopliteal Artery Disease.

BACKGROUND: The purpose of this study is to evaluate outcomes using drug-coated balloon (DCB) in comparison with uncoated balloon as adjunctive treatment after atherectomy for femoropopliteal artery lesions. METHODS: This single-center retrospective and prospective study included 115 patients with 126 femoropopliteal artery lesions treated with endovascular treatment using atherectomy. Of these, 58 patients received adjunctive DCB after atherectomy (group A) and 57 patients were managed with uncoated balloon after atherectomy (group B). Immediate and late clinical outcomes were compared. RESULTS: Baseline clinical and lesion data were comparable between the 2 groups. However, group A included more uses of rotational atherectomy (43.9% vs. 1.7%, P < 0.001) or embolization protection filter (53.0% vs. 6.7%, P = 0.001), and fewer cases requiring provisional stenting (4.5% vs. 18.3%, P = 0.014). Clinical primary patency at 1 year was significantly higher in group A than in group B (76.3% vs. 61.1%, P = 0.039). There was a trend toward higher 1-year target lesion revascularization (TLR)-free survival in group A (89.8% vs. 77.9% at 1 year, P = 0.275) without statistical significance. Proportional hazards regression analysis indicated that age (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.99, P = 0.016) and provisional stenting (HR 9.78, 95% CI 2.20-43.46, P = 0.003) were independent factors associated with restenosis after combined treatment with atherectomy and DCB. CONCLUSIONS: In femoropopliteal artery disease, the combination of atherectomy with adjunctive DCB achieved better clinical outcomes in terms of clinical primary patency compared to atherectomy plus uncoated balloon while TLR-free survival may also be improved.

A Case of Consumptive Hypothyroidism in a 1-Month-Old Boy with Diffuse Infantile Hepatic Hemangiomas.

Consumptive hypothyroidism is a rare paraneoplastic syndrome characterized by excessive inactivation of the thyroid hormones due to increased type 3 iodothyronine deiodinase activity of tumors. We report the case of severe consumptive hypothyroidism in a 1-month-old boy with infantile hepatic hemangiomas who presented with cardiac failure and cholestasis. Diffuse infiltration of hepatic hemangiomas was detected on abdominal imaging studies, and thyroid function screening test revealed severe hypothyroidism, which necessitated the administration of higher-than-usual doses of levothyroxine for the normalization of thyroid function. The patient was successfully treated with propranolol, prednisolone, and levothyroxine, and he showed normal thyroid function at 3 months of age and normal neurodevelopment at 9 months of age. This case highlights the importance of early recognition and prompt management of consumptive hypothyroidism in patients with infantile hepatic hemangiomas.

Relationship between systolic hypertension assessed by 24-hour ambulatory blood pressure monitoring and aortic diameters in young women with Turner syndrome.

OBJECTIVE: Patients with Turner syndrome (TS) are at high risk for cardiovascular morbidity and mortality due to aortic dilation. We evaluated the prevalence of hypertension and its risk factors and investigated the relationship between systolic hypertension and aortic diameter in young patients with TS. DESIGN: Observational, cross-sectional study. PATIENTS AND MEASUREMENTS: Forty-two patients with TS (15-35 years) who had achieved final adult heights underwent 24-h ambulatory blood pressure monitoring (ABPM). Fasting glucose, insulin and lipid profiles were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Echocardiography was performed to evaluate aortic diameters (aortic annulus, aortic root at the sinuses of Valsalva, sinotubular junction and ascending aorta), which were converted into Turner-specific z-scores. RESULTS: Systolic and/or diastolic hypertension was identified in 71.4% (n = 30) of patients, as assessed by 24-hour ABPM. Twenty-eight patients (66.7%) were nondippers. Patients with systolic hypertension (n = 8, 19.0%) had a higher weight, waist circumference and HOMA-IR levels than those without hypertension (P < 0.05 for all). After adjusting for covariates, HOMA-IR was independently associated with systolic hypertension (odds ratio 10.1, P = 0.043). After adjusting for age and bicuspid aortic valve, systolic hypertension was independently related to increased aortic diameter at the aortic annulus (ß = 1.064, P = 0.009) and sinotubular junction (ß = 1.124, P = 0.016). CONCLUSIONS: Hypertension is highly prevalent and independently associated with IR in young patients with TS. The significant relationship between systolic hypertension and aortic diameters underscores the importance of BP and IR control.

Extremely Early Onset Transthyretin Familial Amyloid Polyneuropathy with a Leu55Pro Mutation: A Pediatric Case Report and Literature Review.

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a life-threatening autosomal dominant disease caused by the deposition of amyloid fibrils composed of TTR proteins. Symptoms of this disease include progressive sensorimotor neuropathy, cardiomyopathy, and involvement of other organs. We described a pediatric case of extremely early onset TTR-FAP with a TTR Leu55Pro mutation. A 17-year-old boy began to suffer from lower limb weakness, gait disturbance, and decreased sensation from 14 years of age onward. He presented with hypertrophic cardiomyopathy, periorbital and scleral ecchymosis, anhidrosis, orthostatic intolerance, and gastrointestinal autonomic dysfunction including nausea, vomiting, and diarrhea alternating with constipation. The patient's older sister had developed similar gastrointestinal symptoms from 20 years of age onward and was diagnosed as having hypertrophic cardiomyopathy. The boy's biopsy results showed infiltrated amyloid deposition on subcutaneous fat tissue and endocardium. Genetic analysis of the TTR gene demonstrated that both the patient and his sister had a pathogenic mutation, c.224T > C (Leu55Pro). Both patients were prescribed tafamidis, a TTR stabilizing agent. Although a majority of TTR-FAPs occur during adulthood, it should be suspected, even in pediatric populations, when symmetric length dependent neuropathy occurs in conjunction with a family history of neuropathy, autonomic neuropathy, and/or cardiomyopathy.

The relationship of urinary 3-phenoxybenzoic acid concentrations in utero and during childhood with adiposity in 4-year-old children.

BACKGROUND: Pyrethroid pesticides are reported to be the most commonly used residential insecticides worldwide. We aimed to investigate the relationship between prenatal and postnatal 3-phenoxybenzoic acid (3-PBA) concentrations, and growth and adiposity parameters in 4-year-old children. METHOD: We obtained data from 578 children who participated in the prospective Environment and Development of Children (EDC) study at around 4 years of age (45-55 months) between August 2008 and July 2011. Anthropometric measurements were obtained at age 4 years. Prenatal and postnatal urinary 3-PBA concentration was measured in maternal urine samples at around 20 weeks of gestation, and in the 4-year-old children, respectively. RESULT: The detection frequency of urinary 3-PBA (geometric mean concentration) was 98-99% (0.98 µg/g Cr) in maternal urine, and almost 99-100% (1.34 µg/g Cr) in 4-year-old children. Prenatal urinary3-PBA concentration was not associated with height, weight, or body mass index (BMI) z-scores at 4 years of age, regardless of sex. Postnatal urinary3-PBA concentration was not related to height z-scores, but was positively associated with weight z-scores with marginal significance among only girls (p = 0.058). Analyzed by sex, there was a significant relationship between postnatal urinary 3-PBA concentration and BMI z-scores (p = 0.015) among girls, after adjusting for covariates. CONCLUSION: Childhood urinary 3-PBA concentration measured at 4 years of age was positively associated with BMI z-scores in 4-year-old girls, but prenatal urinary 3-PBA concentration at midterm pregnancy exhibited no association.

Tandem high-dose chemotherapy with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin regimens for pediatric high-risk brain tumors.

BACKGROUND: High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin (TTC/MEC) regimens in pediatric brain tumors. METHODS: We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens. RESULTS: Eleven patients aged < 3 years at diagnosis were eligible for HDC/auto-SCT to avoid or defer radiotherapy. In addition, nine patients with high-risk medulloblastoma (presence of metastasis and/or postoperative residual tumor ≥ 1.5 cm2), eight with other high-risk brain tumor (six CNS primitive neuroectodermal tumor, one CNS atypical teratoid/rhabdoid tumor, and one pineoblastoma), and five with relapsed brain tumors were enrolled. There were three toxic deaths, and two of which were due to pulmonary complications. The main reason for not performing tandem auto-SCT was due to toxicities and patient refusal. The event-free survival (EFS) and overall survival (OS) rates of all patients were 59.4% and 80.0% at a median follow-up with 49.1 months from the first HDC/auto-SCT, respectively. The EFS/OS rates of patients aged < 3 years at diagnosis, high-risk medulloblastoma, other high-risk brain tumor, and relapsed tumors were 50.0/81.8%, 87.5/85.7%, 66.7/88.9%, and 20.0/60.0%, respectively. CONCLUSIONS: Although tandem HDC/auto-SCT with TTC/MEC regimens showed promising survival rates, treatment modifications are warranted to reduce toxicities. The survival rates with relapsed brain tumors were unsatisfactory despite HDC/auto-SCT, and further study is needed.

Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: A meta-analysis of randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Angioedema (AE) caused by angiotensin-converting enzyme inhibitors (ACEIs) requires prompt and appropriate management, but current treatment options are limited to symptomatic treatment. Icatibant is a bradykinin receptor antagonist approved for hereditary AE treatment. Some recent studies showed a potential role for icatibant on ACEI-induced AE while others have shown no promising effect. This meta-analysis of randomized controlled trials (RCTs) was conducted to provide evidence for the use of icatibant in the treatment of ACEI-induced AE. METHODS: Relevant RCTs that examined the effects of icatibant for ACEI-induced AE were retrieved from EMBASE, PubMed and Cochrane Library (Central). Included articles for the meta-analysis were assessed using the Cochrane risk of bias tool. For meta-analysis, the pooled mean differences (MD) with 95% CIs and the pooled relative risk (RR) with 95% CIs were calculated using RevMan 5.3. The systematic review was performed in accordance with the PRISMA statement. RESULTS AND DISCUSSION: A total of 234 records were identified after searching the databases. In total, three RCTs involving 179 patients were included in the meta-analysis. The three RCTs had a low risk of bias and the characteristics of the participants and the outcome measures were similar among the RCTs. Treatment with icatibant shortened the time to achieve complete resolution of ACEI-induced AE symptoms compared to placebo or conventional treatments. However, the difference was not statistically significant (MD: -7.77 hours; 95% CI: -25.18-9.63 hours). There were no differences between groups in terms of drug-related adverse effects, apart from the reactions at the site of injection (RR: 1.35; 95% CI: 0.53-3.45). WHAT IS NEW AND CONCLUSION: This meta-analysis evaluated the effectiveness and tolerability of icatibant therapy for ACEI-induced AE, but the benefit of icatibant therapy over placebo or conventional treatment strategies could not be shown.

Acute Necrotizing Encephalopathy in Children: a Long Way to Go.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare, but potentially life threatening neurological condition in children. This study aimed to investigate its clinical spectrum, diagnostic and therapeutic dilemma, and prognosis. METHODS: Twelve children with ANE were included in the study. The diagnosis was made by clinical and radiological characteristics from January 1999 to December 2017 and their clinical data were retrospectively analyzed. RESULTS: A total of 12 children aged 6 to 93 months at onset (5 male: 7 female) were evaluated. The etiology was found in 4 of them (influenza A, H1N1; coxsackie A 16; herpes simplex virus; and RANBP2 gene/mycoplasma). The most common initial presentations were seizures (67%) and altered mental status (58%). The majority of the subjects showed elevation of aspartate aminotransferase/alanine aminotransferase with normal ammonia and increased cerebrospinal fluid protein without pleocytosis. Magnetic resonance imaging revealed increased T2 signal density in bilateral thalami in all patients, but the majority of the subjects (67%) also had lesions in other areas including tegmentum and white matter. Despite the aggressive immunomodulatory treatments, the long-term outcome was variable. One child and two sisters with genetic predisposition passed away. CONCLUSION: ANE is a distinctive type of acute encephalopathy with diverse clinical spectrum. Even though the diagnostic criteria are available, they might not be watertight. In addition, treatment options are still limited. Further studies for better outcome are needed.

Effects of CYP2C19 and CYP3A5 genetic polymorphisms on the pharmacokinetics of cilostazol and its active metabolites.

PURPOSE: CYP3A4, CYP2C19, and CYP3A5 are primarily involved in the metabolism of cilostazol. We investigated the effects of CYP2C19 and CYP3A5 genetic polymorphisms on the pharmacokinetics of cilostazol and its two active metabolites. METHODS: Thirty-three healthy Korean volunteers were administered a single 100-mg oral dose of cilostazol. The concentrations of cilostazol and its active metabolites (OPC-13015 and OPC-13213) in the plasma were determined by HPLC-MS/MS. RESULTS: Although the pharmacokinetic parameters for cilostazol were similar in different CYP2C19 and CYP3A5 genotypes, CYP2C19PM subjects showed significantly higher AUC0-∞ for OPC-13015 and lower for OPC-13213 compared to those in CYP2C19EM subjects (P < 0.01 and P < 0.001, respectively). Pharmacokinetic differences in OPC-13015 between CYP3A5 non-expressors and expressors were significant only within CYP2C19PM subjects. The amount of cilostazol potency-adjusted total active moiety was the greatest in subjects with CYP2C19PM-CYP3A5 non-expressor genotype. CONCLUSION: These results suggest that CYP2C19 and CYP3A5 genetic polymorphisms affect the plasma exposure of cilostazol total active moiety. CYP2C19 plays a crucial role in the biotransformation of cilostazol.

An interictal EEG can predict the outcome of vagus nerve stimulation therapy for children with intractable epilepsy.

PURPOSE: This study aimed to evaluate the long-term efficacy of vagus nerve stimulation (VNS) in children and adolescents with intractable epilepsy and identify predictive factors for responsiveness to VNS. METHODS: Medical records of pediatric patients who underwent VNS implantation at two Korean tertiary centers were reviewed. At 0.5, 1, 3, and 5 years post-VNS implantation, the frequency of the most disabling seizures in each patient was assessed. Responders were defined as showing an overall 50 % reduction from baseline seizure frequency during follow-up. The clinical characteristics of responders and non-responders were compared. RESULTS: Among 58 patients, approximately half (29/58) were responders. The mean age at implantation was 10.9 years (range, 2.7-20.9) and the mean follow-up duration after VNS implantation was 8.4 years (range, 1-15.5). At 0.5, 1, 3, and 5 years after implantation, 43.1, 50.0, 56.9, and 58.1 % of patients exhibited ≥50 % seizure frequency reduction disabling seizures. The patients with focal or multifocal epileptiform discharges were more likely to be responders than those with generalized epileptiform activities by video or conventional EEG at the time of VNS implantation (Pearson's and χ 2 test, p = 0.001). No other clinical variables were found to be associated with seizure outcomes. Wound infections caused VNS removal in two cases. All other adverse events, including cough and hoarseness, were tolerable. CONCLUSION: VNS is a well-tolerated and effective adjuvant therapy in pediatric patients with intractable epilepsy. Notably, patients with focal epileptiform discharges alone rather than those with generalized epileptiform discharges maybe better candidates for VNS.

Clinical Characteristics of Transplant-associated Encephalopathy in Children.

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0-491 days), 10 days after HT (1-296 days), 49.5 days after HSCT (9-1,405 days), and 39 days after LT (1-1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.

Unfavorable Course of Subclinical Hypothyroidism in Children with Hashimoto's Thyroiditis Compared to Those with Isolated Non-Autoimmune Hyperthyrotropinemia.

Subclinical hypothyroidism (SCH) is a common problem in pediatric population, and the natural history of SCH varies depending on its etiology. Whether Hashimoto's thyroiditis (HT) negatively affects the natural course of SCH was investigated in pediatric patients without concomitant diseases. Predictors for levothyroxine medication were also evaluated. Medical records of 109 children with SCH (91 girls, 5?18 years) diagnosed between 2005 and 2014 were retrospectively reviewed. Patients were classified into HT (n = 37) and isolated non-autoimmune hyperthyrotropinemia (iso-NAHT, n = 72). During median 2 years of follow-up, only 10.1% of SCH patients eventually initiated levothyroxine, and HT patients showed a higher probability of requiring levothyroxine medication than iso-NAHT patients (21.6% vs. 4.2%). Underlying HT independently predicted deterioration of thyroid function, leading to levothyroxine medication (hazard ratios [HRs], 4.6 vs. iso-NAHT, P = 0.025). High titers of anti-thyroglobulin antibodies (TGAbs) predicted later medication in the HT group (HRs, 28.2 vs. normal TGAbs, P = 0.013). Most pediatric SCH showed benign and self-remitting courses. Underlying HT significantly increases the risk for levothyroxine medication, especially with high titers of TGAbs.