A Patient Diagnosed with Spinocerebellar Ataxia Type 5 associated with SPTBN2: Case Repor

Spinocerebellar ataxias (SCAs) are autosomal dominant neurodegenerative disorders which disrupt the afferent and efferent pathways of the cerebellum that cause cerebellar ataxia. Spectrin beta non-erythrocytic 2 (SPTBN2) gene encodes the β-III spectrin protein with high expression in Purkinje cells that is involved in excitatory glutamate signaling through stabilization of the glutamate transporter, and its mutation is known to cause spinocerebellar ataxia type 5. Three years and 5 months old boy with delayed development showed leukodystrophy and cerebellar atrophy in brain magnetic resonance imaging (MRI). Diagnostic exome sequencing revealed that the patient has heterozygous mutation in SPTBN2 (p.Glu1251Gln) which is a causative genetic mutation for spinocerebellar ataxia type 5. With the patient’s clinical findings, it seems reasonable to conclude that p.Glu1251Gln mutation of SPTBN2 gene caused spinocerebellar ataxia type 5 in this patient.ope

Male patients presenting with rapidly progressive puberty associated with malignant tumors

In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.ope

Changes in functional brain network topology after successful and unsuccessful corpus callosotomy for Lennox-Gastaut Syndrome

Corpus callosotomy (CC) is an effective palliative surgical treatment for patients with Lennox-Gastaut Syndrome (LGS). However, research on the long-term functional effects of CC is sparse. We aimed to investigate these effects and their associated clinical conditions over the two years after CC. Long-term clinical EEG recordings of 30 patients with LGS who had good and bad seizure outcome after CC were collected and retrospectively studied. It was found that CC caused brain network 'hubs' to shift from paramedian to lateral regions in the good-recovery group, which reorganized the brain network into a more homogeneous state. We also found increased local clustering coefficients in patients with bad outcomes and decreases, implying enhanced network integration, in patients with good outcomes. The small worldness of brain networks in patients with good outcomes increased in the two years after CC, whereas it decreased in patients with bad outcomes. The covariation of small-worldness with the rate of reduction in seizure frequency suggests that this can be used as an indicator of CC outcome. Local and global network changes during the long-term state might be associated with the postoperative recovery process and could serve as indicators for CC outcome and long-term LGS recovery.ope

Efficacy and Safety of Lamotrigine Adjunctive Therapy in Lennox-Gastaut Syndrome

Purpose: Lamotrigine (LTG) is often used as adjunctive therapy in Lennox-Gastaut syndrome (LGS); however, it may worsen myoclonic and atypical absence seizures in LGS patients. This study reviewed the overall efficacy and safety of LTG in children with LGS. Methods: This retrospective study included 38 patients (aged 50% in 47.4% of patients (18/38). After 6 months, 20 patients (20/36, 55.6%) showed a favorable response. After 12 months, five patients (5/11, 45.5%) responded to treatment. Three patients showed myoclonic seizures at the start of treatment and >50% amelioration in seizure frequency at the 3- and 6-month follow-up visits. Conclusion: This study reaffirms the efficacy and safety of LTG in children with LGS. Therefore, LTG is strongly recommended as an adjunctive therapy for children with LGS.ope

Hypotonic hyponatremia by primary polydipsia caused brain death in a 10-year-old boy

Hypotonic hyponatremia by primary polydipsia can cause severe neurologic complications due to cerebral edema. A 10-year-and-4-month-old boy with a psychiatric history of intellectual disability and behavioral disorders who presented with chief complaints of seizure and mental change showed severe hypotonic hyponatremia with low urine osmolality (serum sodium, 101 mmol/L; serum osmolality, 215 mOsm/kg; urine osmolality, 108 mOsm/kg). The patient had been polydipsic for a few months prior, and this had been worse in the previous few days. A diagnosis of hypotonic hyponatremia caused by primary polydipsia was made. The patient was in a coma, and developed respiratory arrest and became brain death shortly after admission, despite the treatment. The initial brain magnetic resonance imaging showed severe brain swelling with tonsillar and uncal herniation, and the patient was declared as brain death. It has been reported that antidiuretic hormone suppression is inadequate in patients with chronic polydipsia, and that this inadequate suppression of antidiuretic hormone is aggravated in patients with acute psychosis. Therefore, hyponatremia by primary polydipsia, although it is rare, can cause serious and life-threatening neurologic complications.ope

High-Sensitivity C-Reactive Protein Can Reflect Small Airway Obstruction in Childhood Asthma.

PURPOSE: High-sensitivity assays enabled the identification of C-reactive protein (hs-CRP) at levels that were previously undetectable. We aimed to determine if hs-CRP could reflect airway inflammation in children, by comparing hs-CRP with spirometry and impulse oscillometry (IOS) parameters and symptomatic severities. MATERIALS AND METHODS: A total of 276 asthmatic children who visited Severance Children's Hospital from 2012-2014 were enrolled. Serum hs-CRP and pulmonary function tests were performed on the same day. Patients were divided into hs-CRP positive and negative groups (cut-off value, 3.0 mg/L). RESULTS: Of the 276 asthmatic children [median age 7.5 (5.9/10.1) years, 171 boys (62%)], 39 were hs-CRP positive and 237 were negative. Regarding spirometry parameters, we observed significant differences in maximum mid-expiratory flow, % predicted (FEF₂₅₋₇₅) (p=0.010) between hs-CRP positive and negative groups, and a negative correlation between FEF₂₅₋₇₅ and hs-CRP. There were significant differences in the reactance area (AX) (p=0.046), difference between resistance at 5 Hz and 20 Hz (R5-R20) (p=0.027), resistance at 5 Hz, % predicted (R5) (p=0.027), and reactance at 5 Hz, % predicted (X5) (p=0.041) between hs-CRP positive and negative groups. There were significant positive correlations between hs-CRP and R5 (r=0.163, p=0.008), and X5 (r=0.164, p=0.007). Spirometry and IOS parameters had more relevance in patients with higher blood neutrophil levels in comparison to hs-CRP. CONCLUSION: Hs-CRP showed significant correlation with FEF₂₅₋₇₅, R5, and X5. It can reflect small airway obstruction in childhood asthma, and it is more prominent in neutrophil dominant inflammation.ope

Quinidine Trial in a Patient with Epilepsy of Infancy with Migrating Focal Seizure and KCNT1 Mutation

Epilepsy of infancy with migrating focal seizure (MFEI) is an early-onset epileptic encephalopathy characterized by randomly migrating focal seizures and psychomotor deterioration. It is associated with mutations in a variety of genes, with potassium sodium-activated channel subfamily T member 1 (KCNT1) being an example. Previously reported KCNT1 mutations in MFEI are gain-of-function mutations. Therefore, quinidine therapy targeted at reduction of pathologically increased KCNT1 channel-mediated potassium conductance has been proposed as a target treatment for MEFI with KCNT1 mutation. The authors report a case involving a patient with MFEI and a missense mutation in KCNT1 (c.7129G>A; p.Phe346Leu) treated with quinidine therapy. Seizure activity was poorly responsive to quinidine.ope

Efficacy of Stiripentol in Dravet Syndrome with or without SCN1A Mutations

BACKGROUND AND PURPOSE: The aim of this study was to determine the effectiveness of stiripentol (STP) add-on therapy to valproate and clobazam in patients with Dravet syndrome (DS) according to the presence of mutations in the sodium channel alpha-1 subunit gene (SCN1A). METHODS: We performed direct sequencing to analyze SCN1A mutations in 32 patients with clinically confirmed with DS, and classified them into mutation (pathogenic or likely pathogenic) and nonmutation groups based on American College of Medical Genetics and Genomics guidelines. We compared the efficacy of STP in reducing the seizure frequency between the two groups. RESULTS: The 32 patients comprised 15 patients in the mutation group (with definite SCN1A mutations) and 17 patients in the nonmutation group with variants of unknown significance or benign variants. The clinical profile did not differ significantly between the mutation and nonmutation groups. The seizure frequency relative to baseline reduced by 72.53+/-23.00% (mean+/-SD) in the mutation group versus 50.58+/-40.14% in the nonmutation group (p=0.004). The efficacy of STP was better in DS patients with missense mutations that in those with truncation mutations, and was not favorable in patients with mutations at linkers between domains (DII-DIII), linkers between segments of domain I (DI S1-S2), or splice sites, although the small number of patients prevented statistical analyses. CONCLUSIONS: The efficacy of STP was significantly better in DS patients with definite SCN1A mutations than in those without mutations.ope

Adverse Events During Perampanel Adjunctive Therapy in Intractable Epilepsy

BACKGROUND AND PURPOSE: Perampanel is the first alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist developed to treat epilepsy. The effects of either rapid or slow dose titration on adverse events remain to be elucidated. METHODS: Eighty-five patients received perampanel between March 2016 and August 2016. Patients were divided into two groups according to their dosing schedule: rapid dose titration (2-mg increments at intervals of 1 to 2 weeks) and slow dose titration (2-mg increments at intervals of at least 3 weeks). Seizure frequency and adverse events were analyzed over 3 months. RESULTS: Adverse events were reported by 47 (58%) of the 81 patients analyzed, with 12 (15%) patients discontinuing perampanel due to adverse events. Common adverse events included dizziness (n=30, 37%), aggressive mood and behavior (n=19, 24%), gait disturbance (n=16, 20%), and sleep problems (n=10, 12.4%). The overall adverse events were similar in the slow-titration group (38 of 61 patients) and the rapid-titration group (8 of 20 patients, p=0.081). However, none of the 20 patients in the slow-titration group experienced gait disturbance, compared with 16 of the 61 patients in the rapid-titration group (p=0.009), while appetite change was experienced by 4 patients in the slow-titration group but only 1 in the rapid-titration group (p=0.003). No relationship was noted between adverse events and the maximum dose of perampanel (p=0.116). Sex differences were observed, with the response to perampanel being better and the rate of adverse events being higher in females (p=0.015 and p=0.046, respectively). CONCLUSIONS: Slow titration of perampanel may reduce perampanel-related adverse events.ope

베트남 여성의 hsCRP와 식품 및 영양소 섭취와의 관련성 연구

Inflammation is known to cause atherosclerosis and cardiovascular disease progression. High sensitivity C-reactive protein (hsCRP), as a marker of inflammation, is a prognostic indicator of future risk for cardiovascular disease in healthy people. Many studies have demonstrated the association between hsCRP and cardiovascular disease. In addition, numerous studies have reported that hsCRP is closely associated with dietary intake. Although many studies have reported regarding the association between dietary intake and hsCRP, almost all the subjects involved in these studies were Western people. Also, these studies mainly investigated elderly people or those in the middle age range, with not much attention on young adults. Therefore, in the present study, we examined the association between dietary intake and hsCRP in healthy Vietnamese young women. A cross-sectional analysis was performed with 956 Vietnamese women, who voluntarily participated in the Korean Genome Epidemiologic Study (KoGES), from Can Tho University and local clinical centers between March 21 and 27 in 2011. The subject’s mean hsCRP level was 1.3 ± 2.9 mg/L. According to the hsCRP range by American Heart Association (AHA) and Centers for Disease Control (CDC), the High Risk Group showed significantly higher weight, body mass index, waist and hip circumference, waist to hip ratio, body fat and diastolic blood pressure (p<0.0001) compared to the Low and Average Risk Groups. Total cholesterol (p=0.0007), LDL cholesterol (p=0.0022), HDL cholesterol (p=0.0011), triglyceride (p<0.0001) were found to be significantly different among the three groups. With regard to daily food intake of the subjects, the High Risk Group was found to consume less vegetables/mushrooms/seaweeds/fruits (p=0.0024), total plant food (p=0.0406), and total food (p=0.0252) than that of the Low Risk Group. In daily nutrient intake, the High Risk Group was found to consume less potassium (p=0.0292), and folate (p=0.0274) than those of the Low and Average Risk Groups. Also, hsCRP was positively associated with meat and meat products (r=0.0756, p=0.0298), eggs and egg products (r=0.1172, p=0.0461), total fat (r=0.0857, p=0.0082), and animal fat (r=0.0999, p=0.0021). Conversely, hsCRP was inversely associated with vegetables/mushrooms /seaweeds and fruits (r=-0.1226, p=0.0001), total plant food (r=-0.1145, p=0.0004), total food intake (r=-0.0852, p=0.0086), fiber (r=-0.0901, p=0.0054), potassium (r=-0.0750, p=0.0207), vitamin C (r=-0.0750, p=0.0190), and folate (r=-0.0788, p=0.0154). In comparison to dietary intake according to cardiovascular disease risk, potassium (p=0.0386), vitamin B1 (p=0.0263), vitamin B6 (p=0.0244), niacin (p=0.0483) showed significantly higher Low CVD Risk Group after adjustment for potential confounders. A logistic regression analysis showed that compared to women in the lowest quartile of vegetables/mushrooms/seaweeds and fruits, potassium, folate consumption, those in the highest quartile had a reduced risk of having a high hsCRP level [OR(95%CI): 0.389(0.189-0.802)], [OR(95%CI): 0.425(0.192-0.939)], [OR(95%CI): 0.491(0.250-0.966)]. In conclusion, we found that intakes of vegetables/mushrooms/seaweeds and fruits, total plant food, vitamin C, potassium, and folate were inversely associated with hsCRP level. On the other hand, intakes of total fat and animal fat were positively associated with hsCRP. Therefore, to prevent future cardiovascular disease occurrence by reducing the hsCRP level, it is necessary to increase vegetable, fruit and total plant food intakes and decrease fat intake.;염증 반응은 동맥경화 및 심혈관 질환 진행을 야기하는 것으로 알려져 있다. High sensitivity C-reactive protein (hsCRP) 는 간에서 생성되는 급성 반응 단백질로 많은 연구들이 심혈관 질환과 hsCRP 의 관련성에 대해 보고하고 있으며 특히, hsCRP 는 건강한 사람들에서 심혈관 질환의 위험도 평가 및 예후를 추정하는 지표로 알려져 있다. 이 뿐 아니라, 많은 선행연구에서 hsCRP 와 식이요인과의 밀접한 관련성에 대한 연구가 진행되고 있다. 그러나 20~30 대의 젊은 성인을 대상으로 hsCRP 와 식이요인과의 연관성에 대한 연구는 제한적이며 대부분의 연구 대상자들이 서양사람을 대상으로 하고 있어 아시아인을 대상으로 한 연구 또한 제한적이다. 특히, 최근 심혈관 질환으로 인한 사망률이 급증하고 있는 베트남 사람들에 대한 연구는 진행 된 바가 없다. 이에 본 연구에서는 건강한 베트남 20~30 대 여성을 대상으로 하여 그들의 hsCRP 와 식이요인과의 관련성에 대하여 조사하였으며 심혈관 질환 위험 요인에 따라 식이섭취 상태를 비교하였다. 2011년 3월 21일부터 3월 27일까지 모집된 대상자를 대상으로 실시하였으며, 본 연구의 2011년 모집 대상 지역은 Can Tho 지역 (베트남 남부지역, 호치민 근교) 의 Can Tho 대학과 인근 보건소에서 진행되었다. 대상자는 20~30 대 여성 956 명을 대상으로 진행되었으며 그들의 나이는 평균 25.0 (range 18~39) 세이다. 베트남 현지 여성을 대상으로 신체계측, 혈액성상, 식이조사를 수행하였으며 식이 조사의 경우 24시간 회상법을 이용하여 실시되었다. 대상자의 평균 hsCRP 수치는 정상범위에 속하였으며, 아시아 국가와 비교하였을 때에도 비슷한 수치를 보였다. 대상자를 hsCRP 의 범위에 따라 Low Risk Group (< 1 mg/L), Average Risk Group (1 ~ 3 mg/L), High Risk Group (> 3 mg/L) 으로 나누어 비교하였다. 그 결과, High Risk Group 은 Low and Average Risk Group 보다 몸무게, 체질량지수, 허리 둘레, WHR, 복부지방률, 이완기 혈압이 유의적으로 높게 나타났다. High Risk Group 은 Low Risk Group 보다 야채, 버섯, 해조류 및 과일류 (p=0.0024), 총 식물성 식품 (p=0.0406), 총 식품 (p=0.0366), 칼륨 (p=0.0292), 엽산 (p=0.0274)를 유의적으로 낮게 섭취하였다. hsCRP 는 고기류, 달걀류, 총 지방, 동물성 지방과 양의 상관성을 보였으며 야채, 버섯, 해조류 및 과일류와 총 식물성 식품, 식이섬유, 칼륨, 비타민 C, 엽산 과는 음의 상관성을 보였다. 각각의 식품 및 영양소 섭취량에 따른 hsCRP 의 교차비를 알아보고자 섭취량을 4분위로 나누어 상위 섭취군과 하위 섭취군을 비교한 결과, 야채, 버섯, 해조류 및 과일류, 칼륨, 엽산 상위 섭취군의 교차비(95%CI)는 각각 0.389(0.189-0.802), 0.425(0.192-0.939), 0.491(0.250-0.966) 이었다. 대상자를 심혈관 질환 위험요소에 따라 Low CVD Risk Group 과 Not Low CVD Risk Group 두 그룹으로 나누어 식이 상태를 본 결과, Low CVD Risk Group 에서 유의적으로 칼륨 (p=0.0386), 비타민 B1 (p=0.0263), 비타민 B6 (p=0.0244), 니아신 (p=0.0483) 을 Not Low CVD Risk Group 에 비해 높게 섭취하였다. 결론적으로 베트남 성인 여성에서 hsCRP 를 낮추어 심혈관 질환 발생을 예방하기 위해서는 지방의 섭취는 감소하고 야채, 과일과 같은 식물성 식품의 섭취를 높일 것이 권고되며 추후, 베트남 식품 구성표를 보완하여 hsCRP 와 영양상태의 관련성에 대한 전향적 연구가 필요할 것으로 보인다.Ⅰ. Introduction 1 Ⅱ. Materials and Methods 5 A. Study subjects 5 B. Measurements 7 1. General characteristics 7 2. Anthropometric variables and blood pressure 8 3. Blood profiles 9 4. Dietary intakes 10 C. Statistical analysis 11 Ⅲ. Results 13 A. Characteristics of subjects 13 1. General characteristics 13 2. Anthropometric variables and blood pressure 15 3. Blood profiles 17 4. Dietary intakes 19 B. Comparison of subjects according to hsCRP range 22 1. Anthropometric variables and blood profiles 22 2. Food intakes 25 3. Nutrient intakes 27 C. Correlation of hsCRP and related factors 29 1. Anthropometric variables and blood profiles 29 2. Dietary intakes 32 D. Relationship between hsCRP and dietary factors 34 1. hsCRP concentration according to quartile of food intakes 34 2. hsCRP concentration according to quartile of nutrient intakes 36 E. Comparison of subjects according to cardiovascular disease risk 39 1. Anthropometric variables and blood profiles 39 2. Dietary intakes 42 Ⅳ. Discussion 45 References 52 Appendix 60 국문초록 6