Differentiating ictal/subclinical spikes and waves in childhood absence epilepsy by spectral and network analyses: A pilot study

ObjectiveChildhood absence epilepsy (CAE) is a disease with distinct seizure semiology and electroencephalographic (EEG) features. Differentiating ictal and subclinical generalized spikes and waves discharges (GSWDs) in the EEG is challenging, since they appear to be identical upon visual inspection. Here, spectral and functional connectivity (FC) analyses were applied to routine EEG data of CAE patients, to differentiate ictal and subclinical GSWDs.MethodsTwelve CAE patients with both ictal and subclinical GSWDs were retrospectively selected for this study. The selected EEG epochs were subjected to frequency analysis in the range of 1–30 Hz. Further, FC analysis based on the imaginary part of coherency was used to determine sensor level networks.ResultsDelta, alpha and beta band frequencies during ictal GSWDs showed significantly higher power compared to subclinical GSWDs. FC showed significant network differences for all frequency bands, demonstrating weaker connectivity between channels during ictal GSWDs.ConclusionUsing spectral and FC analyses significant differences between ictal and subclinical GSWDs in CAE patients were detected, suggesting that these features could be used for machine learning classification purposes to improve EEG monitoring.SignificanceIdentifying differences between ictal and subclinical GSWDs using routine EEG, may improve understanding of this syndrome and the management of patients with CAE.     

Clinical Impact of Oral Anticoagulation in Patients with Atrial High-rate Episodes

Background: Atrial high-rate episodes (AHREs) are common in pacemaker patients. Our aims were to compare patients with AHREs to those without them and to assess if, in those with AHREs, the initiation of oral anticoagulation (OAC) has any clinical impact on the occurrence of ischemic and hemorrhagic events. Methods: From 2014-2017 we selected patients with pacemaker in whom AHREs were detected. AHREs were defined as episodes lasting more than 6 minutes if the electrogram was available or more than 6 hours if not. We used an age- and gender-matched population with pacemaker but no AHRE as a control group (observational study). Those with AHRE were referred to their assistant physician to decide OAC initiation, based on individual circumstances (interventional study). In interventional study, the primary outcome was a composite of systemic thromboembolism or major bleeding. Secondary outcomes were clinical relevant nonmajor bleeding, major and nonmajor bleeding, CV death, and death from all causes. Results: AHREs were detected in 86 patients: 69 patients initiated OAC and the remaining 17 patients did not. When comparing patients with and without AHRE, baseline characteristics were not different between the groups, except for indexed left atrium volume—40 mL (IQR: 34-50) in AHRE group versus 35 mL (IQR: 34-40) in control group (P?=?.014). AHREs were associated with future development of atrial fibrillation (AF) and the risk was higher if AHRE duration was superior to 6 hours. Death and cardiovascular (CV) death were not significantly different between the groups with and without AHRE. Primary outcome occurred in 4.9 per 100 person-year in OAC group versus 3.4 per 100 person-year in non-OAC group (HR 1.4, 95% CI .2-11.3, P?=?.78). Secondary outcomes were not significantly different in the groups. Conclusions: In this group of patients with pacemakers, the presence of AHREs was useful for predicting the future development of AF and the risk of AF was higher in those with a longer duration of AHRE. In the AHRE group, OAC therapy was not associated with a significant difference in the risk of thromboembolism or major bleeding.     

Pathological fracture of the femur in Alagille Syndrome: A case report

Alagille Syndrome is a rare autosomal dominant genetic disorder, occur only 1:70,000 in population, and characterized by reduced interlobular bile ducts, and resultant nutritional deficiencies associated with the inability to absorb fat-soluble vitamins such as vitamin D. Patients are at risk for secondary osteoporosis, rickets/osteomalacia, and ultimately may result in fracture. The majority of patients suffer from chronic cholestasis, which can have a variety of adverse effects on bone metabolism. Hypothyroidism has been described in some Alagille Syndrome patients, and eventually delayed puberty can occur. Two until fourteen percents of patients of Alagille syndrome will suffer from fractures, in which it primarily occurs in the lower limb long bones in the absence of significant trauma. This study aimed to present a rare case of pathological fracture of femur in Alagille syndrome patient and its management in our hospital.Six-year-old male with pain on his right thigh came to our ER after fell down while putting on his pants. He had been diagnosed with biliary atresia at the age of 3 months and underwent surgical bile duct reconstruction. In addition, he also suffered from congenital hypothyroidism and consequently, stunted growth. The pathological fracture of the femur was treated conservatively with hemispica cast. At 2 months follow up, there is already radiographic evidence of fracture healing occurred by secondary intention and callus formation.By ensuring adequate calcium and vitamin D intake, monitoring for vitamin D deficiency, monitoring for fragility fractures, and avoiding trauma-related accidents, a proper conservative treatment using hemispica cast could still always be considered for managing such diaphyseal fractures in Alagille syndrome, especially in relatively low-resource countries such as Indonesia.     

Topometric and Tomographic Evaluation of Subclinical Keratoconus

ABSTRACT

Purpose

To investigate the corneal topometric and tomographic findings that can be used in the diagnosis of subclinical keratoconus.     

补充维生素D3协同第二代抗组胺药物治疗慢性自发性荨麻疹的临床疗效观察和作用机制研究

目的：评价补充维生素D3（VD3）协同第二代抗组胺药物对控制慢性自发性荨麻疹（CSU）临床症状的疗效。方法：① 90例CSU患者，21例慢性可诱导性荨麻疹(CIndUI)和55例健康自愿者选自武汉大学人民医院皮肤科门诊（2017年10月至2018年10月）；② 受试者进行血清25羟维生素D3［25-(OH)D3］，血浆D-二聚体(D-dimer)、纤维蛋白降解产物（FDP），血沉（ESR）等实验室检查，并给予荨麻疹活动度评分（UAS7）；③ 分离和体外培养正常人与CSU患者各15例外周血单个核细胞（PBMC），经1 nM和10 nM 1α,25-(OH)2D3处理后用实时荧光定量PCR技术检测白介素-6(IL-6)和维生素D受体（VDR）mRNA的表达水平；④ VD3严重缺乏（血清浓度<10 ng/mL）的患者补充大剂量(2400 IU/d)VD3，缺乏者(10~20 ng/mL)给予补充小剂量（800 IU/d）VD3，设未补充患者作对照，于6周和12周时再行UAS7评分。结果：与健康对照组相比，CSU患者血清25-(OH)D3水平明显减少，D-dimer、FDP及ESR水平明显增加，且与UAS7评分呈正相关；qPCR结果显示15例CSU患者PBMC IL-6和VDR mRNA表达水平较正常人明显增加；经1α,25-(OH)2D3处理后，IL-6 mRNA表达减少，VDR mRNA表达增加(P<0.05)；与未补充组比较，VD3严重缺乏组给予补充大剂量VD3 12周，UAS7评分明显下降(P<0.0001)。结论：补充VD3有助于协同控制CSU的临床症状，可能与其抑制了荨麻疹亚临床炎症有关。     

Cyclic alternating pattern in infants with congenital hypothyroidism

Congenital hypothyroidism is defined as thyroid hormone deficiency present at birth which is crucial for brain development. Recently, the cyclic alternating pattern, a rhythm present in electroencephalography recordings in non-Rapid eye movement sleep, has been related to brain development and cognition in different pediatric conditions. Therefore, we evaluated the cyclic alternating pattern rate in infants with congenital hypothyroidism, thyroxine supplementation, and healthy controls. The parameters of the cyclic alternating pattern were evaluated in 19 healthy infants (10 female, mean age 25.5?±?15.5?months) and 21 infants diagnosed with congenital hypothyroidism (19 female, mean age 24.3?±?19.0?months). We considered the transient electro-cortical activations (phase A of the cycle) in non-Rapid eye movement sleep and the subdivisions of the A phase in: A1, A2 and A3, based on their frequency content. All subjects were subjected to polysomnography recording in a standard laboratory setting. Sleep data were stored computer following the International 10–20 System. Data showed that congenital hypothyroidism infants exhibited higher frequency of central apnea, hypopnea, and arousals in comparison to controls. Particularly, central apnea index decreased with age in the control group but not in congenital hypothyroidism group. Regarding to cyclic alternating pattern measurements, congenital hypothyroidism infants exhibit a higher frequency in the percentage of A3 subtype (electroencephalographic desynchrony) and conversely a lower percentage of A1 subtype (electroencephalographic synchrony), than healthy infants. An important finding of this study is the positive correlation between A1 mean duration and age, which is bigger in control group than in congenital hypothyroidism group (time duration in control group (0.52?s/month) versus congenital hypothyroidism group (0.1?s/month). Infants with congenital hypothyroidism showed an increase of A3 subtype, of central apnea, and of arousals. The reduction of percentage and mean duration of A1 subtype could be a valuable indicator of sleep development in patients with congenital hypothyroidism and healthy infants.     

Hypothyroidism and isolated hypothyroxinemia in pregnancy,from physiology to the clinic

Many changes occur in the physiology of the maternal thyroid gland to maintain an adequate level of thyroid hormones (THs) at each stage of gestation during normal pregnancy, however, some factors can produce low levels of these hormones, which can alter the onset and progression of pregnancy. Deficiency of THs can be moderate or severe, and classified as overt or clinical hypothyroidism, subclinical hypothyroidism, and isolated hypothyroxinemia. Overt hypothyroidism has been reported in 0.3–1.9% and subclinical hypothyroidism in approximately 1.5–5% of pregnancies. With respect to isolated hypothyroxinemia, the frequency has been reported in approximately 1.3% of pregnant women, however it can be as high as 25.4%. Worldwide, iodine deficiency is the most common cause of hypothyroidism, however, in iodine-sufficient countries like the United States, the most common cause is autoimmune thyroiditis or Hashimoto's thyroiditis. The diagnosis and timely treatment of deficiency of THs (before or during the first weeks of gestation) can significantly reduce some of the related adverse effects, such as recurrent pregnancy loss, preterm delivery, gestational hypertension, and alterations in the offspring. However, so far there is no consensus on the reference levels of thyroid hormones during pregnancy to establish the diagnosis and there is no consensus on universal screening of women during first trimester of pregnancy to identify thyroid dysfunction, to give treatment and to reduce adverse perinatal events, so it is necessary to carry out specific studies for each population that provide information about it.     

Subclinical Inflammatory Response: Accelerated versus Standard Corneal Cross-Linking

Purpose: To compare the subclinical inflammatory response (as measured by anterior chamber flare) induced after standard (3 mW/cm², 30 min) and accelerated (18 mW/cm², 5 min) corneal cross-linking (CXL).

Methods: In this comparative, non-randomized study, patients with progressive keratoconus who underwent standard or accelerated CXL were studied. Laser flare photometery (FM-600; Kowa, Tokyo, Japan) was used to measure anterior chamber flare preoperatively and at 1 week, 1 month, 3 months, and 6 months after the procedure.

Results: Sixty eyes of 60 patients were studied; 30 eyes in each group. Mean baseline flare values were 4.15 ± 1.19 and 4.57 ± 2.17 ph/ms in standard and accelerated groups, respectively (p = 0.228).and after surgery increased in all follow-up measurements in the both groups similarly (P > 0.05).

Conclusion: Both standard and accelerated CXL results in induction of a subclinical inflammatory response that persists up to 6 month. The response was similar between the two groups.