Fever of unknown origin in 185 paediatric patients: a single-centre experience

Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein-Barr virus (EBV) serology, urine, stool or blood cultures, chest X-ray and tuberculin probe. Results: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self-limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus-associated haemophagocytic syndrome, one with VL and two unknown) died.

Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.     

Sensory evoked potentials in infants with Down syndrome

Aim: To investigate the sensory functions of the peripheral to central pathways in infants with Down syndrome (DS) by sensory evoked potentials. Methods: Fifty-five infants, 30 DS infants and 25 controls, were examined by multimodal evoked potentials, including brainstem auditory evoked potentials (BAEP), visual evoked potentials (VEP) and short-latency somatosensory evoked potentials (SSEP). Results: No obvious difference was found in the peak latencies between the two groups for BAEP. Nine children with DS showed abnormal BAEP; six had hearing loss and three had prolonged wave I latencies. For VEP, the peak latencies of P₂ and N₂ were significantly longer and the amplitudes were smaller in the DS group than in the control group. Of the 30 infants with DS, five had significantly prolonged P₂ latencies and two had lower amplitudes. In SSEP, the mean latencies of N₂₀ and the interpeak latencies of N₁₃-N₂₀ of the infants with DS showed apparent prolongation compared to the controls. Seven of 30 (23.3%) DS patients had prolonged N₂₀ latencies.

Conclusion: Our results indicate that various sensory deficits occur in patients with DS during the first year of life.     

Bacterial aetiology of acute osteoarticular infections in children

Aim: To study the bacterial aetiology of acute osteoarticular infections in children and to analyse the efficiency of culture methods. Methods: Bacteriological data of 407 cases of clinically suspected osteoarticular infections affecting 406 children hospitalized in an orthopaedic surgery department between 1999 and 2002 were retrospectively reviewed. Results: Bacterial cultures from clinical specimens were positive in 74 cases (18%): 38 cases of septic arthritis and 36 cases of bone infections (osteitis, osteomyelitis or osteoarthritis). The use of liquid medium bottles to grow bacteria from articular fluids increased the rate of positive cultures compared to the use of standard solid media (p=0.0001). The most commonly recovered pathogen was Staphylococcus aureus (44%) followed by Kingella kingae (14%), Streptococcus pyogenes (10%) and Streptococcus pneumoniae (10%). K. kingae was most frequently isolated among children under 36 mo of age (p=0.0003), whereas S. aureus was most frequently isolated among children over 36 mo (p=0.0015).

Conclusion: By improving our culture method, we observed a recrudescence of isolation of K. kingae, but S. aureus remains the main pathogen isolated from osteoarticular infections in children. This finding is useful for the adaptation of a probabilistic antibiotic treatment of these infections.     

Abnormalities in plasma fatty acid composition in human immunodeficiency virus-infected children treated with protease inhibitors

Aim: To study plasma fatty acid composition in human immunodeficiency virus-infected children treated with protease inhibitors and its relation with other components of the metabolic syndrome observed after this therapy. Design: Cross-sectional study from collected clinical database. Subjects: 17 children with HIV infection treated with protease inhibitors. Nine patients received ritonavir (20-30 mg/kg/d) and the remaining eight received nelfinavir (60-90 mg/kg/d). Duration of protease inhibitors treatment was 711±208 d. As controls, we used 112 matched blood samples from apparently healthy children admitted for minor surgical procedures. Methods: Plasma fatty acids were determined using a Hewlett Packard GC 5890 gas chromatograph. Results: Plasma levels of cholesterol and triglycerides and insulin-like growth factor 1 (IGF-1) tended to be high in protease inhibitor-treated patients. Plasma content of ω6 long-chain polyunsaturated fatty acids and, in particular, of the highly unsaturated 22:4ω6 and 22:5ω6, was significantly increased. Also, infected children had increased Δ6 and Δ4 desaturase activities and decreased Δ5 desaturase activity. Significant correlations were present between plasma IGF-1 level and plasma triglycerides, plasminogen activator inhibitor-1 activity and Δ6 desaturase activity.

Conclusion: HIV-infected, protease inhibitor-treated children exhibit a metabolic syndrome which is associated with significant changes in plasma fatty acid composition. These changes are similar to those observed in situations of insulin resistance and are linked to variations in plasma IGF-1 concentration.     

Extracorporeal life support for children with meningococcal septicaemia

Objective: To describe the short-term outcome of children with meningococcal sepsis treated with extracorporeal membrane oxygenation (ECMO) in a single centre. Design: Retrospective analysis of case notes. Setting: The Heartlink ECMO Centre, Glenfield Hospital, Leicester. Patients: Eleven children (8 boys) out of a total caseload of 800 patients were treated for meningococcal sepsis with ECMO. Interventions: Extracorporeal membrane oxygenation. Results: All children with meningococcal sepsis treated with ECMO had a Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) ≥12 (positive predictive risk of death of approximately 90%). Five children had adult respiratory distress syndrome (ARDS) and six had refractory shock with multi-organ dysfunction syndrome (MODS) at presentation for ECMO. All five children in the ARDS group survived, four of five receiving veno-venous (VV-) ECMO therapy. In contrast, only one of six children with refractory shock with MODS survived, all of whom required veno-arterial (VA-) ECMO therapy.

Conclusions: Most children with meningococcal sepsis and severe ARDS can be successfully treated with VV-ECMO. In contrast, children with refractory shock and MODS die despite treatment with VA-ECMO. This report does not resolve whether ECMO therapy offers any advantage over conventional therapy in treating severe meningococcal sepsis.     

Urological complications and copper replacement therapy in childhood Menkes syndrome

Background: Urological complications are frequent in Menkes syndrome, a very rare X-linked recessive disorder of copper (Cu) metabolism. Aim: To evaluate the role of Cu therapy in preventing the progression of urological complications. Subjects and methods: We retrospectively enrolled 57 patients with Menkes syndrome (55 published case reports and two of our own unpublished cases) and investigated the reported urological complications, distinguishing the patients with or without Cu replacement therapy and evaluating the efficacy of this therapy in the prevention of urological complications. Results: The most frequent urological complication was bladder diverticulum (38.6% of the total patients); obstruction bladder outflow and rupture of the kidney were less frequent (both 1.8% of the total). The number of congenital urological complications increased progressively by age category; in fact, 77.8% of patients did not report urological complications at the age of 0.4±0.2 y, and 28.6% of them displayed ≥ two congenital urological complications at the age of 9.3±2.6 y. The percentage of urological complications found in younger patients not on Cu therapy did not differ from that of older patients treated with Cu therapy. A comparison between patients of the same age interval, who were or were not treated with Cu, showed that treated children had fewer urological complications than untreated children.

Conclusion: Our investigation suggests that Cu therapy in patients with Menkes syndrome does not prevent the progression of urological complications; however, it might delay their worsening.     

Neuropathology in Patients with Congenital Heart Disease and Down Syndrome

This report examines the relationship between congenital heart disease (CHD) and neuropathological findings in three groups of patients: Down syndrome (45 cases), isolated CHD (296 cases), and CHD with multiple anomalies (92 cases). The increase in brain weight in Down syndrome was similar to control standards up to 1 year of age, after which it was less than normal. Among the three groups, there were differences in frequency in cyanotic CHD, history of operation, and macroscopic and microscopic brain malformations. The incidence of calcification in the brain was increased in Down syndrome. Nine children out of the total cohort had cerebrovascular abnormalities. Although CHD is frequent in Down syndrome, the cerebrovasculature is spared; only infrequent minor abnormalities of the circle of Willis were detected.     

Neuropathology in patients with congenital heart disease and Down syndrome.

This report examines the relationship between congenital heart disease (CHD) and neuropathological findings in three groups of patients: Down syndrome (45 cases), isolated CHD (296 cases), and CHD with multiple anomalies (92 cases). The increase in brain weight in Down syndrome was similar to control standards up to 1 year of age, after which it was less than normal. Among the three groups, there were differences in frequency in cyanotic CHD, history of operation, and macroscopic and microscopic brain malformations. The incidence of calcification in the brain was increased in Down syndrome. Nine children out of the total cohort had cerebrovascular abnormalities. Although CHD is frequent in Down syndrome, the cerebrovasculature is spared; only infrequent minor abnormalities of the circle of Willis were detected.     

Minor malformations in mental retardation of various aetiology

The frequency of minor malformations was determined in 246 mentally retarded children with an I. Q. ranging from 37 to 67. According to the probable aetiology, the patients were divided into 4 groups: Down syndrome (n = 29), other genetic causes (n = 22), perinatal and postnatal environmental damages (n = 68), and unknown aetiology (n = 127). One thousand consecutive newborn infants served as controls. The mean number of minor malformations per subject was the highest in patients with Down syndrome (3.38) and other genetic disorders (2.00). It was significantly lower in the mentally handicapped of unknown (0.88) and of environmental origin (0.37). The number of multiple minor anomalies was high in the genetically determined conditions and the smallest and nearing the control value in the exogenic group. The results support the idea that the presence of minor malformations, and especially of multiple ones, refers to the prenatal onset of mental deficiency.     

足底压力测量技术在足外翻脑性瘫痪患儿康复疗效评定中的应用

目的探讨足底压力测量技术在评估足外翻脑性瘫痪(脑瘫)患儿康复疗效中的应用价值。方法收集2010年3月-2011年3月在本院康复医学科就诊,并进行综合康复治疗的61例脑瘫患儿基本临床资料。患儿均在入院时采用粗大运动功能分级系统(GMFCS)评定患儿粗大运动功能级别,61例患儿122只外翻足采用JPD1600型足底压力测量仪对足底的5个区域进行数据采集,取得足底压力及着地时相等指标,经过6个月的综合康复治疗后,再次评估上述指标,将治疗前后进行统计分析,综合评定康复治疗的疗效。结果足底压力测量技术采集的数据显示治疗前后足前掌外侧及足弓外侧缘压力改变均有统计学意义(Pa<0.05),足前掌内侧、足弓内侧及足跟压力改变差异均有统计学意义(Pa<0.01);后足支撑期中整足接触时相、离地时相改变差异均有统计学意义(Pa<0.01)。运用GMFCS分级统计的结果示足外翻脑瘫患儿治疗前后的运动功能改变差异有统计学意义(P<0.01)。结论综合化康复治疗可有效改善脑瘫患儿足外翻;足底压力测量技术能够为脑瘫足外翻患儿康复疗效评定提供有效的、客观的功能评估。     

Down综合征患儿睡眠特征多导睡眠图的回顾性研究

目的 探讨Down综合征患儿的睡眠结构和基本睡眠参数的特点。方法 选取10例Down综合征患儿为Down组，采用染色体核型检查进行Down综合征的诊断，其中男7例，女3例，年龄中位数8岁2个月；选取声带小结患儿14例及突发性耳聋6例患儿为对照组，其中男12例，女8例，年龄中位数8岁9个月。两组患儿均接受整夜多导睡眠图监测，按中华医学会耳鼻咽喉科学分会制定的儿童阻塞性睡眠呼吸暂停低通气综合征（OSAHS）诊疗指南（草案）中的标准进行呼吸事件的定义和OSAHS的诊断，阻塞性呼吸暂停指数（OAI）每小时≤1次或呼吸暂停低通气指数(AHI) 每小时≤5次，最低血氧饱和度(LSaO2)≥0.92可以排除OSAHS。应用Mann-Whitney U和精确概率检验，比较Down组和对照组的睡眠结构，并进行睡眠期LSaO2、OAI、AHI、脑电醒觉反应指数及睡眠期肢体运动事件指数的比较。结果 ①两组间在年龄、性别和体重指数等差异无统计学意义（P＞0.05）；②Down组和对照组比较，快动眼睡眠比例减少，且差异有显著统计学意义（Z=-2.6，P= 0.009）；③睡眠期LSaO2较对照组显著下降（P＜0.05），OAI、AHI及睡眠期肢体运动事件指数Down组较对照组显著升高（P＜0.05）；④10例Down综合征患儿中有6例符合OSAHS诊断，6例中有5例为男性。结论 Down综合征患儿存在睡眠呼吸紊乱，应使用多导睡眠检测的方法尽早发现睡眠呼吸紊乱的问题。     

Is paediatric assessment of motor development of very preterm and low‐birthweight children appropriate?

Aim: To determine whether paediatricians that examine, in regular clinical practice, very preterm and very-low-birthweight children at 5 y of age detect neurological impairments and functional motor problems in these children.

Methods: We compared a paediatric judgement, a standardized neurological examination (Touwen examination) and a screening of motor development (Denver Developmental Screening Test; DDST) with the Movement ABC in 396 5-y-old very preterm and low-birthweight children.

Results: The Movement ABC detected clinically important motor disorders in 20.5% and borderline disturbances in 22.5% of the children. Compared to the Movement ABC, the sensitivity of the paediatric judgement was 0.19, Touwen examination 0.62 and DDST 0.52; the negative predictive values were 0.61, 0.74 and 0.69, respectively.

Conclusion: Paediatric assessment of motor development in 5-y-old very preterm and low-birthweight children generally is not sensitive enough to detect functional motor problems. The Movement ABC should be added to the assessment of the motor development of very preterm and low-birthweight children at 5 y of age.     

The natural history of idiopathic toe-walking: a long-term follow-up of fourteen conservatively treated children

Aim: To determine the long-term results after conservative treatment (physiotherapy, casting, orthoses, or a combination of these) of idiopathic toe-walking (ITW). Methods: Tiptoe-walking is diagnosed as idiopathic (habitual) if no signs of neurological, orthopaedic, or psychiatric disease are detected. The diagnosis is one of exclusion. Sixteen former patients with ITW, all now at least 13 y old, were asked to participate in a follow-up investigation 7-21 y after being first diagnosed. Two cases were excluded because heel-cord lengthening had been performed later on in other hospitals. The remaining 14 patients completed a questionnaire. Eleven patients consented to a clinical examination, during which they were videotaped and their active and passive ankle-joint dorsiflexion measured. These data were compared with the assessment at the initial evaluation. In one instance, the toe-walking ceased after conservative treatment (plaster cast). In all other cases the toe-walking pattern recurred. Results: At follow-up three patients showed some toe-walking when they were unobtrusively observed. When videotaped, they did not toe-walk, although a distinct heel-strike was missing. The remaining eight patients all walked with a heel-strike. Two patients had slight symptoms possibly related to toe-walking. No fixed contracture was present at the first evaluation, and none was found at follow-up. There was no systematic change in ankle-joint dorsiflexion from initial assessment to follow-up examination.

Conclusion: Non-surgical treatment of ITW does not have a lasting effect and the long-term results in this study are considered to reflect the natural history, i.e. the toe-walking pattern eventually resolves spontaneously in the majority of children. Surgical treatment of ITW should be reserved for the few cases with a fixed ankle-joint contracture.     

Central line-associated venous late effects in children without prior history of thrombosis

Background: The frequency of asymptomatic central line-associated thromboses is high and well recognized among children with cancer, while the long-term consequences are mainly unknown. Aim: In a cross-sectional study, we evaluated clinical and radiological venous outcome in children with previous long-standing intravascular catheters. Methods: The study enrolled 71 children previously treated for malignant or haematological diseases, 4-180 (median 37) mo after removal of their central lines. Inclusion criteria were a prior central line in a jugular vein for a minimum of 6 mo and no previous history of thrombosis. The children had clinical examination for post-thrombotic syndrome (PTS) and Doppler ultrasonography of the central neck veins. Twelve children had additional venous magnetic resonance imaging (MRI). But no kind of venography was performed in the remaining. Results: We observed mild PTS with increased superficial collaterals in four children (6%), but no cases of more severe PTS. None complained of symptoms related to venous late effects. By ultrasonography, post-thrombotic venous alterations were detected in 17 children (24%), and five of these had complete occlusion of the veins. The sensitivity for pathologically increased collaterals to identify occlusive thrombosis was 0.6, while the specificity was 0.98. Occlusive venous thromboembolism was associated with the total number of central venous lines (CVLs; p=0.002), previous severe CVL-associated infections (p=0.001) and duration of central line in place (p=0.042).

Conclusion: In spite of no prior history of thrombosis, children with previous long-term jugular lines frequently had local thrombotic sequelae, while clinical symptoms of PTS were rare.     

A doctor's ability to assess the severity of childhood asthma by simple clinical features

Aims: To ascertain whether the severity of childhood asthma can be reliably assessed by simple clinical features, 94 newly diagnosed, school-aged asthmatic children were investigated. Methods: The study included parental interviews, physical examination, skin prick tests, lung function studies, including a brief visual interpretation of the flow-volume curve, and a 6-min exercise challenge test on a treadmill, which was used as a reference. Results: Baseline lung function studies showed a concave-shaped flow-volume curve in 40 (43%) patients, reduced maximal mid-expiratory flow (MMEF) in 25 (27%) and a reduced ratio of forced expiratory volume in 1 s to forced vital capacity (FEV₁/FVC) in 14 (15%). The drop in peak expiratory flow (PEF) after exercise ranged from 0 to 79% of the baseline (mean 21.3%) and exceeded 12.5% in 52 (55%) patients. There was a small but significant correlation between the baseline FEV₁/FVC and MMEF values and the response to exercise (r=-0.39 and -0.35; p=0.000, respectively), but when studied by linear regression analysis, the response to exercise was best predicted by the past symptom rate and a concave pattern in the pre-test maximal expiratory flow-volume curve. The values of traditional lung function tests or age, atopy, duration of symptoms or history of exercise-induced wheezing did not remain in the model.

Conclusions: These results show that the severity of asthma in school-aged children can be predicted at the first visit based on the past rate of symptoms and a visual interpretation of the maximal expiratory flow-volume curve.     

Down syndrome: orthopedic issues

PURPOSE OF REVIEW: The purpose of this review is to update the role of the orthopedic surgeon in the management of Down syndrome as these patients are living longer and participating in sporting activities. RECENT FINDINGS: Approximately 20% of all patients with Down syndrome experience orthopedic problems. Upper cervical spine instability has the most potential for morbidity and, consequently, requires close monitoring. Other conditions such as scoliosis, hip instability, patellar instability and foot problems can cause disability if left untreated. In some of these conditions, early diagnosis can prevent severe disability. SUMMARY: Surgical intervention in children with Down syndrome has a high risk of complications, particularly infection and wound healing problems. Careful anesthetic airway management is needed because of the associated risk of cervical spine instability.     

Difference in age at regression in children with autism with and without Down syndrome

OBJECTIVE: Autism occurs more frequently in individuals with Down syndrome than it does in the general population. Among children with autism and Down syndrome, regression is reported to occur in up to 50%. The aim of this study was to characterize and compare regression in children with autism with and without Down syndrome. METHODS: In this case-control study, children with Down syndrome and autism characterized by a history of developmental regression (n = 12) were compared to children with autism with regression who did not have Down syndrome, matched for chronologic age and gender. Comparisons were made on age at acquisition of language and age at loss of language and other skills as measured by the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: The mean age at acquisition of meaningful use of single words was 40.6 months (SD = 38.0) in children with Down syndrome and autism compared to 14.9 months (SD = 8.5) in children with autism without Down syndrome (p = .005). The mean age at language loss in children with autism with Down syndrome was 61.8 months (SD = 22.9) compared to 19.7 months (SD = 5.8) for those with autism without Down syndrome (p = .01). The mean age at other skill loss was 46.2 months (SD = 19.1) and 19.5 months (SD = 5.6), respectively (p = .006). CONCLUSIONS: When regression occurs in children with autism and Down syndrome it is, on average, much later than is typically seen in children with autism without Down syndrome.     

Congenital heart disease in Down syndrome: an echocardiographic study.

We evaluated the utility of echocardiography in assessing the frequency and nature of cardiac malformations in children with Down syndrome. Fifty cases of chromosomally proven Down syndrome were studied. A physical examination, electro cardiogram, radiograph of chest and two-dimensional echocardiography was performed on all patients. Twenty-two (44%) children had heart diseases. Endocardial-cushion-defect was the commonest anomaly, followed by ventricular septal defect. Three children with heart disease were asymptomatic and had normal X-ray films of chest and ECGs. The prevalence and specific type of congenital heart disease in this study is comparable to the studies using invasive means for diagnosis. The study further suggests that clinical examination of the cardiovascular system alone may not be sufficient in detecting heart disease. Two-dimensional echocardiography offers an excellent non-invasive tool for diagnosing cardiac malformations in Down syndrome.     

Early post-convulsive prolongation of QT time in children

Aim: An important differential diagnosis of seizures in childhood is the long QT syndrome. Childhood epilepsy occurs about 400 times more often than long QT syndrome. We had observed children with slight post-convulsive prolongation of QT time more often than the reported incidence of long QT syndrome. We therefore conducted a prospective study to define the characteristics of post-convulsive prolongation of QT time in children. Methods: We investigated 30 consecutive infants and children (3 mo to 14 y) within 2 h after seizures. A follow-up ECG was obtained 1-9 d later. We also obtained ECGs from 30 healthy age- and gender-matched controls. We calculated the QT interval corrected for heart rate (QTc) by Bazett's formula in leads II, V5, V6, QT dispersion and the number of notched T waves. Results: We found a QTc interval of more than 440 ms in one or more leads in the first ECG in seven of 30 infants and children compared to 1 of 30 in the follow-up ECG (p=0.0003) and two of 30 in the healthy controls (p=0.14). Average QTc was higher for all leads in the first ECG. This was statistically significant in leads II (414 vs 402 ms, p=0.008), V5 (416 vs 404 ms, p=0.002) and V6 (415 vs 399 ms, p=0.001). Compared to healthy controls, QT dispersion was slightly larger in the early post-convulsive ECG (36 vs 31 ms, p=0.03). Notched T waves occurred more frequently in the early compared to the late post-convulsive ECGs (p=0.009).

Conclusion: Slight to moderate post-convulsive prolongation of the QT interval is not rare but transient in paediatric patients.     

WT1基因检测时机对Wilms肿瘤合并慢性肾脏疾病预后影响的回顾性队列研究

目的 分析在Wilms肿瘤合并慢性肾脏疾病(CKD)的患儿中WT1基因检测对诊断和长期预后的影响。方法 检索上海市肾脏发育与儿童肾脏病研究中心儿童肾脏病基因检测数据库,2001年1月1日至2018年12月31日明确WT1基因突变、年龄<18岁患儿,或Wilms肿瘤合并CKD 2~5期或肾病综合征或有蛋白尿的连续病例。按进展为终末期肾衰竭(ESRD)之前是否明确WT1基因突变分为早诊断组和晚诊断组,以ESRD为终点比较两组的预后。结果 22例患儿明确WT1基因的常染色体显性遗传突变,分别位于第8~9外显子/内含子。依据临床分型,10例为Denys-Drash综合征,3例为Fraiser综合征,9例表型为孤立型肾病综合征,5例合并假两性畸形。随访终点进入ESRD有15例,7例进入CKD 2~4期。应用生存曲线分析证实,早诊断组较晚诊断组进入ESRD病程显著延迟(P=0.011)。结论 在儿童Wilms肿瘤、肾病综合征/蛋白尿、慢性肾功能损害的患儿中,在肾功能进展恶化之前及早明确WT1基因突变,不仅有助于临床诊断分型,还能显著延缓进入ESRD病程。