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Sunday, February 24, 2019

Disease in Childhood

Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review
Objective

To compare the efficacy and safety of theophylline or aminophylline for prevention of acute kidney injury (AKI) in neonates and children.

Design

Systematic review and meta-analysis with application of Grading of Recommendations, Assessment, Development and Evaluation system.

Data sources

PubMed/MEDLINE, Embase, Google Scholar and Cochrane renal group were searched from 1970 to May 2018.

Eligibility criteria

Randomised clinical trials and quasi-randomised trials comparing the efficacy and safety of prophylactic theophylline or aminophylline for prevention of AKI in neonates and children were included. The primary outcomes were: incidence of AKI, serum creatinine levels and all-cause mortality.

Results

A total of nine trials were included in the qualitative synthesis. Six trials including 436 term neonates with birth asphyxia who received a single dose of theophylline were finally included in the meta-analysis. The pooled estimate showed 60% reduction in the incidence of AKI in neonates with severe birth asphyxia (RR: 0.40; 95% CI 0.3 to 0.54; heterogeneity: I2=0%) (moderate quality evidence), decrease in serum creatinine over days 2–5 (very low to low quality evidence) without significant difference in all-cause mortality (RR: 0.88; 95% CI 0.52 to 1.50; heterogeneity: I2=0%) (very low-quality evidence). A significant difference in the negative fluid balance, increase in GFR and decrease in urinary β2 microglobulin was seen in favour of theophylline.

Conclusion and relevance

A single dose of prophylactic theophylline helps in prevention of AKI/severe renal dysfunction in term neonates with severe birth asphyxia (moderate quality evidence) without increasing the risk of complications and without affecting all-cause mortality (very low-quality evidence).

Trial registration number

CRD 42017073600.



Pathways to inequalities in child health

From birth, children living in disadvantaged socioeconomic circumstances (SECs) suffer from worse health than their more advantaged peers. The pathways through which SECs influence children's health are complex and inter-related, but in general are driven by differences in the distribution of power and resources that determine the economic, material and psychosocial conditions in which children grow up. A better understanding of why children from more disadvantaged backgrounds have worse health and how interventions work, for whom and in what contexts, will help to reduce these unfair differences. Macro-level change is also required, including the reduction of child poverty through improved social security systems and employment opportunities, and continued investment in high-quality and accessible services (eg, childcare, key workers, children's centres and healthy school environments). Child health professionals can play a crucial role by being mindful of the social determinants of health in their daily practice, and through advocating for more equitable and child-focussed resource allocation.



Reclaiming the systems approach to paediatric safety
Introduction

Prior to the emergence of the patient safety movement as a distinct science, it was assumed that the safety of patients was an outcome of good professional acumen, and that if healthcare providers could individually perform well then their patients would remain safe at all times.

It is now 20 years since the publication of To Err is Human,1 the first major review of healthcare safety in the USA. In the UK, the publication Organisation with a Memory2 in 2000 supported the view that patient safety required a wider system approach. Both documents reframed safety and error in healthcare as an organisational or system issue rather than one of individual error, whether of omission or of commission. Over the past 20 years, there has been major progress in the understanding of patient safety and the complexity of the systems involved in providing healthcare. In a recent...



No association between abdominal pain and Dientamoeba in Dutch and Belgian children
Objective

To study the association between Dientamoebafragilis colonisation and faecal calprotectin to see whether the parasite is a harmless commensal or a gut pathogen.

Design

Cross-sectional study of previously collected stool samples.

Setting and patients

Two hundred stool samples originated from children aged 5–19 years with chronic abdominal pain and diarrhoea, who were seen in paediatric clinics in the Netherlands and Belgium and in whom somatic gastrointestinal disorders were excluded. Another 122 samples came from a healthy community-based reference population of the same age. All stool samples were analysed with real-time PCR for the detection of D. fragilis and with an ELISA for calprotectin—a biomarker of gastrointestinal inflammation.

Main outcome measures

Prevalence of D. fragilis colonisation and results of stool calprotectin testing.

Results

D. fragilis was detected in 45% (95% CI 38% to 51%) of patients and in 71% (95% CI 63% to 79%) of healthy children. Median (IQR) concentrations of calprotectin in patients and healthy children with a positive PCR result were not different from those with a negative PCR result (40 (40–55) μg/g vs 40 (40–75) μg/g, respectively).

Conclusion

Since D. fragilis colonisation is most prevalent in healthy children and is not associated with an increase in faecal calprotectin concentration, our data do not support the inference that D. fragilis is a pathogenic parasite. Routinely testing for D. fragilis in children with chronic abdominal pain should therefore be discouraged.



Epidemiology of paediatric chronic fatigue syndrome in Australia
Objective

To estimate the paediatrician-diagnosed incidence of chronic fatigue syndrome (CFS) in Australia, and describe demographic and clinical features, as well as approaches to diagnosis and management.

Methods

The Australian Paediatric Surveillance Unit facilitates monthly national surveillance of uncommon conditions seen by paediatricians. Data from young people aged <18 years diagnosed with CFS were collected. Incidence was estimated based on new cases reported from April 2015 to April 2016.

Results

A total of 164 cases of newly diagnosed CFS in young people aged 4–17 years were identified for inclusion. The estimated national incidence for children aged 4–9 years was 0.25 per 100 000 per annum. In children aged 10–17 years, the estimated incidence of paediatrician-diagnosed cases for Victoria (17.48 per 100 000) was substantially greater than other Australian states (range 1.31–5.51 per 100 000). Most cases were female and Caucasian, most commonly presenting after an infectious illness with symptoms gradual in onset. The majority were diagnosed at least 13 months after symptom onset. Symptoms, associations, investigations and management strategies were highly variable.

Conclusions

Current findings suggest that, consistent with other countries, the Australian incidence of CFS in children aged <10 years is very low. In contrast, the national incidence of CFS in older children and adolescents (aged 10–17 years) is more unclear, with marked variability between geographical regions apparent. This may be due to variation in service accessibility and clinician understanding of CFS. Accordingly, national initiatives to improve equity of care for children with CFS may be required.



Persistence of pneumococcal antibodies after primary immunisation with a polysaccharide-protein conjugate vaccine
Introduction

Despite immunisation, antibiotics and intensive care management, infection with Streptococcus pneumoniae remains a major cause of morbidity and mortality in children. The WHO currently recommends vaccinating infants with either a 3+0 schedule (6 weeks, 3–4 and 4–6 months of age) or 2+1 schedule (2 doses before 6 months of age, plus a booster dose at 9–15 months of age). This study investigated pneumococcal antibody responses, including persistence of antibodies, after immunisation of healthy infants with a 3+0 schedule.

Methods

We measured pneumococcal antibody concentrations to all 13 antigens included in the 13-valent pneumococcal conjugate vaccine (PCV13) after immunisation with a 3+0 schedule in 91 infants at 7 months and in 311 infants at 13 months of age. The geometric mean concentrations (GMCs) and the proportion of infants with an antibody concentration above the standard threshold correlate of protection (seroprotection rate) were calculated at both time points.

Results

At 7 months of age, GMCs varied between 0.52 µg/mLand 11.52 µg/mL, and seroprotection rates varied between 69% and 100%. At 13 months of age, GMCs had decreased to between 0.22 µg/mLand 3.09 µg/mL, with the lowest responses against serotype 4, followed by 19A, 3, 6B and 23F. Seroprotection rates at 13 months of age were below 90% for most serotypes, with the lowest rates for serotype 4 (23%) followed by 19A (50%), 23F (61%) and 6B (64%).

Conclusion

Our study shows that at 13 months of age, many infants vaccinated with a 3+0 schedule have pneumococcal antibody concentrations below the standard threshold correlate of protection. To optimise protection against pneumococcal disease through early childhood and to improve antibody persistence and indirect protective effects, immunisation schedules with booster doses might be necessary.



Highlights from the literature
Separating craniopagus twins

Lucina doesn't normally feature surgical case reports, but this one reported in the NEJM is remarkable (Heuer G et al doi:10.1056/NEJMoa1805132). A highly-skilled team from the Children's Hospital of Philadelphia successfully separated conjoined twin girls, who shared skull bones and a common sagittal sinus, but not brain tissue. They were delivered at 30 weeks, and pre-operatively required tissue expansion techniques over several months to make separation easier. Meticulous planning, which involved computerised modelling and 3-D printing, led to an 11 hours separation procedure at age 10 months. Remodelling the venous sinuses was a particular challenge. The girls have done well, with intact skulls and only mild neurocognitive deficits. Conjoined twins are rare and craniopagus even rarer, so each case has to be looked at afresh as new technologies emerge.

EMLA in infants

'Magic cream', or topical local anaesthetic EMLA (eutectic mixture of lidocaine/lignocaine and prilocaine), is frequently used for...



Air pollution and autism

It's clear that genetics plays a major role in the aetiology of autistic spectrum disorder (ASD), but the genuine increase in prevalence over recent decades suggests that environmental factors are also responsible. If ASD is considered to be a neurodevelopmental disorder, rather than a social construct, then antenatal influences during early brain development may be important. Potential prenatal causes suggested thus far are many and varied, including paracetamol (Archivist Oct 2016 doi.org/10.1136/archdischild-2016–3 11 708), antidepressant drugs (Archivist March 2016 doi.org/10.1136/archdischild-2016–3 10 462), ultrasound (Archivist Sept 2018 doi.org/10.1136/archdischild-2018–3 15 816), season of conception (Lucina Dec 2016 doi.org/10.1136/archdischild-2016–3 12 102), and obesity, among many others.

Several studies have hinted at a link with maternal air pollution exposure, but these have been inconsistent or inconclusive. ASD definitions have been imprecise, exposure indicators not sufficiently localised, and types of pollution lumped together. Importantly, confounding factors need to be accounted for, as families with the highest psychosocial risks for autism may tend to live...



Screentime and child health

The media are obsessed with the issue of 21st century children spending too much time staring at screens: some reports have amounted to a moral panic (www.telegraph.co.uk/news/2018/09/26/two-hours-screentime-day-could-damage-childrens-brain-development). The release of a statement from the UK's Royal College of Paediatrics and Child Health (RCPCH) was therefore welcome (rcpch.ac.uk/resources/health-impacts-screen-time-guide-clinicians-parents). It was based on a systematic 'review of reviews' which synthesised the large amount of evidence available (Stiglic N, Viner R. doi: 10. 1136/bmjopen- 2018–0 23 191). Rather than go back to the primary data, they identified 13 reviews of varying quality that had already done this. They assessed each review's conclusions qualitatively, rather than doing further meta-analyses. Screentime use included television (TV), computers, tablets and smartphones. TV-watching predominated in most reviews. Different outcome domains were considered.

With regards to obesity or adiposity, they concluded that there was a positive association with TV screentime, but they could not define a 'safe threshold' of time....



At what weight should preterm infants be transferred from incubator to open cot?
Scenario

A preterm infant born at 28 weeks' gestation is 5 weeks old, weighs 1600 g and nursed in an incubator. During the round, the medical team instructs the nurse to transfer the infant to open cot. The nurse in charge is concerned that weaning the infant from incubator to cot at this weight might affect the temperature stability, weight gain and may delay the discharge of the infant. The third-year paediatric resident offers to review the literature and report the findings to the multidisciplinary team.

Structured clinical question

In a medically stable preterm infant with a birth weight of less than 1600 g, not on any respiratory support, nursed in incubator (patient), whether transferring the infant from incubator to unheated open cot at a lower weight (<1700 g) (intervention) compared with a higher weight (>1700 g) (comparison) will affect the temperature stability, weight gain and length of hospital stay of the...







Highlights from this issue
Global child healthVitamin A

The history of the vitamin A supplementation studies from the initial excitement of the reduction in measles related mortality trials in West Africa 25 years ago has been a chequered one. The routine population supplementation from 6 months to 5 years of age is now established, but the issue over neonatal supplementation and its effect on infant mortality and morbidity has remained unresolved, trials showing different directions of effect, or no effect. The paper from the WHO Vitamin A supplementation group addresses this in a meta-analysis of the 11 published studies. Pooled analysis showed no effect of early (first 2 to 3 days) vitamin A supplementation on mortality at either 6 months (RR 0.97, 95% CI 0.89 to 1.06) or 1 year. There were subtle differences in the sub-analyses stratified by region: in South Asia (but not Africa) where Vitamin A deficiency (defined by established...



Fetal hydrops: diagnosis and prognosis

The causes and outcomes of fetal hydrops have been well described in the literature over many years. Anti-D immunoglobulin has dramatically reduced the rate (and mortality) of immune hydrops such that non-immune hydrops (NIHF) now accounts for 90% of cases.1 Hydrops is a challenging condition to counsel for due to the relative rarity (1 in 1700–3000 pregnancies) and the fact it is the preterminal manifestation of many different pathophysiological processes.2–4

The paper published in our sister journal Fetal & Neonatal by Gilby et al5 addresses two key questions that all expectant parents faced with this problem would ask: what is the cause of the hydrops and will my baby survive? Diagnosis in NIHF is of paramount importance to accurate counselling. The more refined the phenotype the more accurate information a clinician is able to provide on mortality, morbidity and treatment options.



'Death is not the answer: the challenge of measuring the impact of early warning systems

We can all remember individual children in whom a deterioration went unrecognised. Sometimes fatally. Our defences were little more than the pearls offered by senior colleagues of grave warning signs: 'beware grunting in an infant' or 'watch out for a tachycardia after the temperature has fallen'. But this advice was unstructured, and children are so different, and their comorbidities so broad, we failed some of them. Paediatric Early Warning Systems (PEWS) are serious attempts to reduce the unacceptable and dangerous variability in this recognition and response process. Scoring systems should provide age-appropriate thresholds for concern for single parameters or aggregated abnormal physiology and prompt standardised responses. The idea has such natural appeal that PEWS use was soon advocated by a number of national bodies1 2 without evidence. This may have been a mistake. Many of the scores in widespread use were not calibrated or validated....



Biological therapeutic drug monitoring: a step towards precision medicine?

Biological medications including monoclonal antibodies against tumour necrosis factor-α (TNF-α), such as infliximab and adalimumab, have revolutionised the treatment of children and young people with autoimmune conditions such as inflammatory bowel disease, juvenile idiopathic arthritis (JIA) and childhood chronic inflammatory uveitis. Emerging evidence is increasingly supporting the use of therapeutic drug monitoring (TDM) to help optimise biological efficacy, safety and cost-effectiveness.

The pharmacokinetics of biologics is complex and in contrast to traditional medications; predominantly due to their large molecular size and structural complexity, they do not undergo hepatic metabolisation and are instead broken down by intracellular lysosomal proteolytic degradation. Also, unlike traditional medications, they have immunogenic potential and the formation of antidrug antibodies (ADA) can significantly affect their pharmacokinetic profile. ADA directed against the corresponding biologic can trigger proteolytic elimination in the reticuloendothelial system (RES) leading to increased clearance of these molecules. Conversely, an immune complex that does not...



Improving the quality of care delivered to adolescents in Europe: a time to invest
Introduction

While many governments, non governmental organisations (NGOs) and United Nations (UN) agencies have focused in the past on the health of mothers, infants and young children, there is now growing evidence that the healthcare system should also address the well-being and problems of adolescents, defined by WHO as individuals aged 10–19 years. They represent 1.2 billion individuals in the global population and between 10% and 25% of the population in European countries.1 In September 2015, the UN Secretary-General announced that the 'Every Woman, Every Child' agenda would move forward to 2030 as a Global Strategy for Women's, Children's and Adolescents' Health. In 2017, WHO responded to the large number of health problems affecting adolescents by launching a state-of-the-art review of programmes and interventions targeting the health burden of adolescents around the world, the AA-HA initiative ('Accelerated Action for the Health of Adolescents'). Adolescents' morbidities such as sexually transmitted...



Early neonatal vitamin A supplementation and infant mortality: an individual participant data meta-analysis of randomised controlled trials
Background

Biannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results.

Methods

Investigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data.

Findings

Overall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics.

NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol <0.7 µmol/L or 5% or more women with night blindness) (RR 0.87; 95% CI 0.80 to 0.94), early infant mortality was 30 or more per 1000 live births (RR 0.91; 95% CI 0.85 to 0.98), 75% or more of infant mortality occurred in the first 6 months of life (RR 0.92; 95% CI 0.84 to 1.01), or where >32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15).

Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS.

Conclusion

NVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.



Mass antibiotic distribution to reduce mortality among preschool children?

Worldwide, under-fives mortality has halved since 1990 from 93 to 41 deaths per 1000 live births in 2016. However, progress has been very uneven. Child mortality is still highest in Africa (76 per 1000 live births) (figure 1) and neonatal mortality has declined at a slower rate so is now approaching 50% of all under-fives mortality.1 Research and programmatic efforts are focussed on reducing child mortality in the highest burden areas. An intriguing and controversial idea to reduce mortality has arisen from mass antimicrobial distribution programmes for the prevention of blindness caused by trachoma.

Trachoma has a predilection for the poorest, most remote communities with low levels of hygiene. Chlamydia trachomatis is spread by direct contact with fluid from an infected person's eyes or nose, or indirect contact with these fluids via clothing or flies. It is endemic across Africa from South Sudan and Ethiopia...



Linear growth following complicated severe malnutrition: 1-year follow-up cohort of Kenyan children
Background

Stunting is the most common manifestation of childhood undernutrition worldwide. Children presenting with severe acute malnutrition (SAM) are often also severely stunted. We evaluated linear growth and its determinants after medically complicated SAM.

Methods

We performed secondary analysis of clinical trial data (NCT00934492) from HIV-uninfected Kenyan children aged 2–59 months hospitalised with SAM. Outcome was change in height/length-for-age z-score (HAZ) between enrolment and 12 months later. Exposures were demographic, clinical, anthropometric characteristics and illness episodes during follow-up.

Results

Among 1169 children with HAZ values at month 12 (66% of those in original trial), median (IQR) age 11 (7–17) months and mean (SD) HAZ –2.87 (1.6) at enrolment, there was no change in mean HAZ between enrolment and month 12: –0.006Z (95% CI –0.07 to 0.05Z). While 262 (23%) children experienced minimal HAZ change (within ±0.25 HAZ), 472 (40%) lost >0.25 and 435 (37%) gained >0.25 HAZ. After adjusting for regression to the mean, inpatient or outpatient episodes of diarrhoea and inpatient severe pneumonia during follow-up were associated with HAZ loss. Premature birth and not being cared by the biological parent were associated with HAZ gain. Increases in mid-upper arm circumference and weight-for-age were associated with HAZ gain and protected against HAZ loss. Increase in weight-for-height was not associated with HAZ gain but protected against HAZ loss. No threshold of weight gain preceding linear catch-up growth was observed.

Conclusions

Interventions to improve dietary quality and prevent illness over a longer period may provide opportunities to improve linear growth.



Child mortality: how does the USA compare?

In March 2015, an Archives editorial featured a Lancet paper describing neonatal, infant and child mortality trends, comparing UK data to other European countries and Canada, but not the USA (doi: 10.1136/archdischild-2014–3 07 678). The UK was improving more slowly than the comparator countries. Now American authors have done something similar (Khan S et al doi:10.1001/jamapediatrics.2018.3317). Using the US National Centre for Health Statistics database, and comparing to equivalent data from England/Wales (E&W) and Canada, they found that the US is actually doing much worse than the UK. They looked at annual mortality rates for all individuals up to age 24, from 1999 to 2015, throughout the US. As seen in other countries, there was a striking decline in overall mortality rates for most age groups over the 16 year period, except for young adults aged 20–24 where there was a decline until 2012 and then a slight increase. In all age...



Research priorities for childhood chronic conditions: a workshop report
Background

Chronic conditions are the leading cause of mortality, morbidity and disability in children. However, children and caregivers are rarely involved in identifying research priorities, which may limit the value of research in supporting patient-centred practice and policy.

Objective

To identify priorities of patients, caregivers and health professionals for research in childhood chronic conditions and describe the reason for their choices.

Setting

An Australian paediatric hospital and health consumer organisations.

Methods

Recruited participants (n=73) included patients aged 8 to 14 years with a chronic condition (n=3), parents/caregivers of children aged 0 to 18 years with a chronic condition (n=19), representatives from consumer organisations (n=13) and health professionals including clinicians, researches (n=38) identified and discussed research priorities. Transcripts were thematically analysed.

Results

Seventy-eight research questions were identified. Five themes underpinned participants' priorities: maintaining a sense of normality (enabling participation in school, supporting social functioning, promoting understanding and acceptance), empowering self-management and partnership in care (overcoming communication barriers, gaining knowledge and skills, motivation for treatment adherence, making informed decisions, access and understanding of complementary and alternative therapies),strengthening ability to cope (learning to have a positive outlook, preparing for home care management, transitioning to adult services), broadening focus to family (supporting sibling well-being, parental resilience and financial loss, alleviating caregiver burden), and improving quality and scope of health and social care (readdressing variability and inequities, preventing disease complications and treatment side effects, identifying risk factors, improving long-term outcomes, harnessing technology, integrating multidisciplinary services).

Conclusion

Research priorities identified by children, caregivers and health professionals emphasise a focus on life participation, psychosocial well-being, impact on family and quality of care. These priorities may be used by funding and policy organisations in establishing a paediatric research agenda.



Child Neurology Open

  1. Autism Spectrum Disorder and Neonatal Serum Magnesium Levels in Preterm Infants

    Child Neurology Open, vol. 5First Published September 18, 2018.
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    Abstract

    Premature birth is associated with increased risk of autism spectrum disorder. Antenatal maternal magnesium administration is known to reduce subsequent risk of cerebral palsy including among premature infants, suggesting a potentially broader neuroprotective role for magnesium. Our objective was to determine whether magnesium could be protective against autism spectrum disorders in premature infants. A cohort of 4855 preterm children was identified, magnesium levels from 24 to 48 hours of life recorded, and subsequent autism spectrum disorder status determined. Adjusted relative risk of autism spectrum disorder with each 1 mg/dL increase in neonatal magnesium level was 1.15 (95% confidence interval: 0.86-1.53). Analysis of variance indicated that magnesium levels varied by gestational age and maternal antenatal magnesium supplementation, but not autism spectrum disorder status (F1,4824 = 1.43, P = .23). We found that neonatal magnesium levels were not associated with decreased autism spectrum disorder risk. Future research into autism spectrum disorder risks and treatments in premature infants is needed.

  2. Open Access

    Functional Gains in Children With Spastic Hemiplegia Following a Tendon Achilles Lengthening Using Computerized Adaptive Testing—A Pilot Study

    MD1PhD, OT2MSc, OT3MD3MSc, PT3PhD4PhD, OT5
    Child Neurology Open, vol. 5First Published November 14, 2018.
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    Abstract

    This pilot study evaluated the outcomes of tendon Achilles lengthening in 12 children (mean age: 11.2 years) with spastic hemiplegia.

    Cerebral Palsy Computer Adaptive Tests, the timed up-and-go, the Gross Motor Function Measure, the Gillette Functional Assessment Questionnaire, and the Pediatric Outcomes Data Collection Instrument were administered at baseline and at 6, 12, and 24 months postsurgery.

    Significant improvement at the latest follow-up (12-24 months following surgery) was seen in all domains of the Cerebral Palsy Computer Adaptive Test: activity (P = .017), lower extremity (P = .005), global (P = .005), pain (P = .005), and fatigue (P = .028), as well as in the Gross Motor Function Measure-standing domain (P = .02) and the mobility domain of the Pediatric Outcomes Data Collection Instrument (P = .04).

    These findings indicate that the tendon Achilles lengthening improved functional outcome in these children as measured by tests of physical function, walking speed, and activity performance.

  3. Open Access

    Clinical Profile of Pediatric Neurological Disorders: Outpatient Department, Khartoum, Sudan

    Child Neurology Open, vol. 3First Published April 4, 2016.
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    Abstract

    There is no available data from Sudan reflecting the magnitude of the neurological disorders and disabilities in the pediatric age-group. This study aims to evaluate the pattern of neurological disorders among Sudanese children.

    This is a retrospective survey of children with epilepsy and other neurodisability disorders seen at pediatric neurology outpatient clinic, during the period from January 2007 to August 2013. The data of 9600 patients were analyzed.

    A total of 6019 patients were included in the study. The majority of the patients had epilepsy that amounted to 52.8%, followed by cerebral palsy (19.1%), congenital anomalies of the central nervous system (6.2%), neuromuscular disorders (3.2%), stroke (2.4%), ataxia and movement disorders (1.9%), assumed genetic syndromes (1.2%), and others.

    Neurological disorders constitute a major cause of chronic morbidity in pediatric age-group.

  4. Open Access

    A New Observation of an Atypical and Severe Variant of the Guillain-Barre Syndrome in a Child: Remaining Challenges for Diagnosis, Nosologic Classification, and Therapeutic Course

    Child Neurology Open, vol. 2, 4First Published October 26, 2015.
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    Abstract

    Guillain-Barré syndrome is a rare acute polyradiculoneuropathy. Several variants and unusual presentations have been described, particularly in pediatrics. In most cases, making an early diagnosis is challenging due to the treatments that consist in the rapid administration of intravenous immunoglobulin or plasma exchange. The authors present the case of a 7-year-old boy with an atypical and severe axonal Guillain-Barré syndrome, associated with Mycoplasma pneumonia. When he was admitted, febrile respiratory failure was the main focus, and then he presented signs of acute polyneuropathy with cranial nerve palsy and brief hyperreflexia. Mechanical ventilation was required for 48 days as well as 2 cycles of intravenous immunoglobulin. The authors describe all the medical challenges that the authors encountered. This case highlights the fact that respiratory distress can be the main clinical symptom in children. This delays the establishment of a correct diagnosis, even more so when neurological manifestations are abundant and unusual.

  5. Open Access

    Assessing Children With Disabilities Using WHO International Classification of Functioning, Disability and Health Child and Youth Version Activities and Participation D Codes

    Child Neurology Open, vol. 2, 4First Published October 28, 2015.
  6. Open Access

    Newly Identified Characteristics and Suggestions for Diagnosis and Treatment of Diffuse Leptomeningeal Glioneuronal/Neuroepithelial Tumors: A Case Report and Review of the Literature

    Child Neurology Open, vol. 2, 1First Published February 16, 2015.
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    Abstract

    Diffuse leptomeningeal glioneuronal tumor is unique for communicating hydrocephalus, diffuse leptomeningeal enhancement, cystic changes, absence of tumor cells in cerebral spinal fluid, and a cell population of both glial and neuronal copositivity. It has likely been misdiagnosed as mixed glioneuronal tumors, oligodendrogliomas, and neuroepithelial tumors. Children with signs of this tumor are often worked up for infection, rheumatologic disease, or disseminated primary malignancy, resulting in unnecessary testing and treatment. We describe a 14-year-old female with recurrent headaches, hydrocephalus, and diffuse leptomeningeal enhancement discovered to be neoplastic 1 year after initial presentation, owing to extensive and unrevealing infectious and immunologic workups. Biopsies revealed atypical cells with markers of both glial and neuronal cells, positivity for OLIG-2, and focal p53 positivity. Great response was seen with temozolomide and craniospinal irradiation. Additionally, we postulate additional diagnostic indicators that may aid in earlier diagnosis and treatment decisions.

  7. Open Access

    Connexin 43 and Its Hemichannels Mediate Hypoxia–Ischemia-Induced Cell Death in Neonatal Rats

    MD1MD, PhD1MD1MD, PhD1MD, PhD2
    Child Neurology Open, vol. 1, 1First Published August 26, 2014.
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    Abstract

    Wistar rat pups had the left common carotid artery cut, and they were exposed to 8% oxygen with free access to food and water until they were killed at 1, 12, 24, and 48 hours after the hypoxia–ischemia (HI) insult. Connexin 43 (Cx43), hemichannel (HC1), and caspase 3 (Casp3) in cerebral HI tissues were examined by immunohistochemistry and Western blot analyses. Astrocytes cell line, astrocytes transduced with a retroviral empty vector (Psup astrocyte), or a Cx43-specific small hairpin RNA (shRNA) construct (shRNA astrocytes) was treated with oxygen–glucose deprivation (OGD) insult. The viability of astrocytes was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed the expression of Cx43, HC1, and Casp3 in rats' brain, and astrocytes and Psup astrocytes increased significantly after 24 hours of HI/OGD insult. Cell viability decreased after 24 hours of the insult. The results suggest that Cx43 and hemichannel are likely to mediate the astrocytic death after HI insult.


Child Neurology Open

 
  1. Open Access

    De Novo KCNQ2 Mutation in One Case of Epilepsy of Infancy With Migrating Focal Seizures That Evolved to Infantile Spasms

    MD1PhD1MD1PhD1
    Child Neurology Open, vol. 5First Published April 11, 2018.
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    Abstract

    Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare type of early-onset epileptic encephalopathy that is characterized by refractory migratory multifocal seizures that migrate between hemispheres. Its etiology is not well known although it is postulated to occur due to channelopathy. The authors report the first case of EIMFS due to a de novo heterozygous mutation in exon 4(c.881C>T missense mutation, p.Ala294Val, NM_172107.2) in KCNQ2 gene which later evolved into infantile spasms. However, it is the second case of EIMFS with KCNQ2 mutation. He presented with multifocal migratory partial seizures which started at the age of 8 days. Electroencephalogram examination revealed multifocal interictal spikes that migrated from one hemisphere to the other within a seizure. It was intractable with antiepileptic drugs and adrenocorticotropic hormone. He later developed spasms from the age of 8 months. Consequently, our case supports the new association between EIMFS and KCNQ2 mutations. Moreover, it enriches the disease phenotype because of transformation.

  2. Open Access

    Ketogenic Diet in Refractory Childhood Epilepsy: Starting With a Liquid Formulation in an Outpatient Setting

    Child Neurology Open, vol. 5First Published May 29, 2018.
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    Abstract

    Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved.

    The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks.

    Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube.

    Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis.

  3. Open Access

    Atypical Rett Syndrome and Intractable Epilepsy With Novel GRIN2B Mutation

    MDCM1*MD2*MD, FRCP(C), FCCMG3MDCM, FRCP(C)4DPhil, MD, FRCP(C)3MDCM, FRCP(C)1
    Child Neurology Open, vol. 5First Published August 23, 2018.
  4. Open Access

    A Retrospective Analysis of the Long-Term Outcome of Drug-Resistant Epilepsy in Children Treated in Urban India

    Child Neurology Open, vol. 5First Published September 4, 2018.
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    Abstract

    To study the outcome of childhood-onset drug-resistant epilepsy.

    Fifty-five patients with drug-resistant epilepsy, meeting inclusion criteria, were identified from the Pediatric Neurology Clinic database with seizure onset less than age 13 years and a minimum follow-up of 5 years. Seizure remission was defined as no more than 1 seizure/year. Kaplan-Meier analysis was used to calculate the annual probability of seizure remission. Chi-square/Kruskal-Wallis tests were used to detect differences in predictors between those with seizure remission, ≥75% improvement and <75% improvement based on caregiver reports.

    Median follow-up was 11 years. Of 55, 22 (40%) were in seizure remission at last contact; 14 (25.4%) improved by ≥75%; 19 (34.5%) experienced <75% improvement. Annual remission probability was 3% in IQ ≥70 group and 2.48% in IQ <70 group (P = .126).

    This study shows patients with drug-resistant epilepsy treated in urban India can expect an overall remission rate of 2% per year starting from the third year of follow-up.

  5. Open Access

    Epileptic Negative Myoclonus as the First and Only Symptom in a Challenging Diagnosis of Benign Epilepsy With Centrotemporal Spikes

    MD1MS11MS1MS1MS1BS1
    Child Neurology Open, vol. 4First Published July 14, 2017.
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    Abstract

    To investigate the clinical and neurophysiological characteristics of epileptic negative myoclonus as the first and only ictal symptom of benign epilepsy with centrotemporal spikes.

    Electrophysiological evaluations included polygraphic recordings with simultaneous video electroencephalogram monitoring and tests performed with patient's upper limb outstretched in standing posture. Epileptic negative myoclonus manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed.

    The authors report 2 patients with benign epilepsy with centrotemporal spikes, who had epileptic negative myoclonus as the first and only seizure type. Video electroencephalogram monitoring results showed that their negative myoclonus seizures were emanating from the contralateral central and the parietal regions. Epileptic negative myoclonus was controlled by administration of valproate and levetiracetam.

    Epileptic negative myoclonus can be the first and only seizure type of benign epilepsy with centrotemporal spikes, and long-term follow-up monitoring should be the care for the recurrence and/or presence of other types of seizures.

  6. Open Access

    Clinical Profile of Pediatric Neurological Disorders: Outpatient Department, Khartoum, Sudan

    Child Neurology Open, vol. 3First Published April 4, 2016.
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    Abstract

    There is no available data from Sudan reflecting the magnitude of the neurological disorders and disabilities in the pediatric age-group. This study aims to evaluate the pattern of neurological disorders among Sudanese children.

    This is a retrospective survey of children with epilepsy and other neurodisability disorders seen at pediatric neurology outpatient clinic, during the period from January 2007 to August 2013. The data of 9600 patients were analyzed.

    A total of 6019 patients were included in the study. The majority of the patients had epilepsy that amounted to 52.8%, followed by cerebral palsy (19.1%), congenital anomalies of the central nervous system (6.2%), neuromuscular disorders (3.2%), stroke (2.4%), ataxia and movement disorders (1.9%), assumed genetic syndromes (1.2%), and others.

    Neurological disorders constitute a major cause of chronic morbidity in pediatric age-group.

  7. Open Access

    A De Novo Mutation in MTND6 Causes Generalized Dystonia in 2 Unrelated Children

    Child Neurology Open, vol. 3First Published April 4, 2016.
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    Abstract

    Dystonia is often associated with the symmetrical basal ganglia lesions of Leigh syndrome. However, it has also been associated with mitochondrial NDmutations, with or without Leber hereditary optic neuropathy. The m.14459G>A mutation in ND6 causes dystonia with or without familial Leber hereditary optic neuropathy. We report heteroplasmic 14459G>A mutations in 2 unrelated children with nonmaternally inherited generalized dystonia and showing bilateral magnetic resonance imaging lesions in nucleus pallidus and putamen. Both children have reached their teenage years, and they are intellectually active, despite their motor problems.

  8. Open Access

    Chromosome 12p Deletion Spanning the GRIN2B Gene Presenting With a Neurodevelopmental Phenotype: A Case Report and Review of Literature

    Child Neurology Open, vol. 3First Published April 4, 2016.
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    Abstract

    The GRIN2B (glutamate receptor, ionotropic, N-methyl-d-aspartate 2B) gene, located in the short arm of chromosome 12, encoding the NR2B subunit of the N-methyl-D-aspartate receptor, has recently been recognized to play an important role in corticogenesis and brain plasticity. Deletions in the short arm of chromosome 12 are rare. Hemizygous loss of function of the GRIN2B gene results in developmental delay, whereas gain of function leads to epilepsy, and infantile spasms in particular. In addition, GRIN2B variants have been associated with autism spectrum disorder and schizophrenia. Here the authors report a child with global developmental delay, autistic behavioural features, central hypotonia, dysmorphic features and isolated congenital anomalies of the fingers and toes, and a de novo heterozygous deletion in chromosome locus 12p13.2-p13.1, involving loss of several genes, including GRIN2B. This report and our review of the literature help clarify the distinct phenotypes associated with loss or gain of GRIN2B function.

  9. Open Access

    MECP2 Duplications in Symptomatic Females: Report on 3 Patients Showing the Broad Phenotypic Spectrum

    Child Neurology Open, vol. 3First Published April 4, 2016.
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    Abstract

    Xq28 microduplications including the MECP2 gene constitute a 100% penetrant X-linked syndrome in males caused by overexpression of normal MeCP2 protein. A small number of cases of affected females have been reported. This can be due to the location of the duplicated material into an autosome, but it can also be due to the location of the duplicated material into one of the X chromosomes and random or unfavorable skewed X chromosome inactivation, which is much more likely to occur but may be underdiagnosed because of the resulting broad phenotypic spectrum. In order to contribute to the phenotypic delineation of Xq28 microduplications including MECP2 in symptomatic females, the authors present clinical and molecular data on 3 patients illustrating the broad phenotypic spectrum. Our finding underlines the importance of quantitative analysis of MECP2 in females with intellectual disability and raises the question of the indication in females with borderline intellectual performances or learning difficulties.

  10. Open Access

    Brain Inflammation in an Infant With Hemimegalencephaly, Escalating Seizures, and Epileptic Encephalopathy

    MD1MD1MD, PhD2
    Child Neurology Open, vol. 3First Published April 4, 2016.
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    Abstract

    Hemimegalencephaly, a congenital brain malformation typically characterized by enlargement of one hemisphere, is frequently associated with intractable epilepsy. The authors report a case of a 12-month-old girl with hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly escalating seizures, arrested development, and associated encephalopathy. The brain tissue was examined and evaluated for neuroinflammation. Immunohistochemical analysis of the brain tissue revealed the presence of abundant activated CD68-positive microglia and reactive astrogliosis. Detection of active inflammatory changes in the brain of a patient with hemimegalencephaly complicated by intractable epilepsy suggests a potential role of ongoing brain inflammation in seizure exacerbation and epileptic encephalopathy.

  11. Open Access

    An Unusual Triad in Pediatric Neurology: A Case Report on Cerebral Palsy, Epilepsy, and Duchenne Muscular Dystrophy

    Child Neurology Open, vol. 3First Published April 19, 2016.
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    Abstract

    We present a case of an unusual triad in pediatric neurology: a currently 12-year-old boy with cerebral palsy and epilepsy who was later also diagnosed with Duchenne muscular dystrophy. We describe the clinical path that resulted in this exceptional diagnosis. This case report illustrates how different neurological disorders may overshadow each other. In addition, it demonstrates that every child with cerebral palsy and either an atypical clinical course or with inexplicable laboratory values—as well as every infant boy born to a theoretical Duchenne muscular dystrophy carrier—should be subjected to additional investigations.

  12. Open Access

    Vagal Nerve Stimulation in the Treatment of Drug-Resistant Epileptic Encephalopathies in Inborn Errors of Metabolism: Report of 2 Cases

    Child Neurology Open, vol. 2, 4First Published October 25, 2015.
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    Abstract

    Patients affected by inborn errors of metabolism can develop catastrophic epilepsies ineligible for resective surgery. Few reports concerning vagal nerve stimulation in patients with epileptic encephalopathy in the context of metabolic diseases have been published in the literature. Drug-resistant epilepsies in metabolic disease could be a specific target for vagal nerve stimulation, although the efficacy of this technique in these patients still needs to be proved. The authors report our experience in treating refractory epilepsy with vagal nerve stimulation in 2 patients affected by inborn errors of metabolism. The first patient is a 23-year-old patient affected by glutaric aciduria type II, the other one is a 16-month-old child with nonketotic hyperglycinemia. Vagal nerve stimulation reduced seizures up to 50% in the first case and up to 90% in the second one.

  13. Open Access

    Ictal 99mTc-Ethyl Cysteinate Dimer SPECT Findings of a Girl With Refractory Localization-Related Epilepsy Who Developed Transient Ictal Bradycardia

    Child Neurology Open, vol. 2, 3First Published July 21, 2015.
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    Abstract

    Ictal bradycardia, which is considered to be one of the causes of sudden unexplained death in epilepsy, is rare. A 10-year-old girl with focal cortical dysplasia in her right centroparietal region developed transient ictal bradycardia during cluster seizures. Brain magnetic resonance imaging demonstrated a high signal intensity lesion adjacent to the focal cortical dysplasia lesion. Ictal 99mTc-ethyl cysteinate dimer single-photon emission computed tomography (SPECT) detected hyperperfusion in an area containing the high signal intensity lesion, which was located close to the insular cortex. Since the hyperperfusion zone observed on SPECT was considered to reflect seizure propagation, it is possible that the ictal bradycardia experienced in the present case was caused by the following mechanism: The repetitive seizure activity caused the high-intensity lesion seen on MRI to expand into the right insular cortex, which controls cardiac rhythm, resulting in ictal bradycardia.

  14. Open Access

    First Application of Ketogenic Diet on a Child With Intractable Epilepsy in Ghana

    MD12BA1MD1MD1MDPhD1
    Child Neurology Open, vol. 2, 3First Published September 21, 2015.
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    Abstract

    The prevalence of epilepsy in sub-Saharan Africa is higher than in other parts of the world, but it is short of the effective measure on treating intractable epilepsy. Epilepsy surgery is not easy to be performed due to the high cost and demand of operational skills. The authors planned to perform ketogenic diet therapy for the children with intractable epilepsy in Ghana with regard to its low cost and simple procedure. The candidate is a 10-month-old girl with epilepsy with unknown etiology. Her seizures couldn't be controlled by more than 3 antiepileptic drugs. Her development delayed severely due to frequent seizures. The authors successfully applied ketogenic diet for her. Her seizures were completely controlled after 2 weeks' therapy. Her mental condition was improved after that. The authors get much experience from this case for further developing ketogenic diet in Africa. This is the first report that ketogenic diet was applied to control intractable epilepsy in West Africa.

  15. Open Access

    Clinical Phenotype of De Novo GNAO1 Mutation: Case Report and Review of Literature

    MD, PhD12MSc, PhD34MD2MD2MSc45MSc, PhD45MD, PhD6,MD, PhD12
    Child Neurology Open, vol. 2, 2First Published May 5, 2015.
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    Abstract

    Mutations in the guanine nucleotide-binding protein (G protein), α activating activity polypeptide O (GNAO1) gene have recently been described in 6 patients with early infantile epileptic encephalopathies. In the present study, we report the phenotype and the clinical course of a 4-year-old female with an epileptic encephalopathy (Ohtahara syndrome) and profound intellectual disability due to a de novo GNAO1 mutation (c.692A>G; p.Tyr231Cys). Ohtahara syndrome is a devastating early infantile epileptic encephalopathy that can be caused by mutations in different genes, now also including GNAO1. The mutation was found using a targeted next generation sequencing gene panel and demonstrates targeted sequencing as a powerful tool for identifying mutations in genes where only a few de novo mutations have been identified.

  16. Open Access

    Use of Magnesium Sulfate Infusion for the Management of Febrile Illness-Related Epilepsy Syndrome: A Case Series

    PharmD1MCI2MCI3MBBS2MBBS3MBBS3
    Child Neurology Open, vol. 2, 1First Published March 23, 2015.
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    Abstract

    Febrile illness-related epilepsy syndrome is a catastrophic epileptic encephalopathy that is highly refractory to most antiepileptic drugs leading to high morbidity and mortality. The authors report the use of a pediatric infusion protocol of continuous intravenous magnesium sulfate for the control of seizures in 2 children with febrile illness-related epilepsy syndrome refractory to multiple antiepileptic drugs in a pediatric intensive care unit of a tertiary care children's hospital. Both patients, 2 and 16 years of age, respectively, were treated with continuous magnesium sulfate infusion. Serum magnesium concentrations ranging from 2.1 to 5 mmol/L were achieved. Seizure reduction and cessation were noted in 1 patient with magnesium more than 3.0 mmol/L. No significant adverse effects were observed. Magnesium sulfate infusions can be safely used in pediatric refractory status epilepticus. Magnesium sulfate can be considered in the management of children with febrile illness-related epilepsy syndrome.

  17. Open Access

    Encephalocraniocutaneous Lipomatosis: A Rare Association With Tethered Spinal Cord Syndrome With Review of Literature

    Child Neurology Open, vol. 2, 1First Published February 13, 2015.
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    Abstract

    Encephalocraniocutaneous lipomatosis or Haberland syndrome is a rare, congenital neurocutaneous syndrome. It is characterized by unilateral lipomatous hamartomata of the scalp, eyelid, and outer globe of the eye and ipsilateral neurologic malformations. We describe the first case from Lebanon, an infant with classical encephalocraniocutaneous lipomatosis characterized by nevus psiloliparus, unilateral right facial and frontal–temporal subcutaneous lipomas, alopecia, ocular coloboma, aniridia and eyelid nodular tags, ventriculomegaly with intracranial and intraspinal lipomas, and tethered spinal cord. We report this case of rare association between encephalocraniocutaneous lipomatosis and tethered spinal cord syndrome and stress on the importance of spinal cord evaluation in encephalocraniocutaneous lipomatosis.

  18. Open Access

    FOXG1 Mutation is a Low-Incidence Genetic Cause in Atypical Rett Syndrome

    1MD1MD1MD, PhD1MD, PhD1MD, PhD1
    Child Neurology Open, vol. 2, 1First Published February 10, 2015.
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    Abstract

    Due to the genetic and clinical heterogeneity of Rett syndrome, patients with nonclassic phenotypes are classified as an atypical Rett syndrome, that is, preserved speech variant, early seizure variant, and congenital variant. Respectively, MECP2, CDKL5, and FOXG1 have been found to be the causative genes, but FOXG1 variants are the rarest and least studied. We performed mutational analyses for FOXG1 on 11 unrelated patients without MECP2 and CDKL5 mutations, who were diagnosed with atypical Rett syndrome. One patient, who suffered from severe early-onset mental retardation and multiple-type intractable seizures, carried a novel, de novo FOXG1 mutation (p.Gln70Pro). This case concurs with previous studies that have reported yields of ∼10%. FOXG1-related atypical Rett syndrome is rare in Korean population, but screening of this gene in patients with severe mental retardation, microcephaly, and early-onset multiple seizure types without specific genetic causes can help broaden the phenotypic spectrum of the distinct FOXG1-related syndrome.

  19. Open Access

    Connexin 43 and Its Hemichannels Mediate Hypoxia–Ischemia-Induced Cell Death in Neonatal Rats

    MD1MD, PhD1MD1MD, PhD1MD, PhD2
    Child Neurology Open, vol. 1, 1First Published August 26, 2014.
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    Abstract

    Wistar rat pups had the left common carotid artery cut, and they were exposed to 8% oxygen with free access to food and water until they were killed at 1, 12, 24, and 48 hours after the hypoxia–ischemia (HI) insult. Connexin 43 (Cx43), hemichannel (HC1), and caspase 3 (Casp3) in cerebral HI tissues were examined by immunohistochemistry and Western blot analyses. Astrocytes cell line, astrocytes transduced with a retroviral empty vector (Psup astrocyte), or a Cx43-specific small hairpin RNA (shRNA) construct (shRNA astrocytes) was treated with oxygen–glucose deprivation (OGD) insult. The viability of astrocytes was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed the expression of Cx43, HC1, and Casp3 in rats' brain, and astrocytes and Psup astrocytes increased significantly after 24 hours of HI/OGD insult. Cell viability decreased after 24 hours of the insult. The results suggest that Cx43 and hemichannel are likely to mediate the astrocytic death after HI insult.

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