European consensus table 2006 on botulinum toxin for children with cerebral palsy

An interdisciplinary group of experienced botulinum toxin users and experts in the field of movement disorders was assembled, to develop a consensus on best practice for the treatment of cerebral palsy using a problem-orientated approach to integrate theories and methods. The authors tabulated the supporting evidence to produce a condensed but comprehensive information base, pooling data and experience from nine European countries, 13 institutions and more than 5500 patients. The consensus table summarises the current understanding regarding botulinum toxin treatment options in children with CP.     

Nasopharyngeal carcinoma in children and young adults—Beyond 5‐year survival

Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of NPC includes chemotherapy and radiotherapy. With current treatment protocols, survival rates for patients with nonmetastatic disease is over 80%. Data regarding very late events including long‐term treatment‐related morbidities and second malignancies are scarce. We present our data on 42 patients with NPC treated in Israel between 1989 and 2014, and followed until 2019. During follow up, five patients had disease recurrence, and four children developed secondary malignancy. Median time to diagnosis of secondary malignancy was 105 months. Eighty‐eight percent of patients have long‐term treatment‐related morbidities.     

The updated European Consensus 2009 on the use of Botulinum toxin for children with cerebral palsy

An interdisciplinary European group of clinical experts in the field of movement disorders and experienced Botulinum toxin users has updated the consensus for the use of Botulinum toxin in the treatment of children with cerebral palsy (CP). A problem-orientated approach was used focussing on both published and practice-based evidence. In part I of the consensus the authors have tabulated the supporting evidence to produce a concise but comprehensive information base, pooling data and experience from 36 institutions in 9 European countries which involves more than 10,000 patients and over 45,000 treatment sessions during a period of more than 280 treatment years. In part II of the consensus the Gross Motor Function Measure (GMFM) and Gross Motor Function Classification System (GMFCS) based Motor Development Curves have been expanded to provide a graphical framework on how to treat the motor disorders in children with CP. This graph is named “CP^Graph Treatment Modalities – Gross Motor Function” and is intended to facilitate communication between parents, therapists and medical doctors concerning (1) achievable motor function, (2) realistic goal-setting and (3) treatment perspectives for children with CP. The updated European consensus 2009 summarises the current understanding regarding an integrated, multidisciplinary treatment approach using Botulinum toxin for the treatment of children with CP.     

Pharmacological Management of Spasticity in Children With Cerebral Palsy

Cerebral palsy (CP), a nonprogressive disease of the central nervous system, is the most common motor disability in childhood. Patients with CP often have a multitude of associated comorbidities, including impact on muscle tone. There are four main types of CP, with spastic as the most commonly diagnosed. Reduction in spasticity is important because it can affect not only the patient's quality of life, functional abilities, and well-being but also the lives of caregivers. The American Academy of Neurology and Child Neurology Society released a practice parameter regarding the pharmacological management of CP-related spasticity in 2010. Since then, data have been published evaluating the safety and efficacy of oral and parenteral medications to manage spasticity. This continuing education review evaluates the available safety and efficacy evidence for oral and parenteral pharmacological agents used to reduce spasticity in children with CP and provides a reference for practitioners managing these patients.     

Interleukin-2: prospects for lymphocyte-mediated destruction of pediatric malignancies.

Immunologic therapy of cancer was speculated on at the turn of the century. In animals, in vitro, and most recently in patients, irrefutable evidence has been obtained that lymphocyte responses can have a reproducible and beneficial antitumor effect. These results indicate that "biologic response modification" may truly become a fourth modality for cancer treatment, to be integrated into the standard approaches of radiation, chemotherapy, and surgery. To what extent these immune approaches may enable eradication of microscopic amounts of residual diseases in children who would otherwise have a recurrence of their malignancies remains the critical issue for testing over the next decade. Enthusiasm regarding this approach is abundant, but critical evaluation of all clinical trials is essential to best focus these mechanisms into effective therapy.     

Evaluation of faecal calprotectin as a valuable non‐invasive marker in distinguishing gut pathogens in young children with acute gastroenteritis

Aim: The aim of the study is to evaluate faecal calprotectin (f‐CP) in children ≤3 years of age with acute gastroenteritis (AG) as an early predictor of bacterial inflammation. Methods: We prospectively analysed f‐CP levels and diagnostic workup in 107 consecutive children (66 AG, 41 controls). Results: Children with bacterial AG (BAG) was found to have higher diarrheal frequency (p < 0.01), fever (p < 0.01), erythrocyte sedimentation rate (p < 0.001), white blood count (p < 0.01) and C‐reactive protein (CRP) (p < 0.001) compared with viral AG (VAG). Vomiting was frequent in VAG (p < 0.001). f‐CP negatively correlated with age in controls (r = ?0.5998). BAG demonstrated significantly higher f‐CP levels [median, 219 μg/g, interquartile range (IQR): 119–350.2] compared with VAG (49.3 μg/g, IQR: 8.8–131.1) as well as controls (26.5 μg/g, IQR: 14.9–55.1) (p < 0.001). VAG and control f‐CP levels were similar. f‐CP was the best‐rated marker of BAG with a diagnostic accuracy of 92%. Receiver–operator characteristic analysis revealed an area under curve of 0.95 for identifying BAG; sensitivity and specificity of f‐CP were 93% and 88%, respectively, at an adjusted cut‐off point of 103.9 μg/g faeces. Combined f‐CP and CRP yield improved diagnostic accuracy of 94% for BAG. Conclusion: f‐CP facilitates early discrimination between bacterial and viral causes of AG in young children. Combining f‐CP with CRP increases the diagnostic power of diagnosing BAG.     

Botulinumtoxin als Teil einer integrierten Behandlung

After the publication of the interdisciplinary German consensus on botulinum toxin (BoNT) and the treatment of gross motor function disorders in children with cerebral palsy (CP) in 2007, the integrative therapeutic concept has progressively been incorporated into the clinical routine. Paediatric neurologists, social paediatricians, paediatric orthopaedic surgeons, orthoptists, and therapists gathered to hold the first interdisciplinary CP conference of the German-speaking countries in June 2009 (Freiburg, Germany), which received great feedback. Besides the topics described in the preceding articles of this issue, four subjects regarding BoNT treatment in children with CP have (re)emerged: (1) the safety of BoNT treatment, (2) a paradigm shift to BoNT as a modulator of muscular imbalance, (3) newly approved BoNT preparations, and (4) the effect of BoNT treatment over the course of time. This review focuses on these four topics and tries to integrate the information on the basis of the updated European consensus 2009 (in press) and the graphics-supported consensus on the treatment of movement disorders in children with bilateral spastic CP, which was published in this journal in summer 2009.     

Epidemiology of cerebral palsy

Definition of cerebral palsy (CP) has become more precise in recent years and, even if CP remains an umbrella term, a simple classification system for CP types has been proposed. CP is the commonest motor impairment in childhood. New validated motor scales for gross and fine motor functions describe a third of children with CP as severely impaired. Children with CP may also have associated impairments, other than motor, that deserve particular attention and support at school and work, and which are responsible for lower survival rates. The prevalence of CP, 2 per 1000 children, has remained remarkably stable over the last 30 years, particularly for term children who represent half of all children with CP. However, recently, a consistent downward trend has been seen in moderately and very low birth weight children. Prevention measures still seems difficult to define since CP is the result of multifactorial events. Decreasing multiple births and specific health actions during early infancy may have an impact. Followup programmes have been implemented to assess how the consequences of CP are best reduced.     

The impact of prenatal maternal risk, fearless temperament and early parenting on adolescent callous-unemotional traits: a 14-year longitudinal investigation

Objective: Proposals have been submitted to the DSM‐V for the addition of a callous‐unemotional (CU) specifier for conduct problem (CP) youth (CP/CU). While the addition of such a diagnostic category may aid in the identification of homogeneous CP subtypes, evidence on risks for the development of CP/CU remains limited. The present study sought to examine the extent to which CP/CU in early adolescence could be differentiated by family‐ and child‐based risks from pregnancy to age 4 years. Method: Using data from approximately 7,000 mothers and their offspring (51% male) participating in the Avon Longitudinal Study of Parents and Children, the authors examined maternal prenatal risks (psychopathology, criminality, substance use), child’s fearless temperament (age 2 years) and harsh and warm parenting (age 4 years) as predictors of CP and CU at age 13; then used follow‐back analyses to explore pre‐ and early post‐natal risks in more detail. Results: Maternal prenatal risks increased fearless temperament and CP and CU. Fearless temperament was also prospectively associated with higher levels of early adolescent CP and CU, above and beyond parenting and prenatal maternal risks. Follow‐back analyses showed fearless temperament in boys manifested as lower response to punishment cues, while for girls this temperament was indexed by boldness toward novel situations and strangers, particularly for CP/CU youth. Conclusions: The current findings suggest that (i) maternal prenatal risks and fearless temperament showed a dose–response relationship with CP and CU (i.e., higher clustering of risks tended to relate to both higher levels and the co‐occurrence of CU with CP), and (ii) intervention programs that aim to improve behavioural outcomes may consider targeting specific temperamental features in both boys and girls.     

Extended implementation of educational programs for atopic dermatitis in childhood

Children with atopic dermatitis (AD) suffer from chronic relapsing inflammatory skin lesions accompanied by insatiable itching, dryness, excoriated skin, or even (super‐)infections. This burden impairs the quality of life of affected children and their families. Due particularly to the recurrent course of the disease, patients often lose confidence in treatment and fear side effects of steroids. Family education programs for AD have been established in the last decades to provide appropriate education and psychosocial support. However, the need for long‐lasting strategies in treatment and prevention has even increased. Recent findings not only underline the importance of an intact skin barrier in regard to acute therapy but also suggest that an impairment of skin barrier integrity promotes the development of subsequent atopic diseases in the course of the atopic march. Moreover, in addition to the psychosocial burden due to stigmatized appearance or sleep disturbance, new observations document an increased presence of psychosomatic comorbidities in patients with AD. We reviewed recent educational interventions regarding the theoretical background and here will discuss the heterogeneous approaches of existing programs in childhood. Despite high variations of educational strategies, an overriding aim should be the broader integration of supporting programs in the treatment of children with AD to empower the affected child and its caregiver's to obtain the best possible care, quality of life, and to promote (secondary) prevention.     

Editorial Perspective: Exposures in cognitive behavior therapy for pediatric obsessive‐compulsive disorder: addressing common clinician concerns

Professional organizations and expert consensus recommend the use of exposure‐based cognitive‐behavioral therapy (CBT) to treat pediatric obsessive‐compulsive disorder (OCD), but a sizable proportion of clinicians possess hesitancy regarding the use of exposures in treatment. Most notably, this hesitancy relates to concerns about negative patient and parent reactions to exposures. Accordingly, we examine three commonly reported clinician concerns regarding negative patient/parent reactions (e.g. treatment attrition, therapeutic relationship, and treatment satisfaction) among youths receiving exposure‐based CBT compared to a nonexposure‐based treatment. Based on our findings, there is no empirical support that exposure‐based CBT precipitates adverse consequences in treatment (e.g. treatment attrition, poor therapeutic relationship, low treatment satisfaction) relative to nonexposure‐based interventions. These results corroborate existing OCD expert recommendations for the use of exposure‐based CBT and provide information to mitigate clinicians’ concerns about the potentially iatrogenic impact of exposures when treating pediatric OCD. We briefly present best practice recommendations for implementing exposure‐based CBT in pediatric OCD patients.     

Comparing effectiveness and outcomes in asthma and cystic fibrosis

As technology yields new treatments, pediatric pulmonologists need determine how best to use them and how to decide which ones are best for any specific group or individual patient. Physicians have always customized therapies based upon patient response, but the new concept of “Personalized (or precision) medicine” focuses attention to a greater degree on the individual needs of patients based on their genetic, biomarker, phenotypic, or psychosocial characteristics. The newly developed biologics for treatment of asthma and CFTR modulators for treatment of cystic fibrosis (CF) highlight this newer approach. As we have more treatments available, new approaches to testing efficacy and effectiveness of these new therapies is necessary in order to efficiently bring them to market and compare their benefits in real world practice. While comparative effectiveness can be tested in pragmatic clinic trials, the most common approaches make use of observational data such as administrative databases and patient registries but their use for this is fraught with pitfalls that may or may not be methodologically surmountable. Once new therapies have been shown to be efficacious and effective, it is important to be cognizant of methods for ensuring that all patients actually receive the treatments that will be best for them. Comparisons of the effectiveness of clinical practice in the form of benchmarking is helpful for this, and consideration of costs and cost-effectiveness is essential to judging the best treatment for patients in a real-world setting.     

Metastatic Low‐Grade Gliomas in Children: 20 Years' Experience at St. Jude Children's Research Hospital

Background

Patients with low‐grade gliomas (LGG), which are the most common childhood brain tumors, have excellent long‐term survival. Dissemination of LGG is rare. Robust data on the incidence, presentation, patterns of dissemination, disease behavior, outcome, and best‐management approaches do not exist. We describe 20 years of follow‐up of children with metastatic LGG.

Procedure

Data collected during the period 1990–2010 were retrospectively reviewed for the following inclusion criteria: diagnosis of metastatic LGG, age younger than 21 years at initial diagnosis, and magnetic resonance imaging of the brain and/or spine at diagnosis and/or follow‐up. Patient demographics, pathology, treatment modalities, and outcome were reviewed.

Results

Of 599 patients with LGG, 38 (6%) had metastatic disease at either diagnosis or follow‐up. Most tumors (87%) were located in the brain, and half of the patients had metastatic disease at presentation. The most common diagnosis was pilocytic astrocytoma (55%). Chemotherapy was the most common initial treatment modality. Median survival of the group was 6.2 years (range, 0.1–16.9 years). Fifteen (40%) patients died at a median of 6 years from diagnosis (range, 0.8–15 years). Overall survival at 5, 10, and 15 years was 80.7 ± 6.6%, 63.0 ± 10.2%, and 50.9 ± 16.0%, respectively.

Conclusion

This study describes the longest follow‐up of children with metastatic LGG. LGG is underestimated and entails major morbidity and mortality. Prospective studies are needed to learn the true incidence, study the biology, and determine the best approaches to diagnosis, treatment, and follow‐up. Pediatr Blood Cancer 2015; 9999:1–9. © 2015 Wiley Periodicals, Inc.     

A guide to physiotherapy in cerebral palsy

This review aims to elucidate current thinking and physiotherapy practice in the treatment and management of children with cerebral palsy (CP). It discusses established approaches to treatment, such as Bobath/NDT, conductive education and sensory integration, commonly used by therapist to address the problems seen in children with CP. The review also explores interventions that are currently advocated for the treatment of specific groups of people with CP, including constraint induced movement therapy, partial body weight-supported treadmill training and strength-training programmes.     

Risk factors and management of deep venous thrombosis in children following post-surgical hypopituitarism in craniopharyngioma

Post‐operative hypopituitarism following craniopharyngioma (CP) surgery is treated by replacement of various hormones. The risk of deep venous thrombosis (DVT) following CP surgery and initiation of hormones has not been well studied and recognized. We present three patients with DVT who had family history of DVT and procoagulant risk factors such as inherited thrombophilia and elevated Von Willebrand factor levels due to treatment with desmopressin. We discuss the individualized management of anticoagulation and the dilemma of starting estrogen and progesterone replacement therapy in them. Pediatr Blood Cancer 2011;57:175–177. © 2011 Wiley‐Liss, Inc.     

Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome

There are no proven safe and effective therapies for children who develop life‐threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS‐CoV‐2, but has theoretical risks.We present the first report of CP in children with life‐threatening coronavirus disease 2019 (COVID‐19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody‐dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.     

Deep brain stimulation for dystonia due to cerebral palsy: A review

Cerebral palsy (CP) is a heterogeneous group of syndromes that cause a non-progressive disorder of early onset, with abnormal control of movement and posture. Various aetiologies can cause the CP clinical spectrum, but all have a disruption of motor control in common. CP can be divided into four major types based on the motor disability: predominant spastic, dyskinetic, ataxic and mixed form. Dyskinetic CP (DCP) is the most common cause of acquired dystonia in children. The treatment of DCP is challenging because most individuals have mixed degrees of chorea, athetosis and dystonia. Pharmacological treatment is often unsatisfactory. Functional neurosurgery, in particular deep brain stimulation targeting the basal ganglia or the cerebellum, is emerging as a promising therapeutic approach in selected patients with DCP. We evaluated herein the effects of DBS on patients with DCP in a review of published patient data in the largest available studies.     

Paediatric type 2 diabetes in China—Pandemic,progression, and potential solutions

China is gradually taking its place as one of the world's economic giants and concurrently learning to cope with the burden of diseases that are more common in the developed world, such as paediatric type 2 diabetes mellitus. The prevalence of type 2 diabetes has been recently observed among children and adolescents in China; hence, there is a lack of information about the incidence, prevalence, pathogenesis, and pathophysiology of the disease. Diagnosis, treatment, and management have been standardized to a large degree, but there is still a need for data regarding optimal management protocols and how to achieve the best control over current state of the disease. The objective of this review is to consolidate the available information about paediatric diabetes, with a focus on the increasing prevalence of type 2 diabetes in Chinese youth. Here we emphasize the prevention strategies and have included literature with respect to pathogenesis, diagnosis, and treatment published in English and Chinese within the past 10 years.     

Bone marrow transplant for a girl with bone marrow failure and cerebral palsy

Bone marrow transplantation (BMT) has been used with increasing frequency to treat congenital bone marrow failure syndrome (CBMFs) successfully. Decision to perform BMT, however, is difficult in the case of comorbidity because of regimen‐related toxicities. We describe here a child with CBMFs, severe cerebral palsy (CP) at Gross Motor Function Classification System level V and mental retardation (MR) who was transfusion dependent despite various medications. She underwent BMT from an HLA‐1 locus‐mismatched unrelated donor. Although engraftment was successful, no neurological improvement was seen 5 years after BMT. While CBMFs patients who have CP and MR could undergo transplantation safely, they may not benefit neurologically from BMT.     

Severe fasting hypoglycemia in a child after total pancreatectomy with islet autotransplantation

TPIAT is an increasingly utilized treatment option for select children with CP. Post‐TPIAT fasting hypoglycemia, unrelated to exogenous insulin, is a complication recently reported in adults. This phenomenon has not been described in children. We review a case of severe fasting hypoglycemia in an adolescent female occurring 10 months post‐TPIAT. A 12‐year‐old girl underwent TPIAT for CP. Ten months postoperatively she developed recurrent hypoglycemia on a total daily insulin dose of 0.03 units/kg. Consequently, insulin therapy was discontinued. Approximately 20 hours after her last rapid‐acting insulin exposure, she had an episode of fasting hypoglycemia (33 mg/dL on glucometer). Her CGM documented two separate, precipitous drops in glucose overnight. The family was instructed to revise her diet, and there were no subsequent episodes of severe, fasting hypoglycemia. This is the first report of fasting hypoglycemia occurring post‐TPIAT in a pediatric patient. Use of a CGM allowed for documentation of glucose trends and alarm notification of hypoglycemic events. Dietary changes appeared to help mitigate hypoglycemia recurrence. This report demonstrates that fasting hypoglycemia is a potential complication that should be recognized and safeguarded against in post‐TPIAT pediatric patients.