Neurological Disorders In Children Research Articles

Botulinum Toxin in Pediatric Neurology: Switching Lanes From Death to Life.

Botulinum neurotoxins are natural molecules produced by anaerobic spore-forming bacteria called Clostradium boltulinum. The toxin has a peculiar mechanism of action by preventing the release of acetylcholine from the presynaptic membrane. Consequently, it has been used in the treatment of various neurological conditions related to muscle hyperactivity and/or spasticity. Also, it has an impact on the autonomic nervous system by acting on smooth muscle, leading to its use in the management of pain syndromes. The use of botulinum toxin in children separate from adults has received very little attention in the literature. This review presents the current data on the use of botulinum neurotoxin to treat various neurological disorders in children.

Knowledge and practice of schoolteachers towards students with epilepsy in Khamis Mushate, Southern Saudi Arabia.

Objectives:Epilepsy is a very common chronic neurological disorder in children throughout the world. This study was conducted to assess Saudi male schoolteachers’ knowledge of epilepsy and practice in Southern Saudi Arabia.Subjects and Methods:A cross-sectional descriptive study was conducted among male teachers; 315 teachers filled a well-designed and pretested self administered questionnaire.Results:Approximately three-quarters (72.7%) of the schoolteachers had witnessed epileptic fits. Forty-six percent believed that epilepsy was caused by electrical discharges. Most of the school teachers (79.7%) disagreed with the idea of teaching children with epilepsy separately, or preventing them from sporting activity (50.5%). In addition, 94.9% disagreed with the idea that epilepsy was shameful. Unfortunately, 64.1% of the teachers who were exposed to cases of seizures were not able to provide first aid to students having epileptic fits (P = 0.03).Conclusions:The schoolteachers were generally knowledgeable about epilepsy. This fact can be used to design a national program through which teachers can help to bring about a well-informed and tolerant community toward epileptics.

The Therapeutic Options in Childhood Epilepsy: From Pharmaceuticals to Nutraceuticals

Epilepsy is one of the most common neurological disorders of childhood. Treatment of epileptic seizures is governed by weighing the benefit- risk of using anti-epileptic drugs. An important limitation of their use is that, in at least one third of patients, seizures are resistant to the available older and new-generation anti-epileptic drugs. This challenge makes the non-pharmacologic mode of treatment an attractive option. With the global demonstration of the therapeutic benefits of the ketogenic diet signaling a possible paradigm shift, evaluating its risk profile will help to establish its benefit-risk ratio. Multifaceted side effects of the diet have been reported in several studies but have not precluded its use. To promote its world-wide acceptability, its components should be modified to include locallyavailable food stuffs. The present review aims to highlight and compare the benefit-risk ratio of using anti-epileptic drugs and the ketogenic diet in the treatment of refractory childhood epilepsy.

Brain stimulation for treatment and enhancement in children: an ethical analysis.

Davis (2014) called for “extreme caution” in the use of non-invasive brain stimulation (NIBS) to treat neurological disorders in children, due to gaps in scientific knowledge. We are sympathetic to his position. However, we must also address the ethical implications of applying this technology to minors. Compensatory trade-offs associated with NIBS present a challenge to its use in children, insofar as these trade-offs have the effect of limiting the child’s future options. The distinction between treatment and enhancement has some normative force here. As the intervention moves away from being a treatment toward being an enhancement—and thus toward a more uncertain weighing of the benefits, risks, and costs—considerations of the child’s best interests (as judged by the parents) diminish, and the need to protect the child’s (future) autonomy looms larger. NIBS for enhancement involving trade-offs should therefore be delayed, if possible, until the child reaches a state of maturity and can make an informed, personal decision. NIBS for treatment, by contrast, is permissible insofar as it can be shown to be at least as safe and effective as currently approved treatments, which are themselves justified on a best interests standard.

A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

Possible Linkage Between Visual and Motor Development in Children With Cerebral Palsy

AimThe purpose of this study was to examine ophthalmic disorders associated with neurological disorders in children with cerebral palsy. MethodsChildren clinically diagnosed as cerebral palsy with supportive abnormal magnetic resonance imaging results were included in this prospective study. All participants were recommended to have comprehensive ophthalmic exams. To assess motor function, the Gross Motor Function Classification System and the Gross Motor Function Measure were used. To assess motor and cognitive function, the Bayley Scales of Infant Development-II was used. ResultsForty-seven children completed all the evaluations and the data were analyzed. Ametropia was seen in 78.7% and strabismus was seen in 44.7% of the 47 children. When subjects were divided into severely impaired and mildly impaired groups based on Gross Motor Function Classification System level, ametropia was more prevalent in the severely impaired than the mildly impaired (95.8% versus 60.9%, P < 0.05). According to quantitative analysis, the severity of gross motor impairment correlated with the degree of refractive error in the subjects older than 36 months (r = −0.65 for the Bayley Scales of Infant Development-II motor scale, P < 0.05). InterpretationBased on these findings, children with cerebral palsy with poor gross motor function have a high possibility of severe refractive disorder that becomes evident from 36 months after birth. These results suggest that brain injury and impaired motor development negatively affect ophthalmic development. Hence, an ophthalmic examination is recommended for young children with cerebral palsy to start early management.

Diagnostic Screening for Neurological Disorders in Children

A method for EEG processing and a device for neurological disorder diagnosis based on this method are described. The method and device for recording evoked potentials based on the use of self-tuning filter, which separates dominating rhythm from EEG, are discussed.

Advances in neurocritical care.

The neurologically injured child, whether from trauma or other causes, is a common admission into any Pediatric critical care unit. Whatever the cause, the risk for death and life long disability remains very high. Unlike the adult population, neurological diseases in children are diverse and arise from a variety of factors that vary greatly in age and presentation. Nervous system dysfunction is often a complication of critical illness and interventions. While neurointensive care units may be ideal for the at-risk child, in mixed units, 40 % of admissions may be neurological or have neurological complications. Improved quality of care and the application of protocols and bundles, appear to have contributed significantly to improved outcomes. Since we are constantly facing an uphill task of dealing with deterioration while trying to preserve function, detection of early shifts of any nature would be deemed helpful. The intensivist must focus not only on saving life but also on preventing disability with full awareness that responsibility does not end with discharge from the pediatric intensive care unit (PICU). Outcome audits should include not only deaths and discharge from PICU but also one year mortality and even degree of disability at the end of one year from discharge.

Functional difficulties and school limitations of children with epilepsy: Findings from the 2009–2010 National Survey of Children with Special Health Care Needs

BackgroundEpilepsy is a common serious neurologic disorder in children. However, most studies of children's functional difficulties and school limitations have used samples from tertiary care or other clinical settings. ObjectiveTo compare functional difficulties and school limitations of a national sample of US children with special health care needs (CSHCN) with and without epilepsy. MethodsData from the 2009–2010 National Survey of CSHCN for 31,897 children aged 6–17 years with and without epilepsy were analyzed for CSHCN in two groups: 1) CSHCN with selected comorbid conditions (intellectual disability, cerebral palsy, autism, or traumatic brain injury) and 2) CSHCN without these conditions. Functional difficulties and school limitations, adjusted for the effect of sociodemographic characteristics, were examined by epilepsy and comorbid conditions. ResultsThree percent of CSHCN had epilepsy. Among CSHCN with epilepsy 53% had comorbid conditions. Overall CSHCN with epilepsy, both with and without comorbid conditions, had more functional difficulties than CSHCN without epilepsy. For example, after adjustment for sociodemographic characteristics a higher percentage of children with epilepsy, compared to children without epilepsy, had difficulty with communication (with conditions: 53% vs. 37%, without conditions: 13% vs. 5%). Results for school limitations were similar. After adjustment, a higher percentage of children with epilepsy, compared to children without epilepsy, missed 11 + school days in the past year (with conditions: 36% vs. 18%, without conditions: 21% vs. 15%). ConclusionCSHCN with epilepsy, compared to CSHCN without epilepsy, were more likely to have functional difficulties and limitations in school attendance regardless of comorbid conditions.

Erhebung Seltener Neurologischer Erkrankungen im Kindesalter

Recruitment of a sufficiently large cohort of patients is a prerequisite for many research projects in the field of rare disorders. We are establishing the Acquisition of Rare Neurological Disorders in Childhood (Erhebung Seltener Neurologischer Erkrankungen im Kindesalter—ESNEK) which is modeled on the German pediatric surveillance system (Erhebungseinheit seltener pädiatrischer Erkrankungen in Germany, ESPED).

脳磁図の臨床応用に関する文献レビュー(第3報) : 小児疾患

脳磁図の臨床応用に関する文献レビュー(第3報) : 小児疾患

West Nile virus: Should pediatricians care?

Given the recurrent serious outbreaks of West Nile Virus (WNV) in the United States over the past decade, the spread to Canada and South America, the recurrent outbreaks in Europe, and the potential for serious neurological disease even in children under 18 years, paediatricians in affected areas must consider WNV in the differential diagnosis of all children presenting with aseptic meningitis, encephalitis and acute flaccid paralysis. Additionally, given that WNV encephalitis can occur after WNV infection, suspicion for neurological WNV disease must remain high even after otherwise benign febrile illnesses if the child lives in or has traveled to an affected region. Under-diagnosis in the pediatric population is likely a serious problem, necessitating further educational efforts. More follow-up studies of WNV neurological disease in children and youth are needed to better understand the potential long-term sequelae during vulnerable times of neurodevelopment and neural remodeling. Similarly, more research is need on short and long-term fetal outcomes of maternal WNV infection.

Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of neuronal development in trans-placental exposure to bisphenol A.

BackgroundBisphenol A (BPA) is a ubiquitous endocrine disrupting chemical in our daily life, and its health effect in response to prenatal exposure is still controversial. Early-life BPA exposure may impact brain development and contribute to childhood neurological disorders. The aim of the present study was to investigate molecular target genes of neuronal development in trans-placental exposure to BPA.MethodologyA meta-analysis of three public microarray datasets was performed to screen for differentially expressed genes (DEGs) in exposure to BPA. The candidate genes of neuronal development were identified from gene ontology analysis in a reconstructed neuronal sub-network, and their gene expressions were determined using real-time PCR in 20 umbilical cord blood samples dichotomized into high and low BPA level groups upon the median 16.8 nM.Principal FindingsAmong 36 neuronal transcripts sorted from DAVID ontology clusters of 457 DEGs using the analysis of Bioconductor limma package, we found two neuronal genes, sex determining region Y-box 2 (Sox2) and paired box 6 (Pax6), had preferentially down-regulated expression (Bonferroni correction p-value <10−4 and log2-transformed fold change ≤−1.2) in response to BPA exposure. Fetal cord blood samples had the obviously attenuated gene expression of Sox2 and Pax6 in high BPA group referred to low BPA group. Visualized gene network of Cytoscape analysis showed that Sox2 and Pax6 which were contributed to neural precursor cell proliferation and neuronal differentiation might be down-regulated through sonic hedgehog (Shh), vascular endothelial growth factor A (VEGFA) and Notch signaling.ConclusionsThese results indicated that trans-placental BPA exposure down-regulated gene expression of Sox2 and Pax6 potentially underlying the adverse effect on childhood neuronal development.

Aspartoacylase catalytic deficiency as the cause of Canavan disease: a structural perspective.

Canavan disease (CD) is a fatal, childhood neurological disorder caused by mutations in the ASPA gene, leading to catalytic deficiencies in the aspartoacylase (ASPA) enzyme and impaired N-acetyl-l-aspartic acid metabolism in the brain. To study the possible structural defects triggered by these mutations, four ASPA missense mutations associated with different disease severities have been structurally characterized. These mutant enzymes each have overall structures similar to that of the native ASPA enzyme, but with varying degrees of alterations that offer explanations for the respective loss of catalytic activity. The K213E mutant, a nonconservative mutant associated with a mild disease phenotype, has minimal structural differences compared to the native enzyme. In contrast, the loss of van der Waals contacts in the F295S mutant and the loss of hydrophobic and hydrogen bonding interactions in the Y231C mutant lead to a local collapse of the hydrophobic core structure in the carboxyl-terminal domain, contributing to a decrease in protein stability. The structure of the E285A mutant, the most common clinical mutant, reveals that the loss of hydrogen bonding interactions with the carboxylate side chain of Glu285 disturbs the active site architecture, leading to altered substrate binding and lower catalytic activity. Our improved understanding of the nature of these structural defects provides a basis for the development of treatment therapies for CD.

Clinical features and pharmacotherapy of childhood monoamine neurotransmitter disorders.

Childhood neurotransmitter disorders are increasingly recognised as an expanding group of inherited neurometabolic syndromes. They are caused by disturbance in synthesis, metabolism, and homeostasis of the monoamine neurotransmitters, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine neurotransmission will lead to neurological symptoms that often overlap with clinical features of other childhood neurological disorders (such as hypoxic ischaemic encephalopathy, cerebral palsy, other movement disorders, and paroxysmal conditions); consequently, neurotransmitter disorders are frequently misdiagnosed. The diagnosis of neurotransmitter disorders is made through detailed clinical assessment, analysis of cerebrospinal fluid neurotransmitters, and further supportive diagnostic investigations. Early and accurate diagnosis of neurotransmitter disorders is important, as many are amenable to therapeutic intervention. The principles of treatment for monoamine neurotransmitter disorders are mainly directly derived from understanding these metabolic pathways. In disorders characterized by enzyme deficiency, we aim to increase monoamine substrate availability, boost enzyme co-factor levels, reduce monoamine breakdown, and replace depleted levels of monoamines with pharmacological analogs as clinically indicated. Most monoamine neurotransmitter disorders lead to reduced levels of central dopamine and/or serotonin. Complete amelioration of motor symptoms is achievable in some disorders, such as Segawa’s syndrome, and, in other conditions, significant improvement in quality of life can be attained with pharmacotherapy. In this review, we provide an overview of the clinical features and current treatment strategies for childhood monoamine neurotransmitter disorders.

Resultados de la colocación del estimulador del nervio vago en epilepsia y calidad de vida en un hospital pediátrico

IntroductionEpilepsy, which is present in 0.5% to 1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. MethodsDescriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients’ medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. ResultsWe describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1-144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. ConclusionsVNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life.

Induced pluripotent stem cells for modeling of pediatric neurological disorders.

The pathophysiological mechanisms underlying childhood neurological disorders have remained obscure due to a lack of suitable disease models reflecting human pathogenesis. Using induced pluripotent stem cell (iPSC) technology, various neurological disorders can now be extensively modeled. Specifically, iPSC technology has aided the study and treatment of early-onset pediatric neurodegenerative diseases such as Rett syndrome, Down syndrome, Angelman syndrome. Prader-Willi syndrome, Friedreich's ataxia, spinal muscular atrophy (SMA), fragile X syndrome, X-linked adrenoleukodystrophy (ALD), and SCN1A gene-related epilepsies. In this paper, we provide an overview of various gene delivery systems for generating iPSCs, the current state of modeling early-onset neurological disorders and the ultimate application of these in vitro models in cell therapy through the correction of disease-specific mutations.

Central nervous system herpesvirus infections

The herpesviridae family are important causes of central nervous system disease in children. We review the spectrum of disease caused by the viruses in the context of a brief description of their epidemiology and transmission. Herpesviridae establish lifelong latency following primary infection and we clearly categorize those diseases associated with primary infection and those associated with reactivation with a particular emphasis on the immunocompromised child. Though a causal association with neurological disease in children is established for HSV and VZV syndromes, we identify the ongoing challenge of establishing causation for other viruses because of the rarity of presentations and viral latency. We review the diagnosis, management and outcome issues with recognition that more research is required.

The Nordic Five to Fifteen questionnaire could provide the basis for a common neurological disability variable

Assessing disabilities in children is essential and Danish parents provide increasingly important feedback on how their child's disability affects daily living. The Nordic Five to Fifteen (FTF) parent questionnaire is widely used in Nordic countries to detect atypical or delayed development in children. Our study evaluated its internal validity and whether it could be used to generate a common disability variable across childhood neurological disorders and severities. The 28-statement FTF questionnaire was completed by the parents of children with spina bifida, muscular disorders, spinal atrophy, cerebral palsy, blindness, deafness, mental retardation and disability, who received treatment for brain tumours. Psychometric analysis and Rasch analysis of the five FTF code qualifier level data were carried out. A total of 227 of 332 (68.4%) parents participated. The mean qualifier score was 3.06 (standard deviation 0.89, range 2.31-4.26), and the variances mean was 1.57 (range 0.87-2.38). The corrected code-total correlation was 0.65, and reliability was 0.96. The Rasch analysis demonstrated good fit alignment of codes. The FTF questionnaire can be used with children with neurological disabilities, and the Rasch scale analysis results indicate that it could form the analytical basis for developing a common disability variable.

Specifics of the diagnosis of a progressive neurological disorder in children and adolescents

Specifics of the diagnosis of a progressive neurological disorder in children and adolescents