Neurological Disorders In Children Research Articles

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats.

Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus.

Oxidative stress and mitochondrial dysfunction as key players in neurological disorders of childhood

Oxidative stress and mitochondrial dysfunction as key players in neurological disorders of childhood

Oxidative stress and mitochondrial dysfunction as key players in neurological disorders of childhood

An unavoidable consequence of aerobic respiration is the generation of reactive oxygen species (ROS). ROS is a collective term that includes both oxygen radicals and certain oxidizing agents that are easily converted into radicals. They can be produced from both endogenous and exogenous substances. ROS play a dual role in biological systems, since they can be either harmful or beneficial to living systems. They can be considered a double-edged sword: oxygen-dependent reactions and aerobic respiration have significant advantages but overproduction of ROS, a consequence of oxygen-dependent reactions, has the potential to cause damage. Overproduction of ROS may negatively impact neonatal growth and contribute to the aetiology of many developmental disorders. During mitochondrial respiration, an inability to neutralize reactive oxygen species and free radicals leads to oxidative stress. The inner membrane of the mitochondria contains a large number of free radical scavengers including glutathione, vitamin C, and vitamin E, as well as anti-oxidant enzymes such as superoxide dismutase. The brain is particularly vulnerable to free radical attack for several reasons, including exposed to high oxygen concentrations, relatively low antioxidant protection, membranes with high levels of polyunsaturated fatty acids, and high iron and ascorbate content. The brain's high energy demand is primarily supplied by oxidative phosphorylation, the major producer of free radicals. When the level of free radicals overwhelms the cellular antioxidant defense system, a deleterious condition known as oxidative stress occurs. ROS has an intimate relationship with mitochondrial function and oxidative stress is believed to result from mitochondrial dysfunction. This review highlights the role of oxidative stress and mitochondrial dysfunction as key players in the neurodevelopmental pathophysiology. The mechanisms associating these two disease states can lead to neuronal death, neuroinflammation and impairment of energy metabolism. Biomarkers related to both aspects will be highlighted to demonstrate their importance in the early diagnosis of neurodevelopmental disorders like autism, cerebral palsy and others. Treatments trials for oxidative stress or mitochondrial dysfunction using nutritional supplements and antioxidants are reviewed in order to shed light on recent strategies for the early intervention for neurodevelopmental disorders.

NEUROLOGICAL COMPLICATIONS AT OPERATIONS AT CHILDREN WITH CONGENITAL HEART DISEASE

This article presents a literature review of current issues in neurology and cardiac surgery in children with congenital heart disease. During the surgery the patient's brain is exposed to prolonged hypoxia, toxic influences of narcotic drugs, which in turn exacerbate the neurological complications in the postoperative period, are superimposed on existing neurological symptoms. The urgency of the problem of diagnosis of neurological disorders in children with congenital heart disease, due to anatomical and physiological characteristics of the child, as well as the severity of the general condition, as the neurological symptoms are often masked the symptoms of the underlying disease of the central nervous system. Timely diagnosis related neurological disorders in children in this category is also necessary for the proper conduct of preoperative preparation, adequate surgery, as well as a choice of tactics of treatment in the postoperative period.

Nursing Role on the Epilepsy Monitoring Unit: A Historical Perspective

Epilepsy is a significant neurological disorder in children, affecting developmental progress, academic achievement, and employment possibilities. It influences an individual's social potential and family quality of life. Completing a comprehensive and accurate epilepsy evaluation is key toward making the correct diagnosis and, subsequently, providing the best treatment for an affected child or adolescent. Nurses are key team members who can promote complete, safe, efficient, and precise testing for a child and family. Their compassion may also help lessen stress for the person with epilepsy and his support system. Since much of this specialized evaluation occurs on an epilepsy monitoring unit at level 4 sites throughout the United States, it is important to review nursing roles and offer recommendations to guide future role development and practice.

The History of Development of Pharmacologic and NonPharmacologic Treatment of Pediatric Epilepsy

Epilepsy is a common childhood neurological disorder in the United States. Current strategies for treatment of epilepsy in this population include trials with different antiepileptic drugs, vagal nerve stimulator, and ketogenic diet. Development of both pharmacologic and nonpharmacologic treatments in children should take into account their specific pharmacokinetic requirements as well as other ethical and practical challenges that exist for this population. As a result, in many instances detailed information on historical developments of these treatments in children is incomplete or lacking.

The Complexity Signature: Developing a Tool to Communicate Biopsychosocial Severity of Disease for Children with Chronic Neurological Complexity.

Aim For children with medical complexity, interdisciplinary treatment approaches are required to address the various aspects defined within the biopsychosocial model. Methods The present study identifies dimensions of the biopsychosocial model to generate a standardized visualized severity score for chronic neurological diseases in children. We demonstrate the score's applicability and usefulness in clinical practice among clinicians with and without pediatric board certification with the aid of illustrative patient cases. The results are compared by Spearman correlation coefficient. Results Nine dimensions were identified as the basis for the development of the score, which consists of five grades of severity for each of the selected neuropediatric subsections. All board-certified pediatricians would recommend the application of the severity score in clinical routine. Furthermore, a good correlation was revealed between direct and indirect (severity score) assessment. Interpretation The severity score developed in this study takes into account biopsychosocial aspects of chronic diseases while being comprehensible and easily applicable in clinical routine-a biopsychosocial signature serving as an excellent, striking communication basis within the interdisciplinary team. However, upcoming studies including more patient cases are needed for further refinement.

Роль перинатальных повреждений нервной системы в формировании неврологической патологии детского возраста

Роль перинатальных повреждений нервной системы в формировании неврологической патологии детского возраста

Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children

Enterovirus 71 (EV71) causes a spectrum of neurological complications with significant morbidity and mortality. Further understanding of the characteristics of EV71-related neurological disease, factors related to outcome, and potential responsiveness to treatments is important in developing therapeutic guidelines. To further characterize EV71-related neurological disease and neurological outcome in children. Prospective 2-hospital (The Sydney Children's Hospitals Network) inpatient study of 61 children with enterovirus-related neurological disease during a 2013 outbreak of EV71 in Sydney, Australia. The dates of our analysis were January 1, to June 30, 2013. Clinical, neuroimaging, laboratory, and pathological characteristics, together with treatment administered and functional motor outcomes, were assessed. Among 61 patients, there were 4 precipitous deaths (7%), despite resuscitation at presentation. Among 57 surviving patients, the age range was 0.3 to 5.2 years (median age, 1.5 years), and 36 (63%) were male. Fever (100% [57 of 57]), myoclonic jerks (86% [49 of 57]), ataxia (54% [29 of 54]), and vomiting (54% [29 of 54]) were common initial clinical manifestations. In 57 surviving patients, EV71 neurological disease included encephalomyelitis in 23 (40%), brainstem encephalitis in 20 (35%), encephalitis in 6 (11%), acute flaccid paralysis in 4 (7%), and autonomic dysregulation with pulmonary edema in 4 (7%). Enterovirus RNA was more commonly identified in feces (42 of 44 [95%]), rectal swabs (35 of 37 [95%]), and throat swabs (33 of 39 [85%]) rather than in cerebrospinal fluid (10 of 41 [24%]). Magnetic resonance imaging revealed characteristic increased T2-weighted signal in the dorsal pons and spinal cord. All 4 patients with pulmonary edema (severe disease) demonstrated dorsal brainstem restricted diffusion (odds ratio, 2; 95% CI, 1-4; P = .001). Brainstem or motor dysfunction had resolved in 44 of 57 (77%) at 2 months and in 51 of 57 (90%) at 12 months. Focal paresis was evident in 23 of 57 (40%) at presentation and was the most common persisting clinical and functional problem at 12 months (observed in 5 of 6 patients), with 1 patient also requiring invasive ventilation. Patients initially seen with acute flaccid paralysis or pulmonary edema had significantly greater frequencies of motor dysfunction at follow-up compared with patients initially seen with other syndromes (odds ratio, 15; 95% CI, 3-79; P < .001). Enterovirus 71 may cause serious neurological disease in young patients. The distinct clinicoradiological syndromes, predominantly within the spinal cord and brainstem, enable rapid recognition within evolving outbreaks. Long-term functional neurological morbidity is associated with paresis linked to involvement of gray matter in the brainstem or spinal cord.

Dose-response analysis indicating time-dependent neurotoxicity caused by organic and inorganic mercury-Implications for toxic effects in the developing brain.

A latency period preceding neurotoxicity is a common characteristic in the dose-response relationship induced by organic mercury. Latency periods have typically been observed with genotoxicants in carcinogenesis, with cancer being manifested a long time after the initiating event. These observations indicate that even a very small dose may cause extensive adverse effects later in life, so the toxicity of the genotoxic compound is dose and time-dependent. In children, methylmercury exposure during pregnancy (in utero) has been associated with delays in reaching developmental milestones (e.g., age at first walking) and decreases in intelligence, increasing in severity with increasing exposure. Ethylmercury exposure from thimerosal in some vaccines has been associated, in some studies, with autism and other neurological disorders in children. In this paper, we have examined whether dose-response data from in vitro and in vivo organic mercury toxicity studies fit the Druckrey-Küpfmüller equation c·t(n)=constant (c=exposure concentration, t=latency period), first established for genotoxic carcinogens, and whether or not irreversible effects are enhanced by time of exposure (n≥1), or else toxic effects are dose-dependent while time has only minor influence on the adverse outcome (n<1). The mode of action underlying time-dependent toxicity is irreversible binding to critical receptors causing adverse and cumulative effects. The results indicate that the Druckrey-Küpfmüller equation describes well the dose-response characteristics of organic mercury induced neurotoxic effects. This amounts to a paradigm shift in chemical risk assessment of mercurial compounds and highlights that it is vital to perform toxicity testing geared to investigate time-dependent effects.

Optimization of nutritional correction treatment for neurological disorders in children

The paper gives the results of a study project at the Infant Neurology Department, which has shown the urgency of nutritional rehabilitation in children aged 3 months to 5 years with infantile cerebral paralysis. Thirty patients were followed up to study the causes of malnutrition, to assess and correct their nutritional status, and to show the efficiency of the measures implemented. A diet corrected by a nutritionist was combined with nonsurgical interventions, such as positioning, a decision on the transition to nasogastric tube feeding, and maternal work. The complementary foods were FrutoNyanya products as the latter are low-immunogenic, cause no allergic reactions, and may be used both in the feeding of high-risk group children and as ingredients of a therapeutic diet for patients with different diseases. This resulted in 305-g weight gain within 7-10 day of hospital stay in those whose underweight averaged 28%. The emotional status of the patients and their caregivers was improved by 2-3 scores on 5-point rating scale. There were improvements in their emotional tone (in 75%), chewing (in 28%), and swallowing (in 35%) and reductions in reflux episodes (in 19%) and stress in the caregivers (in 86%).

Exonic deletion of SLC9A9 in autism with epilepsy.

Genes encoding proteins critical for intracellular vesicular transport are an emerging area of importance for neurologists. In particular, proteins that create and maintain the correct compartmental pH, such as the endosomal Na(+)/H(+) exchangers (NHEs), have been implicated in a wide range of human diseases, including cardiovascular, inflammatory bowel, renal, and neurologic disorders, which demonstrates the critical cellular function of these proteins.(1-3) Two NHEs, NHE6 and NHE9, have been linked to neurologic disorders in children.(4) Pathologic variants in SLC9A6 encoding NHE6 cause an Angelman-like disorder called Christianson syndrome. Fewer variants have been described in SLC9A9 encoding NHE9, but individuals carrying these variants have been diagnosed with neurologic disorders ranging from autism to epilepsy to attention-deficit/hyperactivity disorder. The majority of described variants are missense, resulting in amino acid substitutions, making it difficult to determine their functional consequence.(4).

Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations.

Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late-onset cerebellar atrophy.

Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes.

Epilepsy is one of the most common neurological disorders in childhood. Epilepsy associated with global developmental delay and cognitive dysfunction is defined as epileptic encephalopathy. Certain inherited metabolic disorders presenting with epileptic encephalopathy can be treated with disease specific diet, vitamin, amino acid or cofactor supplementations. In those disorders, disease specific therapy is successful to achieve good seizure control and improve long-term neurodevelopmental outcome. For this reason, intractable epilepsy with global developmental delay or history of developmental regression warrants detailed metabolic investigations for the possibility of an underlying treatable inherited metabolic disorder, which should be undertaken as first line investigations. An underlying genetic etiology in epileptic encephalopathy has been supported by recent studies such as array comparative genomic hybridization, targeted next generation sequencing panels, whole exome and whole genome sequencing. These studies report a diagnostic yield up to 70%, depending on the applied genetic testing as well as number of patients enrolled. In patients with epileptic encephalopathy, a stepwise approach for diagnostic work-up will help to diagnose treatable inherited metabolic disorders quickly. Application of detailed genetic investigations such as targeted next generation sequencing as second line and whole exome sequencing as third line testing will diagnose underlying genetic disease which will help for genetic counseling as well as guide for prenatal diagnosis. Knowledge of underlying genetic cause will provide novel insights into the pathogenesis of epileptic encephalopathy and pave the ground towards the development of targeted neuroprotective treatment strategies to improve the health outcome of children with epileptic encephalopathy.

Patient Use of Complementary and Alternative Medicines in an Outpatient Pediatric Neurology Clinic

BackgroundThis article describes the use of complementary and alternative medicines in an outpatient pediatric neurology clinic, and assesses family attitudes toward the efficacy of complementary and alternative medicines versus prescription medications. Complementary and alternative medicine is an important element of the modern health care landscape. There is limited information about whether, and to what extent, families perceive its utility in childhood neurological disorders. Design/MethodsSurveys were distributed to 500 consecutive patients at a child neurology clinic in Rochester, Minnesota. Questions pertained to the child's diagnoses, use of complementary and alternative medicines, and the specific complementary and alternative medicine modalities that were used. Opinions were also gathered on the perceived efficacy of complementary and alternative medicines and prescription medications. Data were compared using χ2 or Fisher exact tests as indicated. ResultsA total of 484 surveys were returned, of which 327 were usable. Only 17.4% admitted to use of complementary and alternative medicine to treat neurological problems. However, in follow-up questioning, actually 41.6% of patients recognized that they were using one or more types of complementary and alternative medicines. Disorders associated with a statistically significant increased prevalence of complementary and alternative medicine use were headache (50.8% with headache used complementary and alternative medicine versus 35.7% without headache; P = 0.008, Fisher exact test), chronic fatigue (63.2% vs 38.8%; P = 0.005, Fisher exact test), and sleep disorders (77.1% vs 37.3%; P < 0.0001, Fisher exact test). ConclusionsA large proportion of pediatric neurology patients in our clinic are also using complementary and alternative medicine. Only 38.5% of these recognize themselves as using complementary and alternative medicine, underlining the need to inquire in-depth about its use. Patients who are less satisfied with their prescription medications are more likely to use complementary and alternative medicine, perhaps reflecting the less tractable nature of their disorders.

Quality of life of children with epilepsy (neuropsychiatric and social aspects)

Epilepsy is one of the most common neurological diseases in childhood and adolescence. It is on the third place in the structure of diseases of the nervous system. The social significance of this disease is determined by the highest percentage in disability of patients. Currently, many leading national and foreign epileptologists expresses the same opinion that the one of the most important purposes in helping patients with epilepsy is to improve their quality of life. Cognitive disorders play a leading role in disturbances of patients’ adaptation in the community, so their role can be more considerable in disability than seizures, thus impairing the quality of life. The most common cognitive disorders in patients with epilepsy include memory impairment, retarded intellectual development and attention deficit disorder. In recent years, a special interest is given to the introduction of neuropsychological methods in studying the brain organization of higher mental functions in children with epilepsy. Analysis of neuropsychological features and characteristics of cognitive disorders with various forms of idiopathic epilepsy is of particular interest.

Chapter 26 - Autoimmune neurologic disorders in children

Autoimmune neurologic diseases are of major clinical importance in children. Antibody-mediated diseases of the central nervous system are now increasingly recognized in childhood, where the antibodies bind to cell surface epitopes on neuronal or glial proteins, and the patients demonstrate either focal or more generalized clinical signs depending on the extent of brain regions targeted by the antibodies. The antibodies are directed towards ion channels, receptors, and membrane proteins; and the diseases include limbic encephalitis and N-methyl-d-aspartate receptor-antibody encephalitis, among many others. Additionally there are conditions where the wider immune system is implicated. Neurologic features like seizures, movement disorders, autonomic dysfunction, and sleep disorders, with neuroimaging and electrophysiologic features, may indicate a specific antibody-mediated or immune disorder. Often, phenotypic overlap is observed between these conditions, and phenotypic variation seen in children with the same condition. Nevertheless, many patients benefit from immunotherapy with substantial improvement, although huge efforts are still required to optimize the outcome for many patients. In many patients no antibodies have yet been identified, even though they respond to immunotherapies. Here we describe the known antibodies and associated diseases, discuss conditions that are thought to be immune-mediated but have no known immunologic biomarker, and provide guidelines for the investigation and classification of these disorders.

HMGB1-TLR Signaling in Rasmussens Encephalitis

Rasmussen’s encephalitis is neurological disorder of childhood characterized by uni-hemispheric inflammation, intractable focal epilepsy and progressive cognitive and neurological deficits. Currently, the pathogenesis of Rasmussen’s encephalitis is still enigmatic and hemispherectomy is the only effective method to control the seizures associated with Rasmussen’s encephalitis. Recently data indicated that intrinsic activation of endogenous proinflammation high-mobility group box-1 (HMGB1) and Toll-like receptor (TLR) is involved in the development of Rasmussen’s encephalitis. Activation of HMGB1-TLR signaling plays a critical role in brain inflammation, development of epilepsy and cognitive dysfunction. Targeted therapy on HMGB1-TLR signaling might be a novel strategy with anti-inflammation, anti-epilepsy as well as improving cognitive dysfunction associated with epilepsy in Rasmussen’s encephalitis.

Attention deficit hyperactivity disorder in children with primary monosymptomatic nocturnal enuresis: A case-control study.

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood neurological disorders. The aim of this study was to investigate ADHD in children with primary monosymptomatic nocturnal enuresis (PMNE) and compare it with healthy children. A total of 100 five to 16-year-old children with PMNE and 100 healthy children without NE were included in this case-control study as the cases and control groups, respectively. Subjects were selected from children who were referred to the pediatric clinic of the Amir Kabir Hospital of Arak, Iran, based on inclusion and exclusion criteria. ADHD was diagnosed by Conner's Parent Rating Scale-48 and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria and was confirmed by consultation with a psychiatrist. Data were analyzed by binomial test using SPSS18. ADHD inattentive type was observed in 16 cases (16%) with PMNE and five controls (5%) (P=0.01). Despite these significant differences in the case and control groups, 25 (25%) and 16 (16%) children were affected by ADHD hyperactive-impulsive type (P=0.08) and 15 (15%) and 16 (16%) children were affected by ADHD mixed type (P=0.84), respectively. ADHD inattentive type in children with PMNE was significantly more common than that in healthy children. The observed correlation between ADHD inattentive type and PMNE makes psychological counseling mandatory in children with PMNE.

Analysis of the influence of various factors on the course of neurological disorders in children with spinal cord injury

Background. The study of the influence of various factors on the course of recovery of neurological disorders in children with spinal cord injuries is an important and relevant problem. The main causes of thoracic and lumbar injuries of the spine in children are road accidents and catatraumas. Anatomical and physiological features of the spine and spinal cord in children have a significant influence on the nature of spinal cord injury, clinical manifestations of the injury, and method of treatment. The degree of spinal canal deformity at the level of the damaged segment is directly proportional to the severity of the neurological disorder. The time between injury to when surgery is performed will strongly influence the nature and course of recovery of motor functions. Aim. To assess the influence of different factors in pediatric patients with complicated injuries of the spine at the thoracic and thoracolumbar levels on the recovery of neurological disorders. Materials and methods. The analysis of results of the surgical treatment of 36 children (24 boys and 12 girls) aged 3-17 years with damage to the spine and spinal cord in the thoracic spine and thoracolumbar junction, accompanied with neurological deficit in the form of central or peripheral paresis and paralysis, was performed. All patients underwent surgical intervention depending on the type and extent of damage. Clinical methods (i.e., detailed neurological examination) as well as X-ray, CT, and MRI were used as diagnostic methods. Results. The study revealed that the most severe damage concerning neurological disorders in children with spinal cord injury occurs in the thoracic spine. The extent of neurological changes depends not only on the level of damage to the spinal column but also on the magnitude of spinal canal stenosis. Surgery performed in the first hours of the injury leads to a more rapid and full recovery of the neurological deficit. Conclusion. Therefore, this study found that several factors influence the recovery of neurological disorders in children with spinal cord injury: timing of surgery, localization of the injury, spinal stenosis, the nature of lesions of the spinal cord, and the elements involved.