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Neonatal electroencephalography (EEG) recordings have routinely been performed for more than half a century. ‘‘Old’’ technical difficulties are no longer of concern with the advent of modern digital technology. Still, many ‘‘old’’ issues are at debate: characterization of neonatal EEG features, identification of EEG waveforms with potential clinical correlates, the role of neonatal EEG in prediction of neurodevelopmental outcome, and use of new devices. In the past decades, neonatal EEG and emerging issues’ literature has greatly expanded. In this review, the authors have summarized some of these issues to increase the availability of the information for both clinical and research purposes. They propose an up-to-date concentrated practical approach to this rapidly expanding ‘‘subfield’’ of neonatal neurology.

Aim: To report on a different clinical course of pandemic influenza A (H1N1) infection among children who were neurologically impaired before the acute onset of the disease, in comparison with children who were neurologically intact. Methods: In a period of 6 months, six children with neurological complications associated with pandemic A (H1N1) infection were identified in a single institution paediatric emergency room. The children suffered from seizures or altered mental status during pandemic A (H1N1) infection. All children underwent extensive clinical and laboratory assessment. Three children were neurologically impaired before the acute onset of the H1N1 infection. The other three were neurologically intact before the acute viral infection. Results: In all six patients, pandemic influenza A (H1N1) viral RNA was detected in nasopharyngeal specimens but none in the cerebrospinal fluid. Five children fully recovered or returned to baseline at discharge. The clinical course of the disease and recovery were different between the children who were neurologically impaired before the acute viral infection and those who were neurologically intact. Conclusions: It is possible that children with various neurological conditions are in a higher risk to develop further neurological complications during pandemic influenza A (H1N1) infection.

Mitochondria are probably a target in antiepileptic drug—induced hepatotoxicity accompanied by oxidative stress. Most studies discuss valproic acid. The information regarding other antiepileptic drugs is scarce. Most studies used in vitro methods and animal models. In this study, the authors have investigated the effect of antiepileptic drugs, other than valproic acid, on the oxidative phosphorylation process in children, by measuring mitochondrial adenosine triphosphate (ATP) production and the enzymatic activities of respiratory chain complexes II-IV in peripheral white blood cells. The results demonstrate that several antiepileptic drugs can affect the mitochondrial oxidative phosphorylation. The authors have concluded that the effect of antiepileptic drugs on the mitochondria is not limited only to valproic acid, but can affect different mitochondrial pathways and can be performed in humans by relatively simple methods, using small samples of peripheral white blood cells.

There is a pressing need for consistent, evidence-based guidelines in the management of neonatal seizures by pediatric neurologists and neonatologists. Israeli pediatric neurologists and neonatologists completed a 20-item, self-administered questionnaire on choices of antiepileptic drugs, treatment of intractable neonatal seizures (unremitting seizures after 3 medications), treatment duration, and recommended workup. The responding 36/55 (65%) neurologists and 66/112 (59%) neonatologists made similar antiepileptic drug choices (phenobarbital as first line, phenytoin as second line, and benzodiazepines as third line). Antiepileptic treatment duration was similar for both groups, but varied considerably within them (range, 1-52 weeks). Neurologists tended to recommend longer treatment for seizures secondary to asphyxia or hemorrhage. Neurologists and neonatologists recommended different antiepileptic drugs for intractable neonatal seizures: valproic acid and topiramate by neurologists, vs lidocaine and benzodiazepines by neonatologists (P = 0.0023). Fewer neurologists recommended continuous electroencephalography monitoring after asphyxia than neonatologists (40% vs 70.5%, P = 0.013). These responses reflect both similarities and inconsistencies of the two groups in diagnosing and treating neonatal seizures. Our findings call for controlled clinical trials to establish protocols for (1) diagnosing neonatal seizures, (2) studying the efficacy and safety of new-generation antiepileptic drugs, and (3) determining optimal duration of drug administration.

Attitudes toward pharmacological treatment may be a major factor contributing to adherence to such treatment. In the current study, attitudes toward methylphenidate treatment among 50 children diagnosed with attention-deficit hyperactivity disorder (ADHD) and their parents were assessed. Authors of this study have found that the study population is concerned and suspicious toward methylphenidate treatment. Most participants were exposed to negative information even before treatment initiation, which caused many participants to consult other sources and postpone the treatment initiation. Although experiencing methylphenidate as safe and effective (after 23.5 months of treatment), the leading cause of negative attitudes is the concern regarding long-term effects. The single most effective factor regarding the attitude toward methylphenidate treatment is the neurologist's explanation. It is concluded that the pediatric neurologist has a crucial role in affecting attitudes of children and parents toward methylphenidate treatment.

Decreased attention span, hyperactivity, distractibility, and impulsivity are sensitive but non-specific brain functions and behavioral patterns. These expressions of altered functioning should be acknowledged as non-specific, rather than trying to fit them into existing diagnoses. These abnormalities should be viewed in terms of underlying developmental processes and not as components of discrete non-overlapping disorders. The tendency to squeeze a group of symptoms into a diagnostic entity has the potential to lead to a non-accurate diagnosis, a less than successful treatment plan, and has the potential to be of little prognostic value (Berger and Nevo, 2011). The developmental approach can provide predictions as to how characteristics associated with attention change over time, and how multiple risk and protective factors influence these temporal changes. It also has the potential to more readily anticipate associated co-morbid features and disorders (Berger and Nevo, 2011; Visser et al., 2014). Attention Deficit Hyperactivity Disorder (ADHD) seems to be considerably more common than other diagnoses among “double-diagnoses” given to children with developmental dysfunctions. Yet the exact prevalence, neurobiological mechanisms, genetic and epigenetic modifications, diagnostic difficulties and treatment methods have not been clearly identified or quantified. During the last years, the number of publications in this field has grown substantially, but, in part, due to the wide range of interested professionals, these studies have been published in a wide range of journals, sometimes missing some of their “target” populations.

OBJECTIVE. Our goal was to determine whether the third ventricle is significantly enlarged among neonates with trisomy 21, compared with infants without clinical signs of trisomy 21. This enlargement might be related to hypoplasia of the structures surrounding the third ventricle. These structures participate in cognitive development, and hypoplasia in this area may be responsible for some of the unique cognitive abnormalities observed among children with trisomy 21. METHODS. Measurements of routine head sonographic scans of 57 term infants with trisomy 21 who were born between January 2000 and August 2005 were performed within 7 days after birth and were compared with measurements of head sonographic scans of 21 randomly selected, healthy, term infants without trisomy 21. RESULTS. Although the 2 groups were of similar gestational ages, infants with trisomy 21 were generally smaller, with smaller head circumferences. Despite the smaller overall head circumference, both the width and length of the third ventricle were enlarged among the infants with trisomy 21. Vertical measurements of the lateral ventricles were similar for the 2 groups. CONCLUSIONS. The third ventricle is an important diencephalic space. In our neonatal population, we did show significant enlargement of both the length and width of the third ventricle among the infants with trisomy 21, compared with the control group of unaffected newborns. We suspect that the unique neuropsychological development and cognitive dysfunction associated with trisomy 21 and the enlargement of the third ventricle in the neonatal period might be related.

To assess the efficacy, safety, and tolerability of topiramate in infants younger than 24 months of age, we conducted an open-label, multicenter chart review study of infants who received topiramate. Twenty-eight patients were evaluated. All had refractory epilepsy. The mean age of seizure onset was 3.8 months (range 0—10 months). Refractory infantile spasms were the most common epilepsy syndrome. Among infants without infantile spasms, complex partial seizures were the prominent seizure type in eight, followed by simple partial seizures in six. Topiramate was prescribed as add-on therapy in 25 cases and as monotherapy in 3 cases. Seven of the eight infantile spasms cases improved on topiramate therapy, attaining topiramate monotherapy in three infants. Half of the infants with other seizure types responded to topiramate. The average treatment duration among topiramate responders was 11 months. Topiramate was prescribed after a mean of 3.3 antiepilepsy drugs had been used in these infants. In no case was topiramate the first prescribed antiepilepsy drug. Adverse effects occurred only in five patients, leading to topiramate discontinuation in two patients. Topiramate was efficacious and well tolerated in infants younger than 24 months of age with refractory epilepsy. Prospective data are needed to corroborate this observation. ( J Child Neurol 2003;18:258—262).

Perinatal brain damage is one of the leading causes of life long disability. This damage could be hypoxic-ischemic, inflammatory or both.This mini-review discusses different interventions aiming at minimizing inflammatory processes in the neonatal brain, both before and after insult. Current options of anti-inflammatory measures for neonates remain quite limited. We describe current anti-inflammatory intervention strategies such as avoiding perinatal infection and inflammation, and reducing exposure to inflammatory processes. We describe the known effects of anti-inflammatory drugs such as steroids, antibiotics, and indomethacin, and the possible anti-inflammatory role of other substances such as IL-1receptor antagonists, erythropoietin, caffeine, estradiol, insulin like growth factor and melatonin as well as endogenous protectors, and genetic regulation of inflammation. If successful, these may decrease mortality and long term morbidity among term and preterm infants.

Attention Deficit/Hyperactivity Disorder (ADHD) is considered as a model of neuro-developmental cognitive function. ADHD research previously studied mainly males. A major biological distinction between the genders is the presence of a menstrual cycle, which is associated with variations in sex steroid hormone levels. There is a growing body of literature showing that sex hormones have the ability to regulate intracellular signaling systems that are thought to be abnormal in ADHD. Thus, it is conceivable to believe that this functional interaction between sex hormones and molecules involved with synaptic plasticity and neurotransmitter systems may be associated with some of the clinical characteristics of women with ADHD. In spite of the impact of sex hormones on major neurotransmitter systems of the brain in a variety of clinical settings, the menstrual cycle is usually entered to statistical analyses as a nuisance or controlled for by only testing male samples. Evaluation of brain structure, function and chemistry over the course of the menstrual cycle as well as across the lifespan of women (premenarche, puberty, cycling period, premenopause, postmenopause) is critical to understanding sex differences in both normal and aberrant mental function and behavior. The studies of ADHD in females suggest confusing and non-consistent conclusions. None of these studies examined the possible relationship between phase of the menstrual cycle, sex hormones levels and ADHD symptoms. The menstrual cycle should therefore be taken into consideration in future studies in the neurocognitive field since it offers a unique opportunity to understand whether and how subtle fluctuations of sex hormones and specific combinations of sex hormones influence neuronal circuits implicated in the cognitive regulation of emotional processing. The investigation of biological models involving the role of estrogen, progesterone, and other sex steroids has the potential to generate new and improved diagnostic and treatment strategies that could change the course of cognitive-behavioral disorders such as ADHD.

Four siblings presented with congenital diarrhea and various endocrinopathies. Exome sequencing and homozygosity mapping identified five regions, comprising 337 protein-coding genes that were shared by three affected siblings. Exome sequencing identified a novel homozygous N309K mutation in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, encoding the neuroendocrine convertase 1 precursor (PC1/3) which was recently reported as a cause of Congenital Diarrhea Disorder (CDD). The PCSK1 mutation affected the oxyanion hole transition state-stabilizing amino acid within the active site, which is critical for appropriate proprotein maturation and enzyme activity. Unexpectedly, the N309K mutant protein exhibited normal, though slowed, prodomain removal and was secreted from both HEK293 and Neuro2A cells. However, the secreted enzyme showed no catalytic activity, and was not processed into the 66 kDa form. We conclude that the N309K enzyme is able to cleave its own propeptide but is catalytically inert against in trans substrates, and that this variant accounts for the enteric and systemic endocrinopathies seen in this large consanguineous kindred.

Background Hashimoto encephalopathy (HE) is a rare autoimmune disorder. It is defined as a 'corticosteroid-responsive encephalopathy associated with thyroiditis'. Clinical observation We describe a boy who suffered from HE, responded only to intravenous immunoglobulin therapy. This is the first case report of immunoglobulin therapy in paediatric HE. Conclusion After review of the literature, we recommend that unexplained encephalopathy in children should lead to evaluation of thyroid autoantibody titres. Immunoglobulins should be considered.

The purpose of this article is to describe an unusual presentation of lamotrigine toxicity in an epileptic child treated on a lower than previously reported dosage. This is a case description of a 5-year-old epileptic girl on lamotrigine monotherapy, which caused toxicity. The child presented with ataxia, drowsiness, and acute confusion after ingesting 500 mg (25 mg/kg/d) in two 250-mg doses 12 hours apart. This was followed by vomiting and seizure exacerbation. Discontinuing lamotrigine, intravenous fluids and observation were the mainstays of therapy. Until now, the reported minimum dose of lamotrigine causing toxicity was 800 mg. In this patient, toxic manifestation occurred after the initial 250 mg. This case report demonstrates the low safety margin in children treated with lamotrigine.

While data from behavioral, neuropsychological, and brain studies suggested that Attention-Deficit/Hyperactivity Disorder (ADHD) is related to a developmental lag that reduces with age, other studies have proposed that ADHD represents a deviant brain function. The present study used a cross-sectional approach to examine whether ADHD children show a developmental delay in cognitive performance measured by continuous performance test (CPT). We thus, compared six age groups of ADHD children (N = 559) and their unaffected peers (N = 365), aged 6-11, in four parameters of MOXO-CPT performance: Attention, Timing, Hyperactivity and Impulsivity. Results have shown that despite improvement in CPT performance with age, ADHD children continued to demonstrate impaired performance as compared to controls. In most parameters, CPT performance of ADHD children matched that of 1-3 years younger normal controls, with a delay most prominent in older children. However, in the Hyperactivity parameter, ADHD children's performance resembled that of much younger healthy children, with almost no evidence for a developmental catch up. This study suggests that while some cognitive functions develop slower but normally, other functions (e.g., inhibitory control) show a different trajectory.

This study examined the effect of the incorporation of environmental distractors in computerized continuous performance test (CPT) on the ability of the test in distinguishing ADHD from non-ADHD children. It was hypothesized that children with ADHD would display more distractibility than controls while performing CPT as measured by omission errors in the presence of pure visual, pure auditory, and a combination of visual and auditory distracting stimuli. Participants were 663 children aged 7-12 years, of them 345 diagnosed with ADHD and 318 without ADHD. Results showed that ADHD children demonstrated more omission errors than their healthy peers in all CPT conditions (no distractors, pure visual or auditory distractors and combined distractors). However, ADHD and non- ADHD children differed in their reaction to distracting stimuli; while all types of distracting stimuli increased the rate of omission errors in ADHD children, only combined visual and auditory distractors increased it in non-ADHD children. Given the low ecological validity of many CPT, these findings suggest that incorporating distractors in CPT improves the ability to distinguish ADHD from non-ADHD children.

To assess the suitability of lymphocytes for patient diagnosis and carrier detection of lipoamide dehydrogenase deficiency, the activity of lipoamide dehydrogenase was determined in lymphocytes of six patients, seven obligate heterozygotes and 32 healthy controls. In healthy controls, lipoamide dehydrogenase activity was 80.7 +/- 23.6 nmol/min/mg protein, in obligate heterozygotes it was 36.0 +/- 12.1 nmol/min/mg protein and in the patients it was 13.3 +/- 5.1 nmol/min/mg protein. For the purpose of standardization, the results were also calculated as lipoamide dehydrogenase/citrate synthase activity ratio. The activity of lipoamide dehydrogenase and the lipoamide dehydrogenase/citrate synthase ratio differed significantly between the three groups (P < 0.005). We conclude that lymphocytes are suitable for the diagnosis of lipoamide dehydrogenase deficiency and for carrier detection.

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder that is considered one of the most common neurobehavioral disorders. The symptoms of ADHD should be cast, not as static or fixed neurobehavioral deficits, but rather in terms of underlying developmental processes. Targeting attentional disorders early in life can bring about fundamental alterations in the pathogenesis of ADHD, and thus prevent or moderate the course of the disorder. The developmental approach can enable predictions concerning characteristics of ADHD that develop over time and inform us about multiple risk and protective factors that transact to impact its development, as well as the development of a broad range of associated co-morbid features. In this review, we describe the complex factors that predict and mediate the developmental course of ADHD, providing early cues for ADHD diagnosis and intervention in young children that will optimize outcome.

The molecular etiology of primary intractable epilepsy in infancy is largely unknown. We studied a nonconsanguineous Moroccan-Jewish family, where three of their seven children presented with intractable seizures and died at 18-36 months.Homozygous regions were searched using 250 K DNA single nucleotide polymorphism (SNP) array. The sequence of 50 Mb exome of a single patient was determined using SOLiD 5500XL deep sequencing analyzer.A single homozygous 11.3 Mb genomic region on chromosome 6 was linked to the disease in this family. This region contained 110 genes encoding a total of 1,000 exons. Whole exome sequencing revealed a single pathogenic homozygous variant within the critical region. The mutation, Phe229Leu in the EFHC1 gene was previously shown, in a carrier state, to be associated with juvenile myoclonic epilepsy.Although heterozygosity for the Phe229Leu mutation is known to be associated with a relatively benign form of epilepsy in adolescence; homozygosity for the same mutation is associated with lethal epilepsy of infancy. Given the considerable carrier rate of this mutation worldwide, the sequence of the EFHC1 gene should be determined in all patients with primary intractable epilepsy in infancy.

To report on a different clinical course of pandemic influenza A (H1N1) infection among children who were neurologically impaired before the acute onset of the disease, in comparison with children who were neurologically intact.In a period of 6 months, six children with neurological complications associated with pandemic A (H1N1) infection were identified in a single institution paediatric emergency room. The children suffered from seizures or altered mental status during pandemic A (H1N1) infection. All children underwent extensive clinical and laboratory assessment. Three children were neurologically impaired before the acute onset of the H1N1 infection. The other three were neurologically intact before the acute viral infection.In all six patients, pandemic influenza A (H1N1) viral RNA was detected in nasopharyngeal specimens but none in the cerebrospinal fluid. Five children fully recovered or returned to baseline at discharge. The clinical course of the disease and recovery were different between the children who were neurologically impaired before the acute viral infection and those who were neurologically intact.It is possible that children with various neurological conditions are in a higher risk to develop further neurological complications during pandemic influenza A (H1N1) infection.

Attention-Deficit/Hyperactivity Disorder (ADHD) is among the most prevalent chronic health disorders affecting school-age children [1]. The disorder attracts a lot of controversies [2,3]. One of the main reasons for criticism is the diagnostic process, which in some aspects is subjective and can be relatively easily biased [4]. There is a discrepancy between the expanding scientific biological, genetic and imaging knowledge and the clinical based procedure of ADHD diagnosis [4]. In the absence of available biological markers that would support diagnosis on a routine clinical visit, professionals are asked to continue and use clinical interview, extensive history taking, parent-teacher rating scales, review of psycho-educational test data, and direct observation [4,5]. Shortcomings associated with standard clinical approaches suggest an increasing need to consider complementary strategies for determining diagnostic standing and assessing treatment outcome.

An association between overweight and attention-deficit/hyperactivity disorder (ADHD) in children was previously suggested. We examined the prevalence of overweight, anthropometric changes, and the effect of methylphenidate treatment in 275 children with ADHD without neurological comorbidities and in controls. Data were extracted from medical charts, for up to 17 months of follow-up. Height, weight, body mass index, and their z scores did not differ between the ADHD and control groups. Prevalence of overweight and obesity was lower in the ADHD group compared with controls (19% vs 35%, P = .02, and 7% vs 16%, P = .05, respectively). During a follow-up of up to 17 months, no significant changes in height or body mass index z scores were found, including in a subgroup of overweight children. We conclude that compared with local controls, children with ADHD have rates of overweight and obesity that are lower, but that are similar to national estimates. Methylphenidate treatment did not significantly affect height, weight, or overweight status.

Objectives This study aims to detect seizures by amplitude-integrated electroencephalography (EEG) (aEEG) as compared with conventional EEG (cEEG) by clinicians with different levels of expertise. Methods Simultaneous 10 min aEEG/cEEG recordings were time-locked and assessed for seizure activity. aEEG was assessed by a neonatologist, a fellow and a medical student and cEEG by two child neurologists and a neonatologist. Results A total of 265 paired epochs from 38 simultaneous recording were assessed. Forty-one seizure episodes were diagnosed in 31 epochs in the cEEG recordings of 10 infants. Sensitivity and specificity ranged from 68% to 84% and from 71% to 84%, respectively, per detection of epochs with seizures and from 71% to 84% and from 36% to 96% per detection of individual seizures. No agreement was found between the observations of the student, and those of the fellow or neonatologist. Substantial agreement was found between the fellow and neonatologist. Before cEEG was commenced, seizures were detected by aEEG in 22 infants. Conclusions aEEG has high sensitivity and specificity in the hands of experienced users. Inexperienced new users may have a high rate of misdiagnosed seizures. Early recording of high-risk infants can help in the early diagnosis and treatment of seizures. Significance Diagnosis and treatment of seizures in aEEG should be carried out by experienced users and should be supplemented with cEEG when available.

Edwardsiella tarda, a gram-negative bacterium, is a rare pathogen in the neonatal period. We present a term newborn that developed E. tarda septicemia following maternal amnionitis. The severe neurological outcome in this case, as well as in all other reported cases, highlights the need for meticulous neurological evaluation in neonates presenting with E. tarda septicemia even in the absence of bona fide meningitis.

Birth order is considered one of the most influential environmental factors in child development, affecting cognitive abilities and behavioral traits. This study investigates the effect of birth order in relation to attention-deficit hyperactivity disorder (ADHD), the most common neuro-behavioral disorder of childhood. The study describes birth order of 598 children aged 6 to 18 years diagnosed due to attention-deficit hyperactivity disorder. The cohort contains relatively large size families because 47.1% of the participants were born in families of more than 4 children. The results show no statistically significant differences in birth order of children among all families. We conclude that the chances of first, middle, or later born children, as well as single children, to suffer from attention-deficit hyperactivity disorder are almost equal. This study provides evidence that birth order has no effect in relation to attention-deficit hyperactivity disorder.

Consultation regarding isolated fetal microcephaly is especially difficult in a genetically heterogeneous population, as one of the factors associated with head circumference difference is ethnicity. The study presents four women referred to the neuro-fetal clinic for isolated fetal microcephaly. All fetuses had normal chromosomes, no structural abnormalities, or evidence of intrauterine infection or intoxication. Their head circumference measurements were 2 to 3 standard deviations below average for age on repeat ultrasound and fetal magnetic resonance imaging. Striking differences in chart placements were found between different professionals using different charts. In all children, measured head circumference after birth/termination was within normal limits. This study suggests that national charts should be built measuring fetal size adjusted for ethnicity and based on a genetically heterogeneous population. The charts should be customized between different professionals assessing prenatal and postnatal head circumference.

Myelination is a complex, developmentally regulated process whereby myelin proteins and lipids are coordinately expressed by myelinating glial cells. Homozygosity mapping in nine patients with childhood onset spasticity, dystonia, cognitive dysfunction, and periventricular white matter disease revealed inactivating mutations in the FA2H gene. FA2H encodes the enzyme fatty acid 2-hydroxylase that catalyzes the 2-hydroxylation of myelin galactolipids, galactosylceramide, and its sulfated form, sulfatide. To our knowledge, this is the first identified deficiency of a lipid component of myelin and the clinical phenotype underscores the importance of the 2-hydroxylation of galactolipids for myelin maturation. In patients with autosomal-recessive unclassified leukodystrophy or complex spastic paraparesis, sequence analysis of the FA2H gene is warranted.

Prematurity is a major cause of cerebral palsy (CP). CP in preterm infants usually results from damage to the periventricular white matter, known as periventricular leukomalacia (PVL). The pathogenesis of PVL is controversial, with leading models suggesting either ischemic etiology or infection and inflammation as the root cause for the disease. Advances in understanding the biology of PVL may result in clinical interventions that reduce the burden of CP.

Attention deficit hyperactivity disorder (ADHD) is a developmental neuropsychiatric disorder characterized by inappropriate levels of inattention, impulsivity and hyperactivity. The cause of ADHD is unknown, but may involve both genetic and environmental factors. It has been suggested that exposure to inflammation in infancy may increase the risk for ADHD in later life. Familial Mediterranean Fever (FMF) is the most common inherited autoinflammatory disorder. In many FMF patients the inflammation persists in attack-free periods. The prevalence of ADHD among FMF patients has not been studied previously.

Patients with Cystic fibrosis (CF) need daily treatments to control the disease, which requires time, energy, and persistence. One possible barrier to adherence may be co-morbidity with Attention deficit hyperactivity disorder (ADHD), which has a prevalence of 7% in the general population. ADHD is associated with functional impairment in multiple settings including self-care. Increased inflammatory marker levels were detected in ADHD-patients suggesting a probable association with chronic inflammatory illnesses. It is believed that patients who suffer from comorbid ADHD symptomatology "on top" of chronic diseases may experience greater difficulty in controlling their primary disease. Few studies have analyzed the influence of ADHD in CF patients. Aims To determine the rate and characteristics of ADHD in patients with CF. Methods 122 patients with CF >6 years from the Hadassah, Schneider and Rambam CF centers participated in this cross-sectional study. Patients/parents completed the DSM-5 ADHD questionnaire and patients performed the online d-CPT MOXO analysis. Results 55/122 patients (45%) showed characteristics that may be compatible with ADHD. 20/122 (16%) matched all DSM's criteria, whereas 35/122 (29%) fulfilled only part of the criteria with pathologic results seen in the MOXO analysis requiring further evaluation by a neurologist. Conclusions The occurrence of ADHD in patients with CF is higher than expected in the general population. The specific characteristics of this connection might be related also to chronic inflammatory processes. Early diagnosis and treatment of ADHD might improve quality of life, prognosis and outcome in patients with CF.

Objectives: To describe the clinical and biochemical findings in 3 unrelated patients of Mediterranean origin suffering from aromatic L-amino acid decarboxylase (AADC) deficiency. No detectable mutation in the 5'-UTR and CSD of the AADC gene was found in one male patient. Methods: We describe 3 unrelated children (2F, 1M) who presented with severe developmental delay, hypotonia, hypokinesia, oculogyric crises, autonomic dysfunction and diurnal fluctuation. In 2 patients recurrent episodes of profuse sweating were the prominent autonomic symptoms. Results: All patients had marked reduction of HVA and 5HIAA level in CSF. The AADC activity was severely decreased in all patients, but no mutation was identified in the AADC gene CDS in the male patient. Molecular genetic analysis results of the 2 female patients are pending. None responded to treatment regimens including MAO inhibitors, dopamine agonists, melatonin and Vitamin B6. Conclusion: The clinical and biochemical findings of these 3 patients are similar to previously described data, but the poor response to treatment without gender preferences is unique. Moreover, the lack of detectable mutation in the AADC gene in the one investigated patient suggests a heterogeneous molecular background in AADC deficiency. Further genetic investigation in the 3 patients and their extended families is underway.

During the last decade we have witnessed a sharp rise in the number of premature labors followed by an increase in the survival rate of premature babies. Therefore, there is an increase in the general morbidity in the premature infant population, especially in the long term morbidity. Very low birth weight infants suffer from severe disabilities, but we found that even if they are healthy as a group, they suffer from a larger proportion of developmental difficulties in comparison to the general population. Their academic, social and behavioral achievements are lower as a group than full term AGA infants. The source of the developmental risk factors is both biological and environmental in origin. It is hypothesized that the source of these risk factors is at least partially due to differences in the development of specific brain areas such as the hippocampus. Since premature infants and especially very low birth weight infants suffer from developmental risks, and since early intervention can alter their development, it is imperative that these infants should be evaluated, followed-up and treated as soon as possible, starting from the hospital discharge through their childhood.

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.

Group B streptococcus (GBS) meningitis is one of the most serious infections in the neonatal period. We wish to report a case of transverse myelitis following early onset form of GBS meningitis. The diagnosis and the clinical approach will be discussed.

Lidocaine (a sodium channel blocker) serves as an antiepilepsy drug in neonates. We present a neonate with a seizure disorder who acutely developed pupillary mydriasis secondary to lidocaine overdose. We suggest adding this side effect to the list of untoward effects of lidocaine and to the differential diagnosis of fixed dilated pupils in neonates treated with lidocaine. ( J Child Neurol 2002; 17:400-401).

Carnitine palmitoyl transferase (CPT) II deficiency is usually manifested around puberty by exercise induced myoglobinuria. Two Ashkenazi Jewish sibs with the rare antenatal form of CPTII deficiency are reported. On the 5th gestational month periventricular calcifications and markedly enlarged kidneys were found in both of them. The activity of CPTII in lymphocytes was undetectable and both sibs were homozygous for the 1237delAG mutation. Because of the serious consequences of homozygosity for this mutation, genotype determination of all Ashkenazi patients with the adolescent form of CPTII deficiency is warranted.

Three novel mutations (IVS8+3a → g, N219Y, and E414X) were identified in 6 unrelated patients with mut 0 methylmalonic aciduria. The presence of a wild-type along with rearranged fragments in homozygotes for the IVS8+3a → g mutation may contribute to their later age of onset (3–11 months of age). Nonetheless, delayed onset was not associated with better neurological outcome and prolonged survival. The large number of undiagnosed dead sibs in most families suggests that the disease is largely underdiagnosed in this region.

We studied 13 patients with lipoamide dehydrogenase (LAD) deficiency, originating from seven Ashkenazi Jewish families. Their disease was characterized by recurrent attacks of vomiting, abdominal pain, and encephalopathy accompanied by elevated liver transaminases, prolonged prothrombin time, and occasionally associated with lactic and ketoacidemia or with myoglobinuria. Two patients who presented neonatally suffered from residual neurological damage with attention deficit hyperactive disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or later suffered from exertional fatigue between decompensation episodes but were otherwise asymptomatic. Two patients died because of intractable metabolic acidosis and multi-organ failure. In all patients LAD activity was reduced to 8 to 21% of the control in muscle or lymphocytes. In four patients LAD protein in muscle was reduced to 20 to 60% of the control. Direct sequencing of the cDNA of the LAD gene showed that 12 of the 14 mutated alleles carried the G229C mutation and two carried an insertion mutation 105insA (Y35X). The patients who presented neonatally and had more severe sequelae were compound heterozygotes for the two mutations; patients who presented in early childhood or later were homozygous for the G229C mutation. Using an allele-specific oligonucleotide hybridization technique, nine heterozygotes for the G229C mutation were identified among 845 anonymous individuals of Ashkenazi Jewish origin disclosing a carrier rate of 1:94. Because of the significant morbidity associated with the disease, screening for the G229C mutation among Ashkenazi Jewish couples should be considered.

Corticosteroids continue to be used by many physicians to treat infants with bronchiolitis. The aim of this study was to examine the short-term and long-term efficacy of oral corticosteroid therapy when added to beta2-agonists in infants with mild to moderate bronchiolitis (defined as the first episode of wheezing associated with low grade fever, rhinitis, tachypnea, and increased respiratory effort in a previously healthy infant during the winter months). Infants with mild to moderate bronchiolitis, were randomly assigned to receive either oral prednisone (2 mg/kg/day) or placebo for 3 days. All patients received nebulized albuterol q.i.d. during this period. Upon admission and after 3 days of therapy, a clinical score was assigned based on respiratory rate, use of accessory muscle, and the presence of wheeze. Oxygen saturation (SaO2) was also measured. On day 7, we inquired as to the well-being of each child. Two years later, the development of chronic respiratory symptoms was assessed. Thirty-eight infants were enrolled in the study; 20 received prednisone and 18 received placebo. Both groups were similar in terms of age, duration of illness prior to enrollment, pretrial medication use, clinical severity of bronchiolitis, history of atopy, and family history of atopy. After 3 and 7 days of treatment, both groups showed similar clinical improvement and there were no statistically significant differences between the two groups in the clinical score or in the SaO2. No major side effects were observed. Two years later, 32% of the infants continued to suffer from chronic respiratory symptoms, with a similar prevalence in both groups. We conclude that a 3-day course of oral corticosteroids is of no benefit to infants with mild to moderate bronchiolitis who are also treated with an inhaled beta2-agonist.

Kingella kingae is a fastidious Gram-negative rod that since the 1980s has been appreciated as a cause of a variety of human infections, including bone and joint infections, bacteremia, and rarely endocarditis [2, 6, 7, 9]. K. kingae endocarditis is rare, and only a few cases occur in normal, native valves. We report a case of K. kingae endocarditis in a patient with hair–cartilage hypoplasia who had previously undergone bone marrow transplantation. The combination of these rare conditions is discussed.

We compared the effect of sex and attention-deficit-hyperactivity disorder (ADHD) subtyping in groups of females and males. One hundred and one females with ADHD (mean age 10y 4mo [SD 2y 8mo]; range 5y-18y) were classified according to subtype by Diagnostic and Statistical Manual of Mental Disorders (4th edn) criteria (inattentive [ADHD-I]; combined [ADHD-C]) and balanced by subtype to 101 males (mean age 10y 5mo [SD 2y 9mo]; range 5y 4mo-17y 6mo). All children underwent IQ and reading assessment, and 109 underwent the continuous performance task (Test Of Variables of Attention [TOVA]). Parents completed the Conners' Abbreviated Rating Scale (ABRS), the Child Behavior Checklist (CBCL), learning disability questionnaires, and reported use and efficacy of methylphenidate. Teachers completed the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale. Sex differences were found only on the CBCL; females were more impaired on the attention (p

On routine head sonography of babies with trisomy 21 (T21) we noticed that the third ventricle (3V) seemed to be larger than expected. Objective: To determine whether the size of the 3V, as observed on head ultrasound is statistically different in babies with and without T21. Methods: Measurements of routine head sonography of all term babies with T21 were done within seven days of birth and were compared to those of randomized term infants without T21. Studies were done with 7.5 probe through the anterior fontanel. Statistical significance was calculated by t test and defined by a p