bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Status of Treatments for Dyslexia: Critical Review
Authors: Alexander Ann W. , Slinger-Constant Anne-Marie
Published: January 2017

The acquisition of reading is a complex neurobiologic process. Identifying the most effective instruction and remedial intervention methods for children at risk of developing reading problems and for those who are already struggling is equally complex. This article aims to provide the clinician with a review of more current findings on the prevention and remediation of reading problems in children, along with an approach to considering the diagnosis and treatment of a child with dyslexia. The first part of the review describes interventions targeted at preventing reading difficulties in the at-risk younger child. The second part of the review discusses the efficacy of approaches to treat the older, reading-disabled child (“intervention studies”). Factors that impact the response to treatment are also discussed, as are neuroimaging studies that offer insight into how the brain responds to treatment interventions. With appropriate instruction, at-risk readers can become both accurate and fluent readers. In contrast, although intensive, evidence-based remedial interventions can markedly improve reading accuracy in older, reading-disabled children, they have been significantly less effective in closing the fluency gap. Owing to the dynamic course of language development and the changes in language demands over time, even after a child has demonstrated a substantial response to treatment interventions, his or her subsequent progress should be carefully tracked to ensure optimal progress toward the development of functional reading and written language skills. ( J Child Neurol 2004;19:744—758).
Using Our Current Understanding of Dyslexia to Support Early Identification and Intervention
Authors: Schatschneider Christopher , Torgesen Joseph K.
Published: January 2017

One of the major risk factors for reading disability is difficulty learning to read words in text in an accurate and fluent manner. This is apparent when a child at risk of dyslexia first starts to attempt to read. Dyslexic children struggle to grasp and automate the alphabetic principle (ie, they cannot “sound out” words or use phonemic decoding strategies) and therefore have difficulty deciphering unfamiliar words that they have not encountered before. Even though many of these words are part of the child's oral vocabulary, the child cannot recognize them in printed form. As a result, reading can be extremely laborious and time-consuming, fraught with errors, and altogether an unrewarding, aversive experience. To be an efficient reader, one must be able to rapidly and effortlessly recognize many words by sight, and for a child to acquire this facility requires multiple exposures to these words. The difficulty that dyslexic children have in developing reliable and efficient phonemic decoding ability makes the acquisition of a lexicon of sight words a much slower process than it is for the average reader. Several other factors can affect a child's ability to read, which are reviewed herein. However, early recognition and treatment of deficient phonologic awareness are an extremely important step in the prevention of a reading problem in the child who is at risk of dyslexia. ( J Child Neurol 2004;19:759—765).
Neuroimaging in Disorders of Social and Emotional Functioning: What Is the Question?
Authors: Herbert Martha R.
Published: January 2017

Social and emotional processing uses neural systems involving structures ranging from the brain stem to the associational cortex. Neuroimaging research has attempted to identify abnormalities in components of these systems that would underlie the behavioral abnormalities seen in disorders of social and emotional processing, notably autism spectrum disorders, the focus of this review. However, the findings have been variable. The most replicated anatomic finding (a tendency toward large brains) is not modular, and metabolic imaging and functional imaging (although showing substantial atypicality in activation) are not consistent regarding specific anatomic sites. Moreover, autism spectrum disorder demonstrates substantial heterogeneity on multiple levels. Here evidence is marshaled from a review of neuroimaging data to support the claim that abnormalities in social and emotional processing on the autism spectrum are a consequence of systems disruptions in which the behaviors are a final common pathway and the focal findings can be variable, downstream of other pathogenetic mechanisms, and downstream of more pervasive abnormalities. ( J Child Neurol 2004;19:772—784).
Prefrontal Executive Function Syndromes in Children
Authors: Powell Kristin B. , Voeller Kytja K. S.
Published: January 2017

“Executive function” is a term describing the processes required for conscious control of thought, emotion, and action that are central to the management of one's day-to-day life. Executive function is subserved by the prefrontal cortex and related subcortical structures. Disorders affecting the prefrontal cortex—subcortical system are numerous and heterogeneous, but contemporary research has begun to elucidate the mechanisms and consequences of dysfunction in various subsystems with increasing specificity. Prefrontal executive dysfunction results in impaired regulation of cognition, attention, behaviors, arousal, and emotion, all of which have serious and pervasive consequences for functioning across the life span. These executive function deficits are typically difficult to treat, ameliorate, or remediate and require sensitive handling by caretakers. Executive dysfunction can arise as a consequence of many different factors (metabolic, genetic, certain types of epilepsy, cerebral dysgenesis, prematurity, traumatic brain injury, hypoxia, and toxic exposure). The present review delineates the features of prefrontal executive function deficits in children and proposes a roadmap for their diagnosis, treatment, and management. ( J Child Neurol 2004;19:785—797).
Evidence of Cellular Immune Activation in Children With Opsoclonus-Myoclonus: Cerebrospinal Fluid Neopterin
Authors: Pranzatelli Michael R. , Hyland Keith , Tate Elizabeth D. , Arnold Lauren A. , Allison Tyler J. , Soori Gamini S.
Published: January 2017

To evaluate cellular immune activation in opsoclonus-myoclonus syndrome, we measured the inflammatory marker neopterin in the cerebrospinal fluid of 16 children with opsoclonus-myoclonus and neuroblastoma, 24 children with opsoclonus-myoclonus but no tumor, and 19 age-matched controls. The mean concentration in opsoclonus-myoclonus was 2.3-fold higher than in controls ( P = .008). Neopterin was greatly elevated in four of the most neurologically severe cases, up to 8.3-fold above the highest control level. Thirteen of the 40 children with opsoclonus-myoclonus but no controls had a neopterin concentration > 2 SD above the control mean ( P = .005). In this high neopterin subgroup, neurologic severity was significantly greater and the duration of neurologic symptoms was less. In 16 children re-examined on immunotherapy, including adrenocorticotropic hormone (ACTH) combination therapy, treatment was associated with a significant reduction in both neopterin and neurologic severity. Neopterin did not differ significantly between the tumor and non-tumor opsoclonus-myoclonus etiologies. No abnormalities of tetrahydrobiopterin were found. Although cerebrospinal fluid neopterin lacked the sensitivity to be a biomarker of disease activity in opsoclonus-myoclonus, elevated concentrations do support a role for T-cell activation and cell-mediated immunity in its pathophysiology. ( J Child Neurol 2004;19:919—924).
Seizures as a Predictor of Long-Term Neurodevelopmental Outcome in Survivors of Neonatal Extracorporeal Membrane Oxygenation (ECMO)
Authors: Parish Anjali P. , Bunyapen Chantrapa , Cohen Morris J. , Garrison Tara , Bhatia Jatinder
Published: January 2017

A longitudinal, prospective study was conducted to determine the long-term neurodevelopmental outcome in neonatal extracorporeal membrane oxygenation (ECMO) survivors with and without seizures. One hundred sixty-two ECMO survivors from March 1985 until November 1995 were eligible for follow-up. Sixty-four returned at preschool age (4—6 years). Thirty-nine infants did not experience neonatal seizures (group 1); however, 25 exhibited seizures before or during ECMO (group 2). Twelve infants referred for ECMO, but managed medically, served as a clinical comparison group (group 3). At school age (7—9 years), 32 ECMO children (16 with seizures) returned for neuropsychologic evaluation. The results indicated that the preschool seizure group (group 2) demonstrated a significantly lower mean IQ than group 1 or 3 ( P = .002). Furthermore, 56% of group 2 had IQ scores ≤ 84 (≥ 1 SD below the mean). Group 2 also exhibited significantly higher rates of cerebral palsy ( P ≤ .001) and speech-language disorder than group 1 or 3 ( P < .001). At school age, the seizure group continued to perform below average on intelligence testing, with 50% scoring ≤ 84 and 38% receiving special education. This study extends the previous findings that seizures associated with neonatal ECMO are a primary risk factor for neurodevelopmental sequelae and confirms the need for long-term follow-up to assist with academic programming. ( J Child Neurol 2004;19:930—934).
Retrospective Review of Modafinil Use for Cerebral Palsy
Authors: Hurst Daniel L. , Lajara-Nanson Walter A. , Dinakar Pradeep , Schiffer Randolph B.
Published: January 2017

A retrospective review was undertaken at Texas Tech University Health Sciences Center regarding the use of modafinil for the treatment of spasticity associated with cerebral palsy. Neurology clinic records were reviewed from January 1, 2000, until October 1, 2001. Thirty pediatric patients with cerebral palsy were identified who were treated empirically with modafinil during this time period. Twenty-three (76%) patients reported diminished spasticity with treatment, which was confirmed by physical examination; these patients had improved joint mobility. Seventeen (56%) patients continued treatment with modafinil by the end of the formal review period (September 30, 2001). Twenty-three percent (seven) of the patients stopped taking modafinil during the study owing to one of the following: decreased sleep time (four), decreased appetite (one), hyperactivity, and irritability (two). Thus, this retrospective review shows a reduction in spasticity from cerebral palsy, with only minor and reversible side effects noted from modafinil. A blinded, crossover study using modafinil for spastic cerebral palsy is planned. ( J Child Neurol 2004;19:948—951).
Gingival Enlargement in Children Treated With Antiepileptics
Authors: Tan Hüseyin , Gürbüz Taşkin , Dağsuyu Ilhan Metin
Published: January 2017

This study was conducted to determine the occurrence, severity, and risk factors of gingival enlargement in children treated with valproate and other nonvalproate antiepileptic drugs. A cross-sectional study was carried out in which data obtained from 68 epileptic children under treatment were compared with those from 50 controls. A structured questionnaire was used to collect data on patients' demographics, dental and oral hygiene practices, and medication history. Gingival enlargement, gingival index, plaque index, and probing depth were measured to assess periodontal health. The chi-square and Fisher exact tests were used in statistical analysis. In case of significance, a detailed chi-square analysis was carried out to determine the origin of the difference. Patients in both the valproate and nonvalproate groups showed significantly higher gingival enlargement, gingival index, plaque scores, and pocketing ( P < .001 and P < .01, respectively) than the control group. In the valproate group, the duration of the treatment had a significant effect on gingival enlargement ( P < .001) but not on gingival index, plaque index, and probing depth values ( P > .05). Toothbrushing was most frequent in the control group ( P = .000) and more frequent in the valproate group than the nonvalproate group ( P = .024). Our study showed significant differences regarding gingival enlargement in children treated with valproate. These findings illustrate that epileptic children on valproate are at risk of periodontal problems. ( J Child Neurol 2004; 19:958-963).
Childhood Mesial Temporal Sclerosis
Authors: Ng Yu-tze , McGregor Amy L. , Duane Dawn C. , Jahnke Heidi K. , Bird C. Roger , Wheless James W.
Published: January 2017

The prevalence and clinical characteristics of mesial temporal sclerosis have not been well studied in children. All brain magnetic resonance imaging (MRI) reports of children less than 14 years of age were reviewed from two tertiary institutions. A 52-month period from one institution and a 37-month period from the other were reviewed. All reports of definite or possible mesial temporal sclerosis were noted. These patients' MRIs were then reviewed to confirm the MRI diagnostic criteria of mesial temporal sclerosis. The charts of the patients who satisfied these criteria were reviewed in detail. Three thousand one hundred brain MRI reports were reviewed. Twenty-six reports of mesial temporal sclerosis were found. Twenty-four of the 26 films satisfied the criteria of mesial temporal sclerosis by MRI after the films were reviewed. The prevalence among all pediatric brain MRI studies was 0.77%. All patients had presented with seizures, that is, there were no "incidental" findings of mesial temporal sclerosis. Four patients had a history of febrile seizures. Mesial temporal sclerosis is an uncommon finding in children, but when it occurs, it is always associated with epilepsy. Asymptomatic mesial temporal sclerosis or mesial temporal sclerosis not associated with a seizure disorder did not occur in our series. Febrile seizures can occur in association with mesial temporal sclerosis presenting in childhood. (J Child Neurol 2006;21:512-517; DOI 10.23/7010.2006.00139).
Pontobulbar Palsy and Neurosensory Deafness (Brown-Vialetto-van Laere Syndrome) With Hyperintense Brainstem Nuclei on Magnetic Resonance Imaging: New Finding in Three Siblings
Authors: Koul Roshan , Jain Rajeev , Chacko Alexander , Alfutaisi Amna , Hashim Javad , Chacko Jacob
Published: January 2017

Three siblings (one boy and two girls) with Brown-Vialetto-van Laere syndrome are reported. A peculiar feature of onset with hearing loss in a patient with multiple cranial nerve palsies and a positive family history suggests this diagnosis. In our family, an autosomal recessive mode of inheritance was seen. In addition, we observed that early onset was associated with rapid deterioration and death. Optic nerve involvement and hyperintensity of the brainstem nuclei on magnetic resonance imaging (MRI) are two newfeaturesdescribedin this report.( J Child Neurol 2006;21:523—525; DOI 10.2310/7010.2006.00096).
Reversible Posterior Leukoencephalopathy and Adie's Pupil After Measles Vaccination
Authors: Aydøn Kursad , Elmas Sefika , Guzes Eylem Atølgan
Published: January 2017

Reversible posterior leukoencephalopathy syndrome is an increasingly recognized disorder with typical radiologic findings of bilateral gray- and white-matter abnormalities in the posterior regions of the cerebral hemispheres. The majority of patients with reversible posterior leukoencephalopathy syndrome are adults, and it is rare in children. Previously reported associations of reversible posterior leukoencephalopathy syndrome include hypertension, vasculitis, nephrotic syndrome, severe hypercalcemia, hemolytic uremic syndrome, eclampsia, renal failure, and use of immunosuppressive drugs. Adie's pupil is described as the presence of a large unilateral or bilateral tonic pupil related to virus infections or trauma. In this article, we describe a case of reversible posterior leukoencephalopathy and Adie's pupil association that occurred after measles vaccination. To our knowledge, this association has not been reported. ( J Child Neurol 2006;21:525—527; DOI 10.2310/7010.2006.00100).
Pilot Study of Positron Emission Tomography (PET) Brain Glucose Metabolism to Assess the Efficacy of Tongue and Body Acupuncture in Cerebral Palsy
Authors: Wong Virginia C.N. , Sun Jie-Guang , Yeung David W.C.
Published: January 2017

We aimed to assess the efficacy of tongue and body acupuncture with clinical function and brain glucose metabolism in children with a severe type of cerebral palsy. Four children were recruited. The motor function belonged to grade 5 of the Gross Motor Function Measure (ie, completely nonambulatory). Daily tongue and body acupuncture was applied for 5 days a week for 8 weeks. The Functional Independence Scale for Children (WeeFIM), Clinical Global Impression Scale (CGIS), and positron emission tomography of the brain with [18F]fluorodeoxyglucose (FDG) were performed at baseline and after acupuncture. None of the children had any significant change in the Functional Independence Scale for Children score, despite the fact that all mothers scored 3 on the Clinical Global Impression Scale (ie, 25% improvement) in overall function. The brain glucose metabolism, however, showed a > 10% increase in the frontal, parietal, temporal, and occipital cortices and cerebellum. Thus, a short course of tongue and body acupuncture was shown to increase brain glucose metabolism, despite lacking any clinical functional improvement seen within the 8-week course, possibly owing to the severity of the motor dysfunction and the short duration of treatment. The objective increase in brain glucose metabolism might serve as a surrogate marker for assessing the subclinical efficacy of an alternative treatment before any objective clinical improvement is evident. A larger-scale study for different degrees of severity of cerebral palsy and an impairment model should be undertaken to correlate clinical with neurometabolic change. ( J Child Neurol 2006;21:455—462;
Diagnosis and Molecular Characterization of Nonclassic Forms of Tay-Sachs Disease in Brazil
Authors: Rozenberg R. , Kok F. , Burin M.G. , Sá Miranda M.C. , Vasques C. , Henriques-Souza A.M.M. , Giugliani R. , Vainzof Mariz , Pereira L.V.
Published: January 2017

Molecular analysis of five Brazilian families, including eight patients presenting with nonclassic Tay-Sachs disease, was performed to identify frequent causative mutations and their correlation with clinical course. Three patients were affected by the B1 subacute variant and were shown to carry the R178H mutation (the DN allele), which is also common among Portuguese patients. Two of them were compound heterozygotes, whereas the third presented with the mutation in both alleles. Since Brazil was a Portuguese colony for over two centuries, common ancestry might be the probable explanation. The fourth patient presented with a juvenile phenotype and carries the R499H mutation, which has been reported only once worldwide and is associated with residual enzyme activity, responsible for a slower clinical course. The fifth family, of an Ashkenazi Jewish background, showed an extensive intrafamilial clinical variability among three affected sibs presenting with muscle atrophy, ataxia, and psychiatric symptoms. They were first diagnosed as having atypical spinal muscular atrophy and, subsequently, spinocerebellar ataxia, but, recently, the diagnosis of late-onset Tay-Sachs disease was confirmed based on reduced plasma hexosaminidase A activity and the G269S/InsTATC1278 genotype. It is therefore highly recommended to test patients with a similar clinical history for Tay-Sachs disease. In the same family, one first cousin committed suicide at the age of 24 years, presenting with a clinical phenotype that suggested an undiagnosed case and highlighting the effect of the intrafamilial clinical variability in delaying a prompt diagnosis. It is now recognized that his parents are, in fact, a carrier couple. Additionally, another relative had been previously identified as a heterozygote in a Tay-Sachs disease screening program, but the information was not shared among the family. Since this information might anticipate diagnosis and genetic counseling, it is advisable that heterozygote screening programs encourage families to share genetic information. ( J Child Neurol 2006;21:540—544; DOI 10.2310/7010.2006.00102).
Pilot Study of Efficacy of Tongue and Body Acupuncture in Children With Visual Impairment
Authors: Wong Virginia C.N. , Sun Jie-Guang , Yeung David W.C.
Published: January 2017

We studied the efficacy of tongue and body acupuncture in affecting visual recovery in children with central and peripheral visual disorders. Twelve children (five boys, seven girls) (age range 18 months to 14.5 years) with visual disorder with static functional visual ability for at least 12 months were recruited for the study. The causes of cortical visual impairment (10) included severe perinatal asphyxia (4), postencephalitis (1), traumatic brain injury (1), hydrocephalus (1), and increased intracranial pressure (3). Peripheral causes (2) were due to congenital optic atrophy. We used the following assessment tools: clinical visual improvement, defined as improvement of vision by one grade in one or both eyes with measurement of visual acuity; the functional visual outcome scale of 0 to 5, with positive outcome defined as improvement in one level on a functional scale; visual evoked potential, with positive improvement defined as 10% improvement in P100 latency of one or both eyes; [18 F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) of the brain, with positive improvement defined as a 10% increase in glucose metabolism in one or both occipital lobes; and the Clinical Global Impression Scale (parental report). Tongue and body acupuncture consisted of 60 sessions, with 5 sessions per week. Four children showed clinical or functional improvement (33%). Of nine children with abnormal visual evoked potentials, five had improvement (56%). Of seven children who underwent PET, six had improvement in glucose metabolism in the visual cortex (86%). Seven parents (58%) reported improvement (three children had 75% improvement; four children had 25% improvement). There was a significant correlation between the interval of onset of visual impairment and starting treatment with clinical or functional outcome, with a longer interval resulting in a better outcome ( P = .0282). However, there was no correlation between cause, severity, or clinical or functional visual outcome with improvement in the visual evoked potential or PET. We demonstrated that tongue and body acupuncture can improve the visual status of children with visual disorders, both peripheral and central in origin. As children with chronic visual impairment also showed some visual recovery, more studies should be done to assess the full potential of acupuncture as an adjunct to Western medicine in neuroplasticity. ( J Child Neurol 2006;21:462—473;
Bickerstaff Brainstem Encephalitis Associated With Mycoplasma pneumoniae Infection
Authors: Steer Andrew C. , Starr Mike , Kornberg Andrew J.
Published: January 2017

Bickerstaff brainstem encephalitis is a clinical syndrome of ophthalmoplegia, cerebellar ataxia, and central nervous system signs and is associated with the presence of anti-GQ1b antibodies. There is a clinical continuum between Bickerstaff brainstem encephalitis and Miller Fisher syndrome. We describe the case of an 11-year-old boy with encephalopathy, external ophthalmoplegia, brainstem signs, and ataxia with raised titers of anti-GQ1b antibodies. He presented following a respiratory illness and had laboratory evidence of recent infection with Mycoplasma pneumoniae. M pneumoniae infection has been associated with both Bickerstaff brainstem encephalitis and Miller Fisher syndrome. This is only the second case in the literature of Bickerstaff brainstem encephalitis with raised titers of anti-GQ1b antibodies described in association with M pneumoniae infection. The patient responded to intravenous immunoglobulin administration. ( J Child Neurol 2006;21:533—534;
Hemiconvulsion-Hemiplegia-Epilepsy Syndrome as a Presenting Feature of L-2-Hydroxyglutaric Aciduria
Authors: Lee Céline , Born Mark , Salomons Gajja S. , Jakobs Cornelis , Woelfle Joachim
Published: January 2017

L-2-hydroxyglutaric aciduria was diagnosed in a 9-month-old female infant after a complex febrile convulsion with subsequent transient left-sided hemiplegia. The symptoms were consistent with acute hemiconvulsion-hemiplegia-epilepsy syndrome. Magnetic resonance imaging (MRI) of the brain revealed distinct white-matter abnormalities in the bifrontal and bioccipital periventricular area and increased signal intensity in the lenticular, caudate, and dentate nuclei, consistent with L-2-hydroxyglutaric aciduria. Increased concentrations of L-2-hydroxyglutaric acid were detected in the urine, plasma, and cerebrospinal fluid. The patient was homozyous for the p.Lys81Glu (c.241A>G) missense mutation in the L-2-HGA gene, confirming the diagnosis of L-2-hydroxyglutaric aciduria. Acute hemiconvulsion-hemiplegia-epilepsy syndrome has not been reported as a presenting feature in L-2-hydroxyglutaric aciduria. In patients with prolonged or complicated febrile seizures such as hemiconvulsion-hemiplegia-epilepsy syndrome, L-2-hydroxyglutaric aciduria should be included in the differential diagnosis, especially in children with concomitant macrocephaly. ( J Child Neurol2006;21:538—540; DOI 10.2310/7010.2006.00116).
Metabolic Syndrome Manifestations in Cohen Syndrome: Description of two New Patients
Authors: Pirgon Ozgur , Atabek Mehmet Emre , Sert Ahmet
Published: January 2017

We report on sporadic cases that have the proposed diagnostic criteria for Cohen syndrome associated with metabolic syndrome. The patients, aged 14 and 16 years, had truncal obesity, mild mental retardation, hypotonia, narrow hands and feet, a high-arched palate, prominent upper central incisors, a high nasal bridge, and ocular abnormalities. Both had impaired glucose tolerance, with marked hyperinsulinemia exhibited by an oral glucose tolerance test. Moreover, they had the other metabolic syndrome features of hyperlipidemia and hypertension. We suggest that it is necessary to consider the possibility of metabolic syndrome in a case of Cohen syndrome. ( J Child Neurol 2006;21:536—538; DOI 10.2310/7010.2006.00128).
Stiripentol in Childhood Partial Epilepsy: Randomized Placebo-Controlled Trial with Enrichment and Withdrawal Design
Authors: Chiron Catherine , Tonnelier Sylvie , Rey Elisabeth , Brunet Marie-Lucie , Tran Agnes , d'Athis Philippe , Vincent Jean , Dulac Olivier , Pons Gerard
Published: January 2017

Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol ( n = 17) or to withdraw to placebo ( n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (—75%) than on placebo (—22%) ( P< .025). Twelve patients experienced at least one adverse event on stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons. ( J Child Neurol 2006; 21: 496—502;
Coexistence of Childhood Absence and Rolandic Epilepsy
Authors: Montenegro Maria Augusta , Guerreiro Marilisa M.
Published: January 2017

The coexistence of absence and rolandic epilepsy is extremely rare. This coexistence has been attributed to either the treatment or an atypical course of the disease. However, for some authors, this issue remains controversial. We report the case of a 9-year-old girl presenting with both absence seizures and focal seizures consistent with rolandic epilepsy. ( J Child Neurol 2006;21:535—536; DOI 10.2310/7010.2006.00133).
Visuomotor Tracking Related to Attention-Deficit Hyperactivity Disorder (ADHD)
Authors: Tirosh Emanuel , Perets-Dubrovsky Sharon , Davidovitch Michael , Hocherman Shraga
Published: January 2017

Deficient visuomotor tracking in children with attention-deficit hyperactivity disorder (ADHD) has been described, but the specific influence of attention on this deficit has not yet been elucidated. The present study compares visuomotor tracking under different conditions of attentional loading in children with ADHD with that of age-matched controls. A computerized visuomotor attentional tracking test that incorporated several levels of distraction was administered to 131 typical children. The same test, as well as a standard Matching Familiar Figures Test and the Proteus Maze test, was administered to 32 children with ADHD and 21 control children. Significant differences between children with ADHD and controls in visuomotor attentional tracking indices that relate to pacing and the accuracy of the tracking movements were observed under all levels of distraction. In parallel, a significant performance decrement was observed in all subjects once distraction was introduced. Discriminant analysis, based on the visuomotor attentional tracking test findings, resulted in correct classification of 92.3% of the typical children and 46% of the children with ADHD. Significant correlations between Matching Familiar Figures Test latency, as well as errors and visuomotor attentional tracking indices, were noted among children with ADHD when the visuomotor attentional tracking did not involve distraction. Under distraction, these correlations extended to the control group as well. In conclusion, visuomotor tracking appears to reflect the availability of attentional resources in general and is significantly affected by the presence of ADHD in particular. These results have potential implications related to the evaluation of children with ADHD on and off drugs. ( J Child Neurol 2006;21:502—507; DOI 10.2310/7010.2006.00135
Surfactant-Free Preparation of Biodegradable Hydrogel Microspheres for Protein Release
Authors: Tabata Yasuhiko , Ikada Yoshito , Morimoto Kazuhiro , Katsumata Hideyuki , Yabuta Toshiyuki , Iwanaga Kazunori , Kakemi Masawo
Published: January 2017

The preparation of biodegradable hydrogel microspheres in the absence of surfactants was carried out by a two-step procedure which involved the formation of non-crosslinked microspheres from gelatin based on its inherent gelation nature at low temperatures and the subsequent glutaraldehyde (GA) crosslinking. The size of the microspheres was controlled in the range of 3 to 100 μm by changing the concentration of gelatin or GA, the emulsification method, and the crosslinking time. Neutral aqueous solutions of proteins with different isoelectric points (IEPs) and molecular weights (Mws) were infused into freeze-dried hydrogel microspheres to produce protein-incorporated gelatin microspheres. In vitro protein release from the microspheres depended on the protein's IEP but not on the Mw. The incorporated basic proteins with IEPs > 7.0 were released initially from the acidic gelatin microspheres, followed by no substantial release, whereas a larger initial release of the incorporated acidic proteins with IEPs < 7.0 was observed. The basic gelatin microspheres exhibited an opposite relationship between proteins IEP and protein release. Noncharged dextran rapidly diffused out of acidic gelatin microspheres, irrespective of the Mw. These findings indicate that an ionic interaction with gelatin constituted hydrogel microspheres prevented oppositely charged protein from being released from gelatin under in vitro non-degradation conditions.
pH Sensitive Polymeric Prodrugs Containing Ibuprofen, Ketoprofen and Naproxen as Pendent Groups
Authors: Wang L. F. , Chang C. H.
Published: January 2017

Polymeric prodrugs were prepared by copolymerization of methacrylic acid (MA) with 2-hydroxyethyl methacrylate (HEMA) covalently linked with ibuprofen (HI), ketoprofen (HK) and naproxen (HN). Varying the monomer compositions in the copolymers afforded water-soluble polymeric prodrugs. The dissolution of these polymeric prodrugs was assayed by measuring the absorbance of the drug moiety in the parent prodrug (including the moieties, which were hydrolytically cleaved) after immersing for 3 h in buffer solutions at various pHs. The dissolution profiles were dependent on the copolymer composition. Both ester bonds were cleaved in pH 7.4 as well as pH 10 buffer solutions. The hydrolyzed products, hydroxyethyl ester of ibuprofen (Ibu-EtOH), ketoprofen (Keto-EtOH) and naproxen (Nap-EtOH) were synthesized. The free drugs and their drug-EtOH were qualitatively and quantitatively analyzed by high performance liquid chromatography (HPLC).
An Unusual Coupling of Poly(Ethylene Glycol) to Tyrosine Residues in Epidermal Growth Factor
Authors: Orsatti Laura , Veronese Francesco M.
Published: January 2017

An unusual covalent binding of hydroxysuccinimidyl ester activated polyethylene glycol), PEG, was found in the modification of a genetic variant of mouse epidermal growth factor (EGF): PEG was bound not only to the amino groups of the polypeptide as expected, but to a tyrosine residue as well. This unexpected PEGylation is related to the tyrosine environment in the peptide which does not occur in human EGF; furthermore, it is related to PEG size since it was found to occur to a greater extent with the PEG 5,000 molecular weight, than with the more hindered PEG 10,000.
The Deferred Consent Model in a Prospective Observational Study Evaluating Myocardial Injury in the Intensive Care Unit
Authors: Honarmand Kimia , Belley-Cote Emilie P. , Ulic Diana , Khalifa Abubaker , Gibson Andrew , McClure Graham , Savija Nevena , Alshamsi Fayez , D’Aragon Frederick , Rochwerg Bram , Duan Erick H. , Karachi Tim , Lamontagne François , Devereaux P. J. , Whitlock Richard P. , Cook Deborah J.
Published: January 2017

Background:

Informed consent is a hallmark of ethical clinical research. An inherent challenge in critical care research is obtaining consent when patients lack decision-making capacity. One solution is deferred consent, which is often used for studies that are low risk or involve emergency interventions. Our objective was to describe a deferred consent model in a low-risk critical care study.

Methods:

Prognostic Value of Elevated Troponins in Critical Illness Study was a prospective, pilot observational study of critically ill patients in 3 intensive care units, involving serial electrocardiograms and cardiac biomarkers. Newly admitted patients were enrolled over 1 month. When possible, informed consent was obtained a priori from the patient or substitute decision maker (SDM); otherwise, consent was deferred until the patient regained consent capacity or until their SDM was available. Logistic regression analysis was used to determine the association between patient’s sex, Acute Physiology and Chronic Health Evaluation II score, study center, person providing consent (patient vs SDM), method of consent (telephone vs in person), and the provision or not of informed consent.

Results:

The overall consent rate was 80.1% (213 of 266 persons approached). Of the 53 persons declining consent, 37 (69.8%) agreed to the use of data collected up until that point. Over half of all consent encounters were with patients rather than SDMs. Median interval delay between enrollment and the consent encounter was 1 day. On multivariate analysis, the only variable associated with consent was male sex of the patient (odds ratio for males 2.59, confidence interval: 1.19-5.63).

Conclusion:

Deferred consent facilitates implementation of time-sensitive research protocols until a consent encounter is possible. As a feasible alternative to exclusive a priori consent, the deferred consent model can be useful in low-risk studies in critically ill patients.
Uncontrolled Donation After Circulatory Determination of Death: A Systematic Ethical Analysis
Authors: Dalle Ave Anne L. , Bernat James L.
Published: January 2017

Uncontrolled donation after circulatory determination of death (uDCDD) refers to organ donation after a refractory cardiac arrest. We analyzed ethical issues raised by the uDCDD protocols of France, Madrid, and New York City. We recommend: (1) Termination of resuscitation (TOR) guidelines need refinement, particularly the minimal duration of resuscitation efforts before considering TOR; (2) Before enrolling in an uDCDD protocol, physicians must ascertain that additional resuscitation efforts would be ineffective; (3) Inclusion in an uDCDD protocol should not be made in the outpatient setting to avoid error and conflicts of interest; (4) The patient’s condition should be reassessed at the hospital and reversible causes treated; (5) A no-touch period of at least 10 minutes should be respected to avoid the risk of autoresuscitation; (6) Once death has been determined, no procedure that may resume brain circulation should be used, including cardiopulmonary resuscitation, artificial ventilation, and extracorporeal membrane oxygenation; (7) Specific consent is required prior to entry into an uDCDD protocol; (8) Family members should be informed about the goals, risks, and benefits of planned uDCDD procedures; and (9) Public information on uDCDD is desirable because it promotes public trust and confidence in the organ donation system.
Cytomorphometric Neutrophil and Monocyte Markers May Strengthen the Diagnosis of Sepsis
Authors: Mammen Joy , Choudhuri Jui , Paul Joshua , Sudarsan Thomas Isaiah , Josephine T. , Mahasampath Gowri , Jeyaseelan Vishali , Nair Sukesh C. , Peter John Victor
Published: January 2017

Background:

The diagnosis of sepsis is challenging in the absence of a gold standard test. Recent studies have explored the role of neutrophil and monocyte volume, conductivity, and scatter (VCS), derived from automated hematology analyzers, in diagnosing sepsis. We assessed the diagnostic accuracy of VCS parameters in critically ill patients with sepsis.

Methodology:

In this prospective study, VCS parameters, procalcitonin, and C-reactive protein (CRP) were assessed in patients with proven sepsis (cases) and 2 control groups (intensive care unit [ICU] patients without sepsis and healthy blood donors). The diagnostic property of each test was explored by calculating sensitivity, specificity, negative and positive predictive values, and area under the curve (AUC).

Results:

The study included 65 patients with sepsis, 58 nonseptic ICU controls, and 98 blood donors. Procalcitonin and CRP were not significantly different ( P > .06) between patients with sepsis and nonseptic patients. Mean (95% confidence interval [CI]) neutrophil volume (MNV) was significantly higher ( P < .001) in patients with sepsis (165.5; 95%CI 161.6-169.4) than in nonseptic (157.3; 95%CI 154.6-160.1) patients and donors (148.9; 95%CI 147.9-150). A similar pattern was seen with mean monocyte volume (MMoV). Neutrophil and monocyte conductivity and scatter parameters were variably associated. The AUC was highest for MMoV (0.74) and lowest for CRP (0.62). Among all parameters, MNV and MMoV had the highest specificity of 85% and 80%, respectively.

Conclusion:

In critically ill patients with suspected sepsis, VCS parameters may help strengthen the diagnostic probability of sepsis. Future studies may explore the role of serial monitoring of VCS to track response to antimicrobial therapy.
Interhospital Transfer of Children in Septic Shock: A Clinician Interview Qualitative Study
Authors: Odetola Folafoluwa O. , Anspach Renee R. , Han Yong Y. , Clark Sarah J.
Published: January 2017

Objective:

To determine the factors that influence the decision to transfer children in septic shock from level II to level I pediatric intensive care unit (PICU) care.

Design:

Interviews with level II PICU physicians in Michigan and Northwest Ohio. A hypothetical scenario of a 14-year-old boy in septic shock was presented.

Baseline:

40 mL/kg fluid resuscitation, central venous and peripheral arterial access, and high-dose vasopressor infusions were provided.

Escalation Point:

After 2 hours. When the patient is in catecholamine-resistant shock and oliguric, invasive mechanical ventilation is initiated.

Measurements and Main Results:

All 19 eligible physicians participated. At baseline, respondents would assess measures of perfusion and hemodynamics: blood pressure (BP; 15 [79%]), lactate (12 [63%]), and central venous oxygen saturation (ScvO2; 10 [53%]). Poor clinical response was signified by low BP (11 [58%]), elevated lactate (9 [47%]), low urine output (8 [42%]), and low ScvO2 (6 [32%]). At the escalation point, 13 of 18 respondents felt there was <50% probability of clinical turnaround without escalating treatment, though only 3 (16%) would call to discuss transfer. Seven (37%) respondents would give more fluid, whereas 8 (42%) would use central venous pressure to guide fluid resuscitation. Ultimately, 15 (79%) respondents would transfer for extracorporeal membrane oxygenation (ECMO) or renal replacement therapy if there was no response to escalated care. Four (21%) respondents would not transfer the patient: 1 felt appropriate care could be provided in the level II PICU, 2 felt transfer was unconventional, and 1 was unaware ECMO could be provided in refractory septic shock.

Conclusions:

Level II to level I PICU transfer of children with septic shock is triggered by perceived nonresponse to locally available therapies. Few referring physicians do not transfer children in refractory septic shock. This study provides new insight into decision-making that influences the interhospital transfer of children with septic shock.
Impact of New-Onset Left Ventricular Dysfunction on Outcomes in Mechanically Ventilated Patients With Severe Sepsis and Septic Shock
Authors: Vallabhajosyula Saraschandra , Gillespie Shane M. , Barbara David W. , Anavekar Nandan S. , Pulido Juan N.
Published: January 2017

Background:

Left ventricular systolic dysfunction (LVSD) and LV diastolic dysfunction (LVDD) are commonly seen in severe sepsis and septic shock; however, their role in patients with concurrent invasive mechanical ventilation (IMV) is less well defined.

Methods:

This was a prospective observational study on all patients admitted to all the intensive care units (ICUs) at Mayo Clinic, Rochester from August 2007 to January 2009. All adult patients with severe sepsis and septic shock and concurrent IMV without prior heart failure underwent transthoracic echocardiography within 24 hours. Patients with active pregnancy, prior congenital or valvular heart disease, and prosthetic cardiac valves were excluded. Left ventricular systolic dysfunction was defined as LV ejection fraction (LVEF) <50% and LVDD as E/e′ >15. Primary outcome was hospital mortality, and secondary outcomes included IMV duration, ICU length of stay (LOS), and total LOS. Two-tailed P value of <.05 was considered statistically significant.

Results:

In a total of 106 patients, 58 (54.7%) met our inclusion criteria, with 17 (29.3%), 11 (19.0%), and 5 (8.6%) having LVSD, LVDD, and both, respectively. The cohorts with and without LVSD and LVDD did not differ significantly in their baseline characteristics and laboratory and ventilatory parameters. Compared to those without LVSD, patients with LVSD had higher LV end-systolic diameters but were not different in their left atrial diameters or E/e′ ratio. Patients with LVDD had a higher E velocity and E/e′ ratio compared to those without LVDD. Hospital mortality was not different in patients with and without LVSD (8 [47%] vs 21 [51%], P = 1.00) and LVDD (8 [73%] vs 21 [45%], P = .18). Secondary outcomes were not different between the 2 groups.

Conclusion:

Left ventricular systolic or diastolic dysfunction did not influence in-hospital outcomes in patients with severe sepsis and septic shock and concurrent IMV.
Characterization of Myocardial Dysfunction in Fluid- and Catecholamine-Refractory Pediatric Septic Shock and Its Clinical Significance
Authors: Williams Feifei Z. , Sachdeva Ritu , Travers Curtis D. , Walson Karen H. , Hebbar Kiran B.
Published: January 2017

Purpose:

Myocardial dysfunction is a known complication in patients with pediatric septic shock (PSS); however, its clinical significance remains unclear. The purpose of this study was to characterize left ventricular (LV) and right ventricular (RV) dysfunction and their prevalence in patients with PSS using echocardiography (echo) and to investigate their associations with the severity of illness and clinical outcomes.

Methods:

Retrospective chart review between 2010 and 2015 from 2 tertiary care pediatric intensive care units. Study included 78 patients (mean age 9.3 ± 7 years) from birth up to 21 years who fulfilled criteria for fluid- and catecholamine-refractory septic shock. Echocardiographic parameters of systolic, diastolic, and global function were measured offline. They were correlated with admission Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction scores, vasoactive–inotrope score (VIS), β-type natriuretic peptide (BNP), lactate, type of shock, duration of mechanical ventilation (MV), intensive care unit and hospital length of stay, and mortality.

Results:

Overall, 28-day mortality was 26%, and 88% patients required MV. Prevalence of LV dysfunction was 72% and RV dysfunction was 63%. LV systolic dysfunction (fractional shortening z score <−2) was significantly associated with PRISM III, VIS, and BNP. RV systolic dysfunction (tricuspid annular plane systolic excursion z score <−2) was significantly associated with cold shock. LV and RV diastolic dysfunction did not have any significant clinical associations. No echocardiographic measures were associated with mortality.

Conclusion:

Myocardial dysfunction is highly prevalent in PSS but is not associated with mortality. LV systolic dysfunction is associated with a higher severity of illness, use of vasoactives, and BNP, whereas RV systolic dysfunction is associated with cold shock. Further studies are needed to determine the utility of echo in the bedside management of patients with PSS.